Stony Brook Young Investigators Review Fall 2021 Issue 17

THE SCIENCE OF WELL-BEING

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Facilitated Communication in Children with Autism

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Overcoming Isolation Through Natural Experiences

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Young Investigators Writing Competition Finalists

Fall 2021 Volume 17

EDITORIAL Editor-in-Chief: Shrey Thaker `22 Managing Editors: Riya Gandhi `22 Gabriela Zanko `23

Associate Editors: Elbek Fozilov `22 Nicole Gladstein `23 Farah Hasan `23 Colin St. Aubin `23

Copy Editors: Francesca Serraino `22 Panayiota Siskos `23 Sarah Cheung `24 Megha Gopal `24 Alexander Ye `25

Peer Reviewers: Gaurav Sharma `22 Roma Kidambi `23 Tharun Alamuri `23 Shreya Addepalli `24

LAYOUT CABINET Layout Chief: Komal Grewal `23 Layout Editors: Bee Mitchell `21 Fanny Zhao `22 Judy Liu `22

Isra Ahmed `23 Ujala Dar `24 Robin Bath `24

Heads of Cabinet: Matt Ramirez `22 Aneesha Rompally `24

Graphic Editors: Annie Li `22 Maple Zeng `24

Webmasters: Ruchira Samant `23

Event Coordinators: Jasmine Kumar `22 Hannah Philipose `23 Toby Li `23 Stephanie Shum `22 Prarthi Patel `24

WRITERS Alex Moir `23 Aditi Kaveti `23 Robyn Rutgers `24 Yukta Kulkarni `22 Ishmam Khan `25 Sooraj Shah `24

Ayesha Azeem `23 Ean Tam `22

Bridgette Kovler `23 Fiona Murphy `23 Jessica George `24 Thumyat Noe `23 Joyce Chen `23 Nicole Gladstein `23 Travis Cutter `22 Daphne Siozios `23

Vignesh Subramanian `24

YIWC Finalists:

Juzer Vasi `24

Isabella Oliveros `24

Natalie Dzikowski `22

Sara Maltempi `24 Jennifer Zhong `23 Sophia Augier `23 Angela Zhu `22 Julia Froese `22

A SPECIAL THANK YOU TO OUR

FACULTY ADVISORS Dr. John Peter Gergen, Mr. Joshua Rice (MFA), and Dr. Nicole Leavey

A NOTE FROM OUR

EDITOR-IN-CHIEF In its 13th year running, the Stony Brook Young Investigators Review (SBYIR) has continuously fulfilled and expanded its role of bringing scientific communication, literacy, and awareness to the Stony Brook campus. Having laid the foundation for more student involvement over the past two years, SBYIR has been able to successfully grow to nearly 60 active staff and writer positions. Over the course of the Fall 2021 semester, our teams have written, edited, designed, and compiled the most recent research on Stony Brook Campus and around the world. With pieces from 19 undergraduate writers and six high school writers, we proudly present the 17th volume of the biannual SBYIR Journal: The Science of Well-being.

This theme was chosen to address the contemporary challenges faced by millions of people under the COVID pandemic and highlight research related to not only mental and physical well-being, but also considering the well-being of society, economics, or the planet. To this end, this journal issue undertakes three aspects of well-being: mental, environmental, and physical. Gratefully, our staff rose to above the obstacles posed by returning to campus – harnessing creativity and ingenuity – and excelled in producing our previous volumes, holding events/workshops, and maintaining our presence around the Island.

In addition to the journal, SBYIR’s mission of infusing scientific literacy and communication into the undergraduate community was exercised through an array of workshops and events. These workshops, ran by each of the three SBYIR branches (cabinet, editorial, and layout), communicate skills like editing, peer-review, graphic design, and event planning to the undergraduate community.

Each semester, SBYIR holds a flagship event involving keynote speakers from around the country who deliver informative talks in accordance with the semester’s journal theme. This semester, we held a symposium where student researchers had a platform to practice their scientific presentation skills with real-time expert feedback from the Alan Alda Center for Communicating Science. For the Fall 2021 symposium, we are grateful to have had Dr. Catherine Monk, Professor of Medical Psychology, from Columbia University’s Departments of Obstetrics & Gynecology, and Psychiatry as our keynote speaker.

In the second annual Young Investigators Writing Competition, SBYIR judged nearly 80 pieces from high schools across the Island in four possible disciplines: Biology, Environmental Science, Psychology, and Space Research. These fields were distilled into nuanced prompts that addressed the COVID pandemic in these fields. In this journal issue, we present the six finalists’ pieces from this year’s competition.

The expansion of SBYIR is truly inspirational for me since I joined 4 years ago. Along this path, I would like to thank our hard-working writers and staff in the Editorial, Layout, and Cabinet branches.

I also extend this gratitude to our faculty advisors, Dr. J. Peter Gergen, Dr. Nicole Leavey, and Mr. Joshua Rice (MFA), and the Alan Alda Center for Communicating Science for their ceaseless support of our endeavors. I am incredibly proud of our current work, members, and SBYIR’s potential for the future.

SHREY THAKER

CONTENTS

I: SBU-Related Research 1

Highlights Alex Moir `23 Aditi Kaveti `23 Robyn Rutgers `24 Yukta Kulkarni `22

II: Mental Well-being 3 5 9 12 15

Highlights Ishmam Khan `25 Sooraj Shah `24 Ayesha Azeem `23

Expressive Writing as a Therapeutic Intervention Ean Tam `22

Facilitated Communication in Children with Autism Bridgette Kovler `23

The Unseen Pandemic: How COVID-19 Triggered a Societal Mental Health Crisis Fiona Murphy `23

Esketamine: Novel Drug Effective in Treating Treatment-Resistant Depression Jessica George `24

III: Environmental Well-being 18 19 22

Highlights Thumyat Noe `23 Joyce Chen `23

Stony Brook’s iGEM Chapter: Training Tomorrow’s Scientists Nicole Gladstein `23

Overcoming Isolation Through Natural Experiences Travis Cutter `22

IV: Physical Well-being 26 27 30

Highlights Daphne Siozios `23 Vignesh Subramanian `24

A Nanotechnological Novelty: The Current and Future Role of Lipid Nanoparticles Juzer Vasi `24

The Genetics of Aging: How Variation and Epigenetics May Facilitate a Long, Healthy Life Natalie Dzikowski `22

V: YIWC Finalists 35 38 42

Tenth Grade Finalists Isabella Oliveros, George W. Hewlett High School Sara Maltempi, John F. Kennedy High School

Eleventh Grade Finalists Jennifer Zhong, Smithtown High School East Sophia Augier, Smithtown High School East

Twelfth Grade Finalists Angela Zhu, Jericho Senior High School Julia Froese, Wantagh High School

UNCOVERING THE LINK BETWEEN SARS-COV-2 AND VASCULAR DYSREGULATION ALEX MOIR `23 SARS-CoV-2 is the virus that drove the COVID-19 pandemic. SARSCoV-2 has been shown to infect ciliated epithelial cells (EPCs), which line the upper respiratory tract, through a cell surface receptor known as angiotensin-converting enzyme 2 (ACE2), resulting in Acute Respiratory Distress Syndrome (ARDS). ARDS is characterized by both pulmonary and vascular dysregulation, which presents as shortness of breath, low oxygen, and poor circulation. It is currently unclear whether the vascular components of ARDS pathology are the result of direct infection of the endothelial cells (ECs) that make up the blood vessel walls or changes in how infected EPCs interact with and influence ECs along the epithelial-endothelial barrier in alveoli. To determine whether ARDS-associated vascular dysregulation is directly or indirectly caused by SARS-CoV-2 infection of ECs, Stony Brook researcher Dr. Erich R. Mackow and his team investigated the expression of ACE2 throughout the endothelium, or the population of ECs that line the inside of blood vessels.

The team first isolated EC populations from COVID-19 patient lung, heart, kidney, brain, and umbilical vein tissue samples, and immunostained them for N and Spike SARS-CoV-2 antigens. Analysis revealed no positive staining for these markers of SARS-CoV-2 cellular infection. Analysis of EC-based qRT-PCR and western blots, which search for specific target RNA and proteins respectively, also showed no presence of the ACE2 receptor. The researchers then engineered primary human pulmonary and brain ECs to express ACE2 and exposed the ACE2-expressing EC cultures to SARS-CoV-2. Immunostaining revealed the presence of N antigens and colocalization of virus with ACE2 in the ACE2-expressing ECs. Additionally, analysis of results from mRNA sequencing of infected ACE2-expressing ECs

revealed increased expression of several coagulation and vascular inflammation factors associated with ARDS vascular pathology.

The researcher’s findings provide compelling evidence that ECs do not express ACE2, which is essential for SARS-CoV-2 docking and infection of cells. Additionally, they demonstrate that SARS-CoV-2 infection is dependent on ACE2 expression, and that while SARS-CoV-2 is able to affect ECs, the pathogen is unable to infect those cells in vivo as they don’t express the ACE2 receptor. These findings also suggest that the vascular component of ARDS pathology is not the result of direct EC infection by SARS-CoV-2.

However, the mRNA sequencing results hint that small subpopulations of SARS-CoV-2 infected ECs may still play a role in ARDS vascular pathology, meriting future investigation.

Figure 1 SARS-CoV-2 infected epithelial cells interacting with endothelial cells may cause COVID-19 associated vascular disease.

1. J. Conde, et al., Recombinant ACE2 expression is required for SARS-CoV-2 to infect primary human endothelial cells and induce inflammatory and procoagulative responses. mBio 11, 1-7 (2020). doi: /10.1128/mBio.03185-20.

2. Image retrieved from: https://unsplash.com/photos/Pw9aFhc92P8

A JOURNEY INTO SPACE: WHAT IT MEANS FOR YOUR BONES ADITI KAVETI `23 Since the first instance of space exploration in 1961, many long-term space missions have been accomplished that give us insight into the effect of the microgravity environment in space on the musculoskeletal system.

However, current research does not provide enough concrete evidence that allows scientists to predict the qualitative risk of deterioration and bone loss in a prolonged space mission. A lack of on-board measurements for assessing bone loss and muscle atrophy, as well as a weak understanding of the mechanism and counter measurements contribute to the gap in knowledge surrounding the musculoskeletal deterioration and its associated complications during space exploration. Dr. Yi-Xian Qin, the director of the Orthopedic Bioengineering Research Laboratory and distinguished professor at Stony Brook University studies the physical mechanisms involved in the control of tissue growth, healing, and homeostasis, especially bone

Figure 1 A close-up image of the deteriorated quality of an osteoporotic bone that can result from the microgravity environment experienced during long-term space exploration.

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adaptation and regeneration influenced by the mechanical environment.

Qin and his team have been researching microgravity induced bone loss and noninvasive osteoporosis diagnosis, and proposed new methods in quantitative ultrasound (QUS) in order to directly estimate bone modulus.

QUS offers the advantage of measuring not only bone quantity, but also bone quality, which estimates the mechanical property of bone. The team prepared calcaneus transmitted ultrasound images that were measured by the scanning confocal acoustic technology of ultrasound imaging. They compared the broadband ultrasound attenuation images for a 72 year old male with normal bone density and a 97 year old female with severe osteoporotic bones less. The combined ultrasound attenuation and wave velocity images for the two representative cases provided true images reflecting the respective bones structural and strength properties.

Ultrasound imaging may be applied to bone measurement in the future using many different fundamental physical mechanisms, like ultrasonic wave propagation velocity or speed of sound, in order to identify individuals at risk and age-related human osteoporotic bone density loss, which could be used to understand the rate and pattern of bone loss in a microgravity environment. These noninvasive technologies can aid astronauts in prolonged space missions and assess the bone quality and strength.

1. Qin, Y-X. Challenges to the musculoskeleton during a journey to Mars: assessment and countermeasures. J Cosmology, 12, 3778-3780 (2010).

2. Image retrieved from: https://www.flickr.com/photos/germantenorio/17540697976

SAVING FOR A RAINY DAY: HOW WEATHER CONDITIONS INFLUENCE INVESTING

PREDICTING EXTERNALIZING BEHAVIOR IN INFANTS YUKTA KULKARNI `22

ROBYN RUTGERS `24

Figure 1 Unpleasant weather can influence institutional investors, resulting in delayed stock market reactions to firms’ earnings announcements.

Psychological research indicates that unpleasant weather may influence your physiological and psychological states, leading to pessimism, anxiety, and fatigue. In finance and economics, this weather-induced behavior can impact financial decisions and security prices. Dr. Danling Jiang, a professor of finance at Stony Brook University, studies the influence of psychology on financial markets. To evaluate the impact of experiencing unpleasant weather on immediate market responses, Jiang’s team measured weather conditions at the locations of institutional investors and market response time. Dr. Jiang and her colleagues hypothesized that unpleasant weather prior to market announcements correlates to slowed information processing, resulting in delayed reactions to such announcements.

To determine which weather was “unpleasant,” weather conditions were compared to the previous monthly averages from 1990 to 2016. Factors taken into consideration included cloud coverage, precipitation, and wind speed. Jiang’s team excluded extreme weather conditions, such as hurricanes and blizzards, to rule out the possibility that investors were unable to attend work. The researchers concluded that a one-standard-deviation increase in unpleasant weather prior to earnings announcements, the statements of a company’s profitability, led to a 10% smaller spread in announcement returns (changes in stock market prices). However, the same increase in unpleasant weather led to a 26% larger spread in post-earnings announcement drift, an anomaly in financial markets in which announcement returns do not reflect earnings announcements. Furthermore, Jiang’s team found that the effect of unpleasant weather on institutional investors was stronger for announcements made at the beginning or end of a month, when investors more actively trade and rebalance their portfolios. Additionally, a one-standard-deviation increase in unpleasant weather resulted in an 8% lower trading volume during the pre-announcement period. Jiang’s research provides evidence that unpleasant weather impedes information processing of institutional investors, amplifying market underreaction to earnings news and decreasing trading volume.

The findings of this study demonstrate the power of psychological biases and physiological constraints. Anyone, including institutional investors, can be susceptible to these influences while making decisions. By taking this effect into account, investors, moreover the general public, may be better prepared to avoid biased decision-making when the weather is cloudy, rainy, or windy.

1. J. Danling, et al., Weather, institutional investors, and earnings news. Journal of Corporate Finance, Forthcoming 69, 1-20 (2021). doi: 10.1016/j.jcorpfin.2021.101990 2. Image retrieved from: https://mcgillbusinessreview.com/articles/robinhood-and-the-gamification-of-the-stock-market

The minds of children are malleable and easily influenced by the circumstances they are placed into. Their experiences in early life can elicit certain actions according to the emotions they may not be able to process and control. This can be defined as externalizing behavior. More often than not, children who face trauma or stress such as abuse or poverty have higher rates of behavioral issues and outbursts throughout their life, some even starting before they reach the age of one. Biologically, modifications in stress-response systems are seen in these children. Dr. Allison Frost and her team focused on two such systems called the hypothalamic-pituitary-adrenal axis (HPA) and the autonomic nervous system (ANS). They wanted to determine if the two markers of the aforementioned systems, salivary cortisol and alpha-amylase, respectively, interact with each other and if these interactions could predict how an infant would react to stress.

The researchers focused on poverty as the stressor, including 179 parents and their infants (6-20-month-olds) living in predominantly low-income households. It was determined who could participate in the study by administering a socioeconomic questionnaire. Those who fit the criteria collected their infant’s saliva samples three times a day - once when they woke up, 30 minutes after waking up, and before they went to sleep - for three days. The saliva data was analyzed and illustrated in regression models. The parents also had to take the Infant Externalizing Questionnaire to determine the level of aggressive behavior the infant was expressing, as well as if the infant was being defiant. The results of the analysis show a significant connection between cortisol and alpha-amylase effects in the morning.

When infants in this study showed fewer amounts of externalizing behavior in the morning, their cortisol levels were low, while their alpha-amylase levels were high.

These findings are important because they demonstrate that multiple systems sometimes simultaneously affect behavior. This especially affects infants since they are young and can be easily influenced. This can also change the way parents view their children during a tantrum. If they are educated on how infants process information and react, parents can alter the circumstances the children are placed in. More studies need to take place to concretely conclude that the relationship between salivary cortisol and alpha-amylase can lead to fewer or more outbursts of externalizing behavior.

Figure 1 Infants can respond to the environments they grow in and react accordingly.

1. A. Frost, et al., Externalizing behavior and stress system functioning in infants exposed to early adversity: A multi-system exploration. Developmental Psychobiology 63, 1255-1265 (2021). doi: https://doi.org/10.1002/dev.22091 2. Image retrieved from: https://www.flickr.com/photos/anirudhkoul/3801958288

SBU HIGHLIGHTS

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THE BRIGHT SIDE OF WINTER: BATTLING SEASONAL DEPRESSION WITH A POSITIVE MINDSET ISHMAM KHAN `25 Seasonal Depression, clinically recognized as Seasonal Affective Disorder, is a recurrent pattern of seasonal depression or lack of exposure to sunlight during certain seasons, especially winter. Naturally, researchers have posited several hypotheses about how this disorder originated.

One popular hypothesis of the origins of this condition is the “latitude hypothesis,” which states that the further a location is from the equator, the more likely the inhabitants of that location are to exhibit depressive symptoms and episodes. However, recent studies have begun to contradict this hypothesis, stating that the amount of light has little to do with how one feels internally in regards to the environment. A study done in Norway by Kari Leibowitz and Joar Vitterso in the International Journal of Wellbeing set out to explain these contradictory findings through the lens of “mindset.” The experiment investigated whether certain mindsets about the seasons, specifically winter, actually did contribute

Figure 1 By adopting a wintertime mindset, as seen in inhabitants of Norway, one may be able to prevent or battle seasonal depression.

Figure 2 Despite the enveloping darkness, the Norwegians still find some way to include light in their lives.

This study suggests that shifting perspectives can benefit our mental well-being. Understanding that mindset is something that can be controlled opens up new possibilities and solutions to allow us to see the bright side of winter.

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to a depressive episode among 3 areas in Norway (Svalbard, Tromso, and Oslo) and whether wintertime mindsets contributed to seasonal well-being.

Researchers used two scales to measure the emotions of inhabitants of these places: Subjective Well-being (SWB) and Wintertime Mindset Scale (WMS). The results indicated that a positive wintertime mindset is associated with subjective well-being in Norway, with a positive wintertime mindset correlating with life satisfaction and positive emotions. They also found that wintertime mindset statistically mediated the effect of location on subjective well-being. When the researchers were testing the “latitude hypothesis” with SWB, they found that Svalbard, the northmost location tested, reported the highest SWB. By identifying wintertime mindset as an important factor influencing well-being for residents of northern Norway, researchers have uncovered a psychological approach to winter that may be exported from Norway to improve winter well-being elsewhere.

1. K. Leibowitz., & J. Vittersø., Winter is coming: wintertime mindset and wellbeing in Norway.

International Journal of Wellbeing 10, 1-20 (2020). doi: 10.5503/ijw.v10i4.935 Images retrieved from: 1. https://commons.wikimedia.org/wiki/File:Svalbard_DSCF1400_(23849118591).jpg 2. https://commons.wikimedia.org/wiki/File:Polar-Night_Longyearbyen.jpg

GRIP STRENGTH AS AN AVENUE OF DEPRESSION PREDICTION SOORAJ SHAH `24 Depression is a mental state in which individuals often feel disinterested in everyday activities, preventing them from taking advantage of life’s opportunities. In addition to its psychological effects, depression seems to take a physical form, with muscle strength and functionality being a main area of concern. Unfortunately, muscle failures often go untreated because the majority of people with depression tend to reject treatment. In a study led by Dr. Adilson Marquez, a professor of Human Kinetics at the University of Lisbon in Portugal, hand grip strength (gs) was measured across selected populations of middle-older adults to reveal a value that would be indicative of depression.

The population sample of 20,598 individuals (10,182 men and 10,416 women) was picked according to a European Survey of Health, Aging, and Retirement (SHARE). This survey contained information about individuals fifty or older regarding symptoms of depression from 14 different European countries. Researchers conducted ninety minute interviews with each participant, part of which included physical measurements. Symptoms of depression were recorded on a EURO-D scale measured from 0-12, where a score higher than 4 warrants diagnosis of clinical depression. To measure grip strength, participants squeezed a dynamometer as tightly as possible for five seconds. Diseases and other health conditions were noted as well.

The results showed that more women (29.6%) than men (16.5%) had depression according to the EURO-D scale. The average grip strength values for men and women were 44.6 kg and 27.9 kg, respectively. The gs cut

Figure 1 Grip strength can be a possible indicator of depression.

off-values for each demographic were 43.5 kg for men aged 50-64, 39.5 kg for men older than 64, 29.5 kg for women aged 50-64, and 22.5 kg for women older than 64. Participants above these gs cut-off values are associated with having a lower chance of depression. The results showed that although gs can predict depression in individuals, it should be used as a preliminary rather than primary test for depression. This is due to the weak discriminant capacity (ability for the model to predict individuals with/without depression) reflected in the cutoff gs values. As grip strength is used in other research to detect various types of conditions, some specific adjustments should be made to this research in the future such as noting the daily use of gs in activities, possible focus on just one sex, and expanding the age group observed.

Physical traits of individuals with depression is an important area of the condition which requires further examination. Grip strength is one trait that is indicative of depression, but it is a broad measurement that can be interpreted in various ways. Future research should focus on physical exercise, possible acne breakouts on the facial surface, or weight gains and losses in order to more accurately predict depression.

1. A. Marques, et al., Exploring grip strength as a predictor of depression in middle-aged and older adults. Scientific Reports 11, 15946 (2021). doi: 10.1038/s41598-021-95566-7.

2. Image retrieved from: https://images.unsplash.com/photo-1580893246395-52aead8960dc?ixid=MnwxMjA3fDB8MHxwaG90by1wYWdlfHx8fGVufDB8fHx8&ixlib=rb-1.2.1&auto=format&fit=crop&w=334&q=80

LEISURE TIME OR LOST TIME: HOW NEGATIVE BELIEFS ABOUT LEISURE EXACERBATE MENTAL ILLNESSES

AYESHA AZEEM `23

Although it is enjoyable to take breaks away from work and obligations, certain factors can undermine this enjoyment, like tracked or scheduled leisure time. Leisure provides people with a sense of control in life and can reduce the risk of depression. However, this benefits may be less impactful in people who believe that taking time out for leisure is wasteful.

Rutgers University researcher Gabriella N. Tonietto and her team investigated whether people who believe that leisure time is wasteful have decreased enjoyment during this time, even if it does not interfere with their goals.

The first study examined the role of terminal versus instrumental motivations and initially tested the effect of believing that leisure is wasteful on enjoyment. Terminal motivations lead a person to pursue actions for personal enjoyment, like attending a party; instrumental motivations lead a person to pursue actions for practical reasons, like dropping a child off at school. The researchers asked the participants about their activities on Halloween followed by their beliefs about leisure time. The team found that for terminal leisure activities, a stronger belief in the idea that leisure is wasteful was associated with decreased enjoyment. Conversely, there was

no significance in the association between beliefs about leisure and enjoyment for instrumental leisure activities.

In the second study, the researchers further examined the relationship between beliefs about the wastefulness of leisure and enjoyment by assessing participants’ attitudes towards different leisure activities, and how personal beliefs about leisure affect mental well-being. Three pretests were given to the participants to assess their ideas of leisure activities, whether they believed these activities were terminal or instrumental, and how actively they participated in each activity. The researchers found that socializing, relaxing, watching TV and carrying out hobbies were classified as terminal leisure, whereas exercising and meditating were classified as instrumental. Additionally, negative beliefs about leisure were associated with lower levels of happiness and higher levels of depression and stress.

The researchers concluded that the motivation behind the leisure activity determines how strongly negative beliefs about leisure will impact enjoyment. Future research can focus on implementing interventions to reduce the negative impact of believing leisure is wasteful, or on the relationship between gender or income and the effects of negative beliefs about leisure-time. Longitudinal studies may reveal more information about this phenomenon as well.

1. G. Tonietto, et al., Viewing leisure as wasteful undermines enjoyment. Journal of Experimental Social Psychology 97, 1-13 (2021). doi: 10.1016/j.jesp.2021.104198.

2. Image retrieved from: https://images.pexels.com/photos/92870/pexels-photo-92870.jpeg?auto=compress&cs=tinysrgb&dpr=2&h=750&w=1260

Figure 1 Leisure can be defined as time off from paid work and obligations.

MENTAL WELL-BEING

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Expressive Writing

Therapeutic Intervention

as a

EAN TAM `22 Abstract Stress is not limited to the mental well-being of a person. Stress has physiological manifestations, including altered mental acuity, sleep complications, and rapid heart rate. These physical effects on the body exacerbate the problem as the person can no longer function optimally to resolve the initial stressor (1). There are many forms of stress-relieving treatments, such as therapy (group or individualized), physical exercise, and recreational retreats. However, some therapies may be inaccessible due to cost or lack of resources.

One possible alternative is expressive writing, which evades the aforementioned burdens. Expressive writing allows one to discharge emotions through cognitive processing without the pressure of an audience or utilization of proper grammar. The therapeutic effect is felt through the minimization and/or release of negative emotions.

Figure 1 Illustration of an ink spill.

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In studying the benefits of expressive writing, particular focus has been given to the following sources of stress: educational stress, trauma from pregnancy complications, and loneliness due to lack of social inclusion. These three sources are of particular importance due to their frequency in society and long-term psychological impact; however, current research suggests that expressive writing can diminish or resolve strains on mental health from these sources of stress.

Work or School Related Stress Higher education is a definitive source of stress for young adults. In a study of 157 English university students in Ecuador, researcher Juanita Argudo of the University of Cuenca found that over 70% of the students felt ill because of the education-related stress from the previous six month period. Students self-reported ailments such as an inability to speak and write, sweating, tiredness, low blood pressure, and syncope. Especially concerning to researchers was that almost 40% of students were reluctant to share the endurance of mental health issues with their physicians during these stress-induced ill periods. In addition, students portrayed how stress manifests in their behavior and productivity: nearly 40% of students started accumulating absences and missing homework assignments (1). However, after four sessions of expressive writing and using quantitative analysis of students’ self-reported results, the research-

ers found a significant increase in students’ perception of expressive writing as a stress-reducing tool. In a qualitative analysis of the results, students reported that expressive writing aided in comprehending emotions, facing fears, and importantly, reducing stress and nervousness. The students reported that they planned to use expressive writing in the future, especially in high-stress situations like prior to taking an exam (1). Ultimately, while school related stress can harm students by hindering communication skills and yielding physiological manifestations of stress, expressive writing may serve as an effective intervention to mitigate such stress.

Additionally, expressive writing has been found to facilitate greater long-term social involvement amongst adolescents. In school settings, peer relationships can be a point of contention and source of anxiety. Using a positive and negative affect schedule (PANAS), researchers observed how their students experienced positive and negative emotions before and after treatment. In assessing the PANAS scores, they found that students with pre-existing peer-related problems benefitted the most from expressive writing. The students could engage themselves with stressful anecdotes, produce causal explanations to properly rationalize them, and obtain an emotional release (2). Additionally, for students with difficulties in handling emotions or impulsive behavior, expressive writing allows the writer to control the narrative in a safe and private environment (2). This therapeutic approach to stress allows young adults to transform negative experiences into emotionally controllable ones.

Complications with Pregnancy Another stressful situation in which expressive writing can help is during the course of pregnancy. When a pregnant woman is enduring depression, anxiety, and/or natural disasters, a host of developmental changes can occur in the fetus, and the child’s impending behavior and mental health can be put at risk. Hormones and neurotransmitters that are released during stressful situations can affect cell development and differentiation in the brain. Examples of associated outcomes of prenatal stress include attention-deficit/hyperactivity disorder (ADHD) and more difficult temperament in children (3). Expressive writing has been studied as a possible intervention to minimize prenatal stress.

In 2016, “The Beast” wildfire destroyed over 1.4 million acres of land and 2,400 households in Alberta, Canada. The traumatic evacuations forcibly displaced 1850 pregnant women, inducing significant prenatal stress.

In terms of psychological impact, a natural disaster is more than the initial life-or-death event, which instigates the fight or flight response; rather, it requires victims to handle the consequences, including the loss of property, dignity, and sense of control over one’s life. After “The Beast” wildfire, researchers at the University of Alberta studied

54 displaced pregnant women. The women were given online expressive writing journals. Over four days, the women wrote about their experiences related to the wildfires, including personal resilience, adaptability, and strengthening of personal relationships and self-control (4). When considering the effect the journals had on them, the women explained that articulation of their experiences into expressive writing gave the women an opportunity to recognize those who helped them throughout the wildfire disaster (e.g., significant others, friends). Hence, the potential to strengthen pre-existing personal relationships was granted.

Another source of trauma for pregnant women is the ordeal of terminating a pregnancy due to fetal complications. Women subjected to this experience are four times more likely to develop postpartum depression (depression after pregnancy) and seven times more likely to be diagnosed with post-traumatic stress disorder (PTSD) (5). Researchers at the Zhejiang University School of Medicine investigated the therapeutic effects of expressive writing on women undergoing a pregnancy termination due to fetal abnormalities.

Post-traumatic condition was observed by tracking patients’ responses to specific aspects of their lives such as appreciation of life, spirituality, avoidance of others/activity, and quality of personal relationships. Researchers found expressive writing significantly increased the women’s post-traumatic growth (PTG, the positive emotional development after a traumatic event) and decreased symptoms of PTSD. The increase in PTG continued to be observed one month after their first session of expressive writing, but there was no further decrease in symptoms of PTSD. The benefits of expressive writing occurred due to cognitive reappraisal of the trauma, emotional expression and balance, and reexamining resilience. The researchers concluded that the greatest potential occurs when expressive writing becomes an outlet for patients to create pathways for a future after pregnancy loss (5). Using expressive writing to engage with future ambitions is valuable because symptoms of PTSD and postpartum depression can continue for years after the pregnancy termination, making future pregnancies difficult to pursue.

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Achieving Inclusion Loneliness is a pervasive personal struggle, as no demographic is immune from it. Creative writing in groups is a source of building personal relationships. The activity does not require a writer to confront personal issues directly; instead, the writer produces emotional and behavioral changes within themselves by engaging in the creative process with one another.

Groups may have discussions of their writings, providing the author with new outlooks and ways of processing emotions. Through creative writing, research participants have felt as if they were filling an “existential vacuum” with a renewed understanding of negative experiences (6). Furthermore, a member learns to not only respond to the emotional vulnerabilities of others, but also navigate their own personal insecurities in order to participate in group discussions (7).

In a specific case of creative writing in groups, refugees have used the activity to acclimate to their new countries. In a study lead by Dr. Theodore Stickley and fellow collaborators at the University of Nottingham in England, 144 East European, North African, and Middle Eastern refugees in the United Kingdom engaged in group creative writing. As a result of the exercise, refugees reported a gain in confidence in their interpersonal skills and English proficiency. The refugees also enjoyed the freedom of speaking their mind and being heard by an audience. These were opportunities of which they were once deprived, thus encouraging sentiments of sanctity and renewed self-esteem in their new homes (8).

Limitations of Therapeutic Writing: Children and Culture Despite the tremendous implications from the aforementioned studies, therapeutic writing still encounters constraints. The first limitation of expressive writing lies in children. A French study of fifth graders split 35 students into two groups: an expressive writing group that wrote of a particularly stressful or negative day, and a non-emotional writing group that wrote about an average school day. Working memory, or the capacity to retain information, was the only distinction between groups (9). After writing, researchers used recollection tests on the students, during which students attempt to recall number and letter sequencing. Only the students in the expressive writing group enhanced their working memory. Compared to the non-emotional writing group, the emotional writing group had no significant decrease in depressive or anxiety symptoms. This study, along with previous investigations, shows that emotional processing during the course of expressive writing does not benefit children as much as adults (9).

Therefore, these findings should be taken into account if expressive writing is considered as a therapeutic intervention in school-aged children.

Another shortcoming found with expressive writing is cultural incompatibility. Researchers at the University of Houston found that expressive writing was not helpful for 96 Asian American women diagnosed with breast cancer. The researchers believe cultural differences may have affected how the Asian American women responded to expressive writing.

To observe post-traumatic progress, the researchers used a post-traumatic growth inventory (PTGI) and PTSD symptom scale self-report (PSS-SR).

PTGI provides insights into the positive growth one has had since a traumatic event. PSS-SR evaluates PTSD symptoms in patients.

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“Creative writing in groups is a source of building personal relationships.”

Using these two evaluations, it was found that Asian American women participating in the study actually had increases in PTSD symptoms and decreases in PTG (10). Divulging strong emotions may have been an uncomfortable cultural practice for the Asian American women. Reconstructing their emotional processing of their cancer diagnosis may have actually led to the observed increase in PTSD symptoms and decrease in PTG as observed in their PTGI and PSS-SR results. Additionally, the women were all foreign-born of Asian countries (mostly from China and Taiwan). Unlike later generations, first-generation Asian immigrants do not react as openly to stress and perceive stressful situations as lessons for personal growth (10). Not every person has a cultural upbringing that has equipped them to engage in emotional release.

Conclusion Recent events have put a spotlight on mental health awareness: stressed athletes withdrawing from competitions, personal isolation during the COVID-19 pandemic, socio-political insecurity. Expressive writing should be further recognized as a therapeutic solution to combat these issues because it can facilitate cognitive processing of negative emotions.

Given expressive writing’s accessibility and ease of use, institutions such as schools and hospitals should consider utilizing expressive writing for those experiencing mental health strain. Future research should explore the use of expressive writing in other cultures, patients of different medical conditions, and age groups. This research would help make would help make expressive writing more accessible and effective across all demographics.

References 1. J. Argudo, Expressive writing to relieve academic stress at university level. Profile: Issues in Teachers’ Professional Development 23, 17-33 (2021). doi: 10.15446/profile.v23n2.90448.

2. G. Travagin, et al., Letting oneself go isn’t enough: cognitively oriented expressive writing reduces preadolescent peer problems. Journal of Research on Adolescence 26, 1048-1060 (2016). doi: 10.1111/jora.12279.

3. B. Van den Bergh, et al., Prenatal developmental origins of behavior and mental health: the influence of maternal stress in pregnancy. Neuroscience & Behavioral Reviews 117, 26-64 (2020). doi: 10.1016/j.neubiorev.2017.07.003.

4. S. Brémault-Phillips, et al., Expressive writing for wildfire-affected pregnant women: themes of challenge and resilience. International Journal of Disaster Risk Reduction 50, 101730 (2020). doi: 10.1016/j.ijdrr.2020.101730.

5. J. Qian, et al., Effects of an expressive writing intervention in Chinese women undergoing pregnancy termination for fetal abnormality: A randomized controlled trial. Midwifery 103, 103104 (2021). doi: 10.1016/j.midw.2021.103104.

6. C. Deveney and P. Lawson, Writing your way to well-being: an IPA analysis of the therapeutic effects of creative writing on mental health and the processing of emotional difficulties. Counseling & Psychotherapy Research, early access (2021). doi: 10.1002/capr.12435.

7. B. Malyn, et al., Reading and writing for well-being: A qualitative exploration of the therapeutic experience of older adult participants in a bibliotherapy and creative writing group. Counselling and Psychotherapy Research 20, 715-724 (2020). doi: 10.1002/capr.12304.

8. T. Stickley, et al., “Write here, sanctuary” creative writing for refugees and people seeking asylum. Art & Health 11, 246-263 (2019). doi: 10.1080/17533015.2018.1494450.

9. M. Fartoukh and L. Chanquoy, Expressive writing in school children: effects on well-being and working memory. Journal of Writing Research 11, 505-523 (2020). doi: 10.17239/jowr2019.11.03.04.

10. M. Gallagher, et al., The unexpected impact of expressive writing on posttraumatic stress and growth in Chinese American breast cancer survivors. Journal of Clinical Psychology 74, 1673-1686 (2018). doi: 10.1002/jclp.22636.

Images retrieved from: 1. Graphics illustrated by Ujala Dar `24 2. https://pxhere.com/en/photo/629011 with a graphic illustration by Ujala Dar `24

Figure 2 Expressive writing can be done anywhere and at any time the writer feels the most comfortable.

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Facilitated Communication in Children with Autis M BRIDGETTE KOVLER `23 Language is vital to the educational learning process and in forming meaningful connections through the conveyance of emotions, thoughts, and opinions. However, many non-verbal children with autism struggle to communicate with their loved ones and caregivers due to barriers in language expression. Parents are not able to celebrate the joyous feeling of bonding with their child through conventional means, and thus, turn to various methods to meet the needs of their child. In the 1990s, these methods included facilitated communication, the rapid prompting method, and a picture exchange communication system. Although these techniques were seen as effective in their time, later research suggested that they were merely pseudoscientific and flawed with regards to false authorship of messages and inconsistency in message conveyance. These older methods focused on children’s present communication needs and heavily relied on the aid of a facilitator, but communication interventions and therapies must be developed that take a more holistic approach in considering a child’s early language development, adaptability of use, and autonomy in order to be more effective. Evidence of efficacy in incorporating a more holistic approach is seen in methods such as the brief observation of social communication change, generalized pediatric communication therapy, and discrete trial training.

to images or letters on storyboards. On various occasions, facilitators accused parents and caregivers of child abuse through the use of facilitated communication because they had the authoritative advantage to do so. Rapid prompting method, on the other hand, requires the child to point to letters in order to spell words. In this case, the facilitator holds the letter board instead of the child’s hand. Tactile prompts are more prominent in the rapid prompting method, such as ripping papers or giving the child a writing utensil to point with (1). The rapid prompting method relies heavily on prompt dependency, which weakens the validity of the therapy technique by suggesting that the information being conveyed is not specifically aligned with the exact thoughts of the individual with disabilities. Both methods are flawed with regards to enhancing communication among non-verbal autistic children and therefore, new methods that take on a new, more integrative approach are required.

“...facilitated communication... poses potential flaws, such as false ownership and accusatory messages; it is difficult to identify if the facilitator is speaking for the child...”

Flaws of Facilitated Communication and Rapid Prompting Method Facilitated communication and rapid prompting method were utilized by parents of non-verbal autistic children in the effort to address their children’s needs, thoughts, and emotions. Facilitated communication involves storyboards, which do not require typical modes of communication, such as verbal language, facial expressions, and body language. However, this technique also poses potential flaws, such as false ownership and accusatory messages; it is difficult to identify if the facilitator is speaking for the child, as a facilitator supplements physical function by holding a child’s hand while the child presses keys on a keyboard to type messages or points

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Brief Observation of Social Communication Change Core autistic symptoms progressively change over time, as indicated by alteration in verbal language communication.

A study conducted by Janina Kitzerow, a researcher in the Department of Child and Adolescent Psychiatry at the Frankfurt University Hospital, and her associates utilized a communication strategy called brief observation of social communication change (BOSCC) to assess early intervention techniques. This study selected 21 individuals with autism who were 46 to 69 months old and received one year of the Frankfurt early intervention program prior to the commencement of trials. This intervention program involved training parents and kindergarten teachers to enhance communication with young children. BOSCC consists of 16 behavioral items, which include social communication abilities and restrictive or repetitive behaviors. Clinicians scored the behavior items on a 0-5 scale. Video recordings of the children in social situations were taken before and after the one year of treatment. Two clinicians rated the children’s demonstrations of the be-

Figure 1 In facilitated communication, a facilitator holds the child’s hand to physically assist them in pressing keys on a keyboard to type messages, or pointing to images or letters on storyboards.

havioral items in the videos on a 0-5 scale. A 0 on the scale implied no abnormality and a 5 indicated significant abnormalities that could impair functioning. Thus, the researchers hoped for scores to decrease following intervention. The results demonstrated that the intervention decreased BOSCC scores overall and for most individual behavioral items, supporting the notion that early interventions, particularly those involving training of parents and teachers, are effective in countering communication-related autism symptoms in children within the age range of 46 to 69 months (2).

Generalized Pediatric Communication Therapy In 2016, Andrew Pickles, a professor at the Institute of Psychiatry at Kings College, and his associates investigated whether a type of parent-mediated social communication therapy called Preschool Autism Communication Trial (PACT) had long-term impacts on communicated-related symptoms in autistic children. The PACT program involved twelve 2-hour therapy sessions over a span of 6 months, followed by 6 months of monthly support sessions. During this time, parents also did 20-30 minutes of daily exercises with the children. Symptoms were assessed based on questionnaires and scoring systems immediately after the treatment and then 5-6 years after treatment at approximately the age of 10. The PACT group was compared to a control group, which received a non-PACT traditional treatment (3).

Questionnaires and surveys such as the social communication questionnaire, brief observation of social communication change, and vineland adaptive behavior scales were used. However, the primary outcomes and scoring systems used were autism symptom severity, which was assessed using the autism diagnostic observation schedule (ADOS) comparative severity score and the parent-child dyadic communication measure for autism. The effect size (ES) of PACT immediately following the intervention was found to be 0.64 and during follow-up was found to be 0.70, evidenced by an overall reduction of autism symptom severity (3).

These results demonstrate that generalized pediatric communication therapy such as PACT, which involves practicing communication strategies both during therapy sessions and at home, is highly effective in helping autistic children apply learned communication skills across varying contexts; they are able to practice PACT communication skills at home, school, and in public areas, while facilitated and rapid prompting method were limited in their reach as they were restricted by the presence of the facilitator.

This treatment’s continuing efficacy at later follow-ups also demonstrates its potency as a non-verbal autism intervention. Not only is this therapy effective in providing flexibility in skill applicability, but it provides skillful practice and integrative educational engagement with parents, caregivers, and teachers as well.

Discrete Trial Training To enhance communication among non-verbal individuals, caregivers must focus on breaking down skills into small tasks that are more manageable. In 2018, Dr. Mohammed Akram Hamdan, faculty member at the Department of Special Education at the University of Tabuk, conducted a study containing 20 items measuring attention, imitation, understanding facial expressions, and maintaining eye contact in non-verbal children with autism. The study consisted of 26 children between the ages of 6 and 11 years, who were randomly placed in experimental and control groups. The experimental group was subject to discrete trial training intervention, while the control group was not. Both groups took a pre-test at the beginning of the study and a post-test after the intervention so that their scores could be used as a measure of effective learning. Discrete trial training relies on learning theory, which considers the methods by which students effectively comprehend and retain information while learning, and applies these methods to maximize childhood knowledge growth opportunities in the future (4). The quantitative results of the study demonstrated a mean of 2.6 on the pre-test and 3.34 on the post-test for the experimental group, showing significant improvement and retention of learned information and thereby indicating effective learning as a result of discrete trial training. The control group, however, had a pre-test mean of 2.34 and a post-test mean of 2.44, which was a less profound difference (4). This suggests that discrete trial training’s approach of repetition and positive reinforcement in breaking down topics into smaller concepts independently is an effective learning strategy. Specifically, non-verbal children were found to participate in imitation and symbolic play more as a result of the training, enhancing communication skills.

This approach allows children to generalize the skills they have attained and apply them in a variety of settings, similar to the aims of generalized pediatric communication therapy. Other advantages of this technique include shorter lessons and increased involvement of teachers along with caregivers in knowledge acquisition, such that the need for facilitators is less. In this way, discrete trial training represents an effective communication method for non-verbal autistic children that grants them autonomy and independence, as the aid of facilitators and trained professionals is not necessary.

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Figure 2 Information conveyed through facilitated communication can be unreliable due to the difficulty in identifying if the facilitator is speaking for the child, resulting in possible false ownership and accusatory messages.

Conclusion and Future Directions Past communication methods including facilitated communication and the rapid prompting method were flawed in their approaches to obtaining true authorship of messages by non-verbal autistic children. However, new methods have been more effective in eliciting language using a more integrative approach. The brief observation of social communication change (BOSCC) method considers the critical period of language development in children by delivering early intervention, allowing non-verbal autistic children to acquire enduring language skills. The skills acquired from generalized pediatric communication therapy can be applied to diverse settings, thus enhancing external validity by removing environmental constraints on communication. Lastly, discrete trial training lessened the need for a facilitator, thus granting a child more autonomy in conveying their thoughts and emotions. This also eliminates the concerns of false authorship and illegitimate message conveyal that accompany facilitated communication. All of these interventions look beyond the immediate environment and needs of the child (as facilitated communication and rapid prompting method did) and focus on building skills for life that can be implemented independently in a wide variety of settings. The success of these techniques suggests that a more holistic and integrative approach is needed in order to design the most effective interventions for non-verbal autistic children; additionally, the more integrative elements an intervention involves, the more effective it will be at reducing communication-linked autism symptoms.

As these methods represent a step towards crafting a holistic ap-

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proach to communication in non-verbal autistic children, they should therefore be used as a guideline for future research. Future development of interventions should consider present-day circumstances such as the COVID-19 pandemic and communication tactics, such as adapting to telehealth models to continue to deliver necessary therapies in a convenient, online setting, which may further increase the flexibility of such techniques as the child would be able to access the therapy session from any setting that they are in. Additionally, augmentative and alternative communication methods could be utilized, which involve the use of electronic tablets that let the child independently communicate in any setting without the need for a facilitator. Telehealth, augmentative, and alternative methods all seek to increase accessibility and adaptability of communication interventions, which are holistic in the sense that they consider changing times, circumstances, and allow for a wider reach.

Other contextual factors such as engagement of family members and educators should be considered as well so that the child’s communication skills can be reinforced in these various settings, as in generalized pediatric communication therapy and discrete trial training. By building on BOSCC, generalized pediatric communication therapy, and discrete trial training with factors like telehealth options that would increase reach and accessibility, a more holistic approach to communication interventions is bound to arise, which goes above and beyond the narrow-focused methods of facilitated communication and rapid prompting method.

While all of these methods, new and old, had the general well-meaning intentions of giving autistic children a voice, the efficacy of the interventions ultimately determines to what extent these children’s voices are heard. These methods will give autistic children the ability to effectively communicate with teachers, friends, caregivers, parents, and loved ones, forming valuable bonds and connections. Their opinions and feelings can be validated and acknowledged, granting these children their rightful place in society.

References 1.Rapid prompting method (RPM). American Speech-Language-Hearing Association, (1970).

2. J. Kitzerow, et al., Using the brief observation of social communication change (BOSCC) to measure autism-specific development. Autism Research 9, 940-950 (2016). doi: 10.1002/aur.1588.

3. A. Pickles, et al., Parent-mediated social communication therapy for young children with autism (PACT): long-term follow-up of a randomised controlled trial. The Lancet 388, 2501-2509 (2016). doi: 0.1016/S2215-0366(14)00091-1.

4. M. Hamdan, Developing a proposed training program based on discrete trial training (DTT) to improve the non-verbal communication skills in children with autism spectrum disorder (ASD).

International Journal of Special Education 33, 1-13 (2018).

5. L. Zwaigenbaum, et al., Rethinking autism spectrum disorder assessment for children during COVID-19 and beyond. Autism Research 1, 1-9 (2021). doi: 10.1002/aur.2615.

6.I. Navarro, et al., Using AAC to unlock communicative potential in late-talking toddlers. Journal of Communication Disorders 87, 106025-106025 (2020). doi: 10.1016/j.jcomdis.2020.106025.

7. F. Craig, et al., Social communication in children with autism spectrum disorder (asd): correlation between dsm-5 and autism classification system of functioning—social communication (acsf:sc). Autism research 10, 1249-1258 (2017). doi: /10.1002/aur.1772.

Graphics illustrated by Isra Ahmed `23

The Unseen Pandemic: How COVID-19 Triggered a Societal Mental

Figure 1 A representation of diminished mental health, as experienced throughout many communities during the COVID-19 pandemic.

Health Crisis

FIONA MURPHY `23 Introduction Communities around the world have felt the impact of the COVID-19 virus for almost two years as it continues to burden healthcare systems, economies, and social institutions. The effects of the virus are often frighteningly conspicuous with reports of spiking infection rates, dwindling numbers of ICU beds, and nationwide lockdowns. However, one less visible result of the pandemic is a society-wide mental health crisis.

The pandemic has created unique circumstances — social isolation, telecommuting (working from home) and homeschooling mandates, and increased media coverage of potentially stressful COVID-19 related events — which have led to a deterioration in the mental health of entire communities. Researchers have analyzed these conditions and how they have impacted three distinct groups of people, namely adolescents, college students, and adults, hoping to address weaknesses in public health protocols and understand the psyche of a pandemic society.

Adolescents Recent research has aimed to assess the toll that COVID-19 has had on the mental health of adolescents. According to researcher Kalee De France of Concordia University, along with her colleagues, several factors make adolescents more susceptible to mental health challenges that may be incurred by pandemic circumstances, including a greater aversion to social

isolation at a young age, decreased coping ability due to immature development in the prefrontal cortex — the part of the brain responsible for complex logical thought and reasoning — and a lack of foundational relationships made in a school environment due to remote learning (1). De France and her colleagues’ findings corroborated this predicted propensity towards a decline in mental health as a result of pandemic conditions. Looking at a sample of Canadian adolescents, they found that from pre-pandemic to pandemic conditions, these adolescents overall experienced significant increases in symptoms of both depression and anxiety. During this developmental period of life, negative mental health situations can have life-long consequences, so identifying this trend is important for implementing interventions to help youth build skills allowing them to cope with pandemic circumstances. This study was also conducted in an area with low COVID-19 case numbers and no deaths, revealing that the mental health impact of this pandemic extends far beyond regions with direct and severe physical spread of the virus (1).

College Students Another unique community impacted by the pandemic is that of college students. At Arizona State University, researcher Ashley Fraser, along with her colleagues, analyzed the pandemic’s impact on university students’ media usage and its correlation to a decline in mental health. Finding that

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TV and video game usage increased during the pandemic amongst college students, the researchers posit that this increase may be a result of more free time because of physical distancing measures, unemployment, or possibly greater interest in COVID-19 related news on the television. News regarding the pandemic has been found to increase levels of stress, as the increased viewing among students was positively associated with a “concern for society”, which the study explains is reflected by short term anxiety and depressive symptoms (2). Ultimately, media appears to have been used by many college students as a coping mechanism during pandemic conditions, suggesting that close attention must be paid to the relationship that young adults have with media as increased media usage can potentially precipitate a decline in mental health.

Physical and mental health are equally important for a person’s well-being, yet mental health is not always a focus of public health strategies.

At the City University of New York, Heidi E. Jones and her colleagues investigated the mental health impact of the COVID-19 pandemic on college students in the CUNY system, which can be generalized to college students in other large urban centers. A majority of these students are from low-income backgrounds, and were further financially burdened by the pandemic, with 81.1% of students reporting decreases in their household income due to COVID-19 conditions (3). Jones and her fellow researchers found a trend of decreased mental health among these students, as about half of them reported increased levels of depression and anxiety, and more than half experienced a diminished ability to complete schoolwork as a result of poor mental health. With concerns for the potential impact that decreased mental health could have on students’ academic success and general well-being, the researchers suggest targeted interventions such as increased mental health services on campuses, as well as considerations for the financial insecurity many students are facing because of the pandemic (3).

Adults The remote learning model that has negatively impacted both children and college-aged students has also taken a toll on the mental health of parents. Researcher S. Helene Deacon of Dalhousie University and her collaborators investigated the effect that mandated homeschooling, one of the many strenuous consequences of the pandemic, had on the mental health of parents who now had to take on the role of educator.

Deacon’s team explained that forced homeschooling evokes the Transactional Model of Stress and Coping; instead of the additional role of educator providing a greater sense of structure and meaning for parents, the increased responsibility actually overwhelms parents and their coping abilities (4). Many factors may play

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into this extreme burden caused by homeschooling, such as a lack of support from educational institutions, having to adapt to occupational changes such as telecommuting, as well as other pandemic-related stressors. In their study, Deacon and her colleagues found that couples who homeschooled children during the pandemic had lower levels of optimism as well as higher rates of substance use (cannabis and alcohol) in order to cope with deteriorating mental health. Additionally, they found a positive correlation between hours that an individual or their partner spent homeschooling a child and negative mental health symptoms such as depression, anxiety, or increased alcohol consumption, which Deacon and her fellow researchers postulate may be a result of increased tensions and interpartner conflict.

As suggested by this study, future public health protocols should focus on increasing the optimism levels of parents through intervention techniques such as greater social support systems, as optimism is a flexible trait which could improve the mental health of parents in a remote learning situation (4).

Employees are also struggling through the challenges of the pandemic as they face many issues including telecommuting mandates and other changes within their occupational setting, as well as the threat of rising unemployment rates. Researcher Stephanie Andel from Indiana University and her collaborators identified an increase in work loneliness, or lack of belonging stemming from the isolating working conditions of the pandemic, as a part of their study. The isolation from others in a work setting acted as a psychological stressor for many, contributing to increased levels of depression (5). While working from home was seen to sometimes produce these negative mental health situations, other studies found that employees returning to the workplace after an extended period of time faced a similar predicament. At Fudan University in China, researcher Shuyue Yang and her colleagues conducted a study of employees returning to work in two areas of China afflicted by the virus: one highly impacted area and one area with limited exposure to the COVID-19 virus. Over one fifth of returning workers reported either depression or anxiety, rates which were higher in the region more severely impacted by COVID-19 (6). While this result revealed a decrease in the amount of workers experiencing diminished mental health than during the height of the pandemic, the continued prevalence of

Figure 2 Side effects of

the COVID-19 pandemic such as social isolation due to telecommuting mandates and increased media coverage of pandemic-related news have contributed to community-wide increases in depression and anxiety.

negative mental health symptoms indicates a need for greater intervention strategies in the transition back to normal pre-pandemic conditions.

Explaining the Decline While many researchers aim to assess the impact that the pandemic has had on the mental health of various communities, research is also being done to determine what may be predictors of a decline in mental health during pandemic circumstances.

In their study, Benjamin Gibson of Liverpool John Moores University and his colleagues evaluated how different societal inequalities play a role in a negative mental health outcome during the pandemic. Groups subjected to inequality include females, youth, marginalized ethnic groups or sexual orientations, those with a lack of financial security, or people with pre-existing health conditions (7). Some of these characteristics, such as being female or of younger age, would appear to contradict evidence suggesting that they would not be at risk of negative mental health consequences during the pandemic. For example, although men and women contract COVID-19 at the same rate, men are more likely than women to die from the virus; however, women have experienced more negative mental health symptoms such as depression and anxiety during the pandemic. Gibson posited that this inequality in mental health status between the sexes could be due to social structures, such as gender roles. More women may be struggling with work-life balance during the pandemic as there are increased child care responsibilities, while men may struggle with coping with the emotional effects of the pandemic due to the stigma around men’s mental health (7). Thus, various factors like stigma or existing societal challenges related to inequality can lead to a decline in mental health for certain groups of people more than others. As a result, it is important for communities to understand how social inequalities may exacerbate difficult circumstances — like those created by a pandemic — for some people, and in turn greater support can be directed to these groups.

In another study, researchers Hannah Rettie and Jo Daniels of the University of Bath analyzed how a person’s Intolerance of Uncertainty (IU) contributes to a worsening mental health state during COVID-19. An IU is the adverse thoughts and emotions that a person experiences when they are in a state of uncertainty, like the many circumstances created by the COVID-19 pandemic, and this index has been known to factor into several emotional disorders including Generalized Anxiety Disorder (8). Rettie and Daniels found that in a pandemic setting, people with higher IUs were more inclined to have poorly adapted coping strategies, which in turn resulted in a greater tendency towards depression and anxiety, especially in

regards to health (8). Thus, taking into account an individual’s IU could be a method by which to predict poor mental health outcomes in pandemic circumstances, and may be targeted to help prevent a mental health decline.

Conclusion The outbreak of COVID-19 brought difficult challenges to almost every community around the world, with a widespread deterioration of mental health coming to the forefront as a prominent issue. Physical and mental health are equally important for a person’s well-being, yet mental health is not always a focus of public health strategies. By learning about how mental health is impacted by the COVID-19 virus and policies created to counteract its spread, researchers hope to influence public health policymakers to enact more effective community-level interventions that target the impact of adverse conditions like social isolation or additional familial responsibilities on mental health. In this way, declines in mental health can be limited as the COVID-19 pandemic continues or other pandemics arise in the future. Without any improvement, decreased mental health as a result of COVID-19 is a pandemic that may linger long after we see COVID-19 eradicated.

References 1. K. De France, et al., The mental health implications of COVID-19 for adolescents: follow-up of a four-wave longitudinal study during the pandemic. American Psychologist, 1-16 (2021). doi: 10.1037/amp0000838.

2. A. Fraser, et al., College students’ media habits, concern for themselves and others, and mental health in the era of COVID-19. Psychology of Popular Media, 1-14 (2021). doi: 10.1037/ ppm0000345.

3. H. Jones, et al., The impact of the COVID-19 pandemic on college students’ health and financial stability in New York City: findings from a population-based sample of City University of New York (CUNY) students. J Urban Health 98, 187-196 (2021). doi: 10.1007/s11524-020-00506-x.

4. S. Deacon, et al., Parenting through a pandemic: mental health and substance use consequences of mandated homeschooling. Couple and Family Psychology: Research and Practice, 1-14 (2021). doi: 10.1037/cfp0000171.

5. S. Andel, et al., Depending on your own kindness: the moderating role of self-compassion on the within-person consequences of work loneliness during the COVID-19 pandemic. Journal of Occupational Health Psychology 26, 276-290 (2021). doi: 10.1037/ocp0000271.

6. S. Yang, et al., Depression and anxiety symptoms among returning workers during the COVID-19 period in East China.

Social Psychiatry and Psychiatric Epidemiology 56, 12331240 (2021). doi: 10.1007/s00127-020-01983-w.

7. B. Gibson, et al., The impact of inequality on mental health outcomes during the COVID-19 pandemic: a systematic review. Canadian Psychology/Psychologie Canadienne 62, 101-126 (2021). doi: 10.1037/ cap0000272.

8. H. Rettie, J. Daniels. Coping and tolerance of uncertainty: predictors and mediators of mental health during the COVID-19 pandemic. American Psychologist 76, 427-437 (2021). doi: 10.1037/amp0000710.

Images retrieved from: 1. https://pxhere.com/en/photo/1639768 2. https://pixabay.com/illustrations/covid-19-workfrom-home-quarantine-4938932/ 3. https://www.urevolution.com/how-to-cope-withsocial-isolation-covid19/

Figure 3 The COVID-19 pandemic incited a major public health response to curb the physical health impacts of the disease; however, efforts to reduce the mental health repercussions of the pandemic have often been neglected.

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Esketamine: A Novel Drug for Treating Treatment-Resistant Depression JESSICA GEORGE `24 According to the World Health Organization (WHO), over 264 million people suffer from depression globally (1). The cause of major depressive disorder (MDD) is broad and multifactorial. MDD can present as loss of interest in daily activities, persistent sadness, suicidal thoughts, and various other negative symptoms that impact a person’s well-being. The COVID-19 pandemic only further exacerbated the mental health crisis, increasing the reported rates of anxiety or depression and instances of suicidal thoughts to nearly double the expected pre-pandemic rates (2). As a major contributor to the global burden of disease, MDD requires urgent solutions. While current treatment options include various therapies and antidepressants, they offer no relief from treatment resistant depression (TRD), a subtype of MDD. Ketamine has also been used to treat MDD for years, its anesthetic properties making it useful for catalepsy, analgesia, and sympathetic stimulation effects. However, it was only in March of 2019 that esketamine, a more potent form of ketamine, was approved by the FDA for use in individuals with TRD. Clinical trials have revealed that the drug is not only a viable TRD treatment option for short term relief, but also in the long term through maintaining remission. Despite the shortcomings of these other therapeutic models, the outlook on esketamine looks promising on account of its effectiveness, immediate results, and ability to delay relapse.

Mechanism of Action The unique mechanisms in which esketamine pharmacologically actuates makes it a breakthrough in TRD treatment. Unlike conventional antidepressants that affect monoamine neurotransmitters (serotonin, norepinephrine, and dopamine), esketamine blocks the N-methyl-d-aspartate (NMDA) receptors of inhibitory neurons, thus releasing glutamate (a neurotransmitter used to send signals to other cells) across neurons (3). This process triggers the formation of new neural connections and improves neuroplasticity, which is the brain’s ability to adapt its structure and function, and impairing this role is linked to depression (4). The ability of esketamine to be effective despite operating through a different mechanism of action from other commonly used antidepressants necessitates reevaluating the pathophysiology of MDD. In doing so, a comprehensive understanding of what takes place in an MDD brain would be elucidated and new treatment options would be explored.

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Efficacy of Esketamine Two similar clinical trials have displayed that esketamine’s effects are especially expeditious and successful in treatment of TRD. The first trial, Aspire I, was conducted between June 2017 to December 2018 by a team of researchers led by Dong-Jing Fu of Janssen Research and Development, LLC. The study consisted of 226 adults diagnosed with major depressive disorder (based on criteria found in the Diagnostic and Statistical Manual of Mental Disorders), and that had active and intentful suicidal ideation with intent and need for psychiatric hospitalization (5).

The patients were then randomized into two groups: one group was given 84 mg of esketamine nasal spray twice a week for 4 weeks while the other was given a placebo for the same duration. Both groups were hospitalized for psychiatric ailments and were administered 1 NMDA inhibits the release of glutamate, preventing the oral antidepressants (5). Figure formation of new neural connections and impairing the brain’s ability to improve neuroplasticity, which is linked to depression. Esketamine To quantify the effects inhibits NMDA’s inhibitory function, permitting glutamate release and the formation of new neural connections. of the drug and placebo,

two different endpoints were measured 24 hours post-administration of esketamine or the placebo: the Montgomery-Asberg Depression Rating Scale (MADRS) score, which was used to measure the extent of depressive symptoms, and the change in Clinical Global Impression of Severity of Suicidality Revised version (CGI-SS-r) score, which was used to measure the extent of suicidal ideation.

MADRS is a clinician‐rated measure of depressive severity where a higher score indicates more severe depression and the overall score ranges from 0 to 60 (6). Before esketamine or the placebo was given to the patients, a baseline MADRS score was measured to be 41.1 (5). This score, being above 35, signifies severe depression. After 24 hours, analysis of the MADRS score, or primary endpoint, in both groups displayed a decrease to moderate depression. In the group that was given esketamine, the mean decrease of MADRS score was 16.4 while the mean decrease for the group that was given the placebo was 12.8 (5). A decrease in the MADRS score indicated an improvement in symptoms of depression, suggesting that TRD may not be resistant against esketamine and offering new hope to individuals suffering from TRD. Esketamine has proven to be incredibly valuable in the speed in which it attenuates the symptoms of TRD, eliciting a response in only 24 hours in the trials. This response rate is noteworthy because of the transient nature of the MDD as suicidal thoughts can intensify in the time it takes for other drugs to begin their pharmacological action. Esketamine’s nasal delivery method can be credited for its fast-acting abilities as it allows for the drug to deliver signals to the central nervous system at a quicker rate by acting on numerous neurons simultaneously, unlike the ingestion of a pill.

On the other hand, the CGI-SS-r score endpoint did not substantiate the usefulness of esketamine in managing suicidal ideation. Before administration, it was determined that 88% of patients were rated to be moderately to extremely suicidal according to their CGI-SS-r score (5).

Similarly to the results of the primary endpoint measurements, the results of the secondary endpoint measurement demonstrated a decrease in CGI-SS-r score for both groups after 24 hours. However, the difference between the two groups was insignificant revealing that esketamine is not effective in reducing suicidality. Suicidal ideation is MDD’s most pressing and devastating symptom. Therefore, it’s essential not to rely on eskatime alone to treat MDD, but rather utilize it as part of a comprehensive treatment plan.

A follow up study, Aspire II, led by Dawn F. Ionescu from Janssen

Research and Development reached the same conclusions as its predecessor. From the baseline of 39.7, MADRS scores decreased to 15.7 in the esketamine group and 12.4 in the placebo group after 24 hours of treatment (7). The difference in the decreased CGI-SS-r scores after 24 hours of treatment administration between the two groups was insignificant (7). The replicability of the results from Aspire I supports and further illustrates the efficacy of esketamine. The increased sample size of ASPIRE II in conjunction with Aspire I’s sample size substantiates the therapeutic ability of ketamine as it has consistently proven to be effective in decreasing depressive symptoms in patients suffering from TRD. Relapse Prevention In addition to delivering rapid short term improvement in depressive symptoms, esketamine has demonstratred to be successful in relapse prevention in patients with TRD. A study led by Ella J. Dally of Janssen Research and Development LLC from October 2015 to February 2018 aimed to uncover the long term effects of esketamine. Of the 1097 patients assessed for eligibility in this study, 297 met the criteria of experiencing stable remission or stable response after undergoing esketamine nasal spray plus an oral antidepressant for 16 weeks. The 297 patients were then separated into two groups: patients that experienced stable remission and patients that experienced stable response. Patients in both groups were then further randomized into two groups. One group was administered esketamine nasal spray and oral antidepressant while the other was administered a placebo and oral antidepressant. Patients in these groups were then assessed for relapses, defined as two consecutive assessments of a MADRS total score of 22 or higher, hospitalization as a result of worsening depression, or suicidal behavior.

Results of relapse assessments indicated that esketamine taken along with antidepressant demonstrated clinically meaningful superiority when compared to antidepressant and placebo. Among patients who achieved stable Figure 2 The route of administration for esketamine is intranasal, which can be credited for its

fast-acting abilities, with quicker rates of signal delivery to the central nervous system compared to oral ingestion of a pill.

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remission, 26.7% in the esketamine and antidepressant group and 45.3% in the antidepressant and placebo group experienced relapse and among the patients categorized as achieving stable response, 25.8% in the esketamine and antidepressant group and 57.6% in the antidepressant and placebo group experienced a relapse event (8). Analysis of this data through hazard ratio estimates, a statistical analysis measure that compares the probability of events in a treatment group and control group, revealed that the use of esketamine in conjunction with antidepressant decreased the risk of relapse by 51% among patients who achieved stable remission and by 70% among patients who achieved stable response when compared with treatment with the placebo and antidepressant (8). Continued treatment with esketamine and an antidepressant has shown to be an effective option in treating TRD in the long run in addition to its short term therapeutic effects. This is a particularly pivotal finding in the treatment of TRD given that patients with TRD experience higher rates of relapse than patients with non-treatment-resistant MDD (8). Achieving and maintaining remission is the ideal goal for any depression treatment, and esketamine taken with antidepressant has attained this goal while other medications alone have not been as successful.

Esketamine’s mechanism of action involves restoring patients’ synaptic connections between neurons, and the return of MDD is reduced in patients as a result of this improved neuroplasticity. By delaying relapse, esketamine reduces suicide risk, enhances clinical stability, and improves the overall well-being of patients suffering from TRD.

symptoms of TRD and exhibit esketamine’s safety and effectiveness in children and special clinical populations should be examined in future research.

Esketamine’s mechanisms work uniquely compared to current treatments for MDD and TRD, and its effectiveness calls attention to the importance of developing new clinical perspectives in the mental health sector. Exploration of nonconventional pathways for other mental health issues, such as schizophrenia and dissociative disorders, is imperative in discovering the best treatment options. Additionally, as displayed through the fast acting effects of esketamine, delivery methods of drugs may play a role in their efficacy and should be paid close attention to when developing and reevaluating medications. Esketamine has not only offered hope in treating TRD, but also left the medical world with the valuable lesson that straying away from conventional thinking can open doors for more possibility in treatment of other mental health issues and lead to a healthier public.

“Esketamine has offered immediate relief for many individuals suffering from the debilitating symptoms of TRD... and its effectiveness calls attention to the importance of developing new clinical perspectives in the mental health sector.”

Conclusion Esketamine has offered immediate relief for many individuals suffering from the debilitating symptoms of TRD. Although esketamine may not be fully approved for everyone, it is the first drug to effectively manage

Figure 3 Clinical trials have revealed a treatment for treatment resistant depression, a form of

major depressive disorder, in the form of esketamine that can provide short term relief, as well as long term by delaying relapses.

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References

1. Depression. World Health Organization (2020).

2. J. Gordon, One Year In: COVID-19 and Mental Health.

National Institute of Mental Health (2021).

3. S. Makin, Behind the Buzz: How Ketamine Changes the Depressed Patient’s Brain. Scientific American (2019) 4. J. Minkove, Esketamine: A New Approach for Patients with Treatment-Resistant Depression. Johns Hopkins Medicine (2019).

5. D. Fu, D. Ionescu, X. Li, et al., Esketamine nasal spray for rapid reduction of major depressive disorder symptoms in patients who have active suicidal ideation with intent: double-blind, randomized study (ASPIRE I). J Clin Psychiatry (2020) doi: 10.4088/ JCP.19m13191.

6. Wikipedia contributors, Montgomery–Åsberg Depression Rating Scale. Wikipedia, The Free Encyclopedia (2021).

7. D. Ionescu, D. Fu, X. Qiu, et al., Esketamine Nasal Spray for Rapid Reduction of Depressive Symptoms in Patients With Major Depressive Disorder Who Have Active Suicide Ideation With Intent: Results of a Phase 3, Double-Blind, Randomized Study (ASPIRE II). The international journal of neuropsychopharmacology 24, 22–31 (2021). https://doi.org/10.1093/ijnp/pyaa068.

8. E. Daly, M. Trivedi, A. Janik, et al., Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA psychiatry 76, 893–903 (2019). https://doi.org/10.1001/jamapsychiatry.2019.1189.

Graphics illustrated by Isra Ahmed `23

CaCl2-CaO MIXTURES MAY DECREASE RADIOACTIVITY LEVELS IN CONTAMINATED NUCLEAR WASTES THUMYAT NOE `23

Figure 1 Due to an earthquake, the area near Fukushima Nuclear Power plant has been contaminated by radioactive wastes. Since then, scientists have been focusing on finding efficient ways to remove radioactive components from the contaminated environment.

On March 11th 2011, an earthquake in northeastern Japan caused a leakage of radionuclides from the Fukushima Daiichi Nuclear Power plant.

Fukushima now stores the radioactive waste in designated locations, but there is an immediate need to decrease the radioactivity levels present in the stored wastes to prevent other accidents. Among the radionuclides present in contaminated wastes, scientists have determined radioactive cesium as an important removal target. Previous studies suggest that chlorine-bearing compounds mixed with calcium oxide (CaO) can facilitate the vaporization of radioactive cesium. In this study, researchers at the Chubu University of Japan exposed radioactive cesium-contaminated soil samples from the area near Fukushima Daiichi Nuclear Power plant to thermal treatment with a mixture of CaCl2 and CaO to determine if this method is able to efficiently remove radioactive cesium in contaminated soil.

Prior to thermal treatment, researchers characterized the dried soil sample with X-ray fluorescence spectrometers. Researchers then mixed the sample with 5%, 10%, or 20% CaCl2 or a mixture of CaCl2 and CaO with the same CaCl2 concentrations and an additional 20% CaO. Next, the mixtures underwent thermal treatment in a porcelain boat with lab-scale electrical furnace heating for 30 minutes. During this time, researchers injected 300 mL/min of air into the reactor through an air pump to remove compounds vaporized from the soil sample. Finally, researchers calculated the removal ratio of radioactive cesium.

Researchers found that at 10% and 20% CaCl2 addition, an increase in temperature resulted in a greater removal of radioactive cesium removal; increasing CaCl2 % addition at high temperatures also resulted in greater removal of radioactive cesium. Notably, researchers observed that CaO addition enhanced removal of radioactive cesium possibly due to a delay in the decomposition of CaCl2 in the presence of CaO. Lastly, researchers found that the removal ratio of radioactive cesium is higher in soil with fine particle size. These results suggest that the use of thermal treatment with a mixture of CaCl2 and CaO is a feasible solution to minimizing risks in storing radioactive waste which in turn could improve environmental well-being.

1. F. Jiao, et al., Use of thermal treatment with CaCl2 and CaO to remove 137Cs in the soil collected from the area near the Fukushima Daiichi Nuclear Power Plant. Journal of Hazardous Materials 401, 1-7 (2021). doi: 10.1016/j.jhazmat.2020.123364.

2. Image retrieved from: https://libreshot.com/nuclear-power-plant/

FRESHWATER POND ON SOUTHAMPTON ISLAND CONTAINS TRACES OF THE EXTINCT SADLERMIUT PEOPLE JOYCE CHEN `23 The Sadlermiut were a past civilization that lived on Southampton Island in Nunavut, Canada. Accustomed to the harsh weather of Arctic Canada, the Sadlermiut were natural hunter-gatherers and fishermen. Recovery of past artifacts and skeletal remains suggested that the civilization occupied regions of Southampton Island ranging back to 1250 CE up until 1903, when they were wiped out by a pandemic introduced by European whalers.

Bung Stick Pond, a small freshwater pond found at the “Native Point” of the island, was discovered to contain heavy traces of the Sandlermiut people.

Using biochemical methods, Dr. Finn A. Viehberg and his research team chose to focus on Bung Stick Pond to investigate the environmental changes caused by the ancient inhabitants’ activity.

The team measured sediment distribution, pH, and temperature of the water around the pond for analysis. Specifically, they wanted to determine the amount of carbon and nitrogen isotopes for radioactive dating and gain additional insight about the lives of the Sadlermiut. Based on analyses on the water samples, Bung Stick Pond reportedly contained higher levels of nutrients and organic matter than other bodies of water on Southampton Island. Furthermore, due to the sediment distribution around the pond, the water had an abnormally high alkalinity. Collection of sediment allowed the team to determine the evolution of the marine life of the pond.

The researchers were able to infer that the Sadlermiut people arrived between 1250 to 1300 CE due to the lack of aquatic life and a change in carbon to nitrogen ratio in the sediment deposited on land. In addition, several of the earliest Sadlermiut artifacts were dated to around this time. After the civilization settled at the site, aquatic life began to increase within the pond, leading to an increase in iron concentrations from 1250 CE and onward.

The results of Dr. Viehberg and his team’s study supports previous findings about the whereabouts and disappearance of the Sandlermiut people. Aside from providing insight about the Sandlermiut people’s lifestyle prior to extinction, the biochemical analyses assist in advancements for future studies by providing a baseline methodology for other research teams to follow in their investigations on anthropology. In conclusion, the well-preserved footprints left behind by the Sadlermiut strengthen society’s understanding of how humans and other organisms can leave an impact on their environment for centuries.

1. F.A. Viehberg, et al., The influence of a lost society, the Sadlermiut, on the environment in the Canadian Arctic. Sci Rep 11, 18504 (2021). doi: 10.1038/s41598-021-97631-7 2. Image retrieved from: https://cdn.pixabay.com/photo/2015/09/05/15/15/lyme-regis-924431_1280.jpg

Figure 1 Freshwater biomes are remnants of past human existence and environmental shifts.

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Stony Brook’s iGEM Chapter: Training Tomorrow’s NICOLE GLADSTEIN `23 Scientists

Heera Bandi

Joelle El Hamouche

Nabeel Farrukh

Every year since 2008, a team of Stony Brook students has represented the university at the iGEM competition. In spite of COVID-19, a team of 14 students continued this legacy, collaborating on a synthetic biology research project for the 2021 iGEM competition. Three of those students — Heera Bandi (class of 2024), Nabeel Farrukh (class of 2023), and Joelle El Hamouche (class of 2022) — spoke with SBYIR to provide insight on iGEM, synthetic biology, and the experience of being on the 2021 Stony Brook iGEM team.

Figure 1 iGem logo.

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What is iGEM? iGEM Foundation is a nonprofit organization, with the acronym standing for International Genetically Engineered Machine. The foundation, Heera Bandi explained, hosts an annual competition that “looks at how to solve everyday issues that affect communities all around the world by trying to create novel solutions using synthetic biology.” According to Heera, the appeal lies in putting “young people at the forefront of it, specifically high school, undergraduate, or even postgraduate students.” Nabeel Farrukh elaborated further, saying that the competition invites student-led teams around the world to “engineer bacteria or microorganisms for various uses, whether they be for medical, energy, or environmental use,” the latter of which, he explains, is the focus of the team for this year.

What is synthetic biology?

According to all three students, synthetic biology lies at the heart of iGEM. Nabeel introduced the field as “a growing subfield of biology and engineering that involves genetically engineering microorganisms, such as bacteria or yeast, to serve a certain function.” Heera explained further that “it can be used to redesign and modify naturally-occurring systems.” Joelle mentioned optogenetics, wherein light can be used to induce preferable responses in bacteria, while Nabeel explained the application of synthetic biology to create modified bacteria that produce biodiesel. All three team members emphasized the important role this field plays in our daily lives, in ways we may not even be aware of.

What led you to join iGEM? All three team members were enthusiastic about the prospect of working in the lab and gaining hands-on experience. Joelle was a junior when she applied to the iGEM team, and she was looking to build upon her past research experience: “Sophomore year of college I did a project with genome sequencing in bacteria, and that meshed well with iGEM because a lot of it is looking into genetics.” For Heera, iGEM offered an opportunity to get involved with research, and she was inspired by past teams: “As a freshman I did not have much experience working within the field of science, or even within synthetic biology itself. When I saw an invitation to apply for iGEM, I immediately started looking up previous iGEM projects and I was fascinated by what students did. I found that I wanted to look at creating innovative solutions to everyday problems that we have all over the world.”

Nabeel echoed Heera’s desire for hands-on research experience, explaining that he thought the idea of synthetic biology was very novel and that it was something with which he had no prior experience. It was this interest that led him to join the team.

The team members also spoke of the appeal of iGEM as an undergraduate team. “I wanted to work with a team of other students, and iGEM is very collaborative with a close knit team,” said Joelle. To Heera, the chance to express one’s own ideas and create an independent research project alongside undergraduate members was appealing. While the team receives aid from mentors and supervisors, much of the research is accomplished independently by the team.

What was your role in the team?

All three team members primarily played a role in the wet lab portion of iGEM, which Joelle described as benchwork. Between designing and actually executing the project, wet lab involved “spending hours in the lab trying to go through lab techniques, put together the other solution that our teammates created, and also work on the research and the design of my own solution,” according to Heera.

Why did you choose this role?

Although having had prior research experience, Joelle explained the

importance of obtaining hands-on wet-lab experience. Nabeel had similar motivations for choosing wet lab, explaining that lab work appealed to him from before iGEM even started because of the novelty of it.

Heera also touched upon wanting lab experience, but she explained that it was more specifically the project design process that was appealing: “I think that I like the idea of being able to see how specifically things came together. I liked the design portion of wet lab where you have a solution, but you can break it down into those various parts…. I like having control over that part of the project and having a big role in actually creating the base of what we were actually doing in iGEM.” Heera elaborated on the flexibility afforded by construct design, citing the ability to mix and match different genetic elements, such as promoters, to modify biological systems and make bacteria serve a desired function.

What is something you learned through the experience?

For Nabeel and Joelle, iGEM revealed the importance of failure in scientific research. According to Nabeel, “a huge part of research is failure.

During our time we had a lot of failures and errors. Although most of us are new to research, it is common in general to face trials and errors in research.” Joelle agreed, contrasting iGEM with her undergraduate lab experiences: “My biggest take-away was that science doesn’t work on the first try. My main experience was in college lab classes, and in those types of scenarios, things are designed to work all the time. That’s not how science works. It ends up taking a lot of trial and error and troubleshooting.”

However, in spite of failure, Nabeel and Joelle learned a lot, and said iGEM provided valuable insights for their future career choices. Nabeel concluded that failures do not define a researcher’s success: “The job of a researcher, a good researcher, is to work as a team and to use your scientific knowledge to troubleshoot and figure out what you’re doing wrong. Failure is going to be inevitable, but how you respond to failure and how you try to evaluate and fix those failures, that is the most important part.”

What are some of the challenges you faced?

Working on a tight schedule to develop and carry out a novel research project as an independent undergraduate team is challenging, in more ways than one. Challenges arose in the logistics of obtaining reagents, managing interpersonal relationships, balancing iGEM with schoolwork and other extracurriculars, and more, as the three team members each brought up unique issues. “Within our own team, having good lines of communication and making sure that everyone had a role and was working towards whatever the team’s goals was, be it dry lab or wet lab, was a challenge,” Joelle admitted. Another challenge, according to Nabeel, was “trying to be flexible and balance our schedules as students, while simultaneously troubleshooting a lot of the issues that come with research. It can be very daunting.” Heera also highlighted the issue of acquiring a sufficient amount of materials. “At a certain point we were trying to source certain plasmids and bacteria that we needed, and they

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were either really hard to source or abnormally expensive,” she began. For certain experiements that we conducted, we had to be really careful with them because we didn’t have the funds to try to source those materials again. It would be maybe $300 for an enzyme we were using.”

such a huge project was a worthwhile experience.” Joelle expressed a similar sentiment, following up her answer with “I’m not sure if there’s really that much that I would change because, either way, we’re going to make mistakes and that’s all part of the process of iGEM.”

How did you overcome those challenges?

Trial and error, and learning from experience were significant factors, according to Nabeel. Challenges with time management and maintaining strong lines of communication within the team eased up over time as the team adjusted to the balancing school work with iGEM, and learned to work as a team. He touched upon another invaluable source of support: the iGEM advisors. According to Nabeel, “Asking them for help immensely helped us, especially as we were still learning these things.” Heera also mentioned that reaching out to the advisors was valuable for helping the team procure materials or borrow equipment from faculty labs on campus.

What advice would you give to other students interested in research or iGEM? Despite their different ages, majors, anticipated career paths, and levels of past lab experience, all three teammates SBYIR spoke to found iGEM to be a valuable and memorable experience. They highly encouraged anyone with interest in research to pursue it, be that via iGEM or not. “It’s very important that when you’re doing research, you do research on a topic that you are specifically very interested in. So if you really love synthetic biology, talk to professors who teach that subject and try to find opportunities that relate to that topic,” Nabeel advised. Joelle came to similar conclusions, explaining that “the most important thing is to find something you’re passionate about so that dedicating a large portion of your summer or school year during the semester isn’t going to be burdensome. If you have passion, no matter how time consuming it is, you’ll be able to work through it because you’re passionate about it.”

Heera shared some motivational wisdom regarding qualificationsor the lack thereof, for research: “Don’t let your perceived lack of knowledge hold you back from trying to join any type of research opportunity. I joined iGEM as a freshman who had a very limited knowledge of synthetic biology, especially in comparison to some of my peers who had joined and had years of experience in labs or had experience before on iGEM… I’m here to say that I don’t think you should let that hold you back from doing it, because you have a lot to gain from your peers and all the resources you can have from iGEM such as other iGEM teams, your mentors, and even your advisor.” Ultimately, the resounding message is to pursue research experiences, if that is something you are interested in exploring.

What would you change about the iGEM project if you were to do it over again?

Interestingly enough, despite the myriad of challenges the teammates brought up, there was a consensus regarding what all three of them would do if they could go back and restart iGEM knowing what they know now.

Joelle stated it as wanting “to begin with a more manageable task,” Nabeel worded it as making the project “make it slightly less ambitious,” and Heera concurred that she would have “tried to see if we could focus our work onto one specific solution rather than two.” The problem they are all referring to is one created by the team when they designed the team project over the spring. They chose to work on two different novel approaches to microcystin degradation in parallel, and also simultaneously tried to develop a novel microcystin detection method. This decision split wet lab work into three distinct mini-projects, each with their own roadblocks and challenges. At the end of the summer, the team came to a consensus that they may have bit off more than they could chew.

Despite all wanting to make some retrospective changes to the project, everyone mentioned ultimately not having any regrets. Nabeel qualified his change, adding that “being ambitious and taking that risk of taking on

Figure 3 A group photo of the iGEM team.

Images courtesy of Nicole Gladstein `23 Graphics illustrated by Ujala Dar `24

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Overcoming

ISOLATION

Through Natural Experiences

Figure 1 A lone chestnut tree in the middle of a pine forest.

TRAVIS CUTTER `22 ENVIRONMENTAL WELL-BEING

22

Introduction Due to the COVID-19 pandemic, the first years of the 2020s have been dominated by a need for human beings to self-isolate to slow the spread of the virus.

However, humans are social creatures, and prolonged isolation can easily lead to depression, anxiety, self-esteem issues, and more. As a result, researchers sought out interventions to deal with stresses brought about by imposed isolation, in addition to added agitators that coincide with a global pandemic, such as increased feelings of depression and anxiety. Immersion in nature, it seems, is a great combatant against the depression and solitude that has been a hallmark of the 2020s, but these benefits are not guaranteed. As urban development and technological progress advances, the distribution of greenspaces, such as public parks, decreases. Yet, there is an ever-growing need for the benefits these spaces provide, Figure 2 As urban development and technological progress advances, the distribution of greenspaces, such as public parks, decreases. and so two options present themselves: protect greenspaces that exist, or find suitable artificial alternatives. smelling flowers, listening to birdsongs, and witnessing both - that can buoy one’s mental health. Additionally, those who used greenspaces were The Tokyo Study intuitively encouraged to exercise, improving physical and mental health.

Due to health and safety concerns brought on by the COVID-19 panFinally, public greenspaces allow for some social interaction that would be demic, the city of Tokyo was placed under a state of emergency from April impossible due to the restrictions imposed during the pandemic, providing 7 to May 25, 2020. While not a complete lockdown, schools, businesses a partial loophole to the problem of isolation. and other facilities were requested to close for the period. However, greenSimply having a view of nature also proved beneficial in all five menspaces were still accessible to the masses. In early June of the same year, tal health categories, though the causes are not as distinguishable as comRakuten Insight, Japan, a market research company, distributed an online pared to physical immersion in nature. The multi-sensory experiences still survey, receiving responses from 3,000 adults. Data was collected regardlikely play a factor, as one can see, hear, and smell the same sorts of birds, ing participants’ mental health, experience with nature, lifestyle, and sociobees, and plants typically seen when walking in the park. The more greensdemographic information. paces in the area around the home, the greater the exposure to biodiversity, Mental health data was collected along five metrics: happiness, life increasing the variety of multi-sensory experiences one might have, and satisfaction, self-esteem, loneliness, and depression and anxiety. In all five potentially improving mental health. However, even though the benefits cases, utilizing greenspaces was found to be associated with an improveappear tangible, the specific effects of one’s proximity to nature on mental ment in mental health for several key reasons. First, immersion in nature health is not fully understood, and requires further study (1). provides varied experiences for a number of different senses - including

When discussing motives for people venturing outside, the most common answers were “just getting outside,” “exercise,” “connecting to nature,” and “peace and quiet...”

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Figure 3 “Birdwatching” is one motive for people venturing outside.

The Vermont Study Around the city of Burlington, Vermont, the University of Vermont has maintained seven natural areas which are used for both academic purposes and public activities. One study reconciled these two purposes by conducting an anonymous survey among visitors to these seven university-owned areas, and eighteen other parks and natural areas in the area, to discern the effects of visiting the natural spaces on the well-being of people throughout the pandemic.

The most vital finding of the study was that 70.2% of respondents claimed to have increased their number of park visits since the advent of the pandemic. Only 5.5% of respondents claimed that their frequency of visitation decreased. When inquired about the personal value of these greenspaces, 81.5% of respondents claimed the areas had increased in importance to them since the pandemic began. Only two out of 346 respondents claimed the parks decreased in importance for them.

When discussing motives for people venturing outside, the most common answers were “just getting outside,” “exercise,” “connecting to nature,” and “peace and quiet,” all of which were given by over 10% of the respondents. Other notable responses related to nature were “birdwatching,” given by 5.7% of respondents, and “fishing,” given by 0.6% of respondents. “Socializing” was only given by 2.7% of respondents. This impressive diversity in responses shows that the benefits provided by greenspaces appeal to a wide variety of people with distinct interests. Also of note is that 80% of the respondents who would visit greenspaces alone prior to the pandemic continued to do so after, further solidifying that socialization was not a primary motivator in visiting the parks.

Based on these results, the researchers ultimately concluded that the frequency that people visited greenspaces increased significantly since the pandemic began, and most people were subsequently forced to reevaluate how much they valued such spaces. With the increased health benefits these spaces provided, such as improved happiness, life satisfaction, and self-esteem, most people became more inclined towards them, regardless of whether they were aware of these benefits. Should these results prove to be true on a much larger scale than the state of Vermont, demand for greenspaces would be increasing concurrently with a dramatic decrease in availability of such spaces around the world, notably in the United States and

China. Should these spaces diminish significantly in size or quality, through urban development or administrative negligence, the mental and physical health benefits they provide will also diminish (2).

The Phantom Chorus While the Vermont study indicated that only a small percentage of people sought natural spaces specifically to birdwatch, there may be far greater benefits to interacting with birds than initially believed. Specifically, birdsong may have a positive effect on mental health, improving stress recovery and cognitive function. Using pre-recorded birdsong from various species, a team of researchers led by Danielle Ferraro of California Polytechnic State University broadcasted a so-called “phantom chorus” along two California nature trails. The phantom chorus was designed to be as realistic-sounding as possible in terms of amplitude, location, and volume.

Hikers surveyed by the researchers did not know they were hearing real and artificial songs.

Principal among the phantom chorus’s effects was an increase in the richness of bird species along both trails. The phantom chorus did not replace natural birdsong, instead supplementing and amplifying it. Only on one of the two trails did a significant number of respondents notice the apparent increase in birds and bird species diversity. Despite respondents lacking awareness of the difference, the results found that increased abundance of birdsong led to improved mental well-being on both trails. Why results differed between the two trails was an enigma to the researchers.

The smaller effect relative to other studies could be due to a smaller time frame over which the participants were immersed in greenspaces: hikers were only subjected to increased birdsong for about ten minutes. Difference in terrain between trails also could have contributed to a difference in perception: a flat, straight path is simpler to walk along, allowing the mind to focus elsewhere, while safe navigation of a hilly, winding path requires more focus, limiting one’s ability to observe the environment.

The researchers noted an ethical concern with the study’s implications: replacing real birdsong with facsimiles could be justified if the benefits outweigh the risk of creating a greater disconnect between humans and the natural world. Given an increased reliance on greenspaces in the age of COVID-19, this would be detrimental to both parties. However, the study’s

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findings suggest that carefully and thoughtfully managed greenspaces wherein experiences with wildlife are promoted - would be extraordinarily beneficial to the population’s mental health. So, even if birdwatching is not one’s primary motive in visiting a park or other natural setting, the benefits yielded are invaluable. It is also possible that even if natural experiences are not wholly genuine, the benefits that real experiences provide can be artificially induced (3).

Nature in VR In order to solve the question of whether simulated nature could provide comparable benefits to real experiences in nature, a team of researchers simulated an immersive experience with VR headsets and 360 degree video. This simulated experience was compared with two other groups: one immersed outdoors in nature and one immersed indoors in a completely empty room. Similar to previously discussed experiments, surveys were conducted to gauge participants’ feelings and experiences with nature prior to the experiment. The researchers did not categorize the difference between immersion in nature and the lack thereof in binary terms: rather, they characterized the potential benefits as a spectrum on which simulated nature might fall.

Regarding participants’ moods and the experiment’s effect on them, a statistically significant difference in the positive affects of the experience was found between the outdoor and indoor groups with the latter group’s positive affect declining after the experiment’s conclusion. No change in positive affect was observed for the VR group, yet all three groups reported statistically significant declines in negative affect. Physiologically, both the outdoor and VR groups showed improvement when compared to the indoor group. However, the VR group saw less improvement than the outdoor group, which the researchers attributed to the more varied stimuli that comes from natural environments.

These findings suggest that while simulated nature does not actively improve one’s mental well-being, it does distract from stressors, hence why there was a reduction in negative affects but no increase in positive affects. Reductions in negative affects for the indoor control group may be attributed to participants simply being able to relax despite a lack of immersion in nature, as well as to a restriction in smartphone usage. Taking a break from smartphones and their stressors also applies to the other two groups, potentially contributing to the reduction of negative affects in them.

Overall, while the researchers believe that their experiment showcases the benefits to immersion in simulated nature as opposed to not experiencing any nature at all, they also note that they did not test the effects of other kinds of simulated experiences. It is thus possible that simply engaging with a simulated environment provides benefits to physical and mental health.

Although such benefits would still apply to simulated nature, the benefits of experiencing true greenspaces outweigh the benefits of an artificial experience (4).

Conclusion Nature is often taken for granted, but if humans take care of it, it will take care of them in return. An elevated understanding of this mutually beneficial relationship is one of the few positives of the COVID-19 pandemic. In a time where isolation is required in the interest of public health, humans returning to the natural world is an ironic turn of events. Due to human developments, these spaces are diminishing across the globe, reducing humanity’s access to their benefits. As people are forced to look inward, they seek solace in the outdoors, but might be forced to accept facsimiles if the reducing trend they contributed to continues. In the future, the improved well-being brought on by this increased immersion in nature will hopefully inspire people to treat the natural world with greater care and reverse the anti-green trend, creating a cycle of natural and mental well-being.

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It is thus possible that simply engaging with a simulated environment provides benefits to physical and mental health.

References 1. M. Soga, et al., A room with a green view: the importance of nearby nature for mental health during the COVID-19 pandemic. Ecological Applications 31, 1-10 (2021). doi: 10.1002/eap.2248/ full.

2. N. Grima, et al., The importance of urban natural areas and urban ecosystem services during the COVID-19 pandemic. PLOS One 15, 1-13 (2020). doi: 10.1371/journal.pone.0243344.

3. D. Ferraro, et al., The phantom chorus: birdsong boosts human well-being in protected areas.

Proceedings of the Royal Society B 287, 1-9 (2020). doi: 10.1098/rspb.2020.1811.

4. M. Browning, et al., Can simulated nature support mental health? Comparing short, single-doses of 360-degree nature videos in virtual reality with the outdoors. Frontiers in Psychology 10, 1-14 (2020). doi: 10.3389/fpsyg.2019.02667.

Images retrived from: 1. https://www.flickr.com/photos/colinsd40/37332692424 2. https://commons.wikimedia.org/wiki/File:Global_Citizen_Festival_Central_Park_New_York_ City_from_NYonAir_(15351915006).jpg 3. https://pixabay.com/photos/bird-ornament-garden-2681737/

HIGH FAT DIETS IN COMBINATION WITH TRICLOSAN LINKED TO NONALCOHOLIC LIVER DISEASE DAPHNE SIOZIOS `23 NAFLD, more commonly known as nonalcoholic fatty liver disease, is one of the most prominent chronic liver conditions in the country and is characterized by the accumulation of fat in hepatocytes (liver cells). Nonalcoholic steatohepatitis (NASH), a cousin of NAFLD, is a condition that both encompasses the deposition of fat in the liver and inflammation of the organ. Fibroblast growth factor 21 (FGF21), which is naturally elevated by high-fat diets, has been found to reverse steatohepatitis in obese mice and reduce risk of insulin sensitivity. However, a widely-used antiseptic called Triclosan (TCS) has been shown to promote elevated liver fat levels due to oxidative stress in species such as tadpoles and seemingly diminish the function of FGF21. Researchers at the Department of Pharmacology at the University of California, San Diego sought to find a more solid connection between high-fat diets (HFDs) and TCS toxicology.

Researchers began by grouping 4-week-old mice in 2 separate groups where the control was fed a HFD consisting of 59% fat, 15% protein, and 26% carbohydrates dissolved in 0.2% dimethyl sulfoxide (DMSO). The experimental group was given the same chow fed diet along with 0.35 mM of TCS dissolved in 0.2% DMSO as well. After a 4- to 4.5-month period, the mice’s livers were harvested for gene analysis under histological parameters. At the end of the feeding trial, the mice fed with an HFD showed elevated levels of circulating FGF21 compared to the experimental group. This confirmed previous studies with the conclusion that FGF21 displayed an adaptive response in preventing lipid accumulation and improving insulin stability. However, the group treated with TCS saw lower levels of FGF21 in the mice livers. This proves that exposure to TCS disrupted the regulation

of FGF21 normally stimulated by high fat diets, thus making subjects under HFDs more susceptible to liver diseases.

The rising prevalence of toxicant-associated steatohepatitis (TASH) and NASH mirror a vast increase in obesity and environmental toxicant exposure in modern life. This research not only brings a troubling side effect of a widespread chemical to the scientific community’s attention, but also inspires a push for further investigations. Future avenues of study can aim to explore the chronic exposure of TCS and its impacts on FGF21 levels by studying human cohorts affected by NAFLD to better quantify the effects of this newly uncovered yet worrying phenomenon.

Figure 1 Hepatocytes (liver cells) in a liver biopsy exhibiting inflammation when subjected to a high-fat diet, even without the presence of alcoholic liver disease.

1. M. Yueh, et al., Triclosan leads to dysregulation of metabolic regulator FGF21 exacerbating high fat-diet induced nonalcoholic fatty liver disease. Proceedings of the National Academy of Sciences of the United States of America 49, 31259-31266 (2020). doi: 10.1073/pnas.2017129117.

2. Image retrieved from: https://commons.wikimedia.org/wiki/File:Steatohepatitis_high_mag.jpg

PRESENCE OF SOCIAL SUPPORTS COUNTERACTS PHYSICAL BRAIN CHANGES ASSOCIATED WITH DEMENTIA VIGNESH SUBRAMANIAN `24 Alzheimer’s disease and related disorders (ADRD) are neurodegenerative dementias that cause progressive loss of memory, critical thinking skills, and behavioral capabilities that typically worsen with age. However, certain older adults with significant degrees of ADRD-associated pathologies are not as vulnerable to the age or disease-related physical changes in the brain that precede the development of dementia. These adults are classified as “cognitively resilient” and remain relatively unimpaired, typically not demonstrating symptoms beyond mild cognitive impairment. Cognitive resilience is believed to be enhanced by educational attainment, assistance by loved ones, and physical and mental activity-based lifestyles that ameliorate physio-psychological stress. To better understand the relationship between the presence of such social supports and the early prognosis of ADRD, a study led by Dr. Salinas of New York University explored changes in brain volume in relation to the global cognitive performances of adults with varying support domains.

Researchers used patients from the Framingham Study to enroll and assess three generations of participants, divided between ‘original’ and ‘offspring’ cohorts, for cognitive function testing and brain structure imaging purposes. The 2,171 subjects, all of whom had completed Berkman-Syme Social Network Index (SNI)-based assessments inquiring about their networks and contact with caregivers, were then subjected to neuropsychological test batteries that evaluated their memory, recall, organization and

reproduction abilities. Participants simultaneously underwent brain-dedicated MRI scans to determine cerebral volumes. Adjusting for sample characteristics and risk factors, researchers then performed stratified analyses to determine the correlation between social support and cognitive resilience for these adults and compared them to the results of existing cross-sectional studies.

Researchers found that while the distribution of social support scores was understandably skewed due to subjectivity, differences in social support domains were closely associated with changes in cerebral volume. For participants over 65 years of age with lower mean total cerebral volumes and global cognitive function scores, the presence of social support did provide the neurocognitive benefit that other studies had predicted. Researchers also found that unlike other social support domains, high listener availability - which gives patients reliable opportunities to work through emotional issues or intellectual disabilities tied to ADRD - was directly associated with greater cognitive resilience. This significantly modified the association between brain volume and cognitive function, particularly in the younger cohort. Future research may determine whether more aggressive psychosocial interventions might delay the clinical onset of ADRD or reduce its likelihood of developing.

1. J. Salinas, et al., Association of social support with brain volume and cognition. JAMA Network Open 4, 1-13 (2021). doi: 10.1001/jamanetworkopen.2021.21122

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A Nanotechnological Novelty: JUZER VASI `24

Figure 1 Pfizer-BioNTech vaccine vial containing mRNA-LNPs.

Introduction With more than 4.5 million reported deaths worldwide and 700,000 in the United States alone, it can be difficult to imagine the existence of any silver lining to the COVID-19 pandemic. However, previous pandemics and public health crises have resulted in technological innovations in healthcare, resulting in increased societal wellness. The 1918 Spanish influenza pandemic led to modernized vaccine technology, and 20th century polio outbreaks in Europe led Danish anesthesiologist Bjorn Ibsen to establish the world’s first intensive care unit and develop one of the earliest forms of the ventilator (1). Similarly, the COVID-19 pandemic has yielded revolutionary progress in biomedical technology: specifically, the use of messenger RNA (mRNA) technology to produce viable vaccines in a record time of 11 months. mRNA is an unstable molecule containing instructions for protein synthesis and is extremely difficult to deliver to target cells. To resolve this issue, SARSCoV-2 vaccines developed by biotechnology companies Pfizer and Moderna — which have been developing mRNA technology since 2008 and 2010, respectively — utilize lipid nanoparticles (LNPs) that contain and protect mRNA strands from degradative RNAse enzymes to allow for successful drug delivery and vaccine efficacy (2). This style differs from that of the Janssen, Sputnik V, and Oxford-AstraZeneca viral-vector vaccines, which utilize adenoviruses containing non-replicating DNA that encodes for specific protein antigens (3).

The COVID-19 vaccines were the first mRNA vaccines to be approved for widespread clinical use, with the pandemic contributing to accelerated development and implementation of this novel area of viral defense and drug delivery.

While LNPs used in COVID-19 vaccines are essential in the fight against the SARS-CoV-2 virus, they also have the potential to revolutionize immunotherapy and drug delivery.

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LNP Nanotechnology Within COVID-19 Vaccines To protect mRNA from outside media, LNPs are designed with a specific structure. LNPs used in COVID-19 vaccines consist of four components: neutral phospholipids, cholesterol, ionizable cationic lipids, and polyethylene glycol (PEG) lipids. Due to their amphipathic (partly hydrophobic, partly hydrophilic) nature, phospholipids form a spherical bilayer from which LNPs derive their shape and internal organization. Cholesterol adds structural flexibility to this layer, ensuring stability during injection. Endocytosis, or the process by which cells engulf substances outside the cell in a vesicle, positively charged amino groups of the ionizable cationic lipids bind to the negatively charged mRNA, bringing it within the LNP structure. Hydrophilic PEG lipid polymers surround the exterior of LNPs to prevent aggregation (4). The structural stability of LNPs due to their components and the high degree of protection they offer to mRNAs are key to understanding how LNPs can be used for SARS-CoV-2.

In order to understand the significant and promising role that LNPs have as in vivo vectors for drug delivery, it is necessary to understand the general mechanism of mRNA-LNP vaccines. Research by Dr. Jung Woo Park and a team of collaborators at the Institute of Translational Medicine at the University of Macau summarizes the general principles of the mRNA-LNP mechanism specific to the novel COVID-19 vaccines of Pfizer and Moderna. The synthetic mRNA must first be prepared and loaded into an LNP. The synthetic mRNA — which encodes two protein subunits (S1 and S2) of the “spike” glycoprotein found on the envelope of SARS-CoV-2 — undergoes post-transcriptional modifications similar to cellular mRNA. These modifications include adding an altered guanine nucleotide at the 5’ end of the strand (5’ cap), 200 adenine nucleotides at the 3’ end (polyA tail), and untranslated regions of RNA on either side to increase molecular stability, prevent degradation, and allow for successful translation and subsequent spike-protein synthesis. After the mRNA is inserted into an LNP, the mRNA-LNP complex is injected intramuscularly. Via endocytosis, the complex then enters muscle or antigen-presenting cells, where the mRNA is released from the confines of the LNP and combines with a nearby ribosome to create a translation initiation complex, which then synthesizes the spike protein. While the spike proteins are subjected to further processing, the mRNA is degraded by the cell. Once secreted by the cells, the finished spike proteins can initiate an immune response. Antibodies that defend against future infection of a SARS-CoV-2 virus, and thus confer immunity to individuals, can be created and secreted as a result (5). Park et al. outlines that the transfection efficacy of naked mRNAs is nearly two orders of magnitude lower than that of an mRNA encapsulated by an LNP; ergo this mRNA mechanism would not be possible without the LNP components that deliver the post-transcriptional mRNA to the right cells at the correct time (5).

Therapeutic Use of mRNA-LNPs for Cancer Aside from the use of mRNA-LNPs for vaccine development, the pandemic has displayed the potential of LNPs to not only prevent future pandemics, but to target other diseases and medical conditions as well. In fact, recent studies display that

The Current and Future Role of Lipid Nanoparticles LNP technology can be used to fight a second pandemic facing the world today: cancer. According to Dr. Maria L. Guevara at the Barts Cancer Institute, advances in non-viral gene delivery systems and the mechanism previously described of the mRNA COVID-19 vaccine have made possible the implementation of LNP and mRNA-based anti-tumor treatments and therapies. With the recent developments of LNPs as a delivery system, many of these therapies have the potential of moving onto clinical trials (6).

According to Guevara, the objective of therapeutic anti-cancer vaccines is the stimulation of an immune response to target tumor antigens that are expressed in malignant, or cancerous, cells. This therapeutic mechanism is similar to that of the “spike” glycoprotein process. Dubbed dendritic cell (DC) vaccines, these cancer immunotherapies struggled to enter clinical trials until the development of LNPs as an mRNA vector. A study by Dr. Lena Kranz and collaborators at the University Medical Center of the Johannes Gutenberg University demonstrated that DCs found in lymphoid tissue can be passively targeted in vivo using specifically charged mRNA-lipoplexes (a form of LNP), which efficiently protected the mRNA from ribonucleases and enhanced its uptake by cells. Using bioluminescence imaging, the study found that mRNA-lipoplex vaccines can induce strong tumor growth inhibition due to aggressive T-cell response (7).

According to Guevara, using similar techniques, LNPs could also deliver mRNA encoding monoclonal antibodies: lab-synthesized antibodies from unique white blood cells that bind to one epitope, the specific binding area of an antigen.

Cancer treatments based on monoclonal antibodies targeting immune checkpoints are currently considered the most promising area of cancer immunotherapy. Many recently discovered antibodies, such as CTLA-4 and programmed cell death 1 (PD-1) inhibitors, block T-cell immune checkpoints and allow for the expansion

Figure 2 Possible components of a lipid nanoparticle include RNA (packaged molecule),

cholesterol, DSPC (phospholipid), DODMA (cationic lipid), PEG-lated lipid and PolySarcosine (PEG alternative).

of cytotoxic, cancer-targeting T-cells, and have been approved for clinical use (8).

However, these antibody treatments face several challenges in the manufacturing process; for some time, the antibodies have had to be synthesized ex-vivo, a very expensive process. Nevertheless, mRNA-LNP technology has provided an elegant solution by simply administering the antibody-coding mRNA strand into patients, such that antibody synthesis can happen in-situ — in the original area of the cell (6). A 2017 study conducted by Dr. Christiane Stadler and her partners at BioNTech headquarters in Germany confirmed this solution by reporting in-situ production of bispecific antibodies dubbed RiboMABs, which resulted in the elimination of entire tumors after three separate doses, indicated by strong T-cell infiltration using bioluminescent imaging and tumor measurement using digital calipers (9).

In addition, mRNA-LNPs can also be used in CAR (chimeric antigen receptor) T-Cell therapy to further personalize cancer immunotherapy by injecting CAR genes directly into T-cells using mRNA-LNPs to combat specific solid tumors, rather than producing CAR T-cells ex-vivo (6).

Furthermore, LNPs can deliver key components of the novel CRISPR/Cas9 system to allow for genomic editing and knockout to inhibit uncontrollable gene expression leading to malignancy. The uses of mRNA-LNPs for cancer immunotherapy seem endless due to the versatility of mRNA and subsequent protein production.

Figure 3 Simplified depiction of the contents of an mRNA lipid nanoparticle.

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LNPs as a Novel Drug Delivery System Like cancer, neurological diseases represent some of the toughest challenges facing the medical field. Glioblastoma, ischemic stroke, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis are examples of common diseases that still remain difficult to treat.

However, novel research conducted by Dr. Joana Loureiro and her team at the University of Porto demonstrates the use of drug-carrying LNPs to treat Alzheimer’s disease (AD). AD accounts for more than 80% of dementia cases worldwide, and recent evidence suggests a direct association between the severity of dementia and the concentration of soluble Aβ peptide protein aggregates in the brain, which cause the buildup of senile plaque deposits. According to Loureiro et al., one way to counter this buildup would be to change the conformation of the Aβ peptide by adding a compound capable of this molecular modification: resveratrol. Resveratrol, found naturally in grapes, possesses many neuroprotective abilities such as protection of neurons against oxidative damage and toxicity, and the prevention of apoptotic neuronal death. Upon intravenous injection, resveratrol is rapidly metabolized by the body due to its unstable nature, is unable to cross the blood-brain barrier (BBB), and ergo had been considered limited in its bioavailability and pharmacological benefits.

However, with the use of LNPs as a delivery system for resveratrol, the results of the study demonstrate that the nanoparticles were able to successfully encapsulate the drug and cross the BBB, making them promising tools to aid in the treatment of AD. In fact, compared to natural grape seed extract’s ability to inhibit 97% of aggregation of AB peptides, resveratrol delivered by LNPs was found to inhibit up to 86% — a relatively high percentage that suggests that LNPs are a promising delivery system that could potentially be used to prevent the progression of AD. The results demonstrate that this kind of functionalization of LNPs can be used for targeting the BBB and may be applied to transport other drugs to the brain to combat many other diseases (10).

Novel LNPs will gradually become accepted pharmaceutical carriers for drug delivery with improved pharmacokinetic profiles compared to traditional drug delivery. Other uses of LNPs include oral administration, topical administration, cosmetics, intravenous administration, protein peptide delivery and ocular delivery. Thus, LNPs’ potential for drug delivery has enormous implications for the treatment of a plethora of diseases and conditions affecting the well-being of humans today (11).

Conclusion As recent research suggests, LNPs can be widely applied in both drug delivery and immunotherapy. However, there are limitations to LNP use, as excessive amounts of PEG and cationic lipids have been found to have toxic side effects.

While most LNPs fall within a low risk class, the development of standardized procedures to assess potential risks of LNPs is needed. Furthermore, most LNP research has yet to reach clinical trials, which indicates the availability of LNPs in the pharmaceutical market is still some years away (12). Regardless, LNPs are tethered to the future of nanotechnology in medicine and will play an important role in improving physical wellness. Whether they are used for rapid vaccine development during health crises, or to finally offer viable clinical treatment solutions to cancer and other neurological disorders, LNPs offer the potential to solve these problems efficiently by presenting an innovative approach in healthcare.

Figure 4 “Ball and stick” representation of Resveratrol molecule.

References 1. L. Sénélar, The Danish anesthesiologist Björn Ibsen a pioneer of long-term ventilation on the upper airways. Johann Wolfgang Goethe-Universität, (2009).

2. R. Verbeke, et al., Three decades of messenger RNA vaccine development. Nano Today 28, 1-44 (2019). doi: /10.1016/j.nantod.2019.100766.

3. What are viral vector-based vaccines and how could they be used against COVID-19?. Gavi the Vaccine Alliance, (2020).

4. L. Schoenmaker, et al., mRNA-lipid nanoparticle COVID-19 vaccines: structure and stability. International Journal of Pharmaceutics 601, 1-13 (2021). doi: 10.1016/j.ijpharm.2021.120586.

5. J. Park, et al., mRNA vaccines for COVID-19: what, why and how. International Journal Of Biological Sciences 17, 1446-1460 (2021). doi: 10.7150/ijbs.59233.

6. M. Guevara, F. Persano, and S. Persano, Advances in lipid nanoparticles for mRNA-based cancer immunotherapy. Frontiers in Chemistry, (2020).

7. L. Kranz, et al., Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature 534, 396-401 (2016). doi: 10.1038/nature18300.

8. E. Buchbinder and A. Desai, CTLA-4 and PD-1 pathways similarities, differences, and implications of their inhibition. American Journal of Clinical Oncology 39, 98-106 (2016). doi: 10.1097/ COC.0000000000000239.

9. C. Stadler, et al., Elimination of large tumors in mice by mRNA-encoded bispecific antibodies.

Nature Medicine 23, 815-817 (2017). doi: 10.1038/nm.4356.

10. J. Loureiro, et al., Resveratrol and grape extract-loaded solid lipid nanoparticles for the treatment of Alzheimer’s disease. Molecules 22, 277-293 (2017). doi: 10.3390/molecules22020277.

11. Y. Duan, et al., A brief review on solid lipid nanoparticles: part and parcel of contemporary drug delivery systems. RSC Advances 10, 26777-26791 (2020). doi: 10.1039/D0RA03491F. 12. S. Montoto, G. Muraca, and M. Ruiz, Solid lipid nanoparticles for drug delivery: pharmacological and biopharmaceutical aspects. Frontiers in Molecular Biosciences, (2020).

Images retrieved from: 1.https://commons.wikimedia.org/wiki/File:Pfizer-BioNTech_COVID-19_vaccine_(2020)_C_ (cropped).jpg 2.​http://www.differencebetween.net/science/difference-between-mrna-vaccine-and-traditional-vaccine/attachment/lipid-nanoparticle-loaded-with-rna/ 3.Graphic illustration by Maple Zeng `24 4.https://commons.wikimedia.org/wiki/File:Resveratrol_molecule_ball_from_xtal.png

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the

GENETICS of AGING

How Variation and Epigenetics May Facilitate A Long, Healthy Life

NATALIE DZIKOWSKI `22 Understanding the mechanism of biological aging is vital to the optimization of health in an aging population. Genetic research is currently exploring concerns regarding memory problems, amplified health issues, and losing independence. Molecular mechanisms implicated in this work can reveal therapeutic or lifestyle changes to promote healthy aging. Unlike studies on genetic variants, investigations into gene expression and epigenetic changes have recently yielded consistent results. Thus, researchers today have been focused on seeking out specific genetic variants and epigenetic changes associated with longer lifespan and quality of life in older age in humans, which may inform the scientific community on the kinds of therapeutics that could be developed to improve aging outcomes.

ApoE Genotype Variation: Discovery, Implications, and Limitations The gene found to most significantly influence longevity is ApoE, or apolipoprotein E, which encodes a protein responsible for lipid transport and metabolism. As such, it affects blood cholesterol levels and central nervous system functions (1). In 1994, Schachter et al. hypothesized that comparing the genetics of centenarians (people 100 or older) to those of younger populations could reveal specific alleles correlated to a long life. They found that centenarians carried a higher overall frequency of the ApoE2 allele and lower frequency of the ApoE4 allele compared to the control group of younger adults (2). Today, additional genome-wide association and longitudinal studies have reinforced the conclusion that various single-nucleotide polymorphisms at the ApoE locus are associated with longevity. In 2016, a genome-wide association study Figure 1 Genetics bring us from youth to old age

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of over 2,000 Chinese centenarians identified that single-nucleotide polymorphisms at the ApoE promoter (rs405509) are significantly associated with longevity (3). Variation in this region of the promoter is linked to lower or higher production levels of ApoE (4), adding an additional level of complexity in understanding how ApoE impacts lifespan. It is worth noting that the same study on Chinese centenarians was one of the first to use a sample size of over 2,000, and thus identified additional statistically significant loci associated with aging, such as 5q33.3 and IL6 (3); however, additional studies on other populations with similar sample sizes should be conducted to reach a reliable conclusion on how these regions are associated with aging.

As they have been strongly associated with longevity, ApoE polymorphisms have been established as potential targets of anti-aging therapeutics as well as medications for age-related diseases like atherosclerosis, Alzheimer’s disease, and dementia. Clinical trials are currently testing whether targeting ApoE could serve as a treatment for age-related physical changes and age-related diseases. For example, researchers at Weill Cornell Medical College are currently testing gene therapy on ApoE4 homozygote individuals—that is, they are administering a vector containing DNA coding for the beneficial ApoE2 allele to see if it improves cognitive function and Alzheimer’s related symptoms in adults over 50 who have the genotype thought to be detrimental to longevity (5). There are also interesting clinical trials that are not testing medications, but instead testing the effects of exercise and diet on cognitive functioning in adults possessing the ApoE4 allele (5). The results of the aforementioned clinical trials have not yet been published, but it is clear that carrying out these studies will provide information that will expand our understanding of what can or cannot improve aging outcomes. The discovery of age-related genes like ApoE may not only aid in the development of new drugs or supplements, but it may also reveal key information about how lifestyle and genetic factors work together to influence quality of life in old age. Furthermore, the knowledge that genes controlling age-related health markers, like cardiovascular or cognitive function, may also directly impact longevity, informs scientists of how to seek out other genes that could be studied in future aging research.

While ApoE may be a useful target to improve symptoms of aging or age-related disease, a limitation of studies on the gene is that a complete molecular pathway has not been determined to explain how ApOE4 acts on the body to decrease lifespan or how ApOE2 acts on the body to increase lifespan (1). This limits our current knowledge of which molecules could be targeted by anti-aging therapeutics or medications for age-related diseas-

Figure 2 Effects of aging on hands/skin

es. Furthermore, we now know that alleles in the protein-coding region of ApoE are not the only source of variation in the gene that can impact aging outcomes; upstream single-nucleotide polymorphisms in the promoter or other regulatory regions are also strongly associated with longevity. This further complicates our understanding of how ApoE interacts with other molecules to impact aging. Finally, many genetic variants besides ApoE have been identified as markers of aging, yet the results are rather inconsistent, and it has been a challenge to reach solid conclusions about the effects these variants have on aging. Current genome-wide association studies on age-related genetic variation are limited in that they do not use very large sample sizes of older individuals. Future research using larger sample sizes may not only reveal new genetic variants linked to longevity, but also provide more detailed analyses of different polymorphisms within one particular gene that may work together to impact aging.

Gene Expression/Epigenetics While genotypic variation on a population level is further being investigated in aging research, scientists have also gained interest in the gene expression and epigenetic changes over time that are associated with aging phenotypes in each individual. For instance, the expression of genes involved in the oxidative stress pathway have recently been examined in relation to cognitive decline and brain health in older age. The oxidative stress pathway is the collection of mechanisms cells use to detoxify harmful free radical oxygen species, and it has been a molecular pathway of interest in aging research (6). Saifudeen et al. recently studied the effects of TXNIP, a gene encoding a thioredoxin-binding protein that inhibits its antioxidant activity, on brain aging in mice. They found that TXNIP shows increased expression with older age when comparing older mice to younger mice in controlled laboratory conditions. Upon knocking out the TXNIP gene and inhibiting its activity with the drug verapamil, they were able to successfully reverse inhibition of thioredoxin, reduce indicators of free radical production, and most importantly, improve cognitive and sensorimotor function in aged mice (7). Compared to non-treated mice, the ones that received the experimental treatment, either through gene knockout or inhibition by verapamil, exhibited better novel object recognition and improved gait control (7), which are both markers of cognitive decline in old age. The next step in this area of research would be to see if these results can be translated to treat cognitive side effects of older age in humans.

“...genes like ApoE may not only aid in the development of new drugs or supplements, but it may also reveal key information about how lifestyle and genetic factors work together to influence quality of life in old age.”

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Gene expression research has been useful in framing potential targets to alleviate age-related health problems, rather than to simply develop ways to increase longevity. By determining the genetic mechanisms that underlie aging phenotypes of specific organs, such as the brain, we get one step closer to developing therapies that may improve quality of life in old age, even if they do not have a significant impact on lifespan itself.

Another process that affects gene expression is DNA methylation, and thus, it has likewise been studied in connection to aging phenotypes.

One particular region of the human genome that experiences significant hypermethylation over the course of an individual’s life is the promoter of the ELOVL2 gene, which was found to undergo anywhere between a 10 to 50 percent increase in methylation when comparing the epigenomes of individuals from 0 to 97 years old (8). This difference in methylation was common to 15 tissue types tested in the study, which included skin, adipose, liver, brain, and muscle tissue (8). It turns out that although the entire genome is generally hypomethylated as humans age, there are a few select regions like ELOVL2 that are actually hypermethylated over time.

Understanding these kinds of epigenetic changes in humans is important to the advancement of aging research because gene expression levels can also be modified by certain treatments, as shown in the previously mentioned study of TXNIP expression in mice.

The methylation patterns of ELOVL2 over time have also been examined to understand tissue-specific aging phenotypes and to develop ways to improve their outcomes. In 2020, Chen et al. continued the study of the ELOVL2 promoter in mice by examining its methylation in correlation with specific vision changes in older mice. Using autofluorescence imaging and electroretinography, they observed that 22 month old mice with hypermethylation at the ELOVL2 promoter had larger deposits of extracellular matrix material under their retinas, a trait known to cause greater visual dysfunction with age (9). Furthermore, when a loss-offunction mutation for ELOVL2 was introduced in some of the mice, these large deposits under the retina formed prematurely. Most importantly, a 3-month treatment of older mice with the drug 5-Aza-dc was able to reverse the hypermethylation of the ELOVL2 promoter, increase the gene’s expression levels, and partially restore their visual function (9). These findings indicate that ELOVL2 regulates age-related visual dysfunction and is a promising target to either prevent or treat age-related eye diseases like macular degeneration. We may not have been aware of this gene’s connection to aging if its epigenetic changes, rather than its genetic variants in human populations, had not been examined. If other epigenetic changes related to aging symptoms are continuously evaluated in a similar manner, we may develop many more successful treatments for age-related physiological changes or diseases. Studying the epigenome may fill in the gaps and inconsistencies previously yielded by studies on variation in genotype itself, driving prompt development of anti-aging measures that can improve the well-being of older populations.

Patterns of epigenetic changes over the course of an individual’s life are, in fact, so pronounced that they have been used to construct “epigenetic clocks” for many species, including humans. These epigenetic clocks can be used to predict an organism’s actual age based on DNA methylation pat-

terns or “DNAm Age” (10). The first accurate human epigenetic clock was developed in 2013 by analyzing epigenome samples from 7,844 individuals across 82 publicly available databases. This uncovered 353 uniquely methylated sites in the human genome whose methylation patterns work together to form a clock that indicates the age of any individual with high accuracy (10). Today, this epigenetic clock has given other researchers greater insight into the variety of differentially methylated regions that could potentially be studied in the same way ELOVL2 has. It has also served as a reference for studies of how environmental and lifestyle factors impact aging and for anti-aging clinical trials. In recent years, the epigenetic clock has notably been applied in the Thymus Regeneration, Immunorestoration, and Insulin Mitigation trial—the first ever human clinical trial aimed at slowing down the aging phenotypes of the thymus gland (11). This clinical trial found that after treatment of 9 individuals with a combination of metformin (a diabetes drug), DHEA (an adrenal steroid hormone precursor), and growth hormone for 12 months, their DNA methylation age significantly decreased compared to their chronological age (11). A second part to this clinical trial is currently underway to retest the treatment with a larger sample size and more controls for environmental and lifestyle factors. Ultimately, not only does finding specific regions of DNA methylation reveal the mechanisms of biological aging; examining the overall epigenetic landscape also serves as one of the most useful tools for studying the genetic basis of aging.

“Gene expression research has been useful in framing potential targets to alleviate age-related health problems, rather than to simply develop ways to increase longevity.”

Conclusion It is clear that biological aging is a process that has many levels of complexity. Although longevity seems to be only a mildly heritable trait, genetic factors play a role in the control of aging and age-correlated phenotypes. Examining the genetics of aging through the lens of genetic variation within populations has generally yielded inconsistent results in genome-wide association studies, genetic knockout experiments on model organisms, and clinical trials on humans, proving that genetic variation related to aging is complex and does not provide us with clear-cut answers. However, there are still reliable genetic markers like ApoE that have elucidated the molecular connections between longevity and age-related physiological changes, giving us not only clues about healthy aging but also abnormal, accelerated aging. Still, changes in the structure of DNA —the epigenome— have recently revealed even more reliable biomarkers of the aging process, allowing for the creation of an epigenetic clock that can track normal or accelerated aging. These biomarkers and clocks have been used to support the development of anti-aging therapeutics that will provide relief or preventative measures to those who may suffer from side effects of aging detrimental to their well-being. Epigenetics can also be utilized at the intersection between the environmental and genetic factors that impact aging, making it a more promising direction for future aging research to take.

Even the genetic pathways with inconsistencies in aging studies, such as the oxidative stress pathway, are not lost causes. We may be able to narrow down the exact mechanisms by which these pathways impact longevity and well-being in old age through more in-depth research on a wider variety of populations and species, using different kinds of experimental methods. This inconsistent data can also raise awareness to which anti-aging practices are not entirely evidence-based, helping the general public make

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more informed decisions about their health. We should interpret these unpredictable results as an opportunity to further expand these areas of research and find other angles from which to study these phenomena, whether that means studying a different molecule, using a variety of experimental methods, or running the same kinds of experiments on different model organisms or different human cohorts. Thoroughly researching genetic changes that correlate to age could one day end up benefiting older populations especially those suffering from age-related diseases. However, it is important that this research is still analyzed and communicated in a realistic manner, since genetics is not the only factor impacting aging.

This research does not erase the immense contributions of environmental and lifestyle factors on the aging process, nor does it imply that how we age is entirely intrinsic and unmalleable. While understanding the genetic mechanisms underlying aging can improve well-being in older adults by encouraging the development of evidence-based anti-aging measures, and likewise reduce the public’s concerns about achieving healthy old age, it should be interpreted as just one piece of this complex biological process that still requires much future work to fully understand.

References 1. Z. Li et al. APOE2: protective mechanism and therapeutic implications for Alzheimer’s disease. Mol Neurodegeneration 15, 1-19 (2020). doi: https://doi.org/10.1186/ s13024-020-00413-4.

2. F. Schachter et al. Genetic associations with human longevity at the APOE and ACE loci. Nature 6, 29-32 (1994). doi: https:// doi.org/10.1038/ng0194-29.

3. Y. Zeng et al. Novel loci and pathways significantly associated with longevity. Sci Rep 6, 21243 (2016). https://doi.org/10.1038/ srep21243.

4. D. Wu et al. The Effects of rs405509 on APOEε4 Non-carriers in Non-demented Aging.

Front Neurosci. 15, 677823 (2021). doi:10.3389/ fnins.2021.677823.

5. T. Williams, D.R. Borchelt, and P. Chakrabarty. Therapeutic approaches targeting Apolipoprotein E function in Alzheimer’s disease. Mol Neurodegener 15, (2020). doi:10.1186/s13024-020-0358-9.

6. H.J. Shields, A. Traa, and J.M. van Raamsdonck. Beneficial and Detrimental Effects of Reactive Oxygen Species on Lifespan: A Comprehensive Review of Comparative and Experimental Studies. Cell Dev. Bio 9, 1-27 (2021). doi: 10.3389/ fcell.2021.628157.

7. S. Ismael et al. ​​​​​​Thioredoxin interacting protein regulates age-associated neuroinflammation.

Neurobiology of Disease 156 (2021). doi: 10.1016/j. nbd.2021.105399.

8. R.C. Sliker et al. Age-related DNA methylation changes are tissue-specific with ELOVL2 promoter as exception. Epigenetics & Chromatin 11, (2018). doi: 10.1186/s13072-018-0191-3.

9. D. Chen et al. The lipid elongation enzyme ELOVL2 is a molecular regulator of aging in the retina. Aging Cell 19 (2020). doi: 10.1111/acel.13100.

10. S. ​​ Horvath. DNA methylation age of human tissues and cell types. Genome Biol 14,1-19 (2013) doi: https://doi.org/10.1186/gb-2013-14-10-r115.

11. G.M. Fahy et al. Reversal of epigenetic aging and immunosenescent trends in humans. Aging Cell. 18, (2019). doi:10.1111/acel.13028.

Images retrieved from: 1. Graphic illustration by Annie Li `22 2. https://commons.wikimedia.org/wiki/File:Old_ hands.jpg 3. Graphic illustration by Annie Li `22

Figure 3 As the time on the clock ticks by, humans climb the ladder of age and start growing older

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YOUNG INVESTIGATORS

W RITING

COMPETITION

The Stony Brook Young Investigators Review (SBYIR) is proud to present the winners of the second annual Young Investigators Writing Competition (YIWC). The YIWC aims to provide a platform for critical thinking about how the scientific frontier is intertwined with society, its policies, and its people.

Motivated by an effort to make scientific writing opportunities accessible to a diverse range of Long Island communities, the YIWC accepts and adjudicates submissions from 10-12th graders in response to four scientific prompts in the areas of biology, psychology, environmental science, and space research.

These prompts were made contemporary with regard to the pandemic, and students had to read, analyze, and synthesize science-driven arguments for imminent problems caused by the pandemic. This year, out of 79 submissions from 18 high schools, we feature the following six finalists here.

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PLASTIC PANDEMIC OF 2020: HOW OUR GROWING EXPECTATIONS FOR NATURE CONSERVATION THROUGH RECYCLING TUMBLED BY GLOBAL CRISIS

By Isabella Oliveros, George W. Hewlett High School In 2020, a coronavirus named SARS-CoV-2 left a destructive aftermath on the well-being of the United States of America and the world alike.

The virulent strain was classified as a pandemic on March 11, 2020, and has devastated millions of people, businesses, families, and workers since (1). 14% of Americans have been hospitalized by this global pandemic, and the quality of life in the United States was not the only thing disrupted (2).

COVID-19 has affected health systems, living standards, and the economy.

It has also severely impacted the working efforts of plastic pollution reduction by activists all over the earth. The expectation of decreasing plastic waste in the environment is put “on hold” with the increasing demand for PPE’s (Personal Protective Equipment), such as face shields, gloves, masks, individually-wrapped items, and even plastic wrapping for things such as hand sanitizer and toilet paper (3). Before the pandemic began, several states had banned reusable grocery bags, resulting in the single-use plastic bag taking over once again. According to Mark Murray, the executive director of Californians Against Waste, 500 million additional plastic bags per month have been handed out in California. (4) Before the COVID-19 pandemic, over two billion people lacked access to waste collection while over three billion people lacked access to waste disposal; yet, ensuring reliable and safe services for municipal solid waste management is a necessity to preserve the environment and public health while simultaneously suppressing the spread of the disease (5). This same inaccessibility to proper waste disposal is aggravated by the pandemic. The panic buying of food, toilet paper, cleaning products, and hand sanitizers drastically increased the disposal of both perishable and non-perishable products, generating tonnes of waste throughout the world (6). Reports of hundreds of thousands - even millions of synthetic face masks and gloves improperly disposed of on Hong Kong sidewalks created a polluted city and a harmful environment (7). During the pandemic, the sudden demand for

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PPE was unexpected and surprising. Single-use mask production rocketed to 12 times the typical rate, up to 116 million per day, in China (8). If the global population resumes the practice of using this many standard one-use disposable face masks per day, the pandemic could result in a waste of 129 billion face masks and 65 billion gloves (9).

Researchers have found that the plastic pollution originating in

In order to facilitate the safe discarding of plastic waste in our ecosystem, legislators must consider and develop different approaches to meet the most effective goal.

high-income countries is also greater than normal. But, it is the management of plastic waste that determines the risk of plastic entering our ecosystems. High-income countries have effective and thorough waste management systems in place in order to prevent waste from reaching their waters.

A strong management plan that aims to combat plastic pollution can be seen through the efforts of Jamaica and Morocco. According to the World Bank, community participation and waste collection services in Jamaica improved 18 different communities, created jobs, and contributed to crime prevention and reduction programs. In Morocco, Development Policy Loans which totaled $500 million have improved citizen engagement, strengthened private sector partnerships, increased fee collection, and supported better working conditions for over 20,000 informal workers (10). In contrast, due to the poor waste management systems set across low-income countries, over 90% of waste disposed of from developing nations settles in unregulated dumps or open burning.

These harmful practices create serious complications and affect the health, safety, and environment of those countries. The poorly managed waste is a basket for diseases, methane gas generation, and loss of biodiversity. This results in such countries being the main source of global plastic pollution.

Whilst high-income countries do have effective waste management protocols, they still contribute to plastic pollution through littering (11). In an attempt to mitigate the spread of this plastic pandemic, researchers in the BioProducts Institute at the University of British Columbia have prototyped the very first N95 mask that is compostable and biodegradable. As millions of disposable masks and gloves pollute the streets of our cities, the pressure of finding a solution is crucial. Per Johan Foster, a chemical and biological engineering associate professor in the faculty of applied science, the need for a biodegradable option is essential to making a sizable impact on environmental health. The development of this ecologically friendly face mask is nearly complete, and also the key to taking a new step in “unpausing” the essential protocol in decreasing the amount of waste that is currently present in the environment (12).

As the mask is currently underway, there is an inquiry about the cost and accessibility to it. Those who reside in higher-income countries will most likely be receiving the more sustainable mask, while those in lower-income countries may not have the funds, accessibility, and availability to purchase it.

In order to facilitate the safe discarding of plastic waste in our ecosystem, legislators must consider and develop different approaches to meet the most effective goal. They may consider including bans and restrictions, economic instruments, and extended producer responsibility including the reuse, reducing, and recycling schemes. Sub-legislators may also take part in the efforts to reduce pollution by committing to more casual acts, such as consumer education programs, public procurement requirements, investing in waste management infrastructures, and public-private partnerships.

The COVID-19 pandemic has revealed the urgency of short-term plastic use and how to properly dispose of items that may most likely cause a threat to the planet in future years. PPE such as face shields and masks contain plastics that use lightweight non-woven polypropylene, polycarbonate, polyester, or polyethylene materials (13). These masks consist of non-biodegradable plastics, which contribute to a polluted, plastic planet. Only the adoption of ambitious and innovative preventative policies can address and decrease this plastic pandemic. This beautiful green and blue planet can be

cleaner and safer only with the contribution of all parties involved, including government, companies, civil societies, and the adoption of different preventative policies that will ensure a safer, cleaner planet. (14)

References 1. D. Cucinotta., & M. Vanelli., WHO declares COVID-19 a pandemic. Acta Bio-Medica 91, 157-160 (2020). doi: 10.23750/abm.v91i1.9397 2. R. Heather, et al., Estimated incidence of coronavirus disease 2019 (COVID-19) illness and hospitalization-United States. Clinical Infectious Diseases 72, 1010-1017(2021). doi: 10.1093/cid/ ciaa1780 3. J. Brock, The plastic pandemic: COVID-19 trashed the recycling dream. Reuters, (2021).

4. E. McCormick, It’s all on hold: how COVID-19 derailed the fight against plastic waste. The Guardian, (2020).

5. M. Mehran, et al., Global plastic waste management strategies (technical and behavioral) during and after COVID-19 pandemic for cleaner global urban life. Taylor & Francis, doi: 10.1080/15567036.2020.1869869 6. S. Sarkodie., & P. Owusu. Impact of COVID-19 pandemic on waste management. Environment, Development and Sustainability 23, 7951-7960(2021). doi: 10.1007/s10668-020-00956-y 7. R. Staff, Discarded coronavirus masks clutter Hong Kong’s beaches, trails. Reuters, (2021).

8. T. Adyel, Accumulation of plastic waste during COVID-19. Science 369, 1314-1315(2020). doi: 10.1126/science.abd9925 9. “Solid waste management.” World Bank, https://www.worldbank.org/en/topic/urbandevelopment/brief/solid-waste-management 10. J. Prata, et al., COVID-19 pandemic repercussions on the use and management of plastics.

Environmental Science & Technology 54, 7760-7765(2020). doi: 10.1021/acs.est.0c02178 11. H. Ritchie., & M. Roser., Plastic pollution. Our World in Data, (2018).

12. M. Agawin,. Canadian researchers create biodegradable mask in response to pandemic pollution. Environmental Sciences and Engineering Magazine, (2020).

13. L. Connors, How to dispose face masks in an eco-friendly way. Dumb Little Man, (2020).

14. C. Excell, 4 ways to reduce plastic pollution. World Resources Institute, (2021).

Graphics illustrated by Komal Grewal `23

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SYNTHETIC BIOLOGY IN THE MEDICAL FIELD:

SHOULD IT BE USED IN THE DEVELOPMENT OF VACCINES AND FUTURE MEDICAL RESEARCH?

By Sara Maltempi, John F. Kennedy High School Synthetic biology is a scientific field in which the genomes of organisms are redesigned to give them new useful abilities by combining the principles of engineering and biology (1). Synthetic biology has only been around for a couple of decades, but it has already created a new industry involving the use of engineered cells to produce goods (2). As the field of synthetic biology rapidly develops, controversy over whether it should be embraced has developed

alongside it. One main use of synthetic biology, and arguably its most controversial use, is in the development of vaccines and medical research.

An example of how synthetic biology can be applied in medicine is it has the

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potential to create vaccines for diseases that vaccines cannot be created for using traditional methods because their antigenic diversity and mutation rates are so high. Synthetic biology can be applied to help create virus-like particles, or noninfectious viral structures produced via recombination, that match the genetic makeup of a naturally occurring disease (3). The fact that virus-like particles are noninfectious yet have the same structure as a specific virus is why they can successfully be turned into vaccines because they can properly prepare the body to fight against an invasion of that pathogen without the risk of actually making the person receiving the vaccine sick. With the use of synthetic biology devices, a person can keep immunogens outside or inside the virus-like particle that upon vaccination are able to induce a quick natural immune response that boosts the efficacy of the vaccine by increasing the vaccine’s uptake (4). This shows how the application of synthetic biology to virus-like particles further improves their value in the development of vaccines.

Another way synthetic biology can be used in the medical field is in creating synthetic gene networks which are then used in the research of drugs. An example of this is the synthetic gene network that was developed to screen anti-cancer drugs. This works by simulating the cell population of a person with cancer, meaning the cell population contains abnormally reproducing cells as well as cells whose rapid reproduction is stopped in the G1 phase of the cell cycle, this is achieved by controlling what genes are expressed in the network (5). This synthetic gene network can be used to screen anti-cancer drugs by showing whether the drugs can kill tumor cells without harming healthy cells in a mixed cell population. This demonstrates how synthetic biology can significantly change the way medical research is conducted for the better by presenting a new method for testing drugs.

Of course, as is so in every controversy, there are also downsides to synthetic biology. There are concerns about the safety of synthetic biology.

As the field progresses and its tools and discoveries become more widely available, many people believe that it could easily fall into the wrong hands and give someone the power to create biological weapons that could pose serious safety threats. This was proven in 2002 when scientists in the USA recreated the polio virus from scratch using synthetic biology (1). Lucki-

ly these scientists meant no harm, but if someone who does mean harm learns how they did it, the results could be catastrophic. In response to this, the United States government has been taking steps to prevent information and technology from getting to people who may have malicious intentions by putting new measures in place. These include assessing how potentially dangerous new projects are, more heavily regulating who can access highrisk infectious agents, and keeping more papers classified (1, 6). Despite these concerns, there have been no legitimate biosecurity threats reported yet, making synthetic biology’s safety record very good (6). Its clean record combined with the many new safety measures being implemented helps ease some of the concerns about the field.

In summary, synthetic biology is incredibly useful in the medical field and will have a positive impact on the development of vaccines and future medical research. This is proven by the number of accomplishments that have already taken place in the field’s short lifetime. These include, but are certainly not limited to, the improvement of the method for developing vaccines through the use of engineered virus-like particles that are enhanced with the use of synthetic biology and the creation of a synthetic

gene network that can test anti-cancer drugs. Although, despite all the good synthetic biology can do, there are plenty of hypothetical dangers that come with the breakthroughs such as the threat of biological weapons. However, there are regulations in place to prevent these possibilities from becoming realities. As has already been shown, synthetic biology is capable of allowing many significant advances in the development of vaccines and in future medical research if we embrace it.

References 1. Staff, Synthetic biology. National Human Genome Research Institute, (2019).

2. F. Meng and T. Ellis, The second decade of synthetic biology: 2010–2020. Nature Communications 11, 1-4 (2020). doi: 10.1038/s41467-020-19092-2.

3. H. Charlton Hume, et al., Synthetic biology for bioengineering virus-like particle vaccines. Biotechnology and Bioengineering 116, 919-935 (2019). doi: 10.1002/bit.26890.

4. J. Rosenthal, et al., Pathogen-like particles: biomimetic vaccine carriers engineered at the nanoscale . Current Opinion in Biotechnology 28, 51-58 (2014). doi: 10.1016/j.copbio.2013.11.005.

5. Z. Kis, et al., Mammalian synthetic biology: emerging medical applications. Journal of the Royal Society Interface 12, 1-18 (2014). doi: 10.1098/rsif.2014.1000.

6. G. Gronvall, Safety, security, and serving the public interest in synthetic biology. Biotechnology Methods 45, 463-366 (2018). doi: 10.1007/s10295-018-2026-4.

Graphics illustrated by Komal Grewal `23

THE SAFETY BEHIND SYNTHETIC BIOLOGY

VACCINES

By Jennifer Zhong, Smithtown High School East As COVID-19 deaths and cases rise, rapid vaccine safety, development, and distribution become extremely important to potentially solve this world crisis. A myriad of people, over 105 million, have been infected with COVID-19 and well over 2 million have passed away as of February 2021 (7). The numbers continue to climb. During a global pandemic such as the current COVID-19 pandemic, vaccines need to be manufactured in large quantities and at a low cost in order to fulfill the availability of vaccines needed for herd immunity (10). Synthetic biology is a field that has been utilized to speed the development of COVID-19 vaccines using synthetically engineered organic molecules (2). DNA and RNA vaccines contain synthetic nucleotide transcripts delivered into the patient to produce translated proteins in the cells. There is an immune response triggered by these proteins that can protect the body from the virus (2,5). Synthetic biology has the potential to make a safe, quicker option for vaccine development compared to traditional vaccines and advance medical research worldwide.

There are various benefits to using DNA and RNA vaccines compared to traditional vaccines. Non-viral vaccines provide a less costly, faster op-

tion for vaccine development. Previous development has taken an exceptionally long time to develop and manufacture, anywhere between 10 to 15 years, while it has taken less than one year for the COVID-19 vaccines (3).

After viral genome sequencing, Moderna started human tests for the development of their current mRNA vaccine after only 66 days (10). Although live vaccines produce a very strong immune response, the dead or weakened pathogen may revert (6). There is a chance a live vaccine can become pathogenic if it recombines with a wild strain in nature, which coronaviruses such as SARS-CoV-2 have done in the past (6). On the other hand, RNA vaccines are considered to be safe because the spike protein is unable to reactivate and become dangerous. Despite many concerns, there is also no risk of integration of RNA into the patient’s genome (10). However, there are a few drawbacks to non-viral vaccines. They require multiple vaccinations to achieve immunity. Pfizer, BioNTech, and Moderna have each produced mRNA vaccines that are currently approved by the Food & Drug Association for emergency use (1). Both Moderna and Pfizer, frontrunners for COVID-19 vaccines, require two doses to be fully vaccinated due to the

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first dose only resulting in a weak immune response (6). Pfizer also requires storage at -70 degrees Celsius which can pose a major issue during the transportation and storage of these vaccines at such low temperatures due to necessary special equipment (3). We do not have the industrial capacity needed to produce amounts of doses in the hundreds of millions for future vaccine development yet (12).

Safety is considerably important while developing vaccines for rapid mass immunization such as the case of the COVID-19 pandemic, and potential safety risks must be weighed against benefits. Safety is a necessity for public use and lack of trust can create hesitancy and can fuel the anti-vaccination movement, making it extremely difficult to reach herd immunity during times when it is needed (6). Researchers have used the published SARS-CoV-2 sequence in order to synthesize the virus using synthetic biology which can benefit the development of a vaccine as well as drug research. Unfortunately, this may cause increased leakage of the virus and other safety hazards (11). There is also a large safety risk concerning DNA and RNA vaccines in that they have a higher chance of causing an adverse event after vaccination compared to a live attenuated vaccine (7). There have been major adverse events shown in patients during the development of the COVID-19 vaccine, including those that suspended the vaccine trials for review of such events (11). During the Pfizer Phase II trials, it was shown that 27% of people who had the vaccine reported an adverse event compared to 12% in the placebo group (9). Both mRNA vaccines can cause an allergic reaction such as anaphylaxis, preventing patients with allergies to the ingredients from having the vaccine administered (1). The development of RNA vaccines has had many obstacles and limitations in the past due to the result of inflammatory responses and also to the instability of RNA, which we need to be cautious of during synthetic vaccine development as well (8).

Due to the scarcity of vaccines and other resources during the pandemic, the distribution of COVID-19 vaccines has differences for different populations and socioeconomic levels. More people lower in social class have been severely affected by COVID-19. Even if vaccines were funded publicly, those with a lower income have previously had lower vaccination rates (4). The distribution of vaccines can deepen disparities between socioeconomic status by further separating those who have the availability to be vaccinated and those who don’t. However, with the quick development of synthetic vaccines, doses may become widely available for the public despite socioeconomic level.

As well as in vaccine development, synthetic biology can be incredibly useful in many other cases in medical advancement and research. Cells engineered by synthetic biology can be used for medical diagnosis and treatments. Viruses have been synthetically engineered to kill bacteria that are now resistant to most antibiotics and to attack and prevent the growth of tumor cells for cancer treatment (11). Unfortunately with the advantages of synthetic biology techniques, come detriments. Because of the rapid growth of synthetic biology research, there have been patient deaths and serious side effects due to research rushed without biosafety considerations.

Synthetic biology can be used in developing immunogenic vaccines and furthering medical research beyond vaccinology. DNA and RNA synthetic vaccines can be extremely beneficial, especially during a pandemic.

They ensure a quicker development and distribution of vaccines for the public to create immunity (10). Synthetic biology can help the world become more prepared for future health crises, but we still need to be wary of the potential biosafety risks and be considerate of other factors, including socioeconomic disparities.

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Synthetic biology is a field that has been utilized to speed the development of COVID-19 vaccines using synthetically engineered organic molecules.

References 1. A. Banerji, et al., mRNA vaccines to prevent COVID-19 disease and reported allergic reactions: current evidence and suggested approach . J Allergy Clin Immunol Pract 9, 1423-1437 (2021). doi: 10.1016/j.jaip.2020.12.047.

2. K. Bruynseels, Responsible innovation in synthetic biology in response to COVID-19: the role of data positionality. Ethics Inf Technol 1, 1-9 (2020). doi: 0.1007/s10676-020-09565-9.

3. R. Burgos, et al., The race to a COVID-19 vaccine: opportunities and challenges in development and distribution. Drugs Context 10, 1-10 (2021). doi: 10.7573/dic.2020-12-2.

4. S. Ismail, et al., Navigating inequities: a roadmap out of the pandemic. BMJ Global Health 6, 1-9 (2020). doi: 10.1136/bmjgh-2020-004087.

5. N. Jackson, et al., The promise of mRNA vaccines: a biotech and industrial perspective. npj Vaccines 5, 1-6 (2020).

6. M. Jeyanathan, et al., Immunological considerations for COVID-19 vaccine strategies. Nature Reviews Immunology 20, 615-632 (2020).

7. S. Kashte, et al., COVID-19 vaccines: rapid development, implications, challenges and future prospects . Hum Cell 34, 711-733 (2021). doi: 10.1007/s13577-021-00512-4.

8. N. Pardi, M. Hogan, and D. Weissman, Recent advances in mRNA vaccine technology. Current Opinion In Immunology 65, 14-20 (2020). doi: 10.1016/j.coi.2020.01.008.

9. F. Polack, et al., Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. The New England Journal of Medicine 383, 2603-2615 (2020). doi: 10.1056/NEJMoa2034577.

10. J. Sandbrink and R. Shattock, RNA vaccines: a suitable platform for tackling emerging pandemics?. Frontiers in Immunology 11, 1-9 (2020).

11. J. Li, et al., Advances in synthetic biology and biosafety governance. Frontiers in Bioengineering and Biotechnology 9, 1-14 (2020).

12. R. Rappuoli, et al., Vaccinology in the post−COVID-19 era. PNAS 118, 1-7 (2021). doi: 10.1073/pnas.2020368118.

WHAT WE OWE TO OURSELVES AND THE FUTURE GENERATION

By Sophia Augier, Smithtown High School East

There is an entire universe of endless possibilities just waiting for humankind to uncover.

However, as a nation we struggle to recognize the benefits space research has on human life.

Neither the broadening of earthbound scientific research, or the advancement of space research and exploration are mutually exclusive investments. Each is achievable and vital to sustaining human life, and should be simultaneously pursued. Unfortunately, space research, and the benefits these programs yield, lack saliency across the public sphere, and therefore lack the necessary funding and support (1). In contrast, the globally competitive space programs of the 1960’s inspired our nation which subsequently garnered the financial backing of the U.S. government (2).

Today, public support can be established with clear correlations drawn between space research and its benefits to life on earth. This type of public understanding is paramount in securing the necessary funding for space research.

Space research leads to discoveries and innovations that ultimately feed two overarching workstreams; improving life on

earth and sustaining human life beyond our planet’s atmosphere. This is seen in the life science research data NASA recently shared regarding the effects of long term isolation and confinement on genes, neural circuits, physiological systems, and behavior (3). This data provides great value to researchers focussing on future space travel, exploration, or habitation. Such findings also provide actionable value here on earth, in that they fuel the development of innovative and efficient health screening tools, diagnostic systems, and treatments to mitigate health risks associated with isolation and confinement (3). These timely inputs provide healthcare opportunities for those deeply impacted by isolation during the COVID-19 global pandemic. In space, astronauts remain in the same place, with the same people, doing the same thing day in and day out.

The commonality observed between social isolation during the pandemic and the isolation of space travel, helps us understand and prepare for life post-pandemic (3).

Climate change is another global crisis where we continue to do battle.

Space research has provided us with solutions to monitoring, managing, and mitigating the harsh effects of climate change.

Rising t e m -

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It is our job as human beings to create a better life not just for today, but also for generations to come. Without space research today, there will be no hope for a safe and secure tomorrow when Earth can no longer be called home.

of safely extinguishing the fires in time to minimize loss of lives and damage to forests and property (5). Without putting astronauts and resources in space, the world would never have been able to reap the benefits of this unique perspective and technology.

The NASA budget is less than 1% of the U.S. federal budget. At only $23 billion, NASA spending is significantly less than it was at its peak at the the start of the Apollo missions in 1966. Since that time the NASA budget shrank from 4.5% of the federal budget to .5% today. Comparatively, NASA receives a fraction of the funding seen in other areas of the federal budget; 26% for healthcare or 17% for defense (6). Government funding is driven by interest and need, which explains why the NASA budget decreased by about $40 billion following the cold war (6). When space exploration was driven by competition and political interests it received more support. As a result, NASA was able to achieve and innovate on many fronts. When public interest faded and political winds shifted, funding and support slowly shrank over the course of the next 40 years (6). However, space research continued to provide knowledge that benefited life on earth, be it at a lesser rate.

Consequently when funding slows down, so does space exploration. The commercialization of space travel allows NASA to better collaborate with global research partners by focusing it’s funding and resources on space research, leaving private companies to compete for contracts to handle the routine shuttling of cargo and humans to the International Space Station (ISS) (1). Companies such as SpaceX saw an industry that was lacking in the resources, but had the reputation of discovering and producing great things. Private companies that understand the profit potential surrounding space exploration were eager to invest their time, money, and resources (7).

These private enterprises help offset the impact of decreased government funding (1).

Space exploration takes a toll on the human body. The effects of microgravity cause serious disruption within the body, especially to the cardiovascular and musculoskeletal systems (8)(9). Once astronauts escape the Earth’s gravitational pull, they put their bones and muscles at risk for atrophy that can lead to increased kidney stone formation and bone fractures, as well as harden the intervertebral discs leading to disc disease and pain (8). Without gravity the cardiovascular system also experiences great changes since blood isn’t being pulled toward the feet, it instead pools up in the torso and head and in response the body decreases the blood pumping rate and red blood cell production, negatively impacting other body systems (9). This may seem like reasons not to continue space research, but the opposite is true (8). Just as firefighters put their lives at stake to save civilians, or soldiers risking their lives at war, astronauts are putting their lives at risk for the future generation. It is our job as human beings to create a better life not just for today, but also for generations to come. Without space research today, there will be no hope for a safe and secure tomorrow when Earth can no longer be called home.

References peratures and abnormal precipitation rates have made countries like the United States, Australia, Russia, and Spain increasingly susceptible to extreme and prolonged wildfires and wildfire seasons (4). Astronauts on the International Space Station (ISS) utilize their unique perspective and specialized instruments to provide monitoring and managing services for fighting wildfires. NASA engineers were able to create one of the most effective fire detection systems using tools originally developed for space research (5). Their artificial geostationary satellites are able to quickly detect thermal heat and almost immediately notify field officials back on earth using wireless technology. Being the first to be able to detect and notify officials about early fires burning in distant regions, gives firefighters a much better chance

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1. Nasa, Benefits stemming from space exploration. NASA, (2013).

2. A. Rinaldi, Research in space: in search of meaning. EMBO Reports 17, 1098-1102 (2016). doi: 10.15252/embr.201642858.

3. A. Chouker and A. Stahn, COVID-19 - the largest isolation study in history: the value of shared learnings from spaceflight analogs. npj microgravity 6, 1-7 (2020). doi: 10.1038/s41526-02000122-8.

4. M. Goss, et al., Climate change is increasing the likelihood of extreme autumn wildfire conditions across california. Environmental Research Letters 15, 1-14 (2020).

5. R. Petrescu, et al., NASA satellites help us to quickly detect forest fires. American Journal of Engineering and Applied Sciences 11, 288-296 (2018). doi: 10.3844/ajeassp.2018.288.296 .

6. The Planetary Society, Your guide to NASA’s budget. The Planetary Society, (2021).

7. C. Iacomino and S. Ciccarelli, Potential contributions of commercial actors to space exploration.

Adv. Astronaut. Sci. Technol. 1, 141-151 (2018).

8. K. Kandarpa, V. Schneider, and K. Ganapathy, Human health during space travel: an overview.

Neurology India 67, 176-181 (2019). doi: 10.4103/0028-3886.259123.

9. B. Dunbar, Cardiovascular health in microgravity. NASA, (2020).

Graphics illustrated by Komal Grewal `23

THE ENVIRONMENTAL COST OF COVID-19:

A PLASTIC PANDEMIC

By Angela Zhu, Jericho Senior High School While the COVID-19 virus has halted economies and separated families around the world, it has unintended yet devastating consequences on the environment in the form of plastic. From masks to gloves, the personal protective equipment (PPE) that is necessary in the fight against the pandemic is piling up in landfills and polluting oceans.

While many other industries have been on the decline during the pandemic, manufacturers of plastic have seen their demand and production increase (1). Everyday, an estimated 1.6 million tonnes of plastic are generated (2). Globally, almost 130 billion face masks are disposed of monthly, making the rate of usage over 3 million masks per minute (3). Furthermore, plastic pollution doesn’t just come from biomedical wastes, common conveniences like delivery cartons and plastic bags also contribute greatly to the rise in consumption. Many cities, like California, postponed mandates for using reusable bags out of precaution that they would more easily transmit the virus. In part, the growth of plastic usage has been due to public perception of its ability to resist COVID-19 transmission. However, public perceptions are often misinformed, as leaders of the plastic industry misuse research to induce fear about using reusable alternatives or promises of recycling. In fact, companies are aware that recycling will likely not address the problem of plastics, however, they continue to push out campaigns highlighting the efficacy of recycling in order to give consumers the illusion that they are more environmentally friendly. Despite promises of large sums of money being allocated to plastic recycling and resusage, many plastic wastes that do not have established or cheap recycling methods ended up in landfills.

With less than 10% of plastic actually being recycled, everyday items like PVC containers and food-stained packaging only continue to pollute the environment (1).

The plastic problem has actually been worsened due to the pandemic. Because of the unexpected nature of the pandemic, the sudden surge in single-use plastics that pile up in landfills and litter seabeds is on track to reverse the global momentum to reduce pollution (2). Masks have decorated the faces of people across the world, but now studies are showing that they are also invading beaches and oceans. In 2020 alone, over 1.5 billion face masks polluted the oceans, causing plastics to harmfully affect marine health and also our own (4). What’s more concerning is that the sudden surge in PPE waste may pose a threat since companies were not prepared to properly manage them (5). The production of masks rivals that of plastic bottles, but with one major difference - there are no guidelines

for recycling masks. Because of the lack of regulations after their sudden boom in usage, researchers are concerned about the environmental impacts that they have. Single-use masks are made of plastics that are not readily biodegradable and can splinter into microplastics which negatively affect the health of ecosystems. The fibers that form face masks may make them prone to releasing more microplastics in a short period of time compared to plastic bags (3). Moreover, the toxins created by plastic face masks extend beyond microplastics, as researchers found that the dyes used in face mask production contain traces of potentially toxic heavy metals. Especially with face masks b e i n g submerged under water, the heavy metals can easily accumulate in aquatic systems (4).

With plastics entering oceans and other natural environments, plastics have also made their way into the food chain. As animals ingest mi-

croplastics, the process of trophic transfer causes plastic-produced toxins to accumulate, ultimately ending up in our plates (5).

Plastics are undoubtedly harmful for the environment, especially in regards to ocean and wildlife health. However, plastic also plays a gargantuan role throughout society,

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both for protection against the pandemic and also daily conveniences. For example, the packaging of food often seems wasteful but is a luxury that is often overlooked in America. Without cheap plastics, food security in underdeveloped countries continues to be a big issue and actually generates more food waste due to improper packaging. There is also a balance that must be struck between plastic and plastic alternatives. Plastic is cheap and easy to produce, not generating as much greenhouse gases and water inputs compared to cotton or recycled bags. However, plastic bags are typically single-use items and, because of their non-reactiveness, take years to degrade in a natural environment (5). Thus, the question becomes, how can we properly manage personal and industrial plastic waste while also being mindful of societal limitations?

Considering the benefits of wearing a mask and other PPE, banning masks themselves may not be an effective solution. Instead, new materials and waste management standardization should be enacted to ensure that face masks no longer pose as great an environmental threat (6). Thus, just as with any majorly produced waste, new, pandemic-relevant recycling and management standards must be implemented across the country (3). Additionally, as governments hope to recover economies, there is hope to rebuild businesses and industries that can produce reusable PPEs or those made of alternative materials (2). From mask-only waste bins to mask alternatives that are biodegradable or reusable, steps must be taken to reduce the environmental impact of the pandemic (3).

While big industries should play a role in reducing plastic usage, the everyday person and the internet can play a big part in making sustainability a continuous trend, especially with the world going virtual. In the past years, sales of reusable cups and bottles have skyrocketed, showing that people are becoming more environmentally-focused (7). This large rise in environmental consumers stems greatly from young environmental advocates and growing trends online of choosing sustainable alternatives like buying second hand and supporting local or sustainably-certified businesses (8). Moreover, social media has become a great platform for researching easily-applicable ways to reduce one’s footprint and also marketing for environmentally-friendly brands (7). With large companies and the common consumers consciously choosing to value the environment while still saying safe, we can all play a role in reducing the environmental cost of the pandemic.

References 1. D. Glaun, The plastic industry is growing during COVID. Recycling? Not so much. PBS, (2021).

2. N. Benson, D. Bassey, T. Palanisami, COVID pollution: impact of COVID-19 pandemic on global plastic waste footprint. Heliyon 7, e06343 (2021). doi: https://doi.org/10.1016/j.heliyon.2021. e06343.

3. E. Xu and Z. Ren, Preventing masks from becoming the next plastic problem. Frontiers of Environmental Science & Engineering 15, 125 (2021). doi: https://doi.org/10.1007/s11783-021-1413-7 4. Z. Malin, How to reduce face mask pollution, according to experts. NBC News, (2021).

5. Plastic in food chain. Plastic Soup Foundation.

6. Covid: Disposable masks pose pollutants risk, study finds. BBC, (2021).

7. O. Valentine, Social media’s influence on green consumerism. We Are Social, (2019).

8. S. Nielsen, Retailers and the rising trend of sustainability: what marketers need to know. Sprout Social, (2020).

Graphics illustrated by Komal Grewal `23

THE FUTURE OF EDUCATION:

A BLENDED APPROACH TO

VIRTUAL LEARNING

By Julia Froese, Wantagh High School In the past decade, technology has experienced a pattern of exponential growth within industry, business, and now, education. With the advent of the digital age, communication has become much more fluid and accessible, leading to a rise in investments regarding social media and computer science. However, at the outset of the COVID-19 pandemic, educational institutions had only touched the surface of the possibilities grounded within the field of technology. There had yet to be the introduction of webinars and recording services within the classroom and it was still unclear as to how these advancements could be incorporated into an existing curriculum. Interestingly enough

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though, despite all of the tragedy and loss associated with the pandemic, the situation helped to open educators’ eyes to the opportunity vested within the use of digital advancements. Instead of rejecting technology, as it was previously seen as enhancing cheating and creating unavoidable distractions in class, they started to rely on it as students were unable to safely return for in-person instruction (1). In fact, according to UNESCO, an agency aimed at promoting world peace, 1,500,000,000 students across the globe were unable to attend school at the start of the pandemic (2). During such distressing times, virtual systems helped schools stay open, ultimately making educators realize the value in incorporating technology within the classroom. However, there were still a few caveats to online learning, starting with the fact that not all students had equal access to technology.

Furthermore, these digital devices could cause permanent psychological issues, damaging academic performance. Therefore, while introducing virtual learning processes into the classroom ultimately benefited students in a time of crisis, there were still some striking flaws ridden within existing systems, resulting in the need for a blended model where there is a balanced approach between education and technology.

While technology can make many tasks such as homework and test-

ing much easier, it can also lead to disastrous psychological repercussions.

According to Jonathan Haidt, a professor and psychologist at New York University, time spent using technology may be associated with increased anxiety, depression and other mental health ailments (3). Additionally, since the start of the COVID-19 pandemic, there has been a dramatic rise in the need for mental health services within the United States (4). These two phenomena are no coincidence, as the increase in social distancing made individuals more reliant on technological services, therefore worsening the severity of the mental health epidemic. When translating this to education, it is evident that too much technology in the classroom may create more problems than solutions.

There are already a number of distractions within a normal school setting, let alone one where teachers cannot continually monitor the activity of their students. Educators even found that virtual learning made it harder for students to focus and understand lessons during the pandemic than before (5).

Similarly, in a study conducted about online education, more than half of the student participants indicated a lack of engagement in class, difficulty in maintaining their focus, and Zoom fatigue after attending multiple online sessions (6). While it is important that educators take into account the advantages of incorporating virtual lessons within an existing curriculum, it is also important that they recognize the downsides as well.

One of the most striking flaws with a virtual education is that not all students have equal access to digital resources. According to Cathy Li, the Head of Media at the World Economic Forum, while virtually all 15-yearolds from privileged backgrounds said they had a computer to work on, nearly 25% of those from disadvantaged backgrounds did not in the United States (7). If virtual learning were to be permanently woven into existing educational systems, it could impact the amount of schooling one student gets over another based on their economic status. Furthermore, poor internet connection or an unreliable service can cause educational inequities as well.

According to Carlo Patilan Cortez, a researcher at the Southeast Technical College, without stable and efficient connection, students face many frustrations instead of developing their education (8). Due to the unreliability associated with online learning, it should not be instated as a permanent educational system. Instead, technology should be used within the classroom for in-person instruction. Local, state, and national governments could set aside funds to provide students with digital devices to equalize learning opportunities. Large corporations such as Microsoft and Apple should also provide programs which give all students a fair technological experience in school, ultimately bridging the gap in education between the wealthy and the poor.

... since the start of the COVID-19 pandemic, there has been a dramatic rise in the need for mental health services...

After weighing the pros and cons of a virtual education, it is clear that a blended approach is necessary. Technology should be present within the classroom, such as using SMART Boards and giving students school-owned devices, however full-time virtual education systems should be avoided.

Students are taught best when they are physically in the classroom and it is critical that teachers are able to monitor the activity of their students on a daily basis. If

they cannot do this, students will be unable to focus and will ultimately learn less.

However, that does not mean that virtual learning should be totally abandoned. According to a study on the effectiveness of e-learning in hospitalized children, virtual learning improved their test scores, made it easier for them to receive an education, and improved their social and psychological well-being (9). Due to the clear benefits of a virtual education for students with chronic illnesses, digitized systems should stay in place for individuals who cannot attend school regularly. Furthermore, virtual learning can also improve access to education overall, as students from across the globe could learn the same material from universal educational platforms, such as Khan Academy. All students should have equal access to technology within the classroom. However, virtual learning should remain an accessory to in-person education, rather than a replacement.

References 1. M. Teras, et al., Post-COVID-19 education and education technology ‘solutionism’: a seller’s market. Postdigital Science and Education 2, 863-878 (2020).

2. COVID-19 education disruption and response. UNESCO, (2020).

3. J. Haidt and N. Allen, Digital technology under scrutiny. Nature 578, 226-227 (2020).

4. J. Kluger, The coronavirus pandemic may be causing an anxiety pandemic. TIME, (2020).

5. M. Hebebci and S. Alan, Investigation of views of students and teachers on distance education practices during the coronavirus (COVID-19) pandemic. International Journal of Technology in Education and Science 4, 267-282 (2020). doi: 10.46328/ijtes.v4i4.113.

6. S. Asgari, et al., An observational study of engineering online education during the COVID-19 pandemic. PLOS ONE 16, 1-17 (2021).

7. C. Li and F. Lalani, The COVID-19 pandemic has changed education forever. Here’s how. World Economic Forum, (2020).

8. C. Cortez, Blended, distance, electronic and virtual-learning for the new normal of mathematics education: a senior high school student’s perception. European Journal of Interactive Multimedia and Education 1, 1-6 (2020). doi: 10.30935/ejimed/8276.

9. Z. Aghakasiri, et al., Effectiveness of e-learning among hospitalized elementary students with chronic diseases. Interdisciplinary Journal of Virtual Learning in Medical Sciences 11, 191-199 (2020). doi: 10.30476/ijvlms.2020.86703.1038.

Graphics illustrated by Komal Grewal `23

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Stony Brook Young Investigators Review would like to give a special thank you to all of our benefactors. Without your support, this issue would not have been possible.

Cover image retrieved from: https://unsplash.com/photos/78A265wPiO4 Edited by Komal Grewal `23

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