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AFSANEH KHETRAPAL WRITING PORTFOLIO 2015-2016


SCIENTIFIC SCTIFIC REPORTS Social Media Contributions p2-3


FACEBOOK POST

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Scientific Reports


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Scientific Reports


SCIENTIFIC BBC REPORTS FOCUS Printed Contributions Web Articles p5-10


HOW IT WORKS

Project Soli GOOGLE’S ADVANCED TECHNOLOGY and projects (ATAP) The radar transmits a wave towards a target, such as your division specialises in creating futuristic technology, such as hand. The radar receiver then intercepts the energy that reinteractive clothing and an open source modular smartphone flects back. A lot of information can be interpreted from one platform. One of its most recent prototypes, Project Soli, radar signal because of the gesture recognition system that allows the control of electronic devices without touch. So has been built by Project Soli. Unlike camera-based systems instead of stabbing away at your tablet or smartphone with from companies like Leap Motion, Soli needs no additional your chubby mitts, you make elegant hand movements in hardware and its radar signals are capable of penetrating other mid-air that are translated into commands. Wan to turn up materials. This means that even if the chips are embedded the volume? Just twiddle your fingers. Need to turn a page? inside objects, they can still accurately detect hand gestures. Simply swipe your hand.

The sensors are incredibly accurate and capable of capturing

Project Soli has taken shoebox-sized radar hardware and has shrunk it right down so that so that it can be embedded on a chip. German manufacturer Infineon is working with Project Soli to develop the chips.

motion at 10,000 frames per second from as far as a metre away. As the device is so small, it can be incorporated into a range of electronic gadgets and wearables. Google’s Project Soli is ready for mass production and will be released to developers later in 2015.

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BBC Focus


WEB ARTICLE

Ultrasonic fingerprint sensor could make your smartphone safer than ever Fingerprint sensors are a nifty way to unlock smartphones. Unfortunately, they can also be tricked with a forged print, as was shown with the iPhone 5s and iPhone 6. But a new technology developed in California could change that.

sensor can penetrate a thin layer of tissue near the finger’s surface, making the technology much more difficult to trick.

The chip itself is made from two wafers bonded together: a ‘complementary metal-oxide-semiconductor’ A team led by David Horsley, professor of mechani- (CMOS) wafer and a microelectromechanical systems cal and aerospace engineering at the University of (MEMS) wafer. The CMOS wafer contains the circuitry California, Davis, has developed a new ultra-safe, for processing the signals, while the MEMS wafer ultrasonic sensor. contains the transducers. “Our ultrasonic fingerprint sensors have the ability to Besides the security advantages, the researchers measure a three-dimensional, volumetric image of say that these chips will be extremely cheap to make. the finger surface and the tissues beneath the sur“We were able to use low-cost, high-volume manuface – making fingerprint sensors more robust and facturing processes that produce hundreds of millions secure,” says Horsley. of MEMS sensors for consumer electronics each The sensor uses similar technology to medical ul- year,” says Horsley. trasound imagers. Transducers on the tiny sensor’s So look out for these sensors on a smartphone near you… surface send out ultrasound pulses, which bounce off the fingerprint’s ridges and valleys before returning to the transducers. Using ultrasound means that the

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BBC Focus


WEB ARTICLE

What’s that Skippy? Most kangaroos are left-handed? Thought humans were the only species to show preference for their left or right hands? Well, think again... kangaroos do, too. Thought humans were the only species to show pref- says Yegor Malashichev at Saint Petersburg State erence for their left or right hands? Well, think again... University in Russia. “We observed a remarkable kangaroos do, too. consistency in responses across bipedal species in that they all prefer to use the left, not the right, hand.” Researchers in Russia and Australia have found that some species of ‘roo show a natural preference for their left paws. This makes kangaroos the only non-primate animals to show ‘handedness’ on a large scale in the way that humans do.

These displays of handedness came as something of a surprise, because kangaroos don’t have a corpus callosum - the region of the brain that’s thought to be linked to handedness in humans.

The scientists observed wild eastern grey and red kangaroos over many months in Tasmania and Australia. They noticed that the animals showed a preference for their left hands when performing actions such as grooming their nose, picking a leaf or grabbing a branch.

The researchers believe that further study of the marsupial brain could provide insights into how this behaviour evolved. It might even shed light on neurological conditions such as schizophrenia and autism, which some studies have linked to handedness.

“According to a ... scale of handedness adopted for primates, kangaroos pulled down the highest grades,”

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BBC Focus


WEB ARTICLE

Scientists observe new memories forming inside the brain If you’ve ever wondered how a new memory forms, you’re not the only one. Now, for the first time in humans, scientists in the UK and US have observed new memories forming inside the brain. If you’ve ever wondered how a new memory forms, ing Tower of Pisa. you’re not the only one. Now, for the first time in hu“The remarkable result was that the neurons changed mans, scientists in the UK and US have observed new their firing properties at the exact moment the subjects memories forming inside the brain. formed the new memories – the neuron initially firing Researchers at the University of Leicester and the Ronald Reagan UCLA Medical Center were able to observe a neuron in the brain firing differently when a new memory was forged.

to Jennifer Aniston started firing to the Eiffel Tower at the time the subject started remembering this association,” says Prof Rodrigo Quian Quiroga at the University of Leicester.

Back in 2005, the same group announced the ‘Jennifer The neurons being studied were in a region of the brain Aniston neuron’ – the idea that single neurons react known as the medial temporal lobe (MTL), which is to the faces of specific people. They even found that known to be involved in long-term memory. this ‘Jen’ neuron fired in response to Lisa Kudrow (her “Given the involvement of MTL neurons in memory former castmate in Friends), which suggested that the formation, we hypothesised that we would be able to actresses were associated by memory. see some changes in the firing of the neurons,” says This time, the researchers used a similar approach to lead author Dr Matias Ison, also at the University of show how memories are formed, working with epilepsy patients who’d had electrodes implanted to help treat their condition. The participants were presented with an image of a celebrity in context – Jennifer Aniston at the Eiffel Tower, for example, or Clint Eastwood at the Leaning Tower of Pisa.

Leicester. “But the astonishing fact was that these changes were dramatic, in the sense of neurons changing from being very silent to firing a lot, and that these changes occurred at the exact moment of learning, even after one trial.”

It’s hoped that a better understanding of how neurons The scientists noticed that the neuron that had previ- learn and encode new memories will help scientists ously fired for the celebrity alone – e.g. Jennifer Aniston to treat degenerative neurological disorders such as or Clint Eastwood – now also fired when shown the Alzheimer’s disease. associated image – e.g. the Eiffel Tower or the Lean-

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BBC Focus


WEB ARTICLE

Australian lizard changes sex when the temperature rises When it comes to gender, the Australian bearded dragon is more flexible than most. For the first time in the wild, a reptile has been observed switching sex when the temperature rises. When it comes to gender, the Australian bearded males, we could establish new breeding lines in which dragon is more flexible than most. For the first time temperature alone determined sex,” says Holleley. “In in the wild, a reptile has been observed switching sex doing so, we discovered that these lizards could trigger when the temperature rises. a rapid transition from a genetically-dependent system to a temperature-dependent system.” Dr Clare Holleley and colleagues at the University of Canberra studied 131 adult lizards and showed that What’s more, the females who were genetically 11 who lived in warmer regions were genetically male, male were more fertile than the ‘normal’ mothers, but physically female. It’s the first evidence that an laying more eggs. egg’s temperature during incubation can cause the Further research will help scientists to pin down exactly developing lizards to change gender in the wild. how climate can affect biology and sex. The researchers spotted this peculiar behaviour by “The mechanisms that determine sex have a profound studying the lizards’ sex chromosomes - the thread-like impact on the evolution and persistence of all sexually packages of DNA that determine an organism’s sex. reproducing species,” says Prof Arthur Georges, who In bearded dragons, females have a Z and a W sex was also involved in the study. “The more we learn chromosome, whereas males have two Z chromo- about them, the better equipped we’ll be to predict somes. However, the scientists found that nearly 20 evolutionary responses to climate change and the per cent of the ZZ lizards sampled in the wild were impact this can have on biodiversity globally.” outwardly female. “By breeding the sex-reversed females with normal

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BBC Focus


Talk to the Han SAY HI TO Han, a state-of-the-art robotic head made by Hanson Robotics. His skin has been created using a high-tech flexible material called Frubber, flesh rubber, and it’s even dotted with pores to give it a more human appearance. But Han doesn’t just look human; he can act the part too. Cameras hidden within his eyes and chest allow him to recognise faces and make eye contact with those around him. Once locked onto a subject he can respond to their actions by altering his expressions and can even engage them in banter. “The growing number of elderly in our societies and our ever-increasing

life expectancies are adding press explains Angelo Cangelosi, Direct Plymouth Univer Centre of Roboti both in care ho private residen

companions sh a substitute of social care an PHOTO: CAMERA

SCIENTIFIC REPORTS

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SCIENTIFIC REPORTS

OCTOBER 2015 / FOCUS / 13


SCIENTIFIC AZONETWORK REPORTS White Papers Reviewed Articles p12-94


What is SCHIP? The State Children’s Health Insurance Program (SCHIP) is a program that was proposed and enacted into law as part of the Balanced Budget Act of 1997. It is a firm partnership between the Federal and each individual state government – it is administered by the state governments, but its funding is jointly covered by the federal and state governments with the federal government paying a higher share of SCHIP costs up to a predetermined total amount for each state.

speaking however, each state is responsible for the design of its program – this encompasses eligibility criteria, specific benefit packages, payment levels for coverage, and operating procedures. Individuals must check with the SCHIP office in their home state to confirm their family’s eligibility to receive benefits.

To qualify for this benefit program, one must be under 19 years of age or be a primary guardian of a child under the age of 19, not covered by any form of health The purpose of SCHIP was to provide health coverage care (including Medicaid), and a U.S. national, citizen, in conjunction with Medicaid by targeting insurance permanent resident or legal alien. coverage to the uninsured, low-income children whose Regardless of the approaches a state decides to take family income is too much to be eligible for Medicaid, in providing children’s health insurance coverage, there but still too little to afford private coverage. Those who are federal laws in place to ensure the state delivers a qualify typically earn up to 200 percent of the Federal minimum set of benefits. These include the following Poverty Level (FPL). medical services: Federal SCHIP funds from states are also subject to >> “Well-child” doctor and dental visits free of cost redirection due to the financing structure laid out by CHIPRA. This means that after two years, any unspent >> Preventive care (including doctor’s visits and immunizations) SCHIP funds remaining in a state’s allotment will be redistributed to states that require additional financing. >> Prescriptions Additionally, a state’s total SCHIP spending is calculated using the SCHIP formula that is adjusted every two years. Through appropriate analyses, states that increase their spending of federal SCHIP funds are identified and effectively awarded by securing increases in their allotted SCHIP funding, while those states that do not spend their full federal allotments forfeit a portion of their SCHIP allotments.

>> Hospitalization >> Emergency services >> Vision and Dental care

All states must offer these minimum requirements but many will also provide more comprehensive coverage for children in need. States may also extend SCHIP coverage of prenatal care to pregnant women when With their allocated funding, individual states have certain conditions are met. the responsibility of structuring their own program. Integral to the running of both Medicaid and SCHIP is They have the choice of expanding Medicaid cover- the Medicaid and CHIP Payment and Access Comage, creating an entirely separate SCHIP program, or mission (MACPAC). This is Congressional advisory combining the two options in order to simultaneously commission provides makes policy recommendations provide health benefits for sub-populations of children. to the Congress and states which pertain to issues such The Federal government establishes general guidelines as: eligibility and enrollment, access to healthcare, payregarding the administration of SCHIP benefits. Broadly ment policies, benefits and coverage policies, quality of care, and the interaction of Medicaid and SCHIP —13—

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with Medicare and the health care system.

and also equip the Congress and the public with a better understanding of the function of the Medicaid The commission is required to submit two reports and SCHIP programs, and any highlighted key policy a year which include their policy recommendations and data issues.

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SCHIP History The State Children’s Health Insurance Plan (SCHIP) was a program intended for children in families with too high an income to qualify for Medicaid but too modest to afford private insurance (approximately 100%–200% of the federal poverty level) . At the time of its implementation, the target subpopulation of this program was disproportionately uninsured. Senator Kennedy was a key founding figure in SCHIP. Its legislation was inspired by a children’s health insurance plan in Massachusetts in 1996. In this year, a major health law was passed to authorize the expansion of health insurance coverage for children and restructure the state’s Medicaid program.

such as public health, AIDS, scientific research, child care and civil rights for the disabled population. Unfortunately, the bill was initially unsuccessful as it failed to comply with the existing balanced budget resolution between Congress and the White House. The bill was revived by Kennedy and Hatch a month after its initial defeat with recurring support from the First Lady and even children’s health advocates such as the Girl Scouts of the USA and Children’s Defense Fund. With such overwhelming public pressure on Congress, SCHIP was finally passed and signed into law by President Bill Clinton on August 5, 1997, as part of the Balanced Budget Act of 1997 (BBA).  

Senator Kennedy worked closely with many officials to obtain a necessary Medicaid waiver from the Clinton Administration. Following this, the state was able to expand its health coverage and to finance this expansion through savings redirected from a more efficiently functioning and redesigned Medicaid program. Senator Kennedy used this Massachusetts children’s health expansion as a model for a national program and wrote much of the bill, which would raise the Federal tax on tobacco products as a source of funding for health care for children. At the same time, First Lady Hilary Clinton’s interest had also been roused by children’s health policy. SCHIP was a prominent presence in the second-term of the Clinton administration. Their first attempt to reform health care was in the form of President Bill Clinton’s 1997 State of the Union address, which proposed a new health initiative for kids, with the stated goal of covering up to five million children. The failure of this bill did not deter the pursuit for health reform; the First Lady aligned herself with Kennedy’s cause. In March 1997, Senator Kennedy sought support from Republican Senator Orin Hatch from Utah as a co-sponsor for the legislation. The two had already worked as a pair on legislation concerning issues —15—

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SCHIP Administration The State Children’s Health Insurance Program (SCHIP) is a program designed to improve the availability and accessibility of health coverage to low-income children and pregnant women in families that have annual income above Medicaid eligibility levels but have no health insurance. Under the current SCHIP program, the federal government sets basic requirements for SCHIP in place, but ultimately each state has the flexibility to design its own version of SCHIP within the federal government’s pre-decided framework. It is therefore not surprising that there is significant inter-state variation across for example; some states may extend SCHIP coverage of prenatal care to pregnant women when certain conditions are met. To set up a SCHIP program, each State must first submit a Title XXI plan for approval by the Secretary that details how the State intends to allocate its received funds to fulfill requirements. After each state designs its SCHIP program and health plans they then enroll eligible individuals into their programs and become responsible for assuring SCHIP benefits are delivered to these beneficiaries.

mediate negative impact on low-income individuals’ coverage and access to care as they often cannot afford even nominal out-of-pocket costs. Unlike the case with “crowd out” (when individuals migrate from private to public health coverage), these individuals cannot replace their public with private coverage; instead they become uninsured.

Medicaid expansion SCHIP With this program, a state receives federal funding to expand the eligibility for Medicaid to a wider net of targeted low-income children that meet the requirements of section 2103 of the Social Security Act. As the SCHIP funds are channeled into the state’s Medicaid program, all Medicaid rules and regulations (such as cost sharing and benefits) apply. These programs are required to follow the federal Medicaid rules for cost sharing and benefits, which entitles SCHIP enrollees to mandatory services such as Early and Periodic Screening, Diagnostic, and Treatment coverage and exempts the majority of children from enrollee cost sharing.

Combination SCHIP

The state SCHIP program can be designed in Under this program, a state receives federal funding to one of three ways. implement both expansion of Medicaid and develop a separate SCHIP entity. This usually results in the state Separate SCHIP operating both an expanded Medicaid program and Under this program, a state receives federal funding to one or multiple separate SCHIP programs concurrently provide child health assistance to uninsured, low-income such that there are multiple approached designed to children that meet the requirements of section 2103 address different population sub-groups. of the Social Security Act. These programs provide more flexibility than Medicaid programs by offering As of January 1, 2015, an overwhelming 41 states tailored benefit packages and a great deal of flexibility implemented a combination program, 2 states operated separate SCHIP programs while 8 states and 5 in eligibility and enrollment policies. territories ran a Medicaid expansion SCHIP programs. These programs have the option of charging premiums, This could be partly explained by a shift from separate enrollment fees and cost sharing for beneficiaries. SCHIP to combination programs after two amendUnfortunately, these can have a significant and im- ments in the Patient Protection and Affordable Care —16—

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Act (ACA) were made.

from separate SCHIP programs into Medicaid.

These required states to transfer some separate SCHIP enrollees into Medicaid by effectively raising eligibility levels: a mandatory income disregard equal to 5% of the federal poverty level (FPL) and the mandatory transfer of 6- to 18-year-olds between 100-133% FPL

In addition to designing and implementing these three program types, states are allowed to use their allocated Medicaid and SCHIP funds to establish premium assistance programs that offer aid to eligible individuals to purchase private health insurance.

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SCHIP Reauthorization The State Children’s Health Insurance Program (SCHIP) was established in 1997 as part of the Balanced Budget Act of 1997 (BBA). In conjunction with Medicaid, SCHIP has helped to reduce the number of low-income uninsured children by broadening eligibility requirements and simplifying enrolling procedures.

as: income eligibility, crowd-out, and the treatment of immigrants, childless adults, and parents.

In response, the revised bill would prohibit SCHIP for coverage of children beyond three times the poverty level, require more extensive verification of citizenship status, require all states to implement best Having been established as a decade-long program, practices to limit crowd out, and encourage premium SCHIP required the passage of a reauthorization bill assistance options. in the fiscal year 2007. A House vote in January 2008 failed to override the President’s veto once again and this resulted in the The Initial Children’s Health Insurance Protemporary funding of SCHIP through December 14 gram Reauthorization Act of 2007(HR 976) at current levels that were not sufficient to fund most Both houses of Congress passed this Act in 2007, with states to maintain coverage of children currently enbipartisan support for the expansion of SCHIP. The bill rolled. Like the previous bill, this continued to rely on a would have increased coverage to more than 4 million rise in tobacco tax to pay for an increased $35 billion more beneficiaries by 2012. The bill would have also for children’s coverage. called for an increased budget of $35 billion, over five years, raising the total SCHIP budget to $60 billion. Medicare, Medicaid, and SCHIP ExtenHowever, the opposition to this bill maintained focus

sion Act of 2007

on the increase in government health insurance of $35 Public Law 110-173 was ultimately passed by congress, billion and the illegal immigrants Medicaid benefits which extended SCHIP funding through March 31, costing $6.5 billion. 2009, and the President signed it into law on December 21, 2007. Despite being signed into law, this twoPresident Bush vetoed the bill on October 3, 2007, year reauthorization bill would merely extend current with the concern that passing the bill would “federalize SCHIP services without actually expanding any aspect health care”, and expand the scope of SCHIP beyond of the program. than its original concern. On October 18, 2007, the House of Representatives

2009 Reauthorization

required a two-thirds majority to overturn the president’s veto but fell 13 votes short (273-156), despite even 44 Republicans joining the 229 Democrats in support of the measure.

Following President Barack Obama’s inauguration and with the increased Democratic majority in both houses of Congress, there was a quick move to interrupt the political impasse over SCHIP extension. The House passed on a vote of 290-138 on January 14, 2009.

The Revised CHIPRA Bill (HR 3963)

The bill sanctioned expansion of the health coverage A second revised version of CHIPRA was passed program to include approximately 4 million additional within 7 days of the failed veto override vote by the children (including legal immigrants) by spending an House and Senate. This bill was set to address key additional $32.8 billion. On January 29, the Senate concerns that the initial bill did not touch upon such approved the house bill with two amendments which —18—

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was accepted by the House and signed by President sider reauthorizing SCHIP funding for at least four Obama on February 4, 2009, to take effect on April more years (starting in 2015) or else alter the MOE. 1, 2009. This reauthorization lasts through the end of September 2013. The Medicare Access and CHIP Reauthoriza-

tion Act of 2015

The 2010 Affordable Care Act (ACA)

On April 16, 2015, President Obama signed this into In 2010 Congress passed the ACA, extending SCHIP law as the largest reform in the American health care funding through 2015. system since the Affordable Care Act in 2010. Not only Though funding was only appropriated through Sep- does it extend SCHIP for two years but it also cuts tember 2015, the ACA contains a Maintenance of Effort Medicaid spending and improves the way Medicare (MOE) clause that requires states to continue offering doctors are reimbursed. Furthermore, the legislation Medicaid and SCHIP at the established (2010) levels renews funding for other programs such as the Maternal, until 2019. This MOE would have a slightly different Infant, and Early Childhood Home Visiting Program. effect in each state depending on the SCHIP program structure, but it will ultimately force Congress to con-

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SCHIP Debate The State Children’s Health Insurance Program (SCHIP) is a program established to provide health coverage to children and pregnant women in low-income families that have an annual income that falls above Medicaid eligibility levels but do not earn enough to afford private health insurance. The program is jointly financed by the federal government and states but each individual state is responsible for administering SCHIP.

Estimates of crowd-out have always been controversial among analysts and estimated values tend to vary due to the diversity in populations. Nevertheless, crowd-out is likely to be a particular problem for states expanding their Medicaid eligibility requirements.

expiration of federal funding would still leave Congress with a number of options - taking no action, moving SCHIP enrollees into the Medicaid program, or providing SCHIP beneficiaries subsidized coverage in the health insurance exchanges. These last two options would allow at least some former SCHIP beneficiaries continued coverage through SCHIP, Medicaid, or the health insurance exchanges.

to cover the uninsured without also reaching some individuals who are currently enrolled in private insurance. The question is actually how efficiently can the program be targeted and implemented to uninsured children to minimize crowding out.

For instance, analysis of Medicaid expansions to mothers and children in the 1990s by economists and Obama administration advisers, David Cutler and Jonathan As the time period each SCHIP bill is valid for comes Gruber, calculated that when Medicaid eligibility was to a close, Congress must consider a number of policy broadened, approximately 50% of the new enrollees options - extending federal SCHIP funding to maintain had dropped their private coverage. More recent the program or letting SCHIP funding expire. analyses by Gruber and Kosali Simon estimated that crowd-out for the SCHIP totaled approximately 60%. An extension of SCHIP would further additional consideration such as how long to extend federal funding Thus, it is not the question as to whether crowd out for and whether to implement policy changes. The occurs because it is impossible to target new policies

One of the biggest debates surrounding the reauthorization and expansion of SCHIP involves the occurrence of “crowding out.” This refers to people dropping private insurance in response to an elevated availability of subsidized coverage.

Another debate over SCHIP has been the disguised debate of immigration. Generally speaking, immigrants are more likely to be uninsured than native citizens. They tend to have lower rates of employer sponsored insurance and are less likely to benefit from public coverage programs. Although over 80% of immigrant families have at least one full-time worker, they most likely work in low-wage jobs and in industries that do not offer their employees health insurance.

This concern was a contributing reason for President Bush vetoing the reauthorization of SCHIP in 2007. Fortunately, this concern has been addressed by the His concern was that the bill would lead the American Health Care System in the wrong direction i.e. towards socialized medicine. He further stated that an estimated one out of every three people that would subscribe to the new expanded SCHIP would leave private insurance.” In this way, the focus of the program would also be moving away from those poor children who should be the priority.

Children’s Health Insurance Program Reauthorization Act of 2009 (CHIPRA). This includes a new option for States to provide affordable health coverage in the form of Medicaid and SCHIP to immigrant children and pregnant women who are “lawfully residing” in the United States, including those still within their first 5 years of having certain legal status.

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Prior to this, federal law had imposed an arbitrary re- SCHIP care. With this said, many states still provided striction of a 5-year waiting period before many legal coverage to these residents as a form of reducing immigrants were permitted to access to Medicaid and inefficient and expensive medical costs.

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What Causes Hiccups? Hiccups are experienced by almost everyone during >> alcohol consumption their lives – bouts of hiccups have even been shown to occur in fetuses in utero and in a wide variety of ani- >> excessive smoking mals. The medical term given for hiccups is “singultus”. >> a temporary swollen stomach – this can be caused by overeating or eating too fast, drinking hot or The physiology behind the hiccup is complicated. carbonated drinks, or swallowing air This motor action is an involuntary reflex controlled >> eating too quickly or eating spicy foods by the medulla – it involves the coordinated action of the diaphragm, the muscles that govern opening and >> sudden emotions, such as stress, fear or excitement closing of the trachea and the nerves that innervate >> any illness that irritates the nerves that these muscles. It seems that there is a hiccup centre control the diaphragm in the medulla from where efferent nerve fibers travel >> hyperventilation (because this is when carbon to the diaphragm. dioxide levels in the blood decrease) In a hiccup, the firing of this centre leads to the intense activation of the respiratory muscles followed by the rapid closure of the glottis. This closure occurs approximately 35 milliseconds after the activation and with a noise produced at the top of the trachea that is the characteristic hiccup sound.

While hiccups are not harmful and generally only last for minutes, it is possible for them to last longer than 48 hours. In this case, they are referred to as “persistent” hiccups. Hiccups are also termed as “intractable” if they persist for longer than a month. It is possible for certain disorders to trigger long-term

It is interesting to note that there is not yet a named hiccups. These can interrupt with the body’s usual function for the hiccup. Even though the hiccup reflex control of the hiccup reflex and can include: results in both repetitive and great stimulation of the inspiratory musculature, it normally does not serve any >> encephalitis purpose in respiration because of the prompt closure >> alcoholism of the glotus following the intense inspiratory drive. >> meningitis There are theories that the hiccup has a role in the gastrointestinal tract to remove air from the stomachs >> multiple sclerosis from young mammals – this is thought because of the >> numerous gastrointestinal stimuli observed to elicit them. >> It could be that the hiccup is a fetal development >> tool – although there is a high incidence in utero and infancy, suggestions of its role in suckling, clearance of >> meconium or strengthening of respiratory musculature do not appear completely satisfactory.

stroke traumatic brain injury tumors particular drugs such as barbiturates, anesthesia (following procedures particularly if they involve abdominal organs), corticosteroids, benzodiazepines and tranquilizers

It is just as likely however that the hiccup is a vestigial It is most common for cases of long-term hiccups to reflex with a no longer present purpose. The cause of fade away without any medical treatment. In cases where there is an underlying illness, treatment of this hiccups has been linked to the following: can be effective. —22—

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What is Music Therapy? The concept of using music as a tool for healing purposes is ancient – in fact, it can be traced back to at least the written works of Plato and his student, Aristotle. It emerged as a formal profession after World War I and World War II when the influence of community musicians at hospitals was realized as a positive influence for the veterans suffering from both physical and emotional trauma. In this medical practice, the therapeutic use of music

been shown that such people actually exhibit a great interest in music and therefore respond positively.

Substance Abuse The creativity of music therapy can assist clients in exploring their feelings and self-esteem issues. In forming personal attachment and associations between the individual and music, it becomes possible to educate about substance abuse and steer the individual towards developing skills in forming relations, self-expression, creative thinking, effective communication instead of isolation and denial.

is used to address the numerous needs of individuals (psychological, physical, cognitive etc.). This form of therapy is best when it is tailored to an individual’s requirements - the qualified music therapist provides the decided treatment including composing, singing, moving Stress and Anxiety Management to, or listening to music (if not all the aforementioned). Individuals can be guided into learning how to recognize feelings and behaviors associated with stress. Music A great benefit of music therapy is the ability to use it in therapy can be used to induce relaxation stimuli so to address a great spectrum of needs. This is not least that stress is dealt with in positive, appropriate ways. of all because of the diverse nature of music which can allow a person of any cultural background to benefit. It can also offer a more engaging and interesting form of Palliative Care interaction with people – this could be a reason for the Music therapy can help alleviate fear and anxiety whilst growing interest in the field. In fact, research in music encouraging relaxation to help those suffering from therapy is in support of its use in many areas such as: insomnia. The therapy can also provide an outlet for non-threatening self-expression by inducing a feeling of safety and comfort for the person. Communication Those having just had a stroke find their fluency and Music therapy interventions can be categorized as acproduction of speech can be improved by singing to tive or receptive however a combination of the two is simple melodies. most common in an effective therapy session. These sessions can either be conducted with a group or individually depending on the needs of each person: Physical Rehabilitation Those with poor motor coordination benefit from play- >> Active - this is when a person is making music i.e. ing simple tunes on instruments making music by singing, playing instruments or composing music.

Social Skills

>> Receptive - this is when a person listens to or responds to music in approaches that include Those diagnosed with impaired social skills (autism dance or the analysis of lyrics.   spectrum disorders etc.) can strengthen their ability to both express their own emotions and empathize by considering the feelings of the artist of a song. It has —23—

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What Causes West Syndrome? West Syndrome is characterized by infantile spasms, Postnatal Disorders developmental reversion, and a specific chaotic brain >> Pyridoxine dependency activity pattern called hypsarrhythmia. The definitive pathophysiology of the syndrome still

>> Phenylketonuria,

remains unclear. One hypothesis proposes a dysregula- >> Meningitis tion of the GABA transmission process whilst another >> Biotinidase deficiency suggests elevation in the production of corticotropinreleasing hormone (CRH) is responsible. Both of these Cryptogenic West Syndrome hypotheses are supported by the effect of pharmacoA diagnosis of Cryptogenic West syndrome is made logical treatments devised for the syndrome. when there are no apparent causes identified in a West syndrome can be classified as symptomatic, child with developmental delay or another cognitive cryptogenic, or idiopathic. impairment before the onset of infantile spasms. The incidence of cryptogenic cases ranges greatly from 8-42%. This might be explained by variations in the Symptomatic West Syndrome definition of the term cryptogenic and the age of patients Symptomatic West syndrome is diagnosed when a at diagnosis because the assessment of developmental cause has been determined as responsible. 70-75% level is difficult to do in early infants. of patients with West syndrome are diagnosed with this form and virtually any disorder that can produce brain damage can be an underlying cause. These causes Idiopathic West Syndrome are divided into prenatal, perinatal and postnatal dis- Patients are diagnosed with Idiopathic West syndrome orders, some of which are listed below. when they have normal psychomotor development prior to the onset of spasms. They also present with no abnormal findings during any form of examination Prenatal Conditions and there is no evidence of a presumptive trigger for >> Hydrocephalus the spasms. The percentage of idiopathic cases is ap>> Microcephaly proximately 9-14% however fewer children are being >> Genetic syndromes (such as Down’s syndrome) diagnosed with this form due to advances in medicine. >> Hypoxia or ischemic brain damage

Genetic Predisposition

>> Congenital infections

Tuberous sclerosis complex (TSC) is a rare, autosomal dominant genetic condition which is known to cause the growth of benign tumours in the brain and other organs. It is also a major symptomatic cause of infantile spasms; up to 50% of patients with TSC eventually present with infantile spasms at 4 - 6 months of age.

Perinatal Disorders >> Hypoxia or brain ischemia >> Meningitis >> Encephalitis >> Intracranial hemorrhage

The ARX gene and CDKL5 gene – known to have a role in normal brain development and function - have been shown to cause the early onset of infantile —24—

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spasms when mutated. This form of the disorder is females who may have a healthy copy of the gene on called X-linked West syndrome because these genes their second X chromosome. are present on the X chromosome. On the other hand, a mutated CDKL5 gene is inherited in West syndrome due to a mutated ARX gene is inherited an X-linked dominant manner. This means one mutated in an X-linked recessive manner. While one mutated copy of the gene in each cell is sufficient to cause the copy of the gene in each cell is sufficient to induce syndrome with equal severity in males and females. the syndrome, males are more severely afflicted than

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West Syndrome Diagnosis West syndrome is a severe form of epilepsy most common in infancy. It is characterized by infantile spasms, hypsarrhythmia and mental deficiency. With this said, diagnosis of West syndrome can still be made should 1 of the 3 symptoms be absent.

syndrome. It is important that neuroimaging is done before the start of specific therapies- particularly ACTH or steroid therapy- which are associated with the possible appearance of brain atrophy as therapy progresses.

A computed tomography (CT) scan uses X-rays to The infantile spasms that result are one of three types: generate computerized images of cross-sections of the brain; the detail from these allows the development >> Flexor spasms resemble a brief, self-hugging motion of the brain to be studied. On the other hand, Magnetic and involve flexion of the neck, trunk and limbs. Resonance Imaging (MRI) scans produce detailed >> Extensor spasms involve extension of the neck, images of cross-sections or slices of the brain by trunk, and limbs. using the magnetic properties of particular atoms present in the brain. >> Mixed flexor-extensor spasms are the most common type and involve combinations of neck, trunk, and Both imaging techniques can be used to detect an limb flexion and extension. underlying brain infection or structural abnormalities The most widely-used techniques to diagnose West associated with the syndrome in children. Of the two, syndrome include: the MRI scan is much more sensitive and likely to discover an abnormality of the brain.  In fact, an MRI Electroencephalography (EEG) scan can show many neurologic abnormalities (such An EEG study uses electrodes placed on the scalp to as developmental brain abnormalities) and evidence record the patterns of electrical activity of the brain. of brain injury incidents (such as those resulting from The detection of hypsarrhythmia, especially during trauma, lack of oxygen, or from infection). sleep, can indicate that a patient has infantile spasms. Hypsarrhythmia is a brain wave pattern seen when Laboratory Tests seizures are not occurring and is indicated by chaotic, These may be necessary to determine if there is a high-voltage spikes on an EEG. This pattern is present metabolic or genetic disease responsible for a case in wakefulness but is enhanced during sleep. Thereof West syndrome. In fact, more than 50 genetic or fore, an EEG study should ideally include recordings metabolic diseases have already been associated with taken both during wakefulness and sleep to confirm the syndrome. A blood, urine or cerebrospinal sample a diagnosis of West syndrome. may be taken if family history or examination indicates In some cases, simultaneous video and EEG recording the possibility of a metabolic or genetic disorder. For (“Video-EEG”) can be used to verify particular brain- example, a diagnosis of nonketotic hyperglycemia wave patterns during infantile spasms and document requires a lumbar puncture to test for glycine. the patterns between the spasms.

Molecular genetic testing is also available and is already used to test for tuberous sclerosis complex Neuroimaging Studies (associated with symptomatic West syndrome) and Approximately 70-80% of patients with West syndrome mutations in genes ARX and CDKL5 (associated with present with abnormal findings on neuroimaging stud- X-linked West syndrome). ies; these aim to identify the underlying causes of West It is not uncommon for diagnosis of West syndrome to —26—

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be delayed and this may occur due to many reasons:

from the disorder

>> The EEG study does not show hypsarrythmia

>> The spasms appear atypical; they may change between different seizure types or may occur singly >> The child is considered too old to likely suffer rather than in the characteristic cluster. 

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West Syndrome Treatments West syndrome is an age-related epilepsy syndrome that is most common within the first 12 months of life. Due to the poor prognosis associated with the condition, treatment is usually initiated in a swift and aggressive manner following diagnosis. Treatment aims to deliver the best quality of life by controlling the occurrence of seizures, the fewest side-effects, and the lowest number of medications. Unfortunately, medical treatment options are somewhat different for infantile spasms than for other seizure types and the usual anticonvulsants prove ineffective.

First-line of Treatment Includes: Adrenocorticotropic hormone (ACTH) This is the oldest approved medication for the treatment of West syndrome. Numerous studies have shown that steroid therapy using ACTH causes a reduction or complete stop to the spasms and that it even improves the EEG in approximately 50-75% of patients within a few weeks. It is given as a daily intramuscular injection but uncertainties such as its formulation and the duration of its administration still remain. Even the optimal dose is not known; many doses of ACTH have been trialed but there is still no evidence to suggest that larger doses are more effective than lower doses for treatment.

most side effects are not serious. These include: headache, dizziness, fatigue, weight gain and decreased muscle tone. However, a potentially serious side effect is permanent retinal toxicity which results in visual field constriction (tunnel vision) but no apparent change in central vision. Fortunately, no cases of blindness have been reported and the risk of retinal defects due to VGB appears to be lower with short-term use of VGB, before increasing after 6 months of chronic administration. While more evaluation is necessary, there does not appear to be much difference between treatment with ACTH and VGB in terms of control, outcome and severe side-effects.

Second-line Treatment Includes: When ACTH or VGB prove ineffective, other agents can be tried. Unfortunately, there is not enough evidence to suggest that these are effective in treating West syndrome. These agents include corticosteroids (such as prednisolone and prednisone), anti-seizure medications (such as Levetiracetam and Nitrazepam), Pyridoxine, intravenous immunoglobulin (IVIG), surgery to remove the seizure-generating parts of the brain and a ketogenic diet (a specialized very-high fat diet already used in treating many types of epilepsy).

Side effects are common and include: irritability, Of these, the ketogenic diet has been tested and been hypertension, infection, cerebral atrophy (reversible), shown effective, with up to 70% of children having a hypertension, metabolic abnormalities, osteoporosis, 50% or more reduction in seizure. sepsis, and congestive heart failure.

Surgery

Vigabatrin (VGB) This anti-seizure medication has a success rate of approximately 50% in cases of West syndrome. It appears to be particularly effective in cases associated with tuberous sclerosis complex and acts by increasing the amount of the neurotransmitter GABA in the brain. VGB is generally well-tolerated in children such that

This involves removing the area of cortical abnormality in a procedure called cortical resection. The aim of this is to control the seizures or improve brain development. It is primarily considered as a last resort for patients who: Have not responded to ACTH and/or Vigabatrin therapies

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>> Show structural brain abnormalities in a defined

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region (seen by neuroimaging studies)

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West Syndrome Prognosis The effective treatment of West syndrome still poses a great challenge in pediatric neurology. In the overall long term view, the majority of patients with the syndrome suffer a poor outcome due to chronic epilepsy, mental retardation, and other neurodevelopmental shortcomings.

for treatment was known.

Early pharmacological action would be particularly beneficial for idiopathic cases where, in general, children have the most promising prognosis. In fact, 28-50% of children with idiopathic West syndrome have normal or borderline-normal cognitive development following However, the prognosis for a case is greatly dependent diagnosis compared with only 14% of children with on the underlying etiology of the seizures. Therefore, symptomatic West syndrome. each case of symptomatic, cryptogenic and idiopathic In addition to underlying etiology, treatment is also West syndrome must be considered on an individual known to influence the outcome a patient faces. For basis. For example, while 28-50% of infants with example, a good prognosis might be expected if the age idiopathic West syndrome will have normal or nearat onset is older than 4 months, if there is an absence normal cognitive development, for those suffering from of EEG abnormalities, if the spasms are of a short symptomatic West syndrome this value is only 14%. duration or if there is a rapid response to treatment Clinical spasms very rarely persist in adulthood; these (less than a month) and without recurrence. Therefore, and the typical EEG pattern spontaneously disappear regardless of what the underlying cause is, the aim of by 3 to 4 years of age but up to 50-70% of children treatment is to achieve control of the seizures as soon diagnosed with infantile spasms develop other types as possible, particularly if there is a hope for normal of seizures. In addition to this, mental retardation intellectual development. (usually of a profound nature) also occurs in 70-90% For an unknown reason, West syndrome occurs in 1of patients in the future, accompanied by psychiatric 5% of children with Down’s syndrome and these may problems. Even though epileptic spasms usually realso have a more positive prognosis. They are less duce in number by mid-childhood, 18-50% of children likely to develop Lennox-Gastaut syndrome or other will develop Lennox-Gastaut syndrome or some other forms of epilepsy. On the other hand, if their seizures form of symptomatic generalized epilepsy. are difficult to control, the child is at risk of developing However, early detection and prompt administration an autistic spectrum disorder. of effective treatment have been shown to improve West syndrome is generally not life-threatening but the resultant neurodevelopmental outcomes (such as it occurs more often in children with life-threatening severe-to-profound retardation). Currently, approximately conditions. Furthermore, the treatments used for half of all children with the syndrome become entirely West syndrome can (rarely) cause death. Due to this, free of the attacks with the aid of medication but this only 5 out of every 100 children diagnosed with West would be an even higher value if the optimal regimen syndrome do not survive beyond the age of five years.

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What is Macular Degeneration? This is also called age-related macular degeneration Wet (Neovascular or Exudative) (AMD), as the major risk factor for this is aging. It is an While rarer than dry AMD, this form is both more rapid eye disorder characterized by a number of conditions and severe. In fact, a person’s central vision can detenegatively affecting the macula. riorate in a matter of days if left untreated. The macula is also known as the ‘yellow spot’ - a miniscule, specialized region of the retina containing photoreceptor cells (cone cells) responsible for central sight in conditions of bright lighting in order to distinguish fine detail and color.

In this form of AMD, the retinal pigment cells degenerate and new blood vessels grow from those in the

choroid (choroidal neovascularization) in order to resolve the problem. However, these newly-formed vessels grow in the wrong place are fragile and tend Flanking the central macula is the peripheral macula to leak blood and fluid which can cause scarring in the which is composed of other photoreceptor cells (rod macula eventually. cells) responsible for sight in dim lighting outside the main line of sight. Treatments Treatments have been developed to prevent the progresThe major result of AMD is the loss of central vision, sion of wet but not dry AMD. These treatments include: the consequences of which are: >> Decreased visual acuity – the loss of fine detail Photodynamic Therapy make reading and driving difficult. This involves the injection of a medication (Verteporfin) >> Decreased contrast sensitivity – distinguishing into the bloodstream and the shining of a low-power laser to the center of the macula which activates the between objects is harder. compound. The medication then detects and attaches >> Visual distortion – this makes recognizing facial features difficult and straight lines appear wavy. itself to the newly-formed (and abnormal) blood vessels to destroy them without damaging the surrounding >> Night glare – this is sensitivity to bright lights at night. macular tissue. Repeated treatment might be neces>> Blind spots – these appear in a person’s central sary if the abnormal blood vessels reopen with time. field of vision, progressively increasing in size if left untreated. Two forms of AMD have been categorized:

Anti-VEGF Therapy

This involves the intraocular administration of anti-VEGF medication (eg. Ranibizumab, Bevacizumab). AntiDry (Non-neovascular) VEGF medication prevents the formation of the new This is the most common form of AMD. It appears abnormal blood vessels which is normally induced by to occur due to the specific breakdown, thinning and VEGF (vascular endothelial growth factor) by blocking aging of retinal epithelial cells of a specialized region its vessel-formation action. Repeated treatment may be suggested for prolonged benefits to be achieved. of the retina called the macula. This form of AMD occurs gradually over time and is Laser Treatment also called atrophic MD because it is characterized This is less commonly performed than the aforemenby the death (atrophy) of macular cells. tioned treatment methods. It utilizes a high energy laser

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beam focused on the retinal area with the newly-formed abnormal blood vessels. This isn’t always effective and repeated laser treatment may even be required again after 3-5 years.

Regular monitoring of patient vision is also suggested - the Amsler Grid test can indicate if you see straight lines as wavy or if you do not even see them (both of which are indications of AMD).

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What is Spectroscopy? Spectroscopy is a technique that utilizes the interaction lowing this but it was in the 1860s that spectroscopy of different frequency components of the electromag- experienced a period of great advancements due to its netic spectrum with a sample to perform an analysis. applications in the analysis of compounds. The physicist Gustav Robert Kirchhoff, the chemist Robert Wilhelm Historically, spectroscopy referred to the use of visBunsen and the optician Carl August von Steinheil, ible light dispersed according to its wavelength by a who manufactured a spectroscope in his workshop, prism. This was done by Isaac Newton as part of his lay the foundation for the scientific and technological Optics experiments in 1666 when he constructed an applications of spectroscopy through their published instrument to induce dispersion of a beam of light into “Chemical Analysis through Spectral Observations.” a continuous spectrum of colors. This first analysis of light was the start of the science of spectroscopy. This was centred on the linkage between chemical elements and their unique spectral patterns. They Further experimentation made it clear that the sun’s demonstrated that every metal, whatever compound radiation includes more than just the visible region of it was in, yielded the same spectrum. With this fact, the spectrum that Newton had explored. W Herschel they used spectral testing for numerous trace chemi(1800) discovered the infrared region by studying the cal analyses and discovered the previously unknown heating ability of the colors of the spectrum. The following elements, cesium and rubidium. They even used their year, J.W. Ritter similarly determined the existence of analysis to observe the Sun and determine that it was the ultraviolet region by testing the effect of the colors mostly composed of Hydrogen gas. of the spectrum on silver chloride. In 1861, William and Margaret Huggins detected the Instead of the prism which Newton had used, Joseph same elements in stars as had already been detected von Fraunhofer made use of a diffraction grating to in the Sun by Bunsen and Kirchoff — there was no induce light (wavelength) dispersion. He made this doubt to the claim that the stars are Suns, and theregrating by closely spacing thousands of slits so that fore, the Sun must also be a star too. This conclusion the interference he achieved was improved in both the was reached when the pair combined the telescope spectral resolution and allowed quantification of the to capture the light of a star with the spectroscope to dispersed wavelengths. disperse the starlight into its constituent colors. He then utilized the previously established theories of light interference (Thomas Young, François Arago and Augustin-Jean Fresnel) as the centre of his own experiments to demonstrate the effect of passing light through rectangular slits.

In 1868, when observing the brightest star in the sky (Sirius) they found that the spectral lines were slightly shifted in the direction of the red side of the spectrum. This shift in the spectral lines indicated that Sirius was traveling away from Earth at approximately In the 1820s both John Herschel and William H. F. Talbot 135 miles/second. used flame spectroscopy for the spectral analysis of In a similar way when they measured other stars, they elements. This technique allowed them to demonstrate found that a few exhibited a shift in the direction of the that when a substance is heated and its light is passed blue side of the spectrum, indicating the opposite i.e through a spectroscope, each element emits its own that they were traveling towards Earth. This method characteristic bright lines of colors. (named the Doppler shift), would ultimately be useful There were a great many postulates that arose fol- in studying faint clouds (nebulae) and would eventu—33—

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ally lead to the established discovery of the expanding universe in the 20th century.

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What is Meditation? Meditation has existed for many thousands of years. It even in the most difficult circumstances. is the practice of turning one’s attention to a sole point of reference by eliminating the distracting and stressful thoughts abundant in the external environment. There is also growing research to support the positive effect of meditation on those suffering from a medical The reasoning underlying meditation is that happiness condition – this is particularly true if stress has been is a state of mind and a product of internal thought, one shown to worsen the condition. These conditions include should be able to discard the external environment as anxiety, depression stress and addictive behaviors. irrelevant and still obtain real happiness. Meditation is known for its emotional benefits - of these, the key one is teaching a person how to understand their own mind. This allows one to transform their mental state at will from disturbed or negative to peaceful, positive and constructive.

Unfortunately, not all those suffering from medical conditions benefit from meditation as they may have trouble sitting quietly, comfortably and breathing deeply for prolonged periods of time. Such people include those with attention deficit hyperactivity disorder or

This brings a person closer to a life of true happiness Schizophrenia. even if their external living conditions are not ideal. In order to mediate the following four elements prove After training in meditation, the mind will gradually necessary to know: become more and more peaceful, and it is possible to experience a purer form of happiness. Eventually, one will gain the ability to remain happy at any time, —35—

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A quiet setting

tation because it is what keeps your mind away from This is particularly vital if one is new to meditation – the many distractions which cause stress and worry. with practice, a person becomes more skilled and It requires a passive attitude to prevent your both the will be able to meditate in noisy, crowded places or external environment and internal thoughts from disturbing your mindset. stressful situations. Instead all the distractions should be able to pass A comfortable or poised posture freely through the mind in a detached manner. This need not be in a sitting up position but can be lying With time it becomes easier to discard yourself of down, standing up, walking – as long as the person thoughts and meditate. is comfortable. With this said, meditation postures across numerous traditions all maintain a straight An object of focus spine as important. You may choose to focus your attention on an object, Many postures (Half-Lotus, Lotus, Burmese and Egyptian) exist but the classically practiced one is the Lotus posture i.e. the person is cross-legged but with their feet firmly on their thighs.

a mantra (often a Sanskrit word) or the rhythm of your own inhaling and exhaling. Interestingly, the word “mantra” is derived from the

Sanskrit word “man” which means to think and “tra” which means to liberate – together these mean to liberA passive but receptive attitude ate from thought. Common mantras include those with This is possibly the most important element of medi- peace-bringing associations such as “peace” or “Om.”

Image Copyright: Luna Vandoorne, Image ID: 221677984 via Shutterstock

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What is Teleradiology? Telemedicine is the application of numerous technologies for the transfer of clinical information. The introduction of the internet has enabled telemedicine to expand its reach across every medical specialty – its use in radiology is termed “teleradiology.”

the interpretation of some radiological images may require input from a specialist radiologist.

This recent practice is becoming widely implemented by hospitals, urgent care clinics and specialist imaging companies. The reason for its increased implementation is because it addresses the lack of adequate staff to provide radiological coverage and the lack of expertise in this speciality.

This can also be economical for the hospital as the

Teleradiology can be a means through which medical professionals can collaborate when they are not

otherwise reachable to each other (e.g. they are in Radiology encompasses the diverse techniques used remote locations). This can be an effective input for by medical professionals to capture images of the diagnosis and symptom control as it often helps with internal body (eg. x-rays, MRIs, ultrasounds), to aid in obtaining a second professional opinion. the process of diagnosis or treatment. By using the services of outsourcing companies or Teleradiology is the ability to obtain these medical radiology groups to provide and maintain the required images in one location and their transmission over a radiology coverage, smaller hospitals are able to make distance so that they can be viewed and interpreted better use of their own on-site professionals and allow for diagnostic or consultative purposes by a radiologist. them maintain their normal working hours.

The process of teleradiology is based on an essential triad; an image sending station, a transmission network, and a receiving image station that must have a highquality display screen that has been cleared for clinical purposes. In fact, there are now specialized computer programs that are dedicated to sending radiological images with the same ease associated with sending an email with image attachments.

outsourced institution will only require payment per radiological exam. The provision of these specialist services to manage inpatients at small hospitals without specialists on site has been shown to be an effective way of providing high quality care that would otherwise be unavailable.

Unfortunately, recruiting external teleradiology providers for off-hours coverage may carry a risk to the reputation and professional standing of resident radiologists. Arguably, these professionals may feel or become a less integral member of their institution than if they were to provide all of the professional radiology coverage. Their roles may even be threatened if their superiors perceive what they do as radiologists to be a service Teleradiology improves patient care by allowing radiolothat can be purchased elsewhere. gists to provide their expertise without being present with the patient. This is particularly important when With all the benefits it offers, there is still a limit to what radiologist specialists (e.g. MRI radiologists, pediatric radiologists can achieve with the use of teleradiology. radiologists, neuro-radiologists) are needed, since For example, the transfer of images does not give the these professionals are generally only located in large radiologist receiving the images the opportunity to folwell-established areas working during day time hours. low up with other patient procedures. Therefore, they must convey the appropriate information to the on-site In contrast, smaller hospitals in rural areas may emdoctors. This is not always effective and can often lead ploy only one radiologist or none at all. In some cases to miscommunication and confusion. where these radiologists are not adequately trained, —37—

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Furthermore, teleradiology is entirely dependent on teleradiology is no longer an option and patients will technology so should there be no access to the inter- remain undiagnosed or even untreated. net (e.g. if the hospital’s internet is down for service),

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Telemedicine Benefits Telemedicine is the innovative application of electronic Advantages of Telemedicine communication for the provision of medical informaTelemedicine can be a more comfortable approach tion. The approach arose as early as the 1800s with to seeking health care for those who feel daunted by the discovery of the telephone and continued with the both medical professionals and their associated surradiotelephone, the transmission of medical images. roundings. As the medical information is exchanged Telemedicine has grown to encompass effective com- in strict confidence this can also encourage a good munication through numerous diverse technologies relationship to develop between patients and healthsuch as video conferencing, the internet, networks for care professionals. real-time consultation and diagnosis, and sometimes Telemedicine can be applied in places such as rural, even remote medical procedures. remote, post-disaster communities where there is no constant healthcare made available or the necessary

Interactive Care

transport to a clinic. Therefore, emergency healthcare is This is telecommunication used in real-time interac- provided in dangerous cases without the need for travel. tion between a doctor and patient. It includes live This can be an effective tool in health education by video and audio patient data transfer and simultaneallowing the observation and supervision of newlyous communication between a doctor and patient. qualified healthcare professionals during clinical practice. It is almost like a face-to-face clinical visit where the Teaching files can also be made available in many doctor can perform a physical examination and other forms (eg Web casts of lectures, daily presentations necessary evaluations. of cases, educational conferences) whilst eliminating the necessity of travel.

Store-and-Forward Care (asynchronous, telemedicine)

Electronic search engines (eg. MEDLARS, PUBMED) and online-purchased journals and books provide valuThis form involves one doctor who electronically supable cutting-edge information to health professionals. plies all a patient’s data (pictures, videos, radiology In this way, they can maintain and improve their skills. images) to another doctor. The doctor on the receiving end is usually a specialist who then remotely interprets Telemedicine adds a dimension of clinical protection the information and accordingly comes to a diagnosis for users by eliminating the possibility of transmitting and recommended treatment for the patient. infectious diseases between healthcare profession-

Remote Monitoring (home health telemedicine) This is used for the general observation of patients who are in their own homes, or patients who suffer from a chronic condition who can have a doctor manage their care remotely. It might involve video conferencing, vital signs monitoring and the transmission of patient statistics to the hospital, as well as a warning system should something go wrong with the patient.

als and patients. Computerised medical databases allow health professionals in primary care to access patient records in hospital databases of hospitals. It also allows mobile collaboration between healthcare professionals from multiple locations when cases are particularly critical or might require multidisciplinary insight. Telemedicine facilitates effective monitoring and treatment thereby reducing the number of outpatient

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visits necessary.

solution to this.

For example, patients suffering from hypertension can use an electronic blood pressure monitor to measure their own blood pressure and transmit the results to their GP. As long as prior readings have been accurately recorded with supervision via an audio-visual link, medications can later be prescribed.

Patients and the general population are able to access information to understand the nature of their disease, its prognosis, follow their treatment progression and the possible associated side effects of this.

Patients with renal failure can also benefit from telemedicine. The requirement for dialysis treatments on a day-patient basis can make employment or even employment applications difficult therefore home dialysis with video link supervision may offer a convenient

Having this knowledge at hand could allow a more equal decision-making process to form between patient and their doctors. Of course, it is crucial that the data presented is of good integrity so that patients become more aware of their health and the impact that their lifestyle has on their quality of life.

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Tamoxifen Discovery Tamoxifen has been used for over 40 years as one of the most widely used therapies in the world for the treatment of breast cancer. It has been demonstrated that tamoxifen therapy reduces the rate of breast cancer recurrence for up to at least 15 years following the onset of treatment. Tamoxifen has saved numerous lives since its introduction in cancer therapy however, scientists had not originally intended for its use in this field. In fact, its debut in the clinical setting was as a post-coital contraceptive in a trial led by Arthur L. Walpole in the early 1960s. It was referred to as ICI 46,474 at the time, having been manufactured in the laboratories of Imperial Chemical Industries (ICI) which is now AstraZeneca. While the drug was found to be effective in rat studies, it was actually found to induce the opposite effect in humans i.e. it caused ovulation. Following the failure of ICI 46,474 as a contraceptive in humans, Walpole directed the team and their studies towards cancer research. Even though it showed some promise in breast cancer therapy, further study was held at a standstill. Many reasons contributed to this, the primarily the limited demand for the drug – only a small proportion of people would benefit from the palliative drug therapy and would only require it for only a year. Due to this, the financial return from marketing the drug was not expected to be particularly rewarding. On the other side, there was also no market opportunity for it as a fertility drug.

who had been the scientist to isolate the estrogen receptor in target tissues in 1958. Shortly after, in 1974, an estrogen-receptor assay was determined. This assay would involve quantifying the level (if any) of estrogen receptor present in a tumor through a biopsy. The level of this receptor protein offers great predictive power; in essence, only in the presence of the receptor would there be a high probability that a tumor will respond to hormone-ablative surgery (as this targets that receptor). From the 1980s onwards, numerous clinical trials followed exploring the role of tamoxifen as adjuvant therapy. An interesting finding was that 1 year of tamoxifen adjuvant therapy conveyed no benefit in estrogen receptor-positive, early stage, invasive breast cancer, 2 years was of some benefit, but it was 5 years that was the most effective. Further trials have shown an association between prolonged treatment (10 years), tamoxifen resistance and possible, serious side effects (e.g. clotting abnormalities, endometrial cancer). The incidence of tamoxifen resistance (whether existing or developing) has also been revealed in approximately 20-30% of patients receiving tamoxifen therapy. The resistance is thought to be associated with a change in the estrogen receptor expression which in turn steers the target tissues to proliferate even in the absence of estrogen-induced signalling). Studying this will prove to be incredibly beneficial as a biomarker to predict therapy outcome in an individual patient.

In 1972, Craig Jordan began testing with tamoxifen to successfully prevent the formation of mammary tumors in mice. This experimentation involved using a known carcinogen (dimethylbenzanthracene i.e. DMBA) to induce mammary tumors in rats and then applying tamoxifen to study its action as an anticancer agent. Jordan had received assistance from Elwood Jensen

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Tamoxifen Pharmacogenetics Since its introduction in the 1980s, endocrine therapy with tamoxifen has been the first-line treatment for breast cancer in estrogen-receptor-positive men and women. In addition to being valuable as adjuvant treatment (following surgery, radiation and/or chemotherapy), it is also used to treat metastatic breast cancer and to reduce the overall incidence in women identified as high-risk.

are currently 63 different major alleles known, each of which are associated with a final gene product with increased, decreased, or entirely non-existent function. Once translated, the different CYP2D6 phenotypes associated with these alleles include poor (PM), intermediate (IM), extensive (EM), and ultrarapid (UM) metabolizers. The phenotype distribution that results has been shown to vary between ethnic groups. For example, people exhibiting 2 of approximately 20 known alleles show poor metabolizing action, and 7–10% of these poor metabolizers are present in the European and North American Caucasian population.

Categorized as a classic “pro-drug,” tamoxifen requires metabolic activation in order to elicit its pharmacological effects. Importantly, numerous studies have revealed CYP2D6 as the rate-limiting enzyme responsible for converting the pharmacologically inactive tamoxifen to its metabolites endoxifen (4-OH-N-desmethylIn contrast, individuals with the UM phenotype carry tamoxifen) and 4-hydroxytamoxifen. both gene and functional allele duplication, which results After the metabolites are generated, they interact in a higher CYP2D6 expression and enzyme activity. with the estrogen receptor in target tissues includ- This phenotype is relatively infrequent in Caucasians ing both breast and non-breast tissues to produce and Asians but up to 30% is seen in Ethiopians. a complex phenotype, resulting in both agonist and The concept of genetic variations in the gene impacting antagonist effects. tamoxifen treatment outcome was formed following Despite the existing, wide inter-individual variability in tests conducted in breast cancer patients who were the concentrations of tamoxifen and its metabolites, taking selective serotonin reuptake inhibitors (SSRIs) there was no evidence linking variability in tamoxifen to relieve hot flashes. Specifically, because SSRIs or its metabolite concentrations with patient response inhibit CYP2D6, significantly lower plasma endoxifen or side effects. concentrations were detected in the studies’ patients. There are suggestions that both genetic and environmental factors alter CYP2D6 enzyme activity and in this way affect tamoxifen treatment outcomes. Knowing this might provide a route to individualize the hormonal therapy of breast cancer for patients. The CYP2D6 enzyme is critically involved in the metabolism of approximately 20-25% of all developed drugs and more than 48 different clinical substrates (drugs) for this enzyme have been identified, of which include β-blockers, antidepressants, opioid analgesics, anti-arrhythmics, and antipsychotics. The CYP2D6 gene is highly polymorphic; in fact there

Some newer SSRIs (paroxetine or fluoxetine) have even been shown to have such an effect on the CYP2D6 gene that the EM phenotype was converted to the PM phenotype. In addition to this, further studies have shown the risk of breast cancer recurrence is higher in patients taking both tamoxifen and an SSRI (e.g. Paxil, Prozac, or Zoloft— the most ‘potent’ CYP2D6 inhibitors) in comparison to those taking only tamoxifen. This recurrence was not increased in those taking the ‘weaker’ antidepressants (e.g. Celexa, Lexapro, or Luvox), did not present with an increased risk of breast cancer recurrence.

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It is important to note that despite the evidence for the still much to learn about the cytochrome P450 pathway involvement of the CYP2D6 gene in the metabolism considered responsible for the metabolism of tamoxifen. and resultant outcome of tamoxifen therapy, there is

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Tamoxifen Mechanism Tamoxifen is both the most widely prescribed drug for breast cancer and preventative therapy worldwide. It is a synthetic derivative of triphenylethylene but was originally screened in a drug development program oriented toward discovering new post-coital contraceptive agents.

expression of estrogen-dependent genes to generate multiple growth-promoting signals both inside and outside the nucleus.

Tamoxifen’s pro- and anti-estrogenic actions are mediated by its competitive binding to the estrogen receptors (ERα and/or β) which then undergo a conformational change. The nuclear complexes that form change the

Not all of the pro-estrogenic effects are harmful. Tamoxifen pro-estrogenic action is also evident in bone matter, where it mimics the effects of estrogen and provides the signals required for bone maintenance,

For example, the prolonged binding of tamoxifen to

specific genes can lead to a block in the proliferative actions of endogenous estrogen on mammary In its testing, tamoxifen had proved effective in rats epithelium by reducing DNA Polymerase activity, but not in women. It was only in 1997 that it was FDA blocking estradiol uptake and eventually dampening approved for the clinical treatment of advanced breast the estrogen response. cancer. That had followed animal studies demonstratSuch changes occur because the estrogen receping that it was incredibly effective in preventative action tors function as ligand-activated transcription factors against the development of experimentally-induced which can bind their cognate DNA sequences known breast cancer, caused by known carcinogens dimethas estrogen responsive elements, and activate the ylbenzanthracene and nitrosomethylurea. transcription of factors which can either stimulate While Tamoxifen is commonly known as an anti- estrogen-like actions or oppose estrogen actions estrogen, this is not an accurate description of its in estrogen target tissues. Both these genomic and clinical activity. In actual fact, Tamoxifen boasts both additional non-genomic effects have actually been estrogenic and anti-estrogenic properties depending demonstrated with estradiol administration. on the target tissue. Due to this dual action, Tamoxifen Tamoxifen’s strongly anti-estrogenic properties on is better described with the term selective estrogen mammary epithelium make it appropriate in both the receptor modulator (SERM). prevention and treatment of breast cancer. With this Tamoxifen has a complex mechanism of action owing said, its pro-estrogenic properties on uterine epithelium to its molecular structure. It is chemically very similar have resulted in the current controversy regarding its to estrogen/estradiol however estradiol is a small safety in cancer prevention. carbon-rich steroid and tamoxifen has an extra chain This is particularly due to its association in the increased which is important for its antagonistic action. incidence of endometrial lesions (including hyperplasia, Tamoxifen itself is a pro-drug with a relatively low af- carcinomas, and sarcoma) found in women undergoing finity for the estrogen receptor. It is metabolized by the chronic treatment with tamoxifen. With time, the risk cytochrome P450 family (more specifically CYP2D6) of endometrial cancer increases drastically, which is a to active metabolites such as endoxifen (4-OH-N- reason tamoxifen is typically recommended for 5 years. desmethyl-tamoxifen). Interestingly, this metabolite Because of this associated danger, lowering the risk of has been shown to bind the estrogen receptor (ER) endometrial cancer for tamoxifen users is becoming with an almost 100-fold greater affinity than tamoxifen. an increasingly important target in cancer prevention.

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thereby inhibiting osteoclasts and reducing the risk of osteoporosis in menopausal women in particular.

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What is Liver Cancer? The liver is located in the upper abdomen and just rates being in older men and women (65 years onwards). below the right lung. It is the largest organ inside the Liver cancer exists in two forms; primary and secondhuman body and is necessary due to its many important ary. The secondary form (also called metastatic liver functions some of which include: cancer) is when cancer that first develops in another >> The metabolism and storage of many ingested part of the body spreads to the liver. Conversely, the nutrients (e.g. vitamins and iron). rarer, primary form occurs when cancer originates in >> The production of clotting factors required to stop the liver itself. bleeding (due to injury). Unfortunately, most people do not show signs and >> The production of bile which is key for the symptoms until the cancer is at an advanced stage. assimilation of nutrients. Even then, these symptoms often tend to be vague >> The breakdown and removal of toxic substances and may include: (e.g. drugs and alcohol) from the bloodstream. >> Unexplained weight loss >> Depressed appetite >> Abdominal swelling or pain >> Nausea and vomiting >> Abdominal swelling >> Weakness and fatigue >> Jaundice If liver cancer is suspected, the tests that may be ordered include: >> Abdominal imaging (e.g. CT scan, ultrasound, MRI) – detailed 3D images of the liver are generated. >> Liver biopsy – the removal and testing of a small sample of liver tissue is required to differentiate between a benign and malignant tumor. >> Liver (enzyme) function test. Liver cancer accounts for approximately 1% of all >> Blood tests – liver cancers release a chemical called alpha fetoprotein (AFP), present throughout new cases of cancer in the UK, making it a relatively pregnancy but declines after birth. It acts as a uncommon form here. With this said, it is the sixth tumour marker for liver cancer if elevated serum most common cancer worldwide - this variation may AFP levels are detected in adults. be due to the unequal distribution of risk factors, availThe exact cause of primary liver cancer is unknown ability and use of screening, and diagnostic methods. however there appears to be risk factors associated It more commonly affects men than it does women and with the secondary form. Therefore, measures can is strongly related to age, with the highest incidence be taken to reduce the risk of developing this can—46—

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cer. These include:

>> The shared use of contaminated needles for example in intravenous drug use.

>> Moderate (or little) consumption of alcohol – at the very least a person should avoid drinking more >> Through unprotected sex and childbirth, prevention methods include practising safer sex, such as the than the recommended daily amount (3-4 units sustained use of condoms. for men, 2-3 units for women) A vaccine to help prevent HBV infection is recommended to reduce the risk of hepatitis and liver cancer. >> Prevention and treatment of viral hepatitis (B and C) – On the other hand, there is no vaccine for HCV and These viruses are transmitted between people through: infection must be controlled by educating the public on how these infections occur. >> A healthy diet and regular exercise regimen

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What are Colorectal Polyps? A colorectal polyp is a growth that may present on the lining of the colon or rectum. While these are fairly common and affect 15-20% of the UK population, they are not usually associated with symptoms. Only when a polyp is big enough to cause a bowel obstruction can it result in nausea, vomiting and severe constipation.

35% risk in 3-cm villous adenomas. A somewhat more aggressive type of adenoma called a serrated adenoma may develop from hyperplastic polyps. Following the removal of an adenoma people will need a follow-up examination; new polyps may develop over time which will also need to be removed.

Importantly, the best course of action when a polyp is found is dependent upon the number, type, size, and Hamartomatous Polyp location of the polyp. While bowel polyps are not usuA hamartoma is defined as a tumor-like malformation ally cancerous, if they’re discovered they’ll need to be that presents due to an error in the development at removed and can be done completely and safely, as numerous sites where growth occurs. They are benign some will eventually progress to cancer if left untreated. and may not cause any problems, usually identified Polyps are either pedunculated (attached to the incidentally as they tend to grow at the normal and

intestinal wall by a stalk) or sessile (growing directly non-pathological rate of the host tissue, rarely causing from the wall). On the whole, there are typically three problems such as compression. types of polyps: This does not mean that hamartomas are harmless. Morbidity can arise by means of a variety of mechanisms such as obstruction, infection, infarction, hemorrhage and iron deficiency anemia amongst others.

>> Adenomatous (and malignant), >> Hamartomatous and, >> Inflammatory.

Adenomatous (Neoplastic) Polyp These are of greatest concern as they have the potential to become cancerous after many years. Such adenomas are histologically classified as tubular, tubulovillous, or villous. These adenomas show different growth patterns of which the two major ones are tubular and villous with a mixture of these growth patterns giving a tubulovillous adenoma. Generally, most small adenomas (<1/2 inch) have a

While it may resemble a neoplasm, a hamartoma does not usually show a tendency to evolve into one. With this said, occurrences of neoplastic evolution have been reported in patients suffering from von Recklinghausen disease. Interestingly, an association has also been established between neoplasms and hamartomas which can be seen in some patients with Peutz-Jeghers syndrome. While the polyps themselves carry little potential for malignancy, there is still a 15% chance of colonic malignancy because of potential coexisting adenomas.

tubular growth pattern whilst the larger ones may have a villous growth pattern and increased likelihood of Inflammatory Polyp becoming cancerous. These are polyps which show an association with inflammatory conditions such as Crohn’s disease and The likelihood of cancer in an adenomatous polyp at Ulcerative Colitis. Although the polyps themselves the time of discovery is related to histologic type, size, are not a particularly significant threat, suffering from and degree of dysplasia; a 1.5-cm tubular adenoma these two colon disorders increases the overall risk has a 2% risk of containing a cancer compared to a of colon cancer. —48—

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Risk Factors for Colorectal Cancer

>> Inherited conditions (including hereditary non-polyposis colon cancer and familial It is possible for anyone to get colorectal cancer howadenomatous polyposis) ever it is most commonly reported in people over age 50. Risk factors for colorectal cancer include: >> Obesity >> A history (personal or family) of colorectal >> cancer or polyps >> >> Unhealthy diet (abundant in red and processed meats) >> >> Inflammatory bowel disease (such as Crohnâ&#x20AC;&#x2122;s disease or ulcerative colitis) >>

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Smoking A sedentary lifestyle Alcohol abuse Type 2 diabetes

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What is Marfan Syndrome? Marfan syndrome occurs in approximately 1 in every 5000 individuals. It is an autosomal dominant disorder therefore the majority of people with Marfan syndrome have a 50% chance of inheriting the defective gene from whichever parent who suffers from the disorder. Alternatively, in approximately 25-30% of those with Marfan syndrome the condition has developed due to a spontaneous mutation yielding the defective gene. Marfan syndrome affects the body’s connective tissues – these are required for the body to maintain its structure and provide necessary structural support to other tissues and organs. Connective tissue is usually strong and resilient – it is made up of a number of proteins which include collagen, elastin and fibrillin.

symptoms are similarly dispersed. Fortunately, Marfan syndrome does not impact intelligence but it can affect the following areas and with variable degrees of severity:

Skeletal System Long bones are affected and grow longer than they should. People become tall with unusually long fingers, toes, arms and legs (arachnodactyly).

Eyes Lens dislocation (ectopia lentis) in one or both eyes occurs in more than 50% of those with the disorder. This happens because the connective tissue holding the lens in place becomes weak. As a result, the lens of the eye is held in an abnormal position so that the person is no longer looking through the center of the lens. Complications may occur i.e. retinal detachment, early onset cataracts or glaucoma, or extreme myopia (short-sightedness).

In people with Marfan syndrome, a defect in the FBN1  gene located on chromosome 15 affects the production of the glycoprotein fibrillin (specifically fibrillin-1).  Normally, molecules of fibrillin-1 bind together and form structures called microfibrils. The microfibrils are required to provide elasticity and support to connective tissues such as bones, tissues, muscles, and Cardiovascular System The most serious effects occur when the connective lenses of the eyes. tissue in blood vessels become weakened and stretched. Microfibrils also store transforming growth factor beta The aorta can become widened (aortic dilation) due (TGF-β), a protein which has a function in numerous to this which in turn increases the likelihood of tears cellular processes including the growth, differentiation (aortic dissection) and ruptures that allow leakage of and proliferation of cells. In this way, microfibrils are blood into the atria of the heart. considered as the regulatory switch for TGF-β availability - TGF-β is inactivated when stored in microfibrils Overly elastic valves may also result - in mitral valve

prolapse, the valve between the left atrium and ventricle collapses backward and cannot close properly which In Marfan syndrome, a defect in FBN1 results in can allow leakage of blood into the left atrium (regurgiirregularly-shaped microfibrils which cannot bind tation). The workload of the heart increases to prevent transforming growth factor beta (TGF- β). This results this backflow and can eventually lead to heart failure. in an elevated level of tissue TGF- β and eventually problems in connective tissues throughout the body. and is activated upon its release.

Respiratory System

Connective tissue is widely distributed throughout the Decreased elasticity of the alveoli in the lungs could body as part of the bones, muscles, ligaments, blood increase the likelihood of lung collapse should the vessels. Therefore it should be unsurprising that the alveoli become stretched. —50—

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Spectroscopy Methods Ultraviolent and Visible Light Spectroscopy The techniques associated with these regions of the electromagnetic spectrum are probably the most widely used for analytic work. The molecular substructures that are responsible for interacting with the electromagnetic radiation are called chromophores. In proteins, the relevant types in UV/ Vis spectroscopy are peptide bonds, certain amino acid side chains (primarily tryptophan and tyrosine) and certain prosthetic groups and coenzymes (e.g. porphyrin groups present in haem).

composition and the polarization of fluorescence may all contribute to structural studies.

Intrinsic Protein Fluorescence Proteins possess three intrinsic fluorophores: tyrosine, tryptophan and phenylalanine, although the latter contributes little to protein fluorescence emission. Intrinsic protein fluorescence is usually determined by tryptophan fluorescence which can be selectively excited at 295–305 nm. Excitation at 280 nm leads to tyrosine and tryptophan fluorescence; the resulting spectra might then contain contributions from both types of residues.

Colorimetric assays require a calibration curve to be plotted (concentration versus absorbance) which should be linear as long as the Beer–Lambert law Extrinsic Fluorescence applies. Using this, absorbance of unknowns are then If a molecule of interest is non-fluorescent, an external measured and their concentration can be interpolated fluorophore can be introduced by chemical coupling from the linear region of the plot. or non-covalent binding. 1-anilino-8- naphthalene sulphonate (ANS) is a commonly used extrinsic chroQualitative analysis can be used to identify certain mophore which emits only weak fluorescence in polar classes of compounds both as pure samples and in environment, e.g. in aqueous solution. biological mixtures. This type of spectroscopy is most commonly used for quantification of biological samples However, in non-polar environments, e.g. when bound either directly or via colorimetric assays. to hydrophobic regions of proteins, its fluorescence In many cases, proteins can be directly quantified using their intrinsic chromophores, tyrosine and tryptophan. Protein spectra are acquired by scanning from 500 to 210 nm. The characteristic features in a protein spectrum are a band at 278/280 nm and another at 190 nm. The region from 500 to 300 nm provides valuable information about the presence of any prosthetic groups or coenzymes.

emission significantly increases. These characteristics make ANS valuable for assessing the degree of non-polarity and to monitor binding of ligands and prosthetic groups.

Scattering Spectroscopy

The scattering of light can yield valuable insights into the properties of macromolecules, including the molecular mass, association/dissociation properties and internal dynamics. When incident light strikes a Fluorescence Spectroscopy macromolecule, it is scattered into all directions and Fluorescence occurs where an energy transition from the intensity of the scattered light is only a fraction of a higher to a lower state is accompanied by radiation. the original intensity. There are many and highly varied applications for fluorescence despite the fact that relatively few compounds Most of the scattered light possesses the same waveexhibit this characteristic. The effects of pH, solvent length as the incident light; this phenomenon is called —51—

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elastic light scattering. When the scattered light has a wavelength higher or lower than the incident light, the phenomenon is called inelastic light scattering (Raman spectroscopy). The special properties of lasers with high monochromaticity, narrow focus and strong intensity, make them ideally suited for light scattering applications.

Atomic Spectroscopy With regards to the general theory of electronic transitions, molecules give rise to band spectra while atoms yield clearly defined line spectra. In atomic emission spectroscopy (AES), when the atoms are excited, the wavelengths emitted of particular wavelength (color) may be identified using a spectrophotometer. In a spectrum of an element, the absorption or emission

due to an energy change. Electron transitions in an atom are limited by the availability of empty orbitals and the rules governing how these orbitals are filled together mean that emission and absorption lines are characteristic for an individual element. In order for atoms to emit or absorb monochromatic radiation, they need to be volatilized using high thermal energy. Atomic emission spectroscopy (AES) and atomic absorption spectroscopy (AAS) are generally used to identify specific elements and their concentrations within a sample. The energy absorbed or emitted is proportional to the number of atoms in the optical path. Concentration determination with AES or AAS is carried out by comparison with calibration standards.

wavelengths are associated with electron transitions

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Spectroscopy Types lamps which shine through the flame at wavelengths

X-ray

adjusted according to the type of analyte under study. X-rays of sufficient energy are used to excite the inner The amount of analyte present in the study sample is shell electrons in the atoms of a sample. The electrons determined based on how much light is absorbed after move to outer orbitals then down into the vacated inner passing through the flame. shells and the energy in this de-excitation process is emitted as radiation. The absorption or emission energies are characteristic of the specific atom and small energy variations may occur that are characteristic of particular chemical bonding. The X-ray frequencies can be measured and X-ray absorption and emission spectroscopy is used to

Spark or Arc (emission) Spectroscopy

This is used for analyzing solid metallic elements or non-metallic samples made conductive by being ground with graphite powder. Analysis requires passing an electric spark through it to produce a heat that excites the atoms. The excited atoms emit light determine elemental composition and chemical bonding. of characteristic wavelengths which can be detected In X-ray crystallography, crystalline materials are ana- using a monochromator. lyzed by studying the way they scatter X-rays aimed at Analysis of these metallic elements in solid samples is them. Knowing the wavelength of the incident X-rays qualitative as the spark conditions are not well moniallows calculation and eventually the intensities of the tored on the whole however the recently introduced scattered X-rays give information about the atomic posiusage of spark sources involving controlled discharges tions and their arrangement within the crystal structure. yields quantitative data.

Flame Usually the analyte is in solution form (or converted into one) that is then converted to a free gaseous form in a multistage process (atomization). This method is often used for metallic element analytes present at very low concentration ranges.

Atomic Emission Spectroscopy (AE)

Visible/Ultraviolet (UV) This uses the fact that many atoms are able to emit or absorb visible light. The atoms must be in a gaseous phase in order to obtain a spectrum just as those obtained in flame spectroscopy. It is common for visible absorption spectroscopy to be combined with UV absorption spectroscopy in UV/Vis spectroscopy.

UV spectroscopy can be used to quantify the concentration of protein and DNA in a solution. Many amino acids (including tryptophan) absorb light in the 280 nm range whilst DNA absorbs light in the 260 nm range. Using this knowledge indicates the ratio of 260/280 nm absorbance as a good indicator of the relative purity of a solution in terms of these entities. UV spectroscopy Atomic Absorption Spectroscopy (AA) can also be used to analyze fluorescence from a Compared to AE spectroscopy, a flame of lower tem- sample in a form of absorption spectroscopy. perature is used so as not to excite the sample atoms. Instead, the analyte atoms are actually excited using This method uses atoms excited from the heat of a flame to emit light. The analysis can be done with a high resolution polychromator to produce an emission intensity vs. wavelength spectrum to detect multiple elements simultaneously.

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Infrared (IR) and Near Infrared (NIR)

(genomics, proteomic) and chemical imaging of intact IR spectroscopy is used to show what types of bonds organisms, textiles, forensic lab application and various are present in a sample by measuring different types military applications. of inter-atomic bond vibrations at different frequencies. It relies on the fact that molecules absorb specific Nuclear Magnetic Resonance (NMR) frequencies which is dependent on their chemical This is a prominent method for analyzing organic comstructure. This is determined by factors such as the pounds because it exploits the magnetic properties of masses of the atoms. certain atomic nuclei to determine the properties (both NIR shows a greater penetration depth into a sample than mid-infrared radiation. This indicates a low sensitivity but also that it allows large samples to be measured in each scan by NIR spectroscopy with little (if any) sample preparation. It has numerous practical applications that include: medical diagnosis pharmaceuticals, biotechnology, various analyses

chemical and physical) of these atoms or the molecules containing them. It can provide extensive information about the structure, dynamics, and chemical environment of atoms. Additionally, even different functional groups are distinguishable, and identical functional groups in differing molecular environments still give distinguishable signals.

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What is a Transient Ischemic Attack? A Transient Ischemic Attack (TIA) is a phenomenon >> Paralysis of different limbs depending on caused by a temporary disruption in the blood supply affected brain region. to part of the brain. Unlike a stroke, the circulatory >> Difficulty in speech or understanding. blockage is brief and there is no brain tissue death (i.e. permanent damage) as the blockage breaks >> Numbness of a limb (particularly on one side of the body). away and dissolves. A TIA is similar to a stroke and results in stroke-like

>> Clumsiness during walking or with certain hand movements.

symptoms but these tend to last for only a few minutes >> Lack of balance and coordination. or 1-2 hours before fully resolving within 24 hours.

>> Severe headache. In the days following a TIA, the risk of a stroke increases dramatically; in fact, a third of the people with TIA later Risk Factors have recurrent TIAs and a third have a stroke in the >> Age. Risk increases with age, particularly after age 55. future. Fortunately, one may also consider the occurrence of a TIA as an opportunity to find a cause or >> Sex. The risk of both TIA and stroke is slightly higher in males than in females minimize the risk to prevent a possible stroke. >> Prior or family history of TIA. Prior TIA makes one 10 times more likely to have a stroke and the risk Causes may generally be greater if a family member has suffered from a TIA or stroke. A TIA is characterized by a disrupted blood supply to a region of the brain which very commonly results >> Poor nutrition. High fat and salt intake, in particular, due to blood clots. These can form in the arteries of increase your weight and contribute to your risk of TIA and stroke. Reducing saturated fat and trans the brain (thrombosis) usually following the gradual fats intake may reduce the plaques in arteries. narrowing of the blood vessel by plaque (a fatty build However, if dietary changes alone do not help, cholesterol-lowering medication may be prescribed up) in a process called atherosclerosis. A blood clot (e.g. statins). can form if the plaque ruptures, leading to further blockage of the artery.

>> Cardiovascular disease. This includes heart failure, heart defects, heart infections or If a person is suffering from atrial fibrillation, blood abnormal heart rhythm. clots may float downstream from the heart and get >> Diabetes. This increases the severity of caught in small blood vessels (embolus). Atrial fibrilatherosclerosis and the speed of its progression. lation is characterized by an uncoordinated heart beat >> Elevated homocysteine levels. This amino acid in which allows blood to become stagnant and form the blood can cause arteries to thicken and scar, small clots that can embolize to any organ in the body, thereby increasing the susceptibility to clots. such as the brain. >> Smoking. Cigarette smoking increases the risk of blood clots, elevates blood pressure and contributes to the development of atherosclerosis. Symptoms Due to the complexity of structure and function of the >> Alcohol abuse. Alcohol intake should be limited to a maximum of two drinks daily for a man and one brain, the resulting deficits are grouped based on the drink daily for a woman. anatomy of the brain. Following a TIA, common tests may be â&#x20AC;&#x201D;55â&#x20AC;&#x201D;

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done which include:

>> An electrocardiogram (ECG) and heart rhythm tests to ensure a regular heartbeat.

>> An angiogram to determine if there is vessel blockage or bleeding. >> Cholesterol and triglycerides tests – when elevated, these increase the risk of blood clots and atherosclerosis. >> An ultrasound to check for the narrowing of arteries e.g. carotid arteries. Importantly, while a head CT scan or brain MRI will >> An echocardiogram (echo) to check the blood almost always be ordered, a stroke may show changes flow through the heart and check if there are where a TIA will not. any blood clots.

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What is Tamoxifen? Tamoxifen is a well-known drug discovered by what receptor positive breast cancer in pre- and postis now AstraZeneca. It was originally screened in a menopausal women. development program centered on the introduction of >> As treatment for women categorized as high risk new contraceptive agents. Although it proved effective for the development of breast cancer to reduce the incidence of developing breast cancer. in rats, it was not a useful drug for control of fertility in women; it actually induced ovulation. >> As treatment to reduce contralateral cancer i.e. cancer in the opposite breast. While commonly referred to as an anti-estrogen, this is not entirely accurate. In actual fact, tamoxifen is >> Used occasionally to induce ovulation in women who wish to become pregnant but who do not more appropriately described as a selective estrogen produce eggs naturally. receptor modulator. This is because it expresses both estrogenic and antiestrogenic actions, depending on >> As preventative therapy in those women at a high risk of developing the disease. This may be the target tissue. predisposed due to their age, medical history (both personal and family). On mammary epithelium, its actions are strongly antiestrogenic, which is why itâ&#x20AC;&#x2122;s used in both the prevention For example; Women who have had treatment for DCIS and treatment of breast cancer. In contrast, on uterine (intraductal carcinoma - a less common type of breast epithelium its action is proestrogenic, which has fuelled cancer ) through surgery, chemotherapy and/or radiation the current controversy regarding its safety in cancer are at high risk for developing invasive breast cancer prevention. This is especially since an increased in- in the future, and hormone therapy (with tamoxifen) cidence of endometrial carcinoma has been found in prevents the development of this cancer in a great deal of women within the first five years of treatment. women treated chronically with tamoxifen. Tamoxifen comes as a pill to be taken once or twice The safety of tamoxifen therapy has not been estabdaily with water and each day at a similar time. When lished in children or in those breastfeeding due to the taken, the tablets should be whole; they should not be potential for carcinogenicity. However, the benefits split, chewed, or crushed. Should a person forget to of Tamoxifen therapy generally outweigh the risks in take a dose of tamoxifen, they should take the missed those who are able to have the therapy. With regards dose as soon as they remember it, and take the next to these risks, the associated adverse reactions tend dose as is usual. However, if it is almost time for their to be minor, well-tolerated and often easily controlled next dose, they should ignore the missed dose and by dose reduction. The side effects include: continue following the regular dosing schedule. A >> Depression double dose should never be taken to compensate >> Hot flashes for a missed one. Tamoxifen therapy is used in a number of cases:

>> Weight loss

>> Menstrual irregularities >> As adjuvant therapy (treatment following successful surgery) in those with lymph node negative or >> Vaginal discharge positive breast cancer though cancers with positive estrogen (and progesterone) receptors in both >> Pain/reddening around the site of the tumor females and males. >> Dizziness and severe headache >> As treatment of both early and advanced estrogen â&#x20AC;&#x201D;57â&#x20AC;&#x201D;

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>> Constipation

(neutropenia), very low platelet counts (thrombocytopenia) and very low white blood cell counts (leukopenia)

>> Muscle weakness

>> Vision problems (e.g. risk of cataract development) >> Abnormalities in blood clotting due to prolonged tamoxifen therapy at usual doses: this includes >> Initial adverse reactions (such as increased bone deep vein thrombosis and pulmonary embolus. Patients should seek immediate help if they develop pain) may be a positive tumor response following sudden shortness of breath, chest pain and/or only the onset of tamoxifen therapy. one swollen, red and painful calf. Fortunately, this is a rare side effect. >> Blood cell changes: low neutrophil counts

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Liver Cancer Treatment Treatment aims to eliminate cancer, slow cancer growth, Percutaneous Ethanol Injection improve patient survival or manage symptoms. The This involves the injection of alcohol directly into the choice of treatment depends on several factors: tumor in a generally simple and safe procedure. It is particularly effective in destroying a small tumor (<3 cm). >> The spread of cancer within the liver Side effects include fever and pain after the procedure. >> Whether the cancer has metastasized >> The patient ’s overall c ondition and Radiofrequency Ablation treatment preference Radio waves or laser light of high intensity are passed >> The status of the remaining cancer-free through a needle which is inserted into the tumour. area of the liver This conveys enough heat to kill the cancer cells. This option has largely replaced ethanol injection.

Surgery

This is the removal of the tumor (usually with some Chemoembolization surrounding healthy tissue) during an operation. It is This involves the injection of drugs (in an oily immersion) used particularly in patients with a small tumor (<5 cm) into the hepatic artery supplying the tumour with blood. solely in the liver. The drug-oil solution maintains the chemotherapy in Two types of surgery are used to treat hepatocellular the liver for long enough to destroy the cancer cells. carcinoma (HCC):

This is the primary treatment for HCC, but may also

Hepatectomy

be used to slow tumor growth as patients await a liver transplantation.

This is when the portion of the liver with the cancer is resected. The remaining, healthy section of liver then takes over the functions of the entire organ. It is even possible that the liver may regrow to its normal size within weeks. Regardless of tumour size, this may not be an option if the patient has advanced cirrhosis.

Radiation Therapy This employs high-energy radiation to destroy cancer cells. Measures are taken to protect the other organs from radiation exposure and the treatment side effects (e.g. damage to the stomach and lungs).

The side effects may include pain, weakness, fatigue, There are two types of radiation therapy used to adbleeding, infection and liver failure. dress cholangiocarcinoma and HCC:

Liver Transplantation

Stereotactic Body Radiation Therapy (SBRT)

Patients must fulfil very specific criteria in terms of This treatment involves delivering high doses of radiatumor size and number to qualify for this. Due to the tion to a tumor (£ 5cm) while limiting the amount that limited number of donor livers available transplantation reaches and damages healthy tissues. is not always possible. After a transplant, rejection of the new liver is a real Radioembolization likelihood therefore the patient must take medication This involves strategically placing radioactive beads to prevent this. into the small blood vessels responsible for supplying —59—

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the tumor with blood. When they become trapped in division and spread of cancer cells. these vessels, they also deliver radiation directly into Systemic chemotherapy involves administering drugs the tumor to halt its growth. (one or in combination) via the bloodstream to reach widespread cancer cells. Delivery is typically through an Targeted Therapy intravenous tube (or given orally) in a specific number This therapy addresses the specific and individual of cycles given over a set period of time. This is not genes that contribute to the growth and survival of commonly used for HCC. different forms of cancers. This allows the design of The side effects vary with individual and dosage but effective, more personalized treatments. include nausea, vomiting, hair loss, loss of appetite, Anti-angiogenesis drugs are the most common ex- fatigue, low blood cell count, bleeding or bruising ample of targeted therapy for HCC. These drugs act after superficial cuts or injuries and numbness and by inhibiting angiogenesis (formation of new blood tingling of extremities. These usually stop once treatvessels) to essentially “starve” the tumor of nutrition. ment is concluded. For example, Sorafenib is a pill taken as a treatment for advanced HCC that cannot be entirely removed by

Palliative Care

surgery. The side effects of this include diarrhea and This aims to reduce symptoms and side effects of treatcertain skin problems. ment to improve quality of life. Palliative care can be a combination of medication, dietary changes, relaxation techniques, emotional support, and other therapies. Chemotherapy The use of chemical substances to stop the growth,

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Types of Liver Cancer Liver cancer is the sixth most common cancer worldcan possibly lead to cirrhosis. wide. Almost two thirds of cases occur in men and approximately 8 in 10 cases are in those aged 60 >> Obesity and type 2 diabetes – these are both associated with a higher risk of developing HCC, years or above. even more so if both are present. Liver cancer is broadly categorised as prima- >> Heavy smoking – this has been linked with HCC particularly when present alongside excessive ry and secondary. alcohol consumption or infection with viral hepatitis.

Primary Liver Cancer

>> Anabolic steroids – prolonged use may lead to liver tumours. These are usually benign but they This cancer originates in the liver and its different forms can grow and rupture to cause pain. of are named after the types of cells the cancer has >> Inherited metabolic diseases - People with developed from. hereditary hemochromatosis absorb too much iron from ingested food. The iron settles in tissues The two main types of primary cancer are: throughout the body, including the liver. If enough iron accumulates in the liver, it can lead to cirrhosis and increase the risk of developing liver cancer.

Hepatoma i.e. hepatocellular carcinoma (HCC)

The most prevalent primary liver cancer. It affects the primary cells that constitute the liver, hepatocytes. Usually HCC is confined to the liver, but it may metastasize and spread to other organs. The main risk factors for HCC are: >> Cirrhosis of the liver – Approximately three or four people out of a hundred with cirrhosis will go on to develop HCC each year. Cirrhosis is where the liver has become scarred as a result of damage over a long period of time. Therefore, any disease that causes cirrhosis can potentially lead to HCC, although certain causes of cirrhosis have a particularly strong link with HCC.

>> Rare diseases – Tyrosinemia, porphyria cutanea tarda, glycogen storage diseases, Wilson’s disease etc.

Biliary Tree Cancer (e.g. cholangiocarcinoma and gallbladder cancer) Cholangiocarcinoma (bile duct cancer) is a rare but aggressive form of liver cancer that starts in the cells that line the bile duct. Unlike HCC, this form of primary cancer is more common in women than in men. In most cases, there is no clear reason why cholangiocarcinoma develops but people suffering from the following problems are at a higher risk:

>> Coinfection with viruses (e.g. hepatitis B, hepatitis C or HIV l) - chronic infection with hepatitis B virus >> Cirrhosis of the liver – as is the case with HCC, (HBV) or hepatitis C virus (HCV) is the worldwide this scarring due to disease (e.g. HCV, HBV) and leading cause for HCC. These infections lead to irritants (e.g. alcohol) can predispose a person to cirrhosis of the liver and are responsible for making cholangiocarcinoma. liver cancer the most prevalent cancer in many parts of the world. >> Primary sclerosing cholangitis (PSC) – this is characterized by inflammation of the bile ducts (cholangitis) leading to scar tissue (sclerosis) >> Non-alcoholic steatohepatitis (NASH) - this is liver inflammation and damage due to the accumulation of formation. The cause of the inflammation is fat in the liver. It is a member of a group of conditions not usually known but the risk of this is called non-alcoholic fatty liver disease and is increased by smoking. similar to the kind of liver disease that results from long-term alcohol abuse. While symptoms and >> Bile duct stones – these can cause chronic problems are uncommon in many people, when inflammation that increases the risk of they do occur, liver function is compromised which bile duct cancer. —61—

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>> Rare diseases - Caroli syndrome, polycystic Secondary Liver Cancer liver disease etc. Also called metastatic cancer, this form occurs due to a cancer that first develops elsewhere in the body Fibrolamellar Carcinoma that then spreads (metastasizes) to the liver. The liver This is a rare variation of HCC usually found in people may be susceptible to this because it filters the blood between 20 to 40 years old without cirrhosis being cancer cells in the bloodstream have a high chance of present. Fortunately, it is usually well contained and accumulating in the liver to establish a malignant tumour. can be removed with surgery. Those who are most at risk of secondary liver cancer are those with cancers of the large colon, pancreas, stomach, lung or breast.

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What is Lymphedema? The lymphatic system is characterized by a complex and extensive network of lymph vessels which is responsible for the transport of lymph fluid (containing compounds such as proteins and lipids) to and from tissues. During its transport, the fluid is filtered by the lymph nodes – these contain residential lymphocytes. In this way, the lymphatic system is an integral part of the body’s immunity.

Types of Lymphedema: Primary Lymphedema There are three types of this rare and hereditary form of lymphedema which occur when there is a physiological deformation of the lymphatic system. Unfortunately, family history of lymphedema is not a necessity for its development in a person.

When there is a blockage in the lymph vessels the lymph >> Congenital lymphedema (or Milro disease) – this is fluid is not effectively returned to the bloodstream and an inherited form of lymphedema which appears to be associated with a failure in the lymphatic this can result in localized swelling i.e. lymphedema. system. It is present from birth but may occur This swelling may occur in numerous locations - not at any point up to the age of one year old. This only the legs and arms but also in the head, neck, form represents approximately 20-25% cases of primary lymphedema. breast, trunk or genitals. >> Lymphedema praecox (or Meige disease) – this constitutes 65-80% cases of primary lymphedema. The symptoms most commonly Lymphedema is further categorized according to its stage: become apparent during puberty. The higher incidence in females may suggest an association between pathogenesis and estrogen.

Stages

Stage 0 (subclinical or latent)

This stage can be present for months or years however, >> Late Onset lymphedema (or lymphedema tarda) – this form occurs following 35 years of age but symptoms are not common. Swelling is not visible yet only accounts for approximately 10% of primary lymphedema cases. however the lymphatic system has undergone damage. 

Stage I (mild)

Secondary Lymphedema

Secondary lymphedema occurs when there is damage Visible swelling has begun and the skin indents when it or blockage in an otherwise healthy lymphatic system. is pressed but there is no visible evidence of scarring. The hampered functioning of the lymph system removes Elevating the affected limb can temporary reduce the an essential component of a person’s immunity, thereby swelling until the limb is returned to its normal position. making it more difficult for the body to fight infections.

Stage II (moderate)

Worldwide, filariasis is the largest contributing factor of The swelling increases and elevation does not decrease the disease – it is a parasitic infection spread among swelling. The skin does not indent but becomes firm humans via mosquitoes carrying the parasite Wucherdue to scarring (fibrosis). eria bancrofti. It causes damage to the lymph system which eventually results in the characteristic swellStage III (severe, lymphostatic elephantiasis) ing of lymphedema. The skin becomes very swollen, the affected body Malignant cancer and its treatment by surgery is also a part has swollen in size and volume, and the skin has very common cause of secondary lymphedema. This changed texture. is because it involves the removal of regional lymph —63—

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nodes or lymph vessels which can damage the lymph due to burns and radiation can increase the likelihood nodes and lymph vessels. In the same way damage of this form of lymphedema.

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What is Neuromodulation? Neuromodulation is the process by which nervous A substantial amount of evidence has demonstrated that activity is regulated by way of controlling the physi- this neuromodulator plays a critical role in modulating ological levels of several classes of neurotransmitters. plasticity, learning and memory via the hippocampus within the brain. Neuromodulators are a subset of neurotransmitter. Unlike neurotransmitters, the release of neuromodulators Dopamine (Dopamine system) occurs in a diffuse manner (“volume transmission”). This means that an entire neural tissue may be subject Dopamine is centrally involved in reward, approach to the neuromodulator’s action due to exposure. This, behavior, exploration, and various aspects of cognition. in turn, can tune the neural circuitry of an entire brain Variations in this neuromodulator function appear to be associated with variations in personality. This results region; not just that of an individual neuron. in changes in relatively stable patterns of behavior, This is in contrast with the release of a neurotransmit- motivation, emotion, and cognition that differ among ter, which occurs at a specific synapse during direct individuals. No concrete evidence exists concerning synaptic transmission. Furthermore, neuromodula- its role in personality, and it has been implicated in tors and neurotransmitters act on different types of traits ranging from extraversion to aggression to intelneuroreceptors. ligence to schizotypy. While neurotransmitters target fast-acting “ionic” neuroreceptors that convey electrochemical signals into the Serotonin (Serotonin system) target neuron, neuromodulators target the slower G- Over 90% of the body’s serotonin is found in the protein neuroreceptors (of which there are three types). gastrointestinal tract where it has a role in regulating bowel function and movements. It also plays a part in Importantly, the act of neuromodulation, unlike that reducing the appetite while consuming a meal. of neurotransmission, does not necessarily carry excitation of inhibition from one neuron to another, but With this said, it is most well-known for its role in instead alters either the cellular or synaptic properties the brain where it plays a major part in mood, anxiof certain neurons so that neurotransmission between ety and happiness. them is changed.

Acetylcholine (Cholinergic system)

Some examples of neuromodulators are Acetylcholine (Ach) has a role in the control of autonomic highlighted below: functions but it is likely that it also modulate adaptive responses to environmental and metabolic conditions. Noradrenaline (Noradrenaline system) Cholinergic signaling can influence thermoregulation, Noradrenaline regulates the activity of both neuronal sleep patterns, food intake and endocrine functions and non-neuronal cells. It participates in the rapid including pancreatic insulin and glucagon release. modulation of cortical circuits and cellular energy metabolism, and on a slower time scale in inflammation The hypothalamus is vital in homeostatic responses regulating metabolism, therefore modulation of hypothalamic function by ACh is likely to be important in Of the multiple sources of NE in the brain, the locus adaptation to peripheral autonomic signals to the brain. coeruleus plays a major role in noradrenergic signaling. ACh signaling in a number of brain areas might also and neuroplasticity.

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be important for stress responses as several studies have shown that stress increases its release in a brain region-specific manner.

Pharmacological Applications of Neuromodulation >> Sympathomimetic and sympatholytic drugs: these enhance and block at least some of the effects of noradrenaline released by the sympathetic nervous system, respectively. >> Dopamine reuptake inhibitors: these prevent dopamine reuptake by blocking the action of the dopamine transporter. These drugs are frequently used in the treatment of conditions including ADHD, depression and narcolepsy. >> Selective serotonin reuptake inhibitors: these temporarily prevent the removal of serotonin from specific synapses, thereby enhancing the effect of released serotonin. These are used in the treating depression. >> Cholinesterase inhibitors: these bind to cholinesterase resulting in increased acetylcholine in the synapses. These are used to treat dementia in patients with Alzheimer’s disease. Neuromodulation is also a category of treatment that involves stimulation or direct administration of medications to the body’s nervous system for therapeutic purposes. This aims to modulate activity of target cells as an approach to pain control and neurological dysfunction by treating movement disorders, conditions such as spasticity and epilepsy, as well as pain syndromes.

Spinal Cord Stimulation This common form of neuromodulation involves using a device to deliver electrical current in therapeutic doses to the spinal cord to disrupt pain signals from the spinal cord to the brain, converting them to a more pleasant tingling sensation. This has been proven a safe and effective therapeutic approach for managing chronic pain of the arms and legs, neck and back often after spine surgery, or for other neuropathic conditions.

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Imaging in Nephrology Imaging techniques used in nephrology include the >> Chronic kidney disease (sometimes indicated by following tests: decreased kidney size) >> Congenital anomalies - eg, hypoplasia, agenesis, duplex systems.

Ultrasonography

This is a non-invasive, safe and affordable imaging >> Detection of renal cysts, abscesses and neoplasms technique which relies on the reflections and echoes e.g. simple cysts, polycystic kidneys. of ultrasound pusles which are directed into tissues Nuclear Medicine by a transducer. This encompasses techniques such as nuclear medicine renal scans. This type of scan involves imaging to ultrasound waves and following their reflection against study efficiency of each kidney’s function by considerthe body structures, the returning ultrasound waves are ing the blood supply, function and excretion of urine converted into electrical signals read and presented from each kidney. by a computer as a real-time movie. The transducer converts an electrical current into the

Altering the ultrasound frequency can allow investigaThe scan can be performed with 2 different substances tion of the kidney and bladder even during pregnancy. - diethylenetriaminepentaacetic acid (DTPA) or mercaptoacetyltriglycine (MAG3). It can be useful for the following: >> Acute kidney injury e.g. post-renal obstruction.

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similar, but MAG3 gives significantly better images in CT scans provide more detailed imagery than standard some patients (e.g. very young children and patients kidney, ureter and bladder (KUB) X-rays. CT scans of with poor kidney function). the kidneys are used to detect conditions including tumors or other lesions, obstructive conditions (e.g. A DTPA Scan may also be undertaken to evaluate: kidney stones), congenital anomalies, fluid accumulation surrounding the kidneys, and the location of abscesses. >> Function and perfusion of renal tubules and transplants MRI is an alternative to the CT scan that can be used in all patients except those with pacemakers due to >> Renovascular hypertension the harmful effects of strong magnetic fields. >> Condition of renal tubules due to obstruction, trauma or damage MRI imaging is based on the behavioural change of hydrogen nuclei (i.e. protons) when subjected to a magnetic field (due to the MRI system). The nuclei act as miniature magnets, which can be manipulated in Computed Tomography (CT) Scan CT scans are not routinely used to check for problems – an MRI image in order to distinguish among various normally, the onset of symptoms might call for it. These tissue characteristics. scans involve taking a series of X-rays of the patient’s MRI has emerged as an attractive approach due body at slightly different angles. Then this collection to its non-invasiveness and suitability for repeated of X-ray images is interpreted and superimposed by application. Because of this, they are used to monia computer and displayed as a 2-dimensional form. tor the functioning of renal allografts and accurately CT scans may be done with or without “contrast” in characterize renal tumor aggressiveness in order to which contrast is a substance ingested or injected guide management. >> Renal artery stenosis

into an intravenous (IV) line in order to allow clearer visualisation of the particular organ or tissue under study. If contrast media is used, there is a risk of an allergic reaction, therefore, patients exhibiting allergies or sensitivity to medications or who have had prior reaction to any contrast media, should inform their doctor. A disadvantage of CT is the exposure to significant amounts of ionizing radiation.

Its advantages over CT scanning include its greater soft tissue contrast and increased safety due to the avoidance of ionizing radiation and iodinated contrast compounds. Most importantly, combinatorial techniques exist to probe different aspects of a tumor such as microstructure, vascularity, and oxygenation including dynamic contrast enhanced (DCE), (diffusion weighted imaging) DWI and blood oxygen level dependent (BOLD) MRI.

Ultrasonography of kidney : show left kidney stone ( 2 image for compare ), Image Copyright: Puwadol Jaturawutthichai / Shutterstock

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Kidney Biopsy Procedure The kidneys are the specialized organs that filter and waste products in the blood) purify the blood by removing excess water, salts and >> Acute or chronic kidney disease/renal failure waste products. of unknown cause A kidney biopsy involves taking one or more tissue >> Persistent glomerular hematuria samples of the kidney for clinical tests. This can be useful in diagnosis where other methods such as blood >> Systemic diseases with renal involvement and urine tests, imaging and physical exams are not. >> Renal allograft dysfunction. In most cases, It takes 3-5 days to get the full biopsy A kidney biopsy may also help to: results from the pathologist however it might be possible to receive a partial or full report within 24 hours or less. >> Monitor tegression (or in some cases, progression) of a disease due to treatment

Methods of Biopsy

>> Show an untreatable problem but that can be slowed down by other therapy.

A kidney biopsy may be taken in one of two ways:

Percutaneous biopsy: a needle placed through the skin (percutaneously) that lies over the kidney and guided to the right place in the kidney – this can be done using ultrasound or CT imaging. The skin is cleaned and marked at the biopsy site which is usually the lower pole of the kidney. A local anesthetic is used to numb the needle insertion area and the patient must take in a deep breath and hold it for approximately 45 seconds or less as the needle is inserted. The patient must also stay still until the kidney sample is taken. Finally, the needle is removed and a bandage is placed over the puncture site.

>> Identify the extent of permanent damage in the kidney. >> Decide on further treatment when a transplanted kidney is not working well >> Find a kidney tumor

Before the Test

The patient must inform their doctor of any allergies they have and medicines they require. If the patient takes blood thinning medicines (Warfarin, Aspirin, Clopidogrel) then these are usually stopped a week prior to the procedure as a precaution to reduce the chance of bleeding during and following the biopsy. The patient must also avoid food and fluid for eight Open biopsy: the kidney sample is directly obtained hours before the biopsy. from the kidney during surgery and sent to a pathologist for analysis. This form of biopsy is suggested instead of percutaneous for some patients who may have a After the Test The patient may require bedrest for 12-24 hours after history of bleeding problems. the biopsy. Remaining still in bed helps the biopsy site heal. It will also reduce the chance of bleeding – this is Purpose of Biopsy the main complication and in order to look for any signs Specific reasons to do a kidney biopsy include: of internal bleeding the patient will have their blood pressure and pulse checked. Blood tests are also done. >> Urine abnormalities - blood in the urine (hematuria) and protein in the urine (proteinuria) For two weeks after the biopsy strenuous activities >> Abnormal blood test results such as high creatine should be avoided – these include contact sports, and levels (indicating kidney dysfunction thus increased sexual intercourse. —69—

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A doctor should also be informed if the pa>> Faintness and dizziness tient experiences: >> Bloody urine for more than 24 hours after the biopsy >> Worsening pain, bleeding, swelling or redness in the biopsy site >> Inability to urinate                                                     >> Fever and/or chills

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Nutrition in Kidney Disease The kidneys are two vital organs located in the ab- the blood which the kidneys may not be able to remove. dominal cavity, just below the ribs. They are required On the other hand, protein intake should not be too low, for numerous regulatory functions which include: or it may cause problems in building bone and muscle. >> Removing of liquid waste from the blood as urine

Sodium

>> Maintaining a balance of substances in the blood Intake is usually in the form of salt (sodium chloride) and due to its electric charge, Sodium is necessary >> Producing the hormone erythropoietin for the for muscle contraction and nervous transmission, fluid formation of red blood cells balance and blood volume (hence blood pressure). >> Regulating blood pressure If kidney function is hampered, sodium level in the body Diet and nutrition are important components for anyone is poorly regulated. Too much sodium can cause fluid to maintain a healthy lifestyle. accumulation, swelling, higher blood pressure, and There is evidence that suggests that those who consume strain on the heart. at least five portions daily of their fruit and vegetables Importantly, when trying to reduce sodium intake, salt exhibit an overall lower risk of heart disease, stroke substitutes in some products might be more harmful and some cancers. than good, as many contain potassium, which may Should a person have kidney disease, then their di- also need limited intake. etary needs will likely change with disease progression depending on how much remaining kidney function Potassium there is amongst other factors. Good sources of potassium include bananas, citrus Often there will be an eating plan which is composed fruits, potatoes, lima beans, and most meats and fish. with the help of a dietician – this tends to be individu- Like sodium, potassium is required for muscle and nervous function. However, it specifically affects cardiac alised based on blood test results. muscle contraction due to its role in heart rhythms. People with kidney disease may need to control the following constituents of their diet in order to keep the It also has a role in the metabolism and assimilation levels of electrolytes, minerals, and fluid in the body of carbohydrates and building of muscle. appropriately balanced. Low potassium (hypokalemia) can cause weak muscles, abnormal heart rhythms, and slightly higher blood Protein pressure, although high potassium (hyperkalemia) may Protein is imperative for the maintenance of body tissue, also cause abnormal and dangerous heart rhythms. development of some hormones and antibodies and is involved in necessary molecular transport in the body. Calcium and Phosphorus The amount of protein needed is based on body size, Calcium and phosphorus are key in supporting the extent of kidney function, and the amount of protein skeletal structure and preventing the advancement of bone diseases such as osteoporosis. that may be in the person’s urine. Ingesting too much protein can cause waste buildup in In addition, calcium is involved in cellular signalling, —71—

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wound clotting, muscular activity (contraction) and ner- Without urination, fluid accumulation occurs in the vous function whilst Phosphorus is required in processes heart, lungs, and ankles, which may lead to breathing including energy production and pH homeostasis. difficulties (this requires medical attention). As kidney function worsens, phosphorus levels rise in Additionally, it is important that nutritional intake conthe blood, causing the bones to weaken. Due to this, tains enough calories because many patients become it might be necessary to limit phosphorus intake – this malnourished, particularly in later stages of the disease. may involve consuming less dairy products. As foods rich in phosphorus are often high in calcium

A person suffering from chronic kidney disease should too, limiting phosphorus intake might require the person have a diet with: to take Calcium supplements and Vitamin D.

Fluids

>> Reduced sodium

In the early stages of kidney failure, fluid intake doesn’t >> Reduces phosphate have to be limited but as the condition worsens, or when >> Sufficient calories a person is on dialysis, careful monitoring is required. >> Controlled protein intake (as indicated below) The patient’s doctor will let them know how much should During pre-dialysis, reduced protein is required as be drunk every day, whether this is water or foods that high amounts may damage the nephrons and thereby contain a lot of water, such as soups, grapes and celery. enhance the progression of kidney disease. For those on dialysis, fluid intake is controlled between During dialysis, fluids and compounds such as treatments as most people on dialysis urinate very little. phosphate and potassium should also be carefully

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monitored. More protein is required to replenish the haemodialysis sessions. lost during dialysis and excess catabolism following

Function and nutrition supplement of kidney, Image Copyright: nipada_hong / Shutterstock

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Urine Analysis / Urinalysis Urine analysis, also known as urinalysis, encompasses >> Medical Monitoring: following the diagnosis of kidney all the analytical tests carried out on a urine sample. It disease to track both condition and treatment. usually involves three forms of analysis: >> Specific testing. This includes pregnancy tests and drug screenings e.g. pregnancy tests measure the >> Physical - Assessment of the color, cloudiness hormone human chorionic gonadotropin (HCG). and concentration of the urine Urine analysis encompasses the following >> Chemical - Examination of the chemical constituents testing procedures: of the urine using a test strip >> Microscopic – this allows one to look for bacteria, cells and cell fragments

Rapid Urine Test

Purpose Urine analysis may be required as part of: >> Overall health assessment: for routine medical examination, pre-surgery preparation, or upon hospital admission to screen for disorders including kidney and liver disease. >> Medical Diagnosis: for those experiencing symptoms

This test involves dipping a test strip embedded with colored fields into a urine sample for a few seconds. Depending on the concentration of the particular substance being testing for, the fields on the test strip change color. By using the color table on the test package as reference, one can see if any compounds exhibit abnormal urinary levels.

including abdominal pain, back pain, frequent or painful urination and blood in your urine. The following can be analysed:

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>> Colour: Fluid balance, diet, medicines, and diseases Microscopic Analysis can affect this (e.g. Vitamin B, consumption of This involves centrifugation of a urine sample. Following blackberries and beets). this, the obtained sediment is spread on a slide and >> Clarity: Substances including bacteria, blood, or analysed microscopically to study components such as: sperm can make normal, clear urine cloudy. >> Red or white blood cells: May be present in urine in disease, infection, or injury to the kidneys, ureters, >> Odor: Some diseases may cause a change in the odour of urine( e.g. diabetes can cause a bladder, or urethra. sweet, fruity odour.) >> Casts: The formation of plugs of blood cells, proteins or other substances (casts) in the renal tubules that >> Specific gravity: Indicates production of urine by can occur in some renal diseases checking the concentration of substances in the urine against water content (e.g. when fluid intake is high, the kidneys produce urine with a high level >> Crystals: Few crystals are found in healthy urine of water, which has a low specific gravity.) and many crystals, or certain types, may indicate presence of kidney stones or metabolic dysfunction. >> pH:  normally ranges from approximately 5 to 7 but certain treatments affect this and treatment >> Bacteria, yeast cells, or parasites:  Presence in may be needed to prevent the formation of some urine indicative of an infection. types of kidney stones. As with all tests, the results of urine tests are not always >> Protein: not normally present in the urine, but reliable. For this reason, a more detailed laboratory test strenuous exercise, pregnancy, fever and some diseases (e.g. kidney disease and nephritis) may is suggested following which abnormal results can be discussed with a doctor. cause its appearance. >> Glucose:  normally there is very little or no glucose in urine. When the kidneys are damaged and/ Urine Culture or blood sugar level is very high (uncontrolled This can be used to detect bacteria in the urine. A diabetes), urinary level increases. sample of midstream urine is incubated for 1-2 days >> Nitrites: bacteria that cause a urinary tract infection with an appropriate medium to allow for bacterial (UTI) possess an enzyme that converts nitrates to growth. If any bacteria or fungi are present, there will nitrites. Thus, urinary nitrites indicate a UTI. be colony growth that will be studied based on size, >> Ketones: Fat is metabolised into ketones, which form and color. Often urine cultures are used to test are expelled via urine. Large amounts of ketones in the urine may indicate diabetic ketoacidosis, a for a UTI then appropriate antibiotics are prescribed diet low in sugars and carbohydrates or starvation. for its management.

Check-up. Medical report and urine test strips - Image Copyright: Alexander Raths / Shutterstock

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Could E-Cigarettes Cause Cancer? E-cigarettes are an alternative to smoking the con- Harmful Agents ventional cigarette. The components of one include There is no dispute as to whether formaldehyde and a battery, an atomizer and a replaceable cartridge acetaldehyde are harmful when produced - both are that is designed to hold a nicotine solution and often listed as probable cancer-causing agents by the Enflavorings for taste. vironmental Protection Agency. It works by using a sensor that detects a change in

The issue lies in the question of whether formaldehydeairflow when the user inhales through the device. releasing agents are being produced. Research This begins heating the nicotine solution inside the has found that when e-cigarettes are used at lower, cartridge until it evaporates and the resulting water more realistic voltages, no formaldehyde-releasing vapor is delivered straight into the lungs carrying a agents are detected. certain dose of nicotine with it. The American Vaping Association has argued that such studies proving the alarmingly high production of Research formaldehyde are based on unrealistic vaping conditions The Japanese Ministry of Health has carried out and are therefore misleading to the public. They claim research which claims that e-cigarettes contain 10 that e-cigarette users would preferably avoid using their times the level of carcinogens than traditional todevice at a high voltage of 5V. In this setting, there is bacco products. Both formaldehyde and acetaldehyde extreme overheating of the e-cig coil which results in carcinogens were found in the liquid produced by a the production of formaldehyde. In such a setting the number of e-cigarettes. These two chemicals have ‘dry puff phenomenon’ occurs and the puffs produced also been found in experimentation by the Center for exhibit an acrid, bitter and unpleasant taste which does Environmental Health (CEH). not appeal to e-cig users. It has been shown that when e-cigarettes are run at high voltages the vapor produced contains high enough levels of formaldehyde-containing compounds to drastically increase a person’s risk of developing cancer – this risk can be up to 15 times higher than that incurred by long-term smoking. At this voltage, smoking would prove to be of particular risk to users who use this as a way to increase the delivery of vaporized nicotine. As more recent versions of e-cigs are released which allow users to operate them at higher temperatures, the production of these formaldehyde-containing compounds, and the problems that they result in become even more common. These versions allow users the option to replace their own cartridges, alter the running temperature and consequently, the vapor produced.

On the other hand, using the e-cig at the lower setting of 3.7 volts (considered realistic) yielded only trace levels of formaldehyde – this level has also been observed in an FDA-approved inhaler designed to help smokers quit. Another study from Portland State University also explored the amount of formaldehyde produced with respect to the variable voltage of an e-cigarette atomizer. One has shown no formaldehyde produced at 3.3V, while at 5.0 volts formaldehyde levels up to 15 times higher than in tobacco cigarette smoke were measured. Here, formaldehyde-releasing agents (formaldehyde hemiacetals) were found – this is a combination of formaldehyde and alcohols. Not only was there no actual formaldehyde itself produced but there is also no evidence that hemiacetals are toxic or carcinogenic. In fact, it is even possible that these

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hemiacetals offer protection against damage induced by formaldehyde. Therefore, considering the hemiacetal risk equivalent to that of formaldehyde to calculate the risk of cancer may be unwise.

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Mucinoses Mucinoses encompass a group of diverse skin disorders which can vary from minor cosmetic nuisances to potentially severe conditions involving internal organs. All involve the abnormal accumulation of acid mucopolysaccharide (mucin) either diffusely or locally in the skin or even within the hair follicles.

symptoms include follicular papules (raised spots) often on the neck, face, and scalp that can be singular or in reddened patches of usually 2-5 cm in diameter. Hair loss is common from the affected follicles. In the

early stages, this is reversible and the hair will grow back should the condition clear up. In more severe disease, The mucin is composed of glycosaminoglycans (par- complete follicular destruction disallows normal hair ticularly hyaluronic acid) and is normally produced growth even if the disease is controlled. in small amounts as part of the dermal connective tissue by fibroblasts. Interestingly, mucin plays a vital Papular Mucinosis (lichen myxoedematosus) role in the homeostasis of water and salt in the dermis Some mucinoses such as this have both a localized and and can actually absorb one thousand times its own generalized form. In this case, the localized form has weight of water. Thus, in conditions such as mucinoses a more favorable and manageable course compared where mucin production is increased, there is more to the generalized form, scleromyxoedema, which can water retention so that the dermal connective tissue involve multiple organs and could even prove fatal. For becomes edematous. example, oxygen intake is hampered when the lungs The core reason for this upregulated mucin produc- are affected or the brain and nervous periphery are tion is unknown. Despite this, mucinoses can still be damaged when the nervous system is affected. categorized as either primary mucinoses, where the Examples of localized mucinosis include: main histological occurrence is mucin deposition, or cutaneous disorders, where the mucin deposition only constitutes an additional finding (epiphenomenon).

Connective Tissue Naevi

This mucinosis is usually seen in children. It encompasses disorders in which components of the skin layers develop abnormally â&#x20AC;&#x201C; it is thought that there they are attributed to a genetic defect, forming a component of some inherited disorders including tuberous sclerosis. The disorders can occur due to reasons including too much collagen (a collagenoma), elastic tissue (an Microscopic techniques are required to determine the elastoma), smooth muscle, fat or glycosaminoglycans. specific localization of mucin in order to determine the form of mucinoses present, i.e. primary (dermal or follicular) or secondary (epidermal, dermal or follicular). Myxoid or Digital Mucus Cyst This disorder is most common in those in their sixties. Examples of generalized (extensive) mucinosis include: It is characterized by varying sizes of benign fluid-filled mucous or myxoid cysts which are found at the base Follicular Mucinosis (alopecia mucinosa) of the finger nail (or sometimes toenail) or close to it. This mucinosis is most common in children and adult If the cyst happens to overlie the area where the nail males in their thirties or forties. It appears that the adult forms then it often causes a groove which extends the form tends to induce more lesions and last longer. The length of the nail. Identification of the mucinosis involves determining the presence of mucin by particular histological techniques. For example, alcian blue is a positively charged dye which may be used to detect mucin molecules containing anionic negatively charged sites via attractive forces.

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This mucinosis appears to occur due to one of two reasons – abnormal mucin accumulation in the skin or due to osteoarthritis when there is extension of the lining of the finger joint.

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Mucous Membrane Pemphigoid / Cicatricial Pemphigoid Mucous membrane pemphigoid (MMP) encompasses a heterogeneous group of diseases, which predominantly affects the elderly. The peak incidence is at roughly 70 years. However, rare childhood cases have also been reported. There is no racial or ethnic predilection associated with MMP, but the condition does appear to be twice as common in women than it is in men. For completeness, MMP is also termed cicatricial pemphigoid, oral pemphigoid and ocular pemphigoid.

Clinical Course and Presentation MMP is a chronic autoimmune disease that is recognized by sub-epithelial blistering lesions and eventual scarring of the mucous membranes, skin, or even both. Affected membranes may include the conjunctiva, oesophagus, trachea, nasopharynx, larynx, genitourinary tract, and anus. Of these, the most commonly affected are the oral mucosa and conjunctiva. In less common cases the skin may also be involved. 20-30% of cases present with blistering lesions found on the face, neck and scalp. Lesions of the skin may either be fluid-filled blisters (bullous) or reddish (erythematous) plaques, which may bleed or itch. Scarring may result in patches of discolored skin (hyperpigmentation or hypopigmentation) and areas of hair loss if the scalp is affected. Irrespective of the membrane(s) affected, MMP persists for a long time and remissions and recurrence are both frequent.

mune disorder (i.e. it occurs when the body produces autoantibodies against healthy ‘self’ tissue). In MMP, these produced autoantibodies react with target proteins (antigens) located in mucous membranes and skin tissue. More specifically, the autoantibodies attack the basement membrane zone (BMZ) of the epithelium. The BMZ functions in holding the outer layer of skin onto the underlying tissues. Therefore, when the BMZ is attacked and destroyed by the autoantibodies, the skin is no longer anchored down, allowing it to become detached and produce blister. Immunological studies have revealed that the precise targets of these autoantibodies are antigens, which include BP180 and laminin 5. Other suggestions such as the subunits of the α6β4 integrins, Collagen VII and BP230 have also been postulated. It has been suggested that affected individuals may have a genetic susceptibility to the development of some forms of MMP. The development of such cases would likely be multifactorial by requiring contribution of immunological, genetic, environmental, and several other factors. It might also be the case that MMP is the unfortunate result of the use of certain drugs or following trauma

to the affected area. For example, some cases of MMP predominantly affecting the eyes may become apparent following a form of ocular surgery such as Clinical presentation tends to vary depending on the cataract removal. membrane(s) affected. Chronic inflammation, painful, persistent vesicles, erosion and the common resultant scarring of the mucous membranes may cause significant morbidity by leading to tissue destruction and functional shortcomings. For example, conjunctival scarring may contribute to blindness and gingival scarring and inflammation may result in the loss of teeth.

Pathophysiology

Treatment Treatment of MMP is in the form of symptomatic management. The symptoms can usually be controlled with the right single medication (or combinations) in order to keep the sores and blisters under control. Whilst it is fortunate that the likelihood of death is rare, the possibility of incurring morbidities such as blindness is serious enough to raise concern amongst sufferers.

The exact cause of MMP is unknown. It is an autoim—80—

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Livedoid Vasculopathy / Livedoid Vasculitis Livedoid vasculopathy (LV) is a painful, recurrent and chronic disorder of the microcirculation in the skin. LV is also known as livedoid vasculitis and it is a relatively rare dermatosis that occurs most commonly in women from their youth to middle ages. The lesions are often located in the distal parts of the lower extremities and feet.

area of the affected skin may undergo necrosis and ulceration in cases where there is persistence of the developed ischemic state. This is often the stage at which patients consult a doctor, because the painful ulcerations of the feet, ankles, and legs begin to negatively impact their quality of life.

LV presents clinically with a triad of symptoms. These symptoms do not necessarily need to occur simultaneously or in any particular order. The symptoms are painful ulcerations, livedo racemosa (skin discoloration presenting as irregular broken circles) and scars that are called atrophic blanche.

The ulcerations do not begin as particularly deep; however, as they heal, they undergo a form of remodeling and the skin is left with significant deep atrophic scars known as atrophie blanche. These porcelain-white and stellar scars are irreversible and often surrounded by punctate telangiectasia and hyperpigmentation, of which the latter can in time become partially resorbed.

Pathophysiology of LV

Diagnosis of LV

The pathophysiology of LV is not well understood, but the condition may be categorized as either primary or secondary. The primary form does not appear to have any associations with other diseases. However, the secondary form of LV is associated with diseases that are characterized by hypercoagulability (i.e. thrombophilia). These diseases may arise due to a fibrinolytic disorder like protein C deficiency, hyperhomocysteinemia and prothrombin gene mutations. In other cases, LV appears to be associated with disorders affecting the connective tissue. These include, but are not limited to antiphophospholipid syndrome (APS), systemic lupus erythematosus and cryoglobulinemia.

The appropriate diagnosis of LV requires a specific skin biopsy at a site where the healthy skin transitions into the affected. LV is purely a cutaneous form of ischemia, therefore, no systemic involvement is expected and thus no damage to any other organ and no other diagnostics required.

The disturbed microcirculation seen in LV seems to

Treatment of LV

be due to the deposition of fibrinoid material (clots) both within the walls and lumina of the upper and middermal vessels. This causes a marbled discoloration of the skin which appears lacy – this is associated with livedo racemosa. Following clot formation, there is poor perfusion of blood within areas served by the affected blood vessels. Thus, these areas become ischemic and acute ischemic pain (angina cutis) eventually results. The

Histologic identification might allow for the detection of pro-thrombotic markers in the blood if LV is due to upregulated coagulation. However, even if these markers are present, they cannot definitely be considered as the cause of LV. In fact, one example is lipoprotein (a) which can be altered by dietary or medicinal means.

Part of the reason that there is no prominent and effective treatment for LV is the uncertain nature of its pathogenesis. Due to this, current treatment options might rely on data acquired solely from reports of single cases or a series of them. Many treatments exist to improve the physical manifestations (ulcerations) and reduce the pain. Alternatively, some treatments aim to control the disease process. However, cases can prove difficult to treat and the devised treatments may even

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lead to side effects that hamper enthusiasm for their use.

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Bullous Pemphigoid Bullous pemphigoid (BP) is a condition that affects the skin with an autoimmune etiology. It is often seen in those over the age of 80 and the prevalence is even higher in elderly people with neurological comorbidities such as stroke, Parkinson disease and dementia. It is generally prevalent in people after the fifth decade of life and may occur in younger adults. However, it is rare in infants and children. There is no predisposition towards either sex or associations with HLA to indicate a genetic risk factor.

form a waterproof seal. The autoimmune action in bullous pemphigoid affects the basement membrane zone between the epidermis and dermis. The autoantibodies that bind to the target antigens may lead to a series of immunological reactions, which eventually lead to the destruction of the hemidesmosomes. Ultimately, the skin layers begin to separate and fluid accumulates between them to cause the formation of subepidermal blisters.

Diagnosis and Treatment

Clinical Signs and Symptoms

The diagnosis of BP is often through clinical examina-

The first symptom is often intense itchiness. The skin may develop large areas that are raised before the onset of tense fluid-filled blisters called bullae. These blisters are usually surrounded by areas of either visually normal or inflamed, red skin. Eventually, the blisters burst and leave behind a mark that will crust over. Oral blisters are rare. Instead, blisters tend to arise more in the flexures of joints like inside the elbows or behind the knees.

tion followed by confirmation through a biopsy of the affected tissue. Pathological evaluation of the biopsy can reveal inflammation of the affected skin. Further testing of the biopsy specimen can be used to reveal the location of the autoantibodies in the basement membrane layer or mucosal membrane. Treatment aims to make the disease tolerable by de-

creasing the rate at which bullae form. As the majority of those affected are elderly, treatment can become more complicated, because these patients often presPathophysiology ent with other comorbidities. This makes them more The pathogenesis of Bullous pemphigoid is character- susceptible to the side-effects from systemic agents. ized by the action of autoantibodies directed at target antigens responsible for either cell-to-cell adhesion Therapy can vary depending on the severity of the within the epidermis (skinâ&#x20AC;&#x2122;s outermost layer) or adhe- presenting case. Mild or non-extensive cases may sion of squamous epithelium to the dermis (the layer benefit from twice daily application of potent topical steroids. In support of this, there has been research next to the epidermis). suggesting that large quantities of high-potency topical The mechanism that leads to the autoimmune process corticosteroids applied to the affected surface are safer is still not known. We do know that when it occurs in than oral corticosteroids in controlling localized bullous bullous pemphigoid, primarily IgG autoantibodies are pemphigoid. On the other hand, moderate to severe directed towards the basement membrane zone. More cases require systemic steroids. Oral prednisolone is specifically, they target the residential bullous pemphi- the predominant established treatment used for rapid, goid antigens BP180, or less frequently BP230. These definite remission. are components of the hemidesmosome adhesion complex at the basement membrane, which ensures the epidermal cell layer is secured to the dermis to

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Porphyria Cutanea Tarda (PCT) Porphyria cutanea tarda (PCT) belongs to group of disorders named the porphyrias. A porphyria is characterized by the abnormal metabolism of the blood pigment hemoglobin.

Type 2 PCT shows association with mutation in the gene encoding UROD and significantly less with trigger factors. Interestingly, some people whhave the causal gene mutations for Type 2 PCT are affected by a latent form of this porphyria. i.e. they exhibit none of the symptoms of PCT. Unfortunately, those whdsuffer from the symptoms experience the onset of this at a younger age than in type 1 PCT. The general symptoms of porphyrias are as follows:

In porphyria, cells fail tconvert porphyrins and porphyrin precursors intheme. This biosynthetic pathway for this relies on the functioning of eight enzymes for the appropriate synthesizing of heme. Thus, a deficiency in even one of these enzymes could result in the accumulation of porphyrins and porphyrin precursors >> Hypersensitivity to sunlight exposure - this leads titching and swelling of sun-exposed areas. Thus, it that then cause illness. is recommended in some necessary cases tavoid direct sunlight as much as possible. Protect skin PCT is the most common form of porphyria and from sunlight by wearing light cotton gloves, long results from a dysfunctional enzyme within the liver sleeves, and a hat. named uroporphyrinogen decarboxylase (UROD). >> Sores (erosions) following relatively minor injuries PCT is subdivided intType 1 (sporadic PCT) and Type 2 (familial PCT). >> Fluid filled blisters (vesicles and bullae) eventually healing to form small cysts (milia) Approximately 75-80% of PCT cases are classified as PCT is the most treatable form of the porphyrias. Type 1. These generally begin midway in adulthood Furthermore, the treatment of PCT is almost always following exposure tparticular chemicals now known successful, and the prognosis is usually excellent. televate the synthesis of heme precursors (porphyrins) Treatment involves the removal of the aforementioned in the liver. The factors which trigger the acquired factors responsible for activating the disease in the first disorder include: place. Fortunately, such action appears tbe effective >> Moderately heavy alcohol consumption in both familial and sporadic PCT equally. >> Artificial estrogens - often in the form of oral The main treatment involves a schedule of blood removal contraception (e.g. birth control), hormone replacement therapy, liver disease, and prostate via repeated phlebotomy sessions which aim treduce cancer treatment the hepatic iron level. An alternative treatment may be a low dose regimen of anti-malaria drugs - twice weekly >> Iron overload which can possibly result from; doses of chloroquine or hydroxychloroquine. It is impor>> High intake - often via oral supplementation or tant that these drugs are taken at a carefully selected blood transfusion dosage because otherwise they have the potential >> Viral infections - HIV or hepatitis (especially tinflict temporary but potentially serious liver damage. chronic hepatitis C) Following appropriate treatment for PCT, the regular >> Hereditary hemochromatosis - thus gene monitoring of plasma porphyrins levels may be recabnormalities associated with this are trigger factors. This chronic blood disorder is alsthe ommended. It is of particular importance should a most common disease resulting in over patient require a known trigger factor as part of their absorption of iron lifestyle or health choices, e.g. artificial estrogen pres>> Smoking ent in birth control. â&#x20AC;&#x201D;84â&#x20AC;&#x201D;

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Treatment of Porphyria Cutanea Tarda Porphyria cutanea tarda (PCT) is a common form of hepatic porphyria characterized by symptoms such as fragile, blister-prone skin particularly on sun-exposed areas.

exacerbate PCT and induce liver damage before a remission of PCT is seen.The precise mechanism by which these drugs act with respect to PCT has yet to be determined. However, it is plausible that they bind with lysosomal porphyrins in the hepatocytes until they The condition occurs due to an acquired or inherited are eventually expelled through the urine. deficiency in the activity of hepatic uroporphyrinogen decarboxylase (UROD), an enzyme in the heme >> Iron Awareness – whilst foods high in iron do not usually aggravate PCT significantly, it is strongly biosynthetic pathway. This deficiency leads to the acrecommended that dietary supplements containing cumulation of porphyrins – this is common in states of iron are ceased. Additionally, Vitamin C intake increased oxidative stress in the hepatocytes usually should be adequate as this is necessary for iron absorption in the body. due to increased hepatic iron or less commonly alcohol, smoking, estrogens, or viral infections. >> Avoidance of Environmental Triggers – a wellestablished example of a trigger is alcohol which There is no established cure for PCT; however, it is still not only exacerbates Hepatitis C infection greatly and inflicts liver damage, but may also worsen PCT. considered as one of the most manageable porphyrias Other triggers include the smoking of cigarettes or and the prognosis is very promising. The treatment pharmaceutical intake of estrogen (in birth control approaches include: tablets) which may induce a bout of PCT. Phlebotomy – this is the frontline treatment for PCT. The >> Antiviral treatment – the treatment of concomitant Hepatitis C infection with interferon alpha and procedure involves blood removal via a vein. As the red ribavirin therapy has been shown to be favorable blood cells contain such a considerable proportion of in some with PCT by resulting in a decrease in cutaneous lesions. That said, it appears that PCT the body’s iron repeated phlebotomies (venesection) should be addressed before hepatitis infection. can be effective in lowering the body’s iron levels. Nearly 0.5 L blood is removed every 1-2 weeks until >> Treatment of HIV infection might also be considered in PCT patients due to the association between hemoglobin and iron levels drop to within normal physithe conditions. ological range. Improvement could take 12-24 weeks. >> Iron chelators – These are drugs that bind to iron Sun Protection – avoidance of the sun is recommended in the body and alter its water solubility to allow its expulsion through the kidneys. Therapy with whenever possible in addition to using sufficient proiron chelators is less effective than phlebotomy tection (opaque sunscreen and appropriate clothing) or anti-malarials in treating PCT cases. Despite this, it may have a role in treating a subsection of when outside. This is because porphyrins are known to affected individuals, e.g. individuals suffering from efficiently absorb radiant energy of very long ultraviolet end stage renal disease require hemodialysis and and visible light wavelengths. are therefore not suitable for phlebotomy. Anti-malaria Treatment – this is generally seen as an option when the patient is not eligible for phlebotomies, e.g. if the patient is anemic. A low dosage regime of chloroquine (125mg) or hydroxychloroquine (100mg) is recommended twice a week to reduce excess hepatic porphyrins. The dosage is decided such that it is not high enough to expel porphyrins too rapidly, transiently

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Porphyria Cutanea Tarda Genetics Porphyria cutanea tarda (PCT) is a group of disorders The genetic PCT foundation is heterogeneous with more which are characterized by a deficiency in enzymatic than 50 UROD gene mutations have been associated action of uroporphyrinogen decarboxylase (UROD). with PCT. These mutations reduce the movement of uroporphyrinogen decarboxylase by approximately This enzyme is the fifth in the heme biosynthetic 50% throughout the body. As a result, hemoglobin pathway thus PCT is associated with a problem in precursors (porphyrins) build up to toxic levels in organs synthesizing heme. The simultaneous accumulation and tissues, starting in the liver. When combined with of porphyrins and porphyrin precursors of heme may environmental (non-genetic) factors such as alcohol then cause illness. use, smoking, certain hormones, excess iron, and Symptoms of PCT manifest as cutaneous abnormalities hepatitis C or HIV infections, an individual becomes such as dermal weakness with pigmentation, erosions, severely predisposed to the familial form of PCT. blister formation, early skin aging, and hypertrichosis. PCT can be categorized as sporadic/acquired (type 1) or familial (type 2). Of these, the acquired form known as sporadic PCT is far more common – in fact, as many as approximately 80% of PCT cases are classed as sporadic. These sporadic cases generally begin in midadult life following exposure to particular chemicals now known to increase the production of heme precursors (porphyrins) in the liver. These factors which trigger the acquired disorder include the following:

Interestingly, whilst this genetic (autosomal dominant) deficiency of UROD contributes to development of the disorder, the majority of people with the inherited enzyme deficiency remain latent and never experience or exhibit symptoms. Furthering the genetic aspect of PCT, modifications in the hemochromatosis gene may be involved in the aetiology – some patient populations with PCT carry the hemochromatosis-related HFE mutation, C282Y,

in either heterozygous or homozygous form. It has In the familial form of PCT, individuals present with an even become possible that the occurrence of PCT abnormality in a specific gene i.e. uroporphyrinogen can be an important cutaneous marker for patients decarboxylase (UROD) for which the encoding gene with mutations of the HFE gene. has been mapped to chromosome 1p34. Mutations Thus, it seems reasonable to consider the analysis in this gene are what discriminate familial PCT from of the HFE gene in those with PCT as a potential aid sporadic cases. inthe early diagnosis of hereditary hemochromatosis. In actual fact, mutations in this UROD gene are known to be responsible for two forms of porphyria - PCT and hepatoerythropoietic porphyria. The former is the most common porphyria and is generally characterized by milder symptoms than the latter.

This might not be a surprise as there is already an established association between iron overload due to HFE mutations and PCT such that it is a known triggering factor of PCT independent of other triggering factors.

The risk of developing PCT is increased due to the mutation of one copy of the UROD gene in each cell. On the other hand, if the mutation is in both copies of the UROD gene in each cell then the result would be hepatoerythropoietic porphyria.

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Porphyria Cutanea Tarda Diagnosis Diagnosis of porphyria cutanea tarda (PCT) relies Serum Ferritin and Liver Biopsy on the identification of characteristic symptoms, a Serum ferritin analysis can be useful in gauging comprehensive patient history, and a thorough clinical whether therapeutic phlebotomy is appropriate due evaluation involving specialized tests. to the known association between iron overload and PCT. The degree of iron accumulation can be both Generally, the tests include: assessed by serum ferritin, and by liver biopsy just as in other conditions associated with iron accumulation Skin Biopsy including hemochromatosis and hepatitis C. Whilst blisters, crusted-over lesions, hyperpigmentation, and skin fragility on sun-exposed areas are all characteristic findings associated with PCT, these are Viral Study not necessarily confirmation of the disorder. Thus, a All patients with PCT should be tested for hepatitis skin biopsy will show features of sub-epidermal blister C and HIV infections as these are factors known to precipitate the development of PCT. In fact, HCV apformation, but is not diagnostic for PCT. pears to be such a strong trigger that in HCV-infected individuals PCT is developed at an earlier age than in Urine or Plasma Porphyrin Test uninfected persons with PCT. Elevation in both urine and plasma porphyrin is expected in PCT patients. The specific pattern of Whilst not definitive, there are also reports that show porphyrin levels allows PCT to be distinguished from involvement of HIV infection in PCT patients through other porphyrias such as variegate porphyria and viral activity that impairs the hepatic cytochrome oxierythropoietic protoporphyria. dase system, thus hampering porphyrin metabolism. Testing for HIV might therefore be a wise decision. For example, a 24 hour urine porphyrin profile of a PCT patient would show that most of the excreted porphyrins are uroporphyrin and a 7-carboxyl porphyrin. With this Genetic Testing aid, testing plasma porphyrin levels is considered more Familial PCT can be diagnosed by a reduced amount of accurate because urine porphyrins are more subject the UROD enzyme in erythrocytes. Molecular genetic testing for familial PCT is available and recommended to fluctuations induced by other conditions. if the diagnosis has been confirmed in the patient or a Additionally, urinary examination with a Wood’s lamp family member by porphyrin analysis and/or enzyme can be used to show a coral pink fluorescence due assay of UROD activity. to the excessive porphyrin concentration. This occurs because the porphyrins absorb black light and re-emit Mutations in the hereditary hemochromatosis gene (HFE) should be tested for because these may partly it at a longer wavelength, i.e. visible pink light. explain excess iron accumulation known to trigger A direct fluorometric assay of plasma is also a useful PCT. For example, Cys282Tyr in the hemochromatosis test. In PCT, the plasma porphyrins are elevated with gene is as a susceptibility factor for both acquired and maximal excitation and emission wavelengths at ~400 familial PCT and those homozygous for this mutation and ~620 nm, respectively. Following this fluorometric with hemochromatosis have up to 60-fold greater risk pattern, tests for levels of porphyrins and porphyrin pre- of developing PCT53 and earlier onset. cursors in urine can be used to confirm the diagnosis. —87—

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Reviewed Articles •

The Cell Cycle – An Overview

Restriction Fragment Length Polymorphism (RFLP Technique)

DNA Translation

Primary and Secondary Antibodies – What’s the Difference?

Structure and Function of the Cell Nucleus

What are Organelles?

The Endoplasmic Reticulum and Golgi body – What’s the Difference?

What is Lab-on-a-Chip?

Health Applications of Lab-on-a-Chip

What is Dumping Syndrome

Dumping Syndrome Symptoms and Causes

Dumping Syndrome Diagnosis

Dumping Syndrome Treatment

Flexible Sigmoidoscopy: What to Expect

What is Flexible Sigmoidoscopy?

Affinity Chromatography - How Does it Work?

How Does Ion Exchange Chromatography Work?

Size Exclusion Chromatography (Gel Filtration)

Hemolytic Uremic Syndrome Epidemiology

Endoscopic Retrograde Cholangiopancreatography (ERCP) Procedure

ERCP (Endoscopic Retrograde Cholangiopancreatography) Overview

High Performance Liquid Chromatography (HPLC)

LC-NMR Applications

Hemolytic Uremic Syndrome in Children

Henoch-Schönlein Purpura - IgA Vasculitis —88—

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How is Henoch-Schönlein Purpura Diagnosed?

Henoch-Schönlein Purpura: Treatment and Follow-Up

ADHD Pathophysiology

ADHD Epidemiology

ADHD Management

Vitreous Detachment

What Causes Hemolytic Uremic Syndrome in Children?

Alpha-gal Allergy (Meat Allergy)

Signs and Symptoms of Retinoblastoma

Retinoblastoma Screening

Types of Refractive Disorder

Allergies in Children

Congenital Birth Defects

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Afsaneh khetrapal - Portfolio  

- A compilation of some of my work -

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