Discovery

PRELIMINARY RESEARCH BY HMS scientists at Massachusetts General Hospital indicates that societal and lifestyle disruptions in people uninfected by SARS-CoV-2 may precipitate brain inflammation. When researchers compared brain and blood levels of various inflammatory markers in samples from 57 healthy participants taken before stay-at-home restrictions to those taken from 15 participants after restrictions, they found higher levels of the markers in post-restrictions participants. Participants who reported greater symptoms related to mood and mental and physical fatigue had higher brain levels of one of the markers. The levels of the marker correlated with the expression of several genes involved in immune function.

Brusaferri L et al., Brain, Behavior, and Immunity, February 2022

A RECENT STUDY INVOLVING FORMER National Football League players is adding a new dimension to research investigating whether the trauma resulting from abuse and neglect early in life carries into adulthood.

The study found that although former professional football players experienced childhood adversity at rates similar to the general population, those reporting a childhood history of abuse and neglect were more likely to screen positive for dementia and were placed at significantly greater risk for pain and depression in their later years.

Former NFL players who reported having four or more adverse experiences in childhood were 60 percent more likely to suffer concussion symptoms during their football career, 48 percent more likely to screen positive for dementia, and at greater risk for cognitive problems in later life compared with players who did not report these experiences.

Because instances of childhood adversity were strongly associated with concussion symptoms, the researchers recommend that adverse childhood experiences be investigated in pro football players and other groups as a possible indicator of high concussion risk.

The conclusions are drawn from data gathered for the Football Players Health Study at Harvard University, a study based on surveys of 1,755 former NFL players ages 28 to 92 administered by researchers at HMS and the Harvard T.H.Chan School of Public Health.

Roberts AL et al., JAMA Network Open, March 2022

NEARLY TWO MILLION PEOPLE in this country have type 1 diabetes, a disease marked by the body’s inability to produce enough insulin to control blood sugar levels. The high blood

Cerebral palsy may be linked to underlying genetic factors in some patients

Although cerebral palsy has widely been viewed as resulting from perinatal oxygen deprivation or another birth-related factor such as prematurity, a study by HMS researchers at Boston Children’s Hospital has shown that it may be the result of an underlying genetic condition in up to 25 percent of patients with the disorder. The findings could help doctors make more specific diagnoses and develop more targeted treatment plans for some patients.

Chopra M et al., Annals of Clinical and Translational Neurology, January 2022 Fu J, Shinjo T et al., Journal of Clinical Investigation, March 2022

sugar levels that can result can lead to hyperglycemia and, among other adverse conditions, an increased risk of kidney disease.

In studies involving mouse models, HMS scientists at Joslin Diabetes Center recently shed new light on how hyperglycemia contributes to kidney disease and uncovered a potential therapeutic target. Their work relied on information gleaned from the Medalist study, Joslin’s longrunning observational study of more than 1,000 people with type 1 diabetes who have successfully managed the disease for 50 years or more. Scientists have found that disease outcomes differ for members of the Medalist cohort compared with other people with type 1 diabetes. For example, as many as 30 percent of people with diabetes experience kidney disease, but just 13 percent of Medalists do.

Prior studies of this cohort showed that individuals who were protected from diabetic kidney disease had higher levels of glucose-metabolizing enzymes than people with diabetes who developed diabetic kidney disease.

To understand the role that one of these enzymes, PKM2, may have in protecting against kidney disease, the researchers used a mouse model genetically engineered to overproduce the enzyme, then compared the kidneys of the engineered mice to those of nonengineered mice with and without induced diabetes. Their findings showed that the overexpression of PKM2 prevented multiple pathological changes to the cells of the kidney’s filtration system frequently seen in diabetes, preserved cell function, and prevented disease progression.

The results suggest that blood PKM2 levels could serve as a biomarker for the progression of diabetic kidney disease in patients with diabetes.

DELIRIUM IS A SERIOUS CHANGE in brain function that affects up to 64 percent of older medical patients and up to 50 percent of older surgical patients. It can appear as sudden confusion, agitation, memory loss, or hallucinations and delusions and is linked to longer hospital stays and increased risks of dementia and death.

Although more than thirty instruments can identify delirium in patients, few assess its severity. Now, HMS scientists at Beth Israel Deaconess Medical Center and Hebrew SeniorLife have developed a measure of delirium severity that could improve patientcentered care for delirium. The tool, the DEL-S delirium severity score, provides severity measures significantly associated with clinically relevant outcomes.

Vasunilashorn SM et al., JAMA Network Open, April 2022