Anakinra-Associated Systemic Amyloidosis.

OBJECTIVE: To describe a 41-year-old woman with a history of neonatal onset multisystem inflammatory disease, on treatment with daily subcutaneous injections of 600 mg of recombinant interleukin-1 receptor antagonist (IL-1Ra) protein, anakinra, since the age of 28, who presented with golf-ball size nodules at the anakinra injection sites, early satiety, new onset nephrotic syndrome in the context of normal markers of systemic inflammation. METHODS: Clinical history and histologic evaluation of biopsies of skin, gastric mucosa, and kidney with Congo-red staining and proteomic evaluation of microdissected Congo red-positive amyloid deposits by liquid chromatography-tandem mass spectrometry. RESULTS: The skin, stomach, and kidney biopsies all showed the presence of Congo red-positive amyloid deposits. Mass spectrometry-based proteomics demonstrated that the amyloid deposits in all sites were of AIL1RAP (IL-1Ra protein)-type. These were characterized by high spectral counts of the amyloid signature proteins (apolipoprotein AIV, apolipoprotein E, and serum amyloid P-component) and the amyloidogenic IL-1Ra protein, which were present in Congo red-positive areas and absent in Congo red-negative areas. The amino acid sequence identified by mass spectrometry confirmed that the amyloid precursor protein was recombinant IL-1Ra (anakinra) and not endogenous wild-type IL-1Ra. CONCLUSION: This is the first report of iatrogenic systemic amyloidosis due to an injectable protein drug, which was caused by recombinant IL1Ra (anakinra).

Examining the Effect of Increased Aerobic Exercise in Moderately Fit Adults on Psychological State and Cognitive Function.

Regular physical exercise can decrease the risk for obesity, diabetes, and cardiovascular disease, increase life expectancy, and promote psychological health and neurocognitive functioning. Cross-sectional studies show that cardiorespiratory fitness level (VO2 max) is associated with enhanced brain health, including improved mood state and heightened cognitive performance. Interventional studies are consistent with these cross-sectional studies, but most have focused on low-fit populations. Few such studies have asked if increasing levels of physical activity in moderately fit people can significantly enhance mood, motivation, and cognition. Therefore, the current study investigated the effects of increasing aerobic exercise in moderately fit individuals on psychological state and cognitive performance. We randomly assigned moderately fit healthy adults, 25-59 years of age, who were engaged in one or two aerobic exercise sessions per week to either maintain their exercise regimen (n = 41) or increase their exercise regimen (i.e., 4-7 aerobic workouts per week; n = 39) for a duration of 3 months. Both before and after the intervention, we assessed aerobic capacity using a modified cardiorespiratory fitness test, and hippocampal functioning via various neuropsychological assessments including a spatial navigation task and the Mnemonic Similarity Task as well as self-reported measures including the Positive and Negative Affect Scale, Beck Anxiety Inventory, State-Trait Anxiety Inventory, Perceived Stress Scale, Rumination Scale, Eating Disorders Examination, Eating Attitudes Test, Body Attitudes Test, and Behavioral Regulation of Exercise Questionnaire. Consistent with our initial working hypotheses, we found that increasing exercise significantly decreased measures of negative affect, including fear, sadness, guilt, and hostility, as well as improved body image. Further, we found that the total number of workouts was significantly associated with improved spatial navigation abilities and body image as well as reduced anxiety, general negative affect, fear, sadness, hostility, rumination, and disordered eating. In addition, increases in fitness levels were significantly associated with improved episodic memory and exercise motivation as well as decreased stress and disordered eating. Our findings are some of the first to indicate that in middle-aged moderately-fit adults, continuing to increase exercise levels in an already ongoing fitness regimen is associated with additional benefits for both psychological and cognitive health.

A novel model of obesity prediction: Neurobehaviors as targets for treatment.

Obesity is a worldwide epidemic that is on the rise, with approximately 30% of the world population classified as either overweight or obese. The United States has some of the highest rates of obesity, and in most countries in the world, obesity now poses more of a serious health concern than malnutrition. Obesity is a chronic, relapsing disorder that is both preventable and treatable; however, traditional interventions that target eating less and exercising more have low success rates, especially in the long term. Therefore, identifying the neurobehaviors that predict obesity is important to help identify targets to decrease BMI and improve obesity outcomes. Using the Competing Neurobehavioral Decisions System (CNDS) Theory, we hypothesized that individuals with obesity compared to individuals without obesity would display neurobehaviors marked by a hyperactive impulsive system and a hypoactive executive system. To test this hypothesis, we collected data from a battery of self-reported measures and neurocognitive assessments through Amazon Mechanical Turk from n = 178 obese (BMI ≥ 30) and n = 198 nonobese controls who were weight stable for the past 3 months. We found that compared to the nonobese control group, individuals with obesity showed heightened delay discounting (a marker of CNDS imbalance), impaired motivation, poor self-image, decreased affective state, and impaired executive function. Using a Bayesian network approach, we established a neurobehavioral model that predicts obesity with 64.4% accuracy and indicates an imbalance between impulsive and executive neural systems. Results from our study suggest that interventions targeting neurobehaviors may be integral to help improve obesity outcomes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).