The benefits of undergraduate medical students delivering free preparticipation physical evaluations in collaboration with a K-12 school district.

BACKGROUND: Student-run free clinics are present at many medical schools throughout the United States. While many work with adult homeless or uninsured populations, few work with pediatric populations. We investigated the impact of volunteering at a free preparticipation sports physical clinic on medical students' educational motivation, school engagement, confidence in their clinical skills, connectedness to community, and self-efficacy. METHODS: First and second year undergraduate medical students who volunteered at a preparticipation sports physical clinic were eligible for the study. 30 students participated in the study, some volunteering multiple times, for a total of 55 post-volunteering surveys. Pre- and post-volunteering surveys were administered via REDCap. The surveys were designed using Likert scales and the General Self-Efficacy scale. Paired two tailed t-tests were used to analyze pre- and post-volunteering data. RESULTS: Students had statistically significant increases in their confidence in working with pediatric populations, performing a standard physical exam, working in an interdisciplinary setting, and communicating with patients. They also demonstrated statistically significant increases in their feelings of connectedness to their reason for practicing medicine and to the greater local community. CONCLUSIONS: This research demonstrated measurable increases in motivation and confidence in clinical skills for medical students that participated. This is a valuable experience for medical students and is a model that other medical schools can adopt to help diversify and strengthen their curriculum. In the future, we would like to collect more data to further evaluate the impact of this volunteering on medical students, patients, families, and other community stakeholders.

The role of the shared environment in college attainment: An adoption study.

OBJECTIVE: College attainment is one of the few phenotypes to have substantial variance accounted for by environmental factors shared by reared-together relatives. The shared environment is implicated by the consistently strong parent-to-offspring transmission of college attainment. The mechanisms underlying this relationship remain unclear. We use genetically informative methods with a longitudinal, adoption sample to identify possible environmental mechanisms underlying parent-offspring college transmission. METHOD: Data were drawn from the Sibling Interaction and Behavior Study (SIBS), which includes 409 adoptive and 208 nonadoptive families, consisting of two offspring followed from adolescence into young adulthood and their rearing parents. Four domains of environmental mechanisms were examined: (a) skill enhancement; (b) academic support; (c) material advantage; and (d) supportive family environment. RESULTS: Both shared environmental and genetic factors contributed to the parent-offspring transmission of college attainment. However, highly educated parents did not appear to be increasing their adopted offspring's attainment through skill development. The environmental factors that were associated with increased odds of offspring college attainment were mother's academic expectations and family income. CONCLUSIONS: While complete mediation of the parent-offspring transmission of college attainment was not identified, the results shed light on some of the mechanisms associated with the common environment variance in the college attainment phenotype.

TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy.

Variants in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) were recently found to increase the risk for developing Alzheimer's disease (AD). In the brain, TREM2 is predominately expressed on microglia, and its association with AD adds to increasing evidence implicating a role for the innate immune system in AD initiation and progression. Thus far, studies have found TREM2 is protective in the response to amyloid pathology while variants leading to a loss of TREM2 function impair microglial signaling and are deleterious. However, the potential role of TREM2 in the context of tau pathology has not yet been characterized. In this study, we crossed Trem2+/+ (T2+/+) and Trem2-/- (T2-/-) mice to the PS19 human tau transgenic line (PS) to investigate whether loss of TREM2 function affected tau pathology, the microglial response to tau pathology, or neurodegeneration. Strikingly, by 9 mo of age, T2-/-PS mice exhibited significantly less brain atrophy as quantified by ventricular enlargement and preserved cortical volume in the entorhinal and piriform regions compared with T2+/+PS mice. However, no TREM2-dependent differences were observed for phosphorylated tau staining or insoluble tau levels. Rather, T2-/-PS mice exhibited significantly reduced microgliosis in the hippocampus and piriform cortex compared with T2+/+PS mice. Gene expression analyses and immunostaining revealed microglial activation was significantly attenuated in T2-/-PS mice, and there were lower levels of inflammatory cytokines and astrogliosis. These unexpected findings suggest that impairing microglial TREM2 signaling reduces neuroinflammation and is protective against neurodegeneration in the setting of pure tauopathy.

Performance of a motor task learned on levodopa deteriorates when subsequently practiced off.

Studies in animals and in people with Parkinson's disease (PD) demonstrate complex effects of dopamine on learning motor tasks; its effect on retention of motor learning has received little attention. Recent animal studies demonstrate that practicing a task in the off state, when initially learned in the on state, leads to progressive deterioration in performance. We measured the acquisition and retention of 3 different motor tasks in the presence and absence of levodopa. Twenty individuals with Hoehn and Yahr Stage 1.5 to 3 PD practiced the tasks daily for two 4-day weeks, one half practicing on L-dopa the first week and off the second week. The other half practiced off l-dopa both weeks. The tasks were (1) alternate tapping of 2 keys, (2) moving the body toward 2 targets on a posturography device, and (3) mirror drawing of a star. For the tapping and body movement tests, those who practiced on the first week had a progressive decline in performance with practice during week 2, while subjects off during week 1 maintained or improved. In contrast, for the mirror task, subjects on L-dopa initially had much more difficulty completing the task compared to subjects who practiced off. Both groups improved with practice the first week and had flat performance the second week. These data suggest that performance of speed-accuracy tasks learned in the on state may progressively worsen if subsequently practiced in the off state. In addition, performance, but not learning, of some tasks may be impeded by L-dopa.

Unearthing who and Y at Harewood Cemetery and inference of George Washington's Y-chromosomal haplotype.

An excavation conducted at Harewood Cemetery to identify the unmarked grave of Samuel Washington resulted in the discovery of burials presumably belonging to George Washington's paternal grandnephews and their mother, Lucy Payne. To confirm their identities this study examined Y-chromosomal, mitochondrial, and autosomal DNA from the burials and a living Washington descendant. The burial's Y-STR profile was compared to FamilyTreeDNA's database, which resulted in a one-step difference from the living descendant and an exact match to another Washington. A more complete Y-STR and Y-SNP profile from the descendant was inferred to be the Washington Y profile. Kinship comparisons performed in relation to the descendant, who is a 4th and 5th degree relative of the putative individuals, resulted in >37,000 overlapping autosomal SNPs and strong statistical support with likelihood ratios exceeding one billion. This study highlights the benefits of a multi-marker approach for kinship prediction and DNA-assisted identification of historical remains.

Evaluating the Usefulness of Human DNA Quantification to Predict DNA Profiling Success of Historical Bone Samples.

This study assessed the usefulness of DNA quantification to predict the success of historical samples when analyzing SNPs, mtDNA, and STR targets. Thirty burials from six historical contexts were utilized, ranging in age from 80 to 800 years postmortem. Samples underwent library preparation and hybridization capture with two bait panels (FORCE and mitogenome), and STR typing (autosomal STR and Y-STR). All 30 samples generated small (~80 bp) autosomal DNA target qPCR results, despite mean mappable fragments ranging from 55-125 bp. The qPCR results were positively correlated with DNA profiling success. Samples with human DNA inputs as low as 100 pg resulted in ≥80% FORCE SNPs at 10X coverage. All 30 samples resulted in mitogenome coverage ≥100X despite low human DNA input (as low as 1 pg). With PowerPlex Fusion, ≥30 pg human DNA input resulted in >40% of auSTR loci. At least 59% of Y-STR loci were recovered with Y-target qPCR-based inputs of ≥24 pg. The results also indicate that human DNA quantity is a better predictor of success than the ratio of human to exogenous DNA. Accurate quantification with qPCR is feasible for historical bone samples, allowing for the screening of extracts to predict the success of DNA profiling.

Familial resemblance, citizenship, and counterproductive work behavior: A combined twin, adoption, parent-offspring, and spouse approach.

Given the well-documented importance of counterproductive workplace behavior and organizational citizenship behavior (together nontask performance), it is important to clarify the degree to which these behaviors are attributable to organizational climate versus preexisting individual differences. Such clarification informs where these behaviors stem from, and consequently has practical implications for organizations (e.g., guiding prioritization of selection criteria). We investigated familial resemblance for nontask performance among twins, nontwin and adoptive siblings, parents and offspring, and midlife and late-life couples drawn from two, large-scale studies: the Minnesota Twin Family Study and the Sibling Interaction Behavior Study. Similarity among family members' (e.g., parents-offspring, siblings) engagement in nontask performance was assessed to estimate the degree to which preexisting individual differences (i.e., genetic variability) and the environment (i.e., environmentality) accounted for variation in counterproductive and citizenship behavior. We found that degree of familial resemblance for nontask performance increased with increasing genetic relationship. Nonetheless, genetically identical individuals correlated only moderately in their workplace behavior (r = .29-.40), highlighting the importance of environmental differences. Notably, family members were more similar in their counterproductive than citizenship behavior, suggesting citizenship behavior is comparatively more environmentally influenced. Spouse/partner similarity for nontask behavior was modest and did not vary between midlife and late-life couples, suggesting spousal influence on nontask performance is limited. These findings offer insight to organizations regarding the degree of nature (individual differences) and nurture (including organizational factors) influences on nontask performance, which has implications for the selection of interventions (e.g., relative value of applicant selection or incumbent interventions). (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Stroke Incidence and Outcome Disparity in Rural Regions of Southern West Virginia.

INTRODUCTION: West Virginia has the highest incidence of obesity, smoking, and diabetes within the United States, placing its population at higher risk of stroke. In addition to these endemic risk factors, Appalachia faces various socioeconomic and health care access challenges that could negatively impact stroke incidence and outcomes. At present, there are limited data regarding geographic variables on stroke outcomes in rural Appalachia. We set out to quantify Appalachian geographic patterns of stroke incidence and outcomes. METHODS: This is a retrospective analysis of all patients hospitalized with a diagnosis of stroke in West Virginia's largest tertiary hospital. During the study (2000-2018), 14,488 patients were analyzed, with an emphasis on those who died from stroke (n = 1022). We first used institutional ICD-9/10 data alongside demographics information and chart reviews to evaluate disease patterns while also exploring emerging hot spot pattern changes over time; we then exploited an emerging time series analysis using temporal trends to assess differing instances of stroke occurrence regionally with hot spots defined as higher than expected incidences of stroke and stroke death. RESULTS: Data analysis revealed several hot spots of increasing stroke and mortality rates, many of which achieved statistically significant variance compared to expected norms (P = 0.001). Moreover, this study revealed high-risk zones in rural West Virginia wherein the incidence and mortality rates of stroke are suggestively higher and less resistance to economic change than urban centers. CONCLUSIONS: Stroke incidence and mortality were found to be higher than expected in many areas of rural West Virginia. The higher stroke risk populations correlate with area that may be impacted by socioeconomic factors and limited access to primary care. These high-risk areas may therefore benefit from investments in infrastructure, patient education, and unrestricted primary care.

A Unique Case Of Tenofovir-Induced DRESS Syndrome Associated With Raynaud's Of The Tongue.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a potentially fatal severe adverse reaction to medications. Numerous drugs have been implicated, with carbamazepine and allopurinol being the most common. Tenofovir-induced DRESS is extremely rare. We report a case of a 65-year-old male patient with a diffuse exfoliative maculopapular rash across his entire body of five weeks of duration. The patient also had icteric sclera, abnormal liver enzymes and Raynaud's of the tongue, nose and the left fifth finger. After discontinuation of tenofovir, the case resolved over a span of ten days. A high index of suspicion is crucial along with the prompt withdrawal of the offending medication for a good outcome.

ApoE facilitates the microglial response to amyloid plaque pathology.

One of the hallmarks of Alzheimer's disease is the presence of extracellular diffuse and fibrillar plaques predominantly consisting of the amyloid-ß (Aß) peptide. Apolipoprotein E (ApoE) influences the deposition of amyloid pathology through affecting the clearance and aggregation of monomeric Aß in the brain. In addition to influencing Aß metabolism, increasing evidence suggests that apoE influences microglial function in neurodegenerative diseases. Here, we characterize the impact that apoE has on amyloid pathology and the innate immune response in APPPS1ΔE9 and APPPS1-21 transgenic mice. We report that Apoe deficiency reduced fibrillar plaque deposition, consistent with previous studies. However, fibrillar plaques in Apoe-deficient mice exhibited a striking reduction in plaque compaction. Hyperspectral fluorescent imaging using luminescent conjugated oligothiophenes identified distinct Aß morphotypes in Apoe-deficient mice. We also observed a significant reduction in fibrillar plaque-associated microgliosis and activated microglial gene expression in Apoe-deficient mice, along with significant increases in dystrophic neurites around fibrillar plaques. Our results suggest that apoE is critical in stimulating the innate immune response to amyloid pathology.

The long-duration response to levodopa: phenomenology, potential mechanisms and clinical implications.

The antiparkinsonian response to levodopa is characterized by an immediate motor improvement lasting hours and a more sustained response lasting days. These two responses have been referred to as the short-duration response (SDR) and the long-duration response (LDR). The LDR represents a substantial component of the clinical effect of levodopa and has been clinically recognized for several decades, but it remains poorly understood. This review will focus on the LDR phenomenology and theories about its origin, with the goal of promoting inquiry into this important but as yet poorly understood aspect of levodopa therapy for PD.