A 360 Degree View of the Jefferson Health Mentors Program: Students, Administrator and Faculty Weigh in on Seven Years of Interprofessional Education

Learning Objectives •List three strategies for successful implementation of an Interprofessional Education (IPE) curriculum •Develop a roadmap for starting, expanding or evaluating an existing IPE program •Discuss challenges and shared lessons learned with CQI in implementing IPE with a panel hosted by HMP students, administrator and facult

A discursive review of the textual use of ‘trapped’ in environmental migration studies: The conceptual birth and troubled teenage years of trapped populations

First mooted in 2011, the concept of Trapped Populations referring to people unable to move from environmentally high-risk areas broadened the study of human responses to environmental change. While a seemingly straightforward concept, the underlying discourses around the reasons for being ‘trapped’, and the language describing the concept have profound influences on the way in which policy and practice approaches the needs of populations at risk from environmental stresses and shocks. In this article, we apply a Critical Discourse Analysis to the academic literature on the subject to reveal some of the assumptions implicit within discussing ‘trapped’ populations. The analysis reveals a dominant school of thought that assisted migration, relocation, and resettlement in the face of climate change are potentially effective adaptation strategies along a gradient of migrant agency and governance

Atrial arrhythmogenicity in aged Scn5a+/∆KPQ mice modeling long QT type 3 syndrome and its relationship to Na+ channel expression and cardiac conduction

Recent studies have reported that human mutations in Nav1.5 predispose to early age onset atrial arrhythmia. The present experiments accordingly assess atrial arrhythmogenicity in aging Scn5a+/∆KPQ mice modeling long QT3 syndrome in relationship to cardiac Na+ channel, Nav1.5, expression. Atrial electrophysiological properties in isolated Langendorff-perfused hearts from 3- and 12-month-old wild type (WT), and Scn5a+/∆KPQ mice were assessed using programmed electrical stimulation and their Nav1.5 expression assessed by Western blot. Cardiac conduction properties were assessed electrocardiographically in intact anesthetized animals. Monophasic action potential recordings demonstrated increased atrial arrhythmogenicity specifically in aged Scn5a+/ΔKPQ hearts. These showed greater action potential duration/refractory period ratios but lower atrial Nav1.5 expression levels than aged WT mice. Atrial Nav1.5 levels were higher in young Scn5a+/ΔKPQ than young WT. These levels increased with age in WT but not Scn5a+/ΔKPQ. Both young and aged Scn5a+/ΔKPQ mice showed lower heart rates and longer PR intervals than their WT counterparts. Young Scn5a+/ΔKPQ mice showed longer QT and QTc intervals than young WT. Aged Scn5a+/ΔKPQ showed longer QRS durations than aged WT. PR intervals were prolonged and QT intervals were shortened in young relative to aged WT. In contrast, ECG parameters were similar between young and aged Scn5a+/ΔKPQ. Aged murine Scn5a+/ΔKPQ hearts thus exhibit an increased atrial arrhythmogenicity. The differing Nav1.5 expression and electrocardiographic indicators of slowed cardiac conduction between Scn5a+/ΔKPQ and WT, which show further variations associated with aging, may contribute toward atrial arrhythmia in aged Scn5a+/ΔKPQ hearts

FACT Prevents the Accumulation of Free Histones Evicted from Transcribed Chromatin and a Subsequent Cell Cycle Delay in G1

The FACT complex participates in chromatin assembly and disassembly during transcription elongation. The yeast mutants affected in the SPT16 gene, which encodes one of the FACT subunits, alter the expression of G1 cyclins and exhibit defects in the G1/S transition. Here we show that the dysfunction of chromatin reassembly factors, like FACT or Spt6, down-regulates the expression of the gene encoding the cyclin that modulates the G1 length (CLN3) in START by specifically triggering the repression of its promoter. The G1 delay undergone by spt16 mutants is not mediated by the DNA–damage checkpoint, although the mutation of RAD53, which is otherwise involved in histone degradation, enhances the cell-cycle defects of spt16-197. We reveal how FACT dysfunction triggers an accumulation of free histones evicted from transcribed chromatin. This accumulation is enhanced in a rad53 background and leads to a delay in G1. Consistently, we show that the overexpression of histones in wild-type cells down-regulates CLN3 in START and causes a delay in G1. Our work shows that chromatin reassembly factors are essential players in controlling the free histones potentially released from transcribed chromatin and describes a new cell cycle phenomenon that allows cells to respond to excess histones before starting DNA replication

Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain

Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of ch

High prevalence of SARS-CoV-2 antibodies in care homes affected by COVID-19: Prospective cohort study, England.

Background: We investigated six London care homes experiencing a COVID-19 outbreak and found high rates of SARS-CoV-2 infection among residents and staff. Here we report follow-up investigations including antibody testing in the same care homes five weeks later. Methods: Residents and staff in the initial investigation had a repeat nasal swab for SARS-CoV-2 RT-PCR and a blood test for SARS CoV-2 antibodies using ELISA based on SARS-CoV-2 native viral antigens derived from infected cells and virus neutralisation. Findings: Of the 518 residents and staff in the initial investigation, 186/241 (77.2%) surviving residents and 208/254 (81.9%) staff underwent serological testing. Almost all SARS-CoV-2 RT-PCR positive residents and staff were seropositive five weeks later, whether symptomatic (residents 35/35, 100%; staff, 22/22, 100%) or asymptomatic (residents 32/33, 97.0%; staff 21/22, 95.5%). Symptomatic but SARS-CoV-2 RT-PCR negative residents and staff also had high seropositivity rates (residents 23/27, 85.2%; staff 18/21, 85.7%), as did asymptomatic RT-PCR negative individuals (residents 61/91, 67.0%; staff 95/143, 66.4%). Neutralising antibody was detected in 118/132 (89.4%) seropositive individuals and was not associated with age or symptoms. Ten residents (10/79 re-tested, 12.7%) remained RT-PCR positive but with higher RT-PCR cycle threshold values; 7/10 had serological testing and all were seropositive. New infections were detected in three residents and one staff. Interpretation: RT-PCR provides a point prevalence of SARS-CoV-2 infection but significantly underestimates total exposure in outbreak settings. In care homes experiencing large COVID-19 outbreaks, most residents and staff had neutralising SARS-CoV-2 antibodies, which was not associated with age or symptoms. Funding: PHE

Investigation of SARS-CoV-2 outbreaks in six care homes in London, April 2020.

BACKGROUND: Care homes are experiencing large outbreaks of COVID-19 associated with high case-fatality rates. We conducted detailed investigations in six London care homes reporting suspected COVID-19 outbreaks during April 2020. METHODS: Residents and staff had nasal swabs for SARS CoV-2 testing using RT-PCR and were followed-up for 14 days. They were categorized as symptomatic, post-symptomatic or pre-symptomatic if they had symptoms at the time of testing, in the two weeks before or two weeks after testing, respectively, or asymptomatic throughout. Virus isolation and whole genome sequencing (WGS) was also performed. FINDINGS: Across the six care homes, 105/264 (39.8%) residents were SARS CoV-2 positive, including 28 (26.7%) symptomatic, 10 (9.5%) post-symptomatic, 21 (20.0%) pre-symptomatic and 46 (43.8%) who remained asymptomatic. Case-fatality at 14-day follow-up was highest among symptomatic SARS-CoV-2 positive residents (10/28, 35.7%) compared to asymptomatic (2/46, 4.3%), post-symptomatic (2/10, 20.0%) or pre-symptomatic (3/21,14.3%) residents. Among staff, 53/254 (20.9%) were SARS-CoV-2 positive and 26/53 (49.1%) remained asymptomatic. RT-PCR cycle-thresholds and live-virus recovery were similar between symptomatic/asymptomatic residents/staff. Higher RT-PCR cycle threshold values (lower virus load) samples were associated with exponentially decreasing ability to recover infectious virus (P<0.001). WGS identified multiple (up to 9) separate introductions of different SARS-CoV-2 strains into individual care homes. INTERPRETATION: A high prevalence of SARS-CoV-2 positivity was found in care homes residents and staff, half of whom were asymptomatic and potential reservoirs for on-going transmission. A third of symptomatic SARS-CoV-2 residents died within 14 days. Symptom-based screening alone is not sufficient for outbreak control. FUNDING: None