Creative group performances to assess core competencies in a first-year patient-centered medicine course

Introduction: A novel assessment of systems-based practice and practice-based learning and improvement learning objectives, implemented in a first-year patient-centered medicine course, is qualitatively described. Methods: Student learning communities were asked to creatively demonstrate a problem and solution for health care delivery. Skits, filmed performances, plays, and documentaries were chosen by the students. Video recordings were reviewed for themes and the presence of course competencies. Results: All performances demonstrated not only the index competencies of team work and facilitation of the learning of others, but many other core objectives of the course. The assignment was rated positively both by the faculty and the students, and has been added to the assessment modalities of the course

Protein Recognition by Short Peptide Reversible Inhibitors of the Chromatin-Modifying LSD1/CoREST Lysine Demethylase.

The combinatorial assembly of protein complexes is at the heart of chromatin biology. Lysine demethylase LSD1(KDM1A)/CoREST beautifully exemplifies this concept. The active site of the enzyme tightly associates to the N-terminal domain of transcription factors of the SNAIL1 family, which therefore can competitively inhibit the binding of the N-terminal tail of the histone substrate. Our enzymatic, crystallographic, spectroscopic, and computational studies reveal that LSD1/CoREST can bind to a hexapeptide derived from the SNAIL sequence through recognition of a positively charged α-helical turn that forms upon binding to the enzyme. Variations in sequence and length of this six amino acid ligand modulate affinities enabling the same binding site to differentially interact with proteins that exert distinct biological functions. The discovered short peptide inhibitors exhibit antiproliferative activities and lay the foundation for the development of peptidomimetic small molecule inhibitors of LSD1

Predictors of progression free survival, overall survival and early cessation of chemotherapy in women with potentially platinum sensitive (PPS) recurrent ovarian cancer (ROC) starting third or subsequent line(> 3) chemotherapy – the GCIG Symptom Benefit Study (SBS)

Background: Potentially platinum sensitive recurrent ovarian cancer (PPS ROC) is defined by a platinum-free interval of >6 months, and usually treated with platinum-based chemotherapy with variable response and benefit in women who have had 3 or more lines of chemotherapy(≥3). We identified baseline characteristics (health-related quality of life[HRQL] and clinicopathological factors), associated with PFS, OS and early progression (within 8 weeks). The goal is to improve patient selection for chemotherapy based on a nomogram predicting PFS. Methods: HRQL was assessed with EORTC QLQ-C30/QLQ-OV28. Associations with PFS and OS were assessed with Cox proportional hazards regression. Variables significant in univariable analysis were included in multivariable analyses using backward elimination to select those significant. Associations with stopping chemotherapy early were assessed with logistic regression. Results: 378 women were enrolled, with median(m)OS and PFS of 16.6 months and 5.3 months, respectively. The majority had ECOGPS 0–1. Chemotherapy was stopped early in 45/378 participants (12%); with mOS 3.4 months (95% CI: 1.7–7.2). Physical function(PF), role function(RF), cognitive function(CF), social function(SF), Global Health Status(GHS) and abdominal/GI symptoms(AGIS) were significant univariable predictors of PFS(p < 0.030). SF remained significant after adjusting for clinicopathological factors; p = 0.03. PF, RF, CF, SF, GHS and AGIS were significant univariable predictors of OS (p < 0.007); PF, RF, SF and GHS remained significant predictors of OS in multivariable models; p < 0.007. Poor baseline PF and GHS were significant univariable predictors of stopping chemotherapy early (p < 0.007) but neither remained significant after adjusting for clinicopathological factors. Conclusion: Baseline HRQL is simple to measure, is predictive of PFS and OS and when used in conjunction with clinicopathological prognostic factors, can assist with clinical decision making and treatment recommendations for women with PPSROC≥3

Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans.

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome-wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European-Americans (EA; 2927 cases) and 3132 African-Americans (AA: 1315 cases) participating in the family-based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome-wide significant (GWS; P &lt; 5E-08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion-deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans-ancestral meta-analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward-related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non-European samples with distinct patterns of substance use may lead to the identification of novel ancestry-specific genetic markers of risk

Comparative assessment of multiple COVID-19 serological technologies supports continued evaluation of point-of-care lateral flow assays in hospital and community healthcare settings

There is a clear requirement for an accurate SARS-CoV-2 antibody test, both as a complement to existing diagnostic capabilities and for determining community seroprevalence. We therefore evaluated the performance of a variety of antibody testing technologies and their potential use as diagnostic tools. Highly specific in-house ELISAs were developed for the detection of anti-spike (S), -receptor binding domain (RBD) and -nucleocapsid (N) antibodies and used for the cross-comparison of ten commercial serological assays-a chemiluminescence-based platform, two ELISAs and seven colloidal gold lateral flow immunoassays (LFIAs)-on an identical panel of 110 SARS-CoV-2-positive samples and 50 pre-pandemic negatives. There was a wide variation in the performance of the different platforms, with specificity ranging from 82% to 100%, and overall sensitivity from 60.9% to 87.3%. However, the head-to-head comparison of multiple sero-diagnostic assays on identical sample sets revealed that performance is highly dependent on the time of sampling, with sensitivities of over 95% seen in several tests when assessing samples from more than 20 days post onset of symptoms. Furthermore, these analyses identified clear outlying samples that were negative in all tests, but were later shown to be from individuals with mildest disease presentation. Rigorous comparison of antibody testing platforms will inform the deployment of point-of-care technologies in healthcare settings and their use in the monitoring of SARS-CoV-2 infections

Methylation and Loss of Secreted Frizzled-Related Protein 3 Enhances Melanoma Cell Migration and Invasion

Wnt signaling is important in development and can also contribute to the initiation and progression of cancer. The Secreted Frizzled Related Proteins (SFRPs) constitute a family of Wnt modulators, crucial for controlling Wnt signaling. Here we investigate the expression and role of SFRP3 in melanoma

Time dependent ethnic convergence in colorectal cancer survival in hawaii

BACKGROUND: Although colorectal cancer death rates have been declining, this trend is not consistent across all ethnic groups. Biological, environmental, behavioral and socioeconomic explanations exist, but the reason for this discrepancy remains inconclusive. We examined the hypothesis that improved cancer screening across all ethnic groups will reduce ethnic differences in colorectal cancer survival. METHODS: Through the Hawaii Tumor Registry 16,424 patients diagnosed with colorectal cancer were identified during the years 1960–2000. Cox regression analyses were performed for each of three cohorts stratified by ethnicity (Caucasian, Japanese, Hawaiian, Filipino, and Chinese). The models included stage of diagnosis, year of diagnosis, age, and sex as predictors of survival. RESULTS: Mortality rates improved significantly for all ethnic groups. Moreover, with the exception of Hawaiians, rates for all ethnic groups converged over time. Persistently lower survival for Hawaiians appeared linked with more cancer treatment. CONCLUSION: Ethnic disparities in colorectal cancer mortality rates appear primarily the result of differential utilization of health care. If modern screening procedures can be provided equally to all ethnic groups, ethnic outcome differences can be virtually eliminated

International Association of Dental Traumatology guidelines for the management of traumatic dental injuries: 2. Avulsion of permanent teeth

Avulsion of permanent teeth is one of the most serious dental injuries. Prompt and correct emergency management is essential for attaining the best outcome after this injury. The International Association of Dental Traumatology (IADT) has developed these Guidelines as a consensus statement after a comprehensive review of the dental literature and working group discussions. It represents the current best evidence and practice based on that literature search and expert opinions. Experienced researchers and clinicians from various specialties and the general dentistry community were included in the working group. In cases where the published data did not appear conclusive, recommendations were based on consensus opinions or majority decisions of the working group. They were then reviewed and approved by the members of the IADT Board of Directors. The purpose of these Guidelines is to provide clinicians with the most widely accepted and scientifically plausible approaches for the immediate or urgent care of avulsed permanent teeth. The IADT does not, and cannot, guarantee favorable outcomes from adherence to the Guidelines. However, the IADT believes that their application can maximize the probability of favorable outcomes

Development of Genomic Resources for Pacific Herring through Targeted Transcriptome Pyrosequencing

Pacific herring (Clupea pallasii) support commercially and culturally important fisheries but have experienced significant additional pressure from a variety of anthropogenic and environmental sources. In order to provide genomic resources to facilitate organismal and population level research, high-throughput pyrosequencing (Roche 454) was carried out on transcriptome libraries from liver and testes samples taken in Prince William Sound, the Bering Sea, and the Gulf of Alaska. Over 40,000 contigs were identified with an average length of 728 bp. We describe an annotated transcriptome as well as a workflow for single nucleotide polymorphism (SNP) discovery and validation. A subset of 96 candidate SNPs chosen from 10,933 potential SNPs, were tested using a combination of Sanger sequencing and high-resolution melt-curve analysis. Five SNPs supported between-ocean-basin differentiation, while one SNP associated with immune function provided high differentiation between Prince William Sound and Kodiak Island within the Gulf of Alaska. These genomic resources provide a basis for environmental physiology studies and opportunities for marker development and subsequent population structure analysis