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BACKGROUND Victims of human trafficking (HT) are predisposed to numerous health concerns. Many encounter health care practitioners during captivity, but awareness and knowledge among front-line physicians is low. Limited data exist on attempts to address this within residency training programmes. Formal curriculum time in residency is limited and online modules may be a useful educational option. METHODS Residents in family medicine, emergency medicine and general paediatrics at the University of Alberta were invited to participate. They completed short surveys to assess knowledge both before and after completing an online learning module either individually (n = 15) or in a facilitated session (n = 17). Baseline and post-intervention changes in self-reported and tested knowledge were assessed. RESULTS Thirty-two residents completed the pre-intervention survey: only 6% self-identified as somewhat knowledgeable on HT and 16% knew the red flags used to identify victims. Eighty-one percent wanted this topic incorporated into residency training, but only 6% and 25% had received education previously in residency or medical school, respectively. Thirteen percent were comfortable supporting victims, and 6% reported knowing how to provide support. Twenty residents completed the post-intervention survey, with improvements in both self-reported (p

New heterocycle compound 2-(4-fluorophenyl)-5-(5-iodo-2-methylbenzyl)thiophene (1), designed using 5-iodo-2-methylbenzoic acid (2) as the starting material is successfully obtained via the multiple synthesis route and finally characterized by IR, 1H NMR, and single crystal X-ray crystallography. In addition, the in vitro anticancer activity of compound 1 on three human lung cancer cells (H20, H2227, and H69) is further determined, which suggests that compound 1 may be a potential anticancer agent.

Marine actinobacteria particularly from marine environments are believed to be inexhaustible sources of biologically active molecules for biomedical and industrial applications. We isolated 126 strains of marine actinomycetes from marine invertebrates such as corals, sponges and gastropod molluscs from Daya Bay and Nansha Islands. The chemical diversity of the metabolites from the isolated strains was evaluated using HPLC-UV fingerprinting and their antibacterial activity was estimated. Preliminary chemical screening and antibacterial activity clearly illustrate that the marine invertebrates-associated actinomycetes are a rich source of novel biologically active compounds. Among the isolates, strain SCSIO-PTE-L054 was further investigated for its unique metabolic profile and antibacterial activity. The bioassay-guided isolation rendered a polycyclic tetramate macrolactam (PTM) as a major chemical constituent with potent antibacterial activity. Our results revealed that the Streptomyces sp., strain SCSIO-L054 is a new source of PTMs which could pave a way to isolation of new series of PTMs with a broad spectrum of activity. In summary, the present investigation makes it possible to select marine actinomycetes from Daya Bay and Nansha Islands as new potential sources to produce potent compounds for a wide range of applications in future drug discovery.

Cellular immunity is critical for controlling intracellular pathogens, but individual cellular dynamics and cell–cell cooperativity in evolving human immune responses remain poorly understood. Single-cell RNA-sequencing (scRNA-seq) represents a powerful tool for dissecting complex multicellular behaviors in health and disease1,2 and nominating testable therapeutic targets3. Its application to longitudinal samples could afford an opportunity to uncover cellular factors associated with the evolution of disease progression without potentially confounding inter-individual variability4. Here, we present an experimental and computational methodology that uses scRNA-seq to characterize dynamic cellular programs and their molecular drivers, and apply it to HIV infection. By performing scRNA-seq on peripheral blood mononuclear cells from four untreated individuals before and longitudinally during acute infection5, we were powered within each to discover gene response modules that vary by time and cell subset. Beyond previously unappreciated individual- and cell-type-specific interferon-stimulated gene upregulation, we describe temporally aligned gene expression responses obscured in bulk analyses, including those involved in proinflammatory T cell differentiation, prolonged monocyte major histocompatibility complex II upregulation and persistent natural killer (NK) cell cytolytic killing. We further identify response features arising in the first weeks of infection, for example proliferating natural killer cells, which potentially may associate with future viral control. Overall, our approach provides a unified framework for characterizing multiple dynamic cellular responses and their coordination. Single-cell RNA-sequencing of blood from HIV-1-infected individuals obtained before initiation of antiretroviral therapy provides insights into the initial immune responses during early infection that might shape future outcomes.

BackgroundCompetence committees play a key role in a competency-based system of assessment. These committees are tasked with reviewing and synthesizing clinical performance data to make judgments regarding residents’ competence. Canadian emergency medicine (EM) postgraduate training programs recently implemented competence committees; however, a paucity of literature guides their work.ObjectiveThe objective of this study was to develop consensus-based recommendations to optimize the function and decisions of competence committees in Canadian EM training programs.MethodsSemi-structured interviews of EM competence committee chairs were conducted and analyzed. The interview guide was informed by a literature review of competence committee structure, processes, and best practices. Inductive thematic analysis of interview transcripts was conducted to identify emerging themes. Preliminary recommendations, based on themes, were drafted and presented at the 2019 CAEP Academic Symposium on Education. Through a live presentation and survey poll, symposium attendees representing the national EM community participated in a facilitated discussion of the recommendations. The authors incorporated this feedback and identified consensus among symposium attendees on a final set of nine high-yield recommendations.ConclusionThe Canadian EM community used a structured process to develop nine best practice recommendations for competence committees addressing: committee membership, meeting processes, decision outcomes, use of high-quality performance data, and ongoing quality improvement. These recommendations can inform the structure and processes of competence committees in Canadian EM training programs.

Adjustable gastric band (AGB) failures frequently require conversion to sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB); the ideal conversional procedure is not established. We report on management of AGB failures at a university hospital along with literature review and proposed treatment algorithm. From October 2012 to January 2017, 32 patients underwent laparoscopic AGB removal with conversion to SG (n = 23) or RYGB (n = 9). Patient characteristics and outcomes were abstracted from medical records and a quality improvement database. Twenty-three patients (71.9%) were female with mean age of 43 ± 10.6 years and mean BMI of 42.7 ± 5.9 kg/m2; 62.5% (n = 20) had 2-staged conversion while 37.5% (n = 12) had 1-stage conversion to SG/RYGB. GERD significantly increased likelihood of conversion to RYGB vs. SG (44.4% vs. 0, p = 0.03). Preoperative diagnostics included upper gastrointestinal series (n = 15,46.7%), esophagogastroduodenoscopy (n = 32,100%), and high-resolution esophageal manometry (HRM) (n = 11,34.4%). Overall complication rate was 9.4% (n = 3). AGB-to-SG patients had mean % total body weight loss of 17.0% ± 5.9 compared to 28.3% ± 15 in AGB-to-RYGB, and mean follow-up of 11.7 ± 12.9 months compared to 18.9 ± 14.4 months. Validated criteria for conversional procedure selection following AGB failure do not exist; appropriate procedure selection requires thorough workup. Future research may elucidate the role of HRM in the diagnostic armamentarium.

New heterocycle compound 2-(4-fluorophenyl)-5-(5-iodo-2-methylbenzyl)thiophene (1), designed using 5-iodo-2-methylbenzoic acid (2) as the starting material is successfully obtained via the multiple synthesis route and finally characterized by IR, 1H NMR, and single crystal X-ray crystallography. In addition, the in vitro anticancer activity of compound 1 on three human lung cancer cells (H20, H2227, and H69) is further determined, which suggests that compound 1 may be a potential anticancer agent.

Vaginal microbiota composition affects many facets of reproductive health. Lactobacillus iners-dominated microbial communities are associated with poorer outcomes, including higher risk of bacterial vaginosis (BV), compared with vaginal microbiota rich in L. crispatus. Unfortunately, standard-of-care metronidazole therapy for BV typically results in dominance of L. iners, probably contributing to post-treatment relapse. Here we generate an L. iners isolate collection comprising 34 previously unreported isolates from 14 South African women with and without BV and 4 previously unreported isolates from 3 US women. We also report an associated genome catalogue comprising 1,218 vaginal Lactobacillus isolate genomes and metagenome-assembled genomes from300 women across 4 continents. We show that, unlike L. crispatus, L. iners growth is dependent on L-cysteine in vitro and we trace this phenotype to the absence of canonical cysteine biosynthesis pathways and a restricted repertoire of cysteine-related transport mechanisms. We further show that cysteine concentrations in cervicovaginal lavage samples correlate with Lactobacillus abundance in vivo and that cystine uptake inhibitors selectively inhibit L. iners growth in vitro. Combining an inhibitor with metronidazole promotes L. crispatus dominance of defined BV-like communities in vitro by suppressing L. iners growth. Our findings enable a better understanding of L. iners biology and suggest candidate treatments to modulate the vaginal microbiota to improve reproductive health for women globally.

家族性高胆固醇血症（FH）是一种常见遗传病，以低密度脂蛋白胆固醇（LDL-C）水平升高为特征，伴早发动脉粥样硬化性心血管疾病。该文报道FH的一家系，先证者系12岁女性患者，血浆LDL-C异常升高、有黄色瘤且早发冠心病，符合纯合子FH（HoFH）或复合杂合子FH（CHeFH）的临床表现。采用下一代测序技术对该家系成员进行遗传筛查，发现先证者携带LDLR基因的无义变异LDLR：c.1257CG/p.Tyr419Ter和错义变异LDLR：c.1879GA/p.Ala627Thr，分别源于其父母，符合CHeFH。先证者的父母、同胞兄弟和舅舅是FH的杂合子（HeFH）患者。基于遗传学诊断，个体化地给予该家系内每个患者他汀类药物、依折麦布和前蛋白转化酶枯草溶菌素9型（PCSK9）抑制剂治疗。先证者接受肝移植，接受冠状动脉支架置入。.

Human immunoglobulin G (IgG) molecules, IgG1, IgG2 and IgG3, exhibit substantial inter-individual variation in their constant heavy chain regions, as discovered by serological methods. This polymorphism is encoded by theIGHG1,IGHG2, andIGHG3genes and may influence antibody function. We sequenced the coding fragments of these genes in 95 European Americans, 94 African Americans, and 94 Black South Africans. Striking differences were observed between the population groups, including extremely low amino acid sequence variation in IGHG1 among South Africans, and higher IGHG2 and IGHG3 diversity in individuals of African descent compared to individuals of European descent. Molecular definition of the loci illustrates a greater level of allelic polymorphism than previously described, including the presence of common IGHG2 and IGHG3 variants that were indistinguishable serologically. Comparison of our data with the 1000 Genome Project sequences indicates overall agreement between the datasets, although some inaccuracies in the 1000 Genomes Project are likely. These data represent the most comprehensive analysis of IGHG polymorphisms across major populations, which can now be applied to deciphering their functional impact.

HIV persistence in tissue sites despite ART is a major barrier to HIV cure. Detailed studies of HIV infected cells and immune responses in native lymph node (LN) tissue environment is critical for gaining insight into immune mechanisms impacting HIV persistence and clearance in tissue sanctuary sites. We compared HIV persistence and HIV-specific T cell responses in LN biopsies obtained from 14 individuals who initiated therapy in Fiebig stages I/II, 5 persons treated (Tx) in Fiebig stages III-V and 17 late Tx individuals who initiated ART in Fiebig VI and beyond. Using multicolor immunofluorescence staining and in situ hybridization, HIV RNA and/or protein was detected in 12 of 14 Fiebig I/II Tx persons who were on suppressive therapy for 1 to 55 months, while all late Tx persons had persistent antigens. CXCR3+T follicular helper T cells harbored the greatest amounts of gag mRNA transcripts. Notably, HIV-specific CD8+ T cells responses associated with lower HIV antigen burden in LNs, suggesting that these responses may contribute to HIV suppression in LNs during therapy. These results reveal HIV persistence despite the initiation of ART in hyperacute infection and highlight the contribution of virus-specific responses to HIV suppression in tissue sanctuaries during suppressive ART.

HIV persistence in tissue sites despite ART is a major barrier to HIV cure. Detailed studies of HIV-infected cells and immune responses in native lymph node tissue environment is critical for gaining insight into immune mechanisms impacting HIV persistence and clearance in tissue sanctuary sites. We compared HIV persistence and HIV-specific T cell responses in lymph node biopsies obtained from 14 individuals who initiated therapy in Fiebig stages I/II, 5 persons treated in Fiebig stages III-V and 17 late treated individuals who initiated ART in Fiebig VI and beyond. Using multicolor immunofluorescence staining and in situ hybridization, we detect HIV RNA and/or protein in 12 of 14 Fiebig I/II treated persons on suppressive therapy for 1 to 55 months, and in late treated persons with persistent antigens. CXCR3+ T follicular helper cells harbor the greatest amounts of gag mRNA transcripts. Notably, HIV-specific CD8+ T cells responses are associated with lower HIV antigen burden, suggesting that these responses may contribute to HIV suppression in lymph nodes during therapy. These results reveal HIV persistence despite the initiation of ART in hyperacute infection and highlight the contribution of virus-specific responses to HIV suppression in tissue sanctuaries during suppressive ART.