A qualitative study of an undergraduate online emergency medicine education program at a teaching Hospital in Kampala, Uganda.

BACKGROUND: Globally, half of all years of life lost is due to emergency medical conditions, with low- and middle-income countries (LMICs) facing a disproportionate burden of these conditions. There is an urgent need to train the future physicians in LMICs in the identification and stabilization of patients with emergency medical conditions. Little research focuses on the development of effective emergency medicine (EM) medical education resources in LMICs and the perspectives of the students themselves. One emerging tool is the use of electronic learning (e-learning) and blended learning courses. We aimed to understand Uganda medical trainees' use of learning materials, perception of current e-learning resources, and perceived needs regarding EM skills acquisition during participation in an app-based EM course. METHODS: We conducted semi-structured interviews and focus groups of medical students and EM residents. Participants were recruited using convenience sampling. All sessions were audio recorded and transcribed verbatim. The final codebook was approved by three separate investigators, transcripts were coded after reaching consensus by all members of the coding team, and coded data were thematically analyzed. RESULTS: Twenty-six medical trainees were included in the study. Analysis of the transcripts revealed three major themes: [1] medical trainees want education in EM and actively seek EM training opportunities; [2] although the e-learning course supplements knowledge acquisition, medical students are most interested in hands-on EM-related training experiences; and [3] medical students want increased time with local physician educators that blended courses provide. CONCLUSIONS: Our findings show that while students lack access to structured EM education, they actively seek EM knowledge and practice experiences through self-identified, unstructured learning opportunities. Students value high quality, easily accessible EM education resources and employ e-learning resources to bridge gaps in their learning opportunities. However, students desire that these resources be complemented by in-person educational sessions and executed in collaboration with local EM experts who are able to contextualize materials, offer mentorship, and help students develop their interest in EM to continue the growth of the EM specialty.

Seasonal influence of tuberculosis diagnosis in Rwanda.

BACKGROUND: Tuberculosis (TB) remains a major global health concern. Previous research reveals that TB may have a seasonal peak during the spring and summer seasons in temperate climates; however, few studies have been conducted in tropical climates. This study evaluates the influence of seasonality on laboratory-confirmed TB diagnosis in Rwanda, a tropical country with two rainy and two dry seasons. METHODS: A retrospective chart review was performed at the University Teaching Hospital-Kigali (CHUK). From January 2016 to December 2017, 2717 CHUK patients with TB laboratory data were included. Data abstracted included patient demographics, season, HIV status, and TB laboratory results (microscopy, GeneXpert, culture). Univariate and multivariable logistic regression (adjusted for age, gender, and HIV status) analyses were performed to assess the association between season and laboratory-confirmed TB diagnoses. RESULTS: Patients presenting during rainy season periods had a lower odds of laboratory-confirmed TB diagnosis compared to the dry season (aOR=0.78, 95% CI 0.63-0.97, p=0.026) when controlling for age group, gender, and HIV status. Males, adults, and people living with HIV were more likely to have laboratory-confirmed TB diagnosis. On average, more people were tested for TB during the rainy season per month compared to the dry season (120.3 vs. 103.3), although this difference was not statistically significant. CONCLUSION: In Rwanda, laboratory-confirmed TB case detection shows a seasonal variation with patients having higher odds of TB diagnosis occurring in the dry season. Further research is required to further elucidate this relationship and to delineate the mechanism of season influence on TB diagnosis.

The SuperCam Instrument Suite on the NASA Mars 2020 Rover: Body Unit and Combined System Tests.

The SuperCam instrument suite provides the Mars 2020 rover, Perseverance, with a number of versatile remote-sensing techniques that can be used at long distance as well as within the robotic-arm workspace. These include laser-induced breakdown spectroscopy (LIBS), remote time-resolved Raman and luminescence spectroscopies, and visible and infrared (VISIR; separately referred to as VIS and IR) reflectance spectroscopy. A remote micro-imager (RMI) provides high-resolution color context imaging, and a microphone can be used as a stand-alone tool for environmental studies or to determine physical properties of rocks and soils from shock waves of laser-produced plasmas. SuperCam is built in three parts: The mast unit (MU), consisting of the laser, telescope, RMI, IR spectrometer, and associated electronics, is described in a companion paper. The on-board calibration targets are described in another companion paper. Here we describe SuperCam's body unit (BU) and testing of the integrated instrument. The BU, mounted inside the rover body, receives light from the MU via a 5.8 m optical fiber. The light is split into three wavelength bands by a demultiplexer, and is routed via fiber bundles to three optical spectrometers, two of which (UV and violet; 245-340 and 385-465 nm) are crossed Czerny-Turner reflection spectrometers, nearly identical to their counterparts on ChemCam. The third is a high-efficiency transmission spectrometer containing an optical intensifier capable of gating exposures to 100 ns or longer, with variable delay times relative to the laser pulse. This spectrometer covers 535-853 nm ( 105 - 7070 cm - 1 Raman shift relative to the 532 nm green laser beam) with 12 cm - 1 full-width at half-maximum peak resolution in the Raman fingerprint region. The BU electronics boards interface with the rover and control the instrument, returning data to the rover. Thermal systems maintain a warm temperature during cruise to Mars to avoid contamination on the optics, and cool the detectors during operations on Mars. Results obtained with the integrated instrument demonstrate its capabilities for LIBS, for which a library of 332 standards was developed. Examples of Raman and VISIR spectroscopy are shown, demonstrating clear mineral identification with both techniques. Luminescence spectra demonstrate the utility of having both spectral and temporal dimensions. Finally, RMI and microphone tests on the rover demonstrate the capabilities of these subsystems as well.

Comparison of Online and Classroom-based Formats for Teaching Emergency Medicine to Medical Students in Uganda.

OBJECTIVES: Severe global shortages in the health care workforce sector have made improving access to essential emergency care challenging. The paucity of trained specialists in low- and middle-income countries translates to large swathes of the population receiving inadequate care. Efforts to expand emergency medicine (EM) education are similarly impeded by a lack of available and appropriate teaching faculty. The development of comprehensive, online medical education courses offers a potentially economical, scalable, and lasting solution for universities experiencing professional shortages. METHODS: An EM course addressing core concepts and patient management was developed for medical students enrolled at Makerere University College of Health Sciences in Kampala, Uganda. Material was presented to students in two comparable formats: online video modules and traditional classroom-based lectures. Following completion of the course, students were assessed for knowledge gains. RESULTS: Forty-two and 48 students enrolled and completed all testing in the online and classroom courses, respectively. Student knowledge gains were equivalent (classroom 25 ± 8.7% vs. online 23 ± 6.5%, p = 0.18), regardless of the method of course delivery. CONCLUSIONS: A summative evaluation of Ugandan medical students demonstrated that online teaching modules are effectively equivalent and offer a viable alternative to traditional classroom-based lectures delivered by on-site, visiting faculty in their efficacy to teach expertise in EM. Web-based curriculum can help alleviate the burden on universities in developing nations struggling with a critical shortage of health care educators while simultaneously satisfying the growing community demand for access to emergency medical care. Future studies assessing the long-term retention of course material could gauge its incorporation into clinical practice.

Teplizumab therapy for type 1 diabetes.

IMPORTANCE OF THE FIELD: Type 1 diabetes mellitus (T1D) is a T-cell mediated autoimmune disease with selective destruction of beta cells. Immunological interventions are directed at arresting the loss of beta-cell function with the promise that this will make it easier for patients to control their glucose levels. AREAS COVERED IN THIS REVIEW: This review provides a summary of the preclinical and clinical research published between 1992 and 2009 using teplizumab and other anti-CD3 antibodies to arrest the loss of beta-cell function in new onset T1D. Data from animal and human studies on the probable mechanism of action of teplizumab are also reviewed. WHAT THE READER WILL GAIN: A broad perspective on the use of teplizumab in inducing disease specific tolerance. TAKE HOME MESSAGE: In Phase I/II randomized control trials, in patients with new onset T1D, teplizumab slowed the rate of loss of beta-cell function over 2 years of follow-up. Treated patients had better glycemic control and lower insulin requirements. Adverse events so far are mild and of limited duration. Phase III clinical trials are underway to confirm these results and to determine if two courses of drug have greater efficacy in arresting loss of beta-cell function.

Endobronchial granular cell tumor: a case report.

Granular cell tumors (GCTs) are benign neoplasms that are most commonly found in the head and neck region. We present a case of endobronchial granular cell tumor presenting as hemoptysis in a 22-year-old African American female. Patient subsequently underwent a right upper and middle lobectomy, and upon histologic analysis was found to have GCT with borders impinging upon cartilage and adjacent peribronchial lymph nodes.

Surviving sepsis in low-income and middle-income countries: new directions for care and research.

Sepsis is a disorder characterised by systemic inflammation secondary to infection. Despite recent progress in the understanding and treatment of sepsis, no data or recommendations exist that detail effective approaches to sepsis care in resource-limited low-income and middle-income countries (LMICs). Although few data exist on the burden of sepsis in LMICs, the prevalence of HIV and other comorbid conditions in some LMICs suggest that sepsis is a substantial contributor to mortality in these regions. In well-resourced countries, sepsis management relies on protocols and complex invasive technologies not widely available in most LMICs. However, the key concepts and components of sepsis management are potentially translatable to resource-limited environments. Health personnel in LMICs should be educated in the recognition of sepsis and the importance of early and appropriate antibiotic use. Simple and low-cost standardised laboratory testing should be emphasised to allow accurate diagnosis, prognosis, and monitoring of treatment response. Evidence-based interventions and treatment algorithms tailored to LMIC ecology and resources should thus be developed and validated.

The three-dimensional structure of MAP kinase p38beta: different features of the ATP-binding site in p38beta compared with p38alpha.

The p38 mitogen-activated protein kinases are activated in response to environmental stress and cytokines and play a significant role in transcriptional regulation and inflammatory responses. Of the four p38 isoforms known to date, two (p38alpha and p38beta) have been identified as targets for cytokine-suppressive anti-inflammatory drugs. Recently, it was reported that specific inhibition of the p38alpha isoform is necessary and sufficient for anti-inflammatory efficacy in vivo, while further inhibition of p38beta may not provide any additional benefit. In order to aid the development of p38alpha-selective compounds, the three-dimensional structure of p38beta was determined. To do so, the C162S and C119S,C162S mutants of human MAP kinase p38beta were cloned, expressed in Escherichia coli and purified. Initial screening hits in crystallization trials in the presence of an inhibitor led upon optimization to crystals that diffracted to 2.05 A resolution and allowed structure determination (PDB codes 3gc8 and 3gc9 for the single and double mutant, respectively). The structure of the p38alpha C162S mutant in complex with the same inhibitor is also reported (PDB code 3gc7). A comparison between the structures of the two kinases showed that they are highly similar overall but that there are differences in the relative orientation of the N- and C-terminal domains that causes a reduction in the size of the ATP-binding pocket in p38beta. This difference in size between the two pockets could be exploited in order to achieve selectivity.

Diagnosis of acute HIV infection in Connecticut.

Acute HIV infection (AHI) is the earliest stage of HIV disease, when plasma HIV viremia, but not HIV antibodies, can be detected. Acute HIV infection often presents as a nonspecific viral syndrome. However, its diagnosis, which enables linkage to early medical care and limits further HIV transmission, is seldom made. We describe the experience of Yale's Center for Interdisciplinary Research on AIDS with AHI diagnosis in Connecticut, as a participating center in the National Institute of Mental Health Multisite AHI Study. We sought to identify AHI cases by clinical referrals and by screening for AHI at two substance abuse care facilities and an STD clinic. We identified one case by referral and one through screening of 590 persons. Screening for AHI is feasible and probably cost effective. Primary care providers should include AHI in the differential diagnosis when patients present with a nonspecific viral syndrome.

Isolation, enzyme-bound structure and antibacterial activity of platencin A1 from Streptomyces platensis.

Natural products continue to serve as one of the best sources for discovery of antibacterial agents as exemplified by the recent discoveries of platensimycin and platencin. Chemical modifications as well as discovery of congeners are the main sources for gaining knowledge of structure-activity relationship of natural products. Screening for congeners in the extracts of the fermentation broths of Streptomyces platensis led to the isolation of platencin A(1), a hydroxy congener of platencin. The hydroxylation of the tricyclic enone moiety negatively affected the antibacterial activity and appears to be consistent with the hydrophobic binding pocket of the FabF. Isolation, structure, enzyme-bound structure and activity of platencin A(1) and two other congeners have been described.

International emergency medicine: a review of the literature from 2008.

As the specialty of emergency medicine (EM) continues to evolve in countries around the world, and as interest in international emergency medicine (IEM) continues to grow within the United States, the IEM Literature Review Group recognizes a need for a high-quality, consolidated, and easily accessible evidence base of literature. In response to that need, the group created an annual publication that strives to provide readers with access to the highest quality and most relevant IEM research. This publication represents our fourth annual review, covering the top 26 IEM research articles published in 2008. Articles were selected for the review according to explicit, predetermined criteria that include both methodologic quality and perceived impact of the research. It is our hope that this annual review will act as a forum for disseminating best practices while also stimulating further research in the field of IEM.

HIV/AIDS, conflict and security in Africa: rethinking relationships.

The effect of conflict on HIV transmission and regional and global security has been the subject of much recent discussion and debate. Many long held assumptions regarding these relationships are being reconsidered. Conflict has long been assumed to contribute significantly to the spread of HIV infection. However, new research is casting doubt on this assumption. Studies from Africa suggest that conflict does not necessarily predispose to HIV transmission and indeed, there is evidence to suggest that recovery in the "post-conflict" state is potentially dangerous from the standpoint of HIV transmission. As well, refugee populations have been previously considered as highly infected vectors of HIV transmission. But in light of new investigation this belief is also being reconsidered. There has additionally been concern that high rates of HIV infection among many of the militaries of sub-Saharan Africa poses a threat to regional security. However, data is lacking on both dramatically elevated prevalence amongst soldiers and a possible negative effect on regional security. Nevertheless, HIV/AIDS remain a serious threat to population health and economic well being in this region. These issues are of vital importance for HIV programming and health sector development in conflict and "post-conflict" societies and will constitute formidable challenges to the international community. Further research is required to better inform the discussion of HIV, conflict, and security in sub-Saharan Africa.

International emergency medicine: a review of the literature from 2007.

The subspecialty of international emergency medicine (IEM) continues to grow within the United States, just as the specialty of emergency medicine (EM) continues to spread to both developed and developing countries around the world. One of the greatest obstacles, however, faced by IEM researchers and practitioners alike, remains the lack of a high-quality, consolidated, and easily accessible evidence-base of literature. In response to this perceived need, members of the Emergency Medicine Resident Association (EMRA) International Emergency Medicine Committee, in conjunction with members of the Society for Academic Emergency Medicine (SAEM) International Health Interest Group, have embarked on the task of creating a recurring review of IEM literature. This publication represents the third annual review, covering the top 30 IEM research articles published in 2007. Articles were selected for the review according to explicit, predetermined criteria that included both methodologic quality and perceived impact of the research. It is hoped that this annual review will act as a forum for disseminating best practices, while also stimulating further research in the field of IEM.

A paradoxical peace: HIV in post-conflict states.

Conflict has traditionally been thought to contribute to the epidemic spread of HIV. New data call into question this assumption, and there is concern that the 'post-conflict phase' may be a particularly dangerous time for HIV transmission. The post-conflict phase is characterized by a potentially disastrous confluence of factors including demobilization of combatants, the presence of peacekeeping forces, the return of potentially infected soldiers and refugees, high-risk behaviours and persistent economic and social debilitation. These factors, along with the concentration of populations into cities and urban areas, may further increase the risk to these populations of HIV infection. Further research and study are required to adequately inform and address the issue of HIV transmission in post-conflict societies.

Anti-arrhythmic and vasopressor medications for the treatment of ventricular fibrillation in severe hypothermia: a systematic review of the literature.

OBJECTIVE: To determine the rate of return of spontaneous circulation (ROSC) in animal models performing resuscitation from induced ventricular fibrillation (VF) in severe hypothermia (<30 degrees C). MATERIALS AND METHODS: A medical literature database search from 1966 to present was performed identifying placebo controlled trials using anti-arrhythmic or vasopressor medications to treat ventricular fibrillation in the setting of severe hypothermia. RESULTS: 7 controlled studies were identified (n=117) testing 6 combinations of resuscitative medications. ROSC rates for treatment versus control groups were as follows: amiodarone (6% vs. 18%, p=0.6, n=34), bretylium (35% vs. 35%, p=1.0, n=40), intermediate- and high-dose epinephrine (adrenaline) (36% vs. 27%, p=1.0, n=22), vasopressin (60% vs. 0%, p<0.0001, n=39), vasopressin and amiodarone (0% vs. 0%, p=NS, n=11), low-dose epinephrine and amiodarone (91% vs. 30%, p=0.0075, n=21). Cumulatively, among all studies administering vasopressors, the rate of ROSC was 62% in treatment groups contrasted to 17% in control groups (p<0.0001, n=77). CONCLUSIONS: In controlled animal models of severe hypothermia, ROSC rates for induced ventricular fibrillation are higher with utilization of vasopressor medications. Current guidelines which recommend withholding these medications in the setting of hypothermic cardiac arrest should be re-evaluated.

Identification of a potent synthetic FXR agonist with an unexpected mode of binding and activation.

The farnesoid X receptor (FXR), a member of the nuclear hormone receptor family, plays important roles in the regulation of bile acid and cholesterol homeostasis, glucose metabolism, and insulin sensitivity. There is intense interest in understanding the mechanisms of FXR regulation and in developing pharmaceutically suitable synthetic FXR ligands that might be used to treat metabolic syndrome. We report here the identification of a potent FXR agonist (MFA-1) and the elucidation of the structure of this ligand in ternary complex with the human receptor and a coactivator peptide fragment using x-ray crystallography at 1.9-A resolution. The steroid ring system of MFA-1 binds with its D ring-facing helix 12 (AF-2) in a manner reminiscent of hormone binding to classical steroid hormone receptors and the reverse of the pose adopted by naturally occurring bile acids when bound to FXR. This binding mode appears to be driven by the presence of a carboxylate on MFA-1 that is situated to make a salt-bridge interaction with an arginine residue in the FXR-binding pocket that is normally used to neutralize bound bile acids. Receptor activation by MFA-1 differs from that by bile acids in that it relies on direct interactions between the ligand and residues in helices 11 and 12 and only indirectly involves a protonated histidine that is part of the activation trigger. The structure of the FXR:MFA-1 complex differs significantly from that of the complex with a structurally distinct agonist, fexaramine, highlighting the inherent plasticity of the receptor.

Surface-entropy reduction approaches to manipulate crystal forms of beta-ketoacyl acyl carrier protein synthase II from Streptococcus pneumoniae.

A series of experiments with beta-ketoacyl acyl carrier protein synthase II (FabF) from Streptococcus pneumonia (spFabF) were undertaken to evaluate the capability of surface-entropy reduction (SER) to manipulate protein crystallization. Previous work has shown that this protein crystallizes in two forms. The triclinic form contains four molecules in the asymmetric unit (a.u.) and diffracts to 2.1 A resolution, while the more desirable primitive orthorhombic form contains one molecule in the a.u. and diffracts to 1.3 A. The aim was to evaluate the effect of SER mutations that were specifically engineered to avoid perturbing the crystal-packing interfaces employed by the favorable primitive orthorhombic crystal form while potentially disrupting a surface of the protein employed by the less desirable triclinic crystal form. Two mutant proteins were engineered, each of which harbored five SER mutations. Extensive crystallization screening produced crystals of the two mutants, but only under conditions that differed from those used for the native protein. One of the mutant proteins yielded crystals that were of a new form (centered orthorhombic), despite the fact that the interfaces employed by the primitive orthorhombic form of the native protein were specifically unaltered. Structure determination at 1.75 A resolution reveals that one of the mutations, E383A, appears to play a key role in disfavouring the less desirable triclinic crystal form and in generating a new surface for a packing interaction that stabilizes the new crystal form.