A simple methodology to assess endolysosomal protease activity involved in antigen processing in human primary cells

Background: Endolysosomes play a key role in maintaining the homeostasis of the cell. They are made of a complex set of proteins that degrade lipids, proteins and sugars. Studies involving endolysosome contribution to cellular functions such as MHC class I and II epitope production have used recombinant endolysosomal proteins, knockout mice that lack one of the enzymes or purified organelles from human tissue. Each of these approaches has some caveats in analyzing endolysosomal enzyme functions. Results: In this study, we have developed a simple methodology to assess endolysosomal protease activity. By varying the pH in crude lysate from human peripheral blood mononuclear cells (PBMCs), we documented increased endolysosomal cathepsin activity in acidic conditions. Using this new method, we showed that the degradation of HIV peptides in low pH extracts analyzed by mass spectrometry followed similar kinetics and degradation patterns as those performed with purified endolysosomes. Conclusion: By using crude lysate in the place of purified organelles this method will be a quick and useful tool to assess endolysosomal protease activities in primary cells of limited availability. This quick method will especially be useful to screen peptide susceptibility to degradation in endolysosomal compartments for antigen processing studies, following which detailed analysis using purified organelles may be used to study specific peptides

What You Don’t Know Can Hurt You: Communicating Health Law with Vermont Physicians

Background: Physicians today need a working knowledge of pertinent medical law. With an increased focus on patients’ rights in health care, states are encouraged to set specific laws protecting patients. The additional medical legislation places a challenge on physicians to continually update their medical-legal acumen such as disease reporting, malpractice issues, and medical information access.Little research has been conducted on physicians’ knowledge of the law and medicine. In an effort to expand upon these topics and to find an efficient way to make information about the law and medicine accessible to Vermont physicians, the University of Vermont College of Medicine partnered with the Vermont Board of Medical Practice to answer the following questions: • How well do Vermont physicians understand laws that relate to the practice of medicine? • How do Vermont physicians access nformation on law and medicine? • What topics are most relevant and important to Vermont physicians? • What educational methods willbe effective and how can the Vermont Board of Medial Practice best serve such education needs?https://scholarworks.uvm.edu/comphp_gallery/1018/thumbnail.jp

High Power Amplifier and Power Supply

A document discusses the creation of a high-voltage power supply (HVPS) that is able to contain voltages up to -20 kV, keep electrical field strengths to below 200 V/mil (approximately equal to 7.87 kV/mm), and can provide a 200-nanosecond rise/fall time focus modulator swinging between cathode potential of 16.3 kV and -19.3 kV. This HVPS can protect the 95-GHz, pulsed extended interaction klystron (EIK) from arcs/discharges from all sources, including those from within the EIK fs vacuum envelope. This innovation has a multi-winding pulse transformer design, which uses new winding techniques to provide the same delays and rise/fall times (less than 10 nanoseconds) at different potential levels ranging from -20 kV to -16 kV. Another feature involves a high-voltage printed-wiring board that was corona-free at -20 kV DC with a 3- kV AC swing. The corona-free multilayer high-voltage board is used to simulate fields of less than 200 V/mil (approximately equal to 7.87 kV/mm) at 20 kV DC. Drive techniques for the modulator FETs (field-effect transistors) (four to 10 in a series) were created to change states (3,000-V swing) without abrupt steps, while still maintaining required delays and transition times. The packing scheme includes a potting mold to house a ten-stage modulator in the space that, in the past, only housed a four-stage modulator. Problems keeping heat down were solved using aluminum oxide substrate in the high-voltage section to limit temperature rise to less than 10 while withstanding -20 kV DC voltage and remaining corona-free

Prevalence, risk factors, and impact on outcome of cytomegalovirus replication in serum of Cambodian HIV-infected patients (2004-2007)

BACKGROUND: In developing countries, the study of cytomegalovirus (CMV) coinfection in HIV-infected patients remains neglected. Quantitative CMV polymerase chain reaction (PCR) is the gold standard diagnostic tool for analyzing serum CMV replication and for predicting CMV disease. We estimated the prevalence of replicating CMV in sera of newly diagnosed HIV-infected Cambodian patients and examined its impact on mortality. METHODS: This cohort study was based on 2 highly active antiretroviral therapy treatment programs in Cambodia between 2004 and 2007. Quantitative CMV PCR was performed on baseline serum samples of 377 HIV-infected patients. RESULTS: The prevalence of serum CMV DNA was 55.2% (150 of 272) in patients with CD4 count <100/mm. In multivariate analysis, hemoglobin <9 g/dL, CD4 count <100/mm, and Karnofsky index <50 were independently associated with positive serum CMV DNA at baseline. During a 3-year follow-up period, CMV viral load >or=3.1 log10 copies per milliliter was significantly associated with death independently of CD4 count, other opportunistic infections, and highly active antiretroviral therapy. CONCLUSIONS: As in industrialized countries, serum CMV replication is highly prevalent among HIV-infected Cambodian patients and is associated with increased mortality. This underscores the importance of diagnostic CMV infection by PCR in sera of HIV-infected patients with CD4 count <100/mm and treating this opportunistic infection to reduce its associated mortality

A Community in Bloom: An affordable housing needs assessment of West Bloomington

Purpose of Report This report was written in response to a request from Habitat for Humanity of McLean County. The report expands upon and updates an affordable homeownership needs assessment for the Bloomington-Normal community – with an emphasis on West Bloomington – that was created in 2004. Because the housing market and economic conditions of the area have changed drastically in the last 6 years, an updated report is necessary. Data Sources and Methodology This report uses a combination of primary and, mainly, secondary data sources. Interviews were conducted with representatives of, among others, Bloomington Housing Authority, the Economic Development Council (EDC) of Bloomington-Normal Area, Mid Central Community Action, Prairie State Legal Services, and the West Bloomington Revitalization Project. A variety of data were gathered from secondary sources, such as the U.S. Department of Housing and Urban Development (HUD), the U.S. Census, the City of Bloomington, the U.S. Bureau of Labor Statistics, Mid Central Community Action, the National Association of Realtors, and the National Low Income Housing Coalition (NLIHC)

Expanding workplace HIV/AIDS prevention activities for a highly mobile population: Construction workers in Ho Chi Minh City

In Ho Chi Minh City, the locus of the HIV epidemic in Vietnam, efforts have been under way for several years to implement prevention efforts for migrant worker populations. The main activity has been volunteer health communicators (HCs) visiting workplaces and conducting HIV education activities. These efforts have reached only a small number of the intended audience, and the impact is unclear. Local authorities want to scale up their efforts but need information on the most effective and least costly activities, and their potential for scale up. The Horizons Program, the Population Council/Vietnam, and partners compared two programs for highly mobile construction workers: the existing HC workplace program, where social work students deliver HIV-prevention education, and a new peer-education program. Concerns exist about the turnover of health communicators in the HC program and whether social work students, about half of whom are female, are the most effective HIV-prevention educators for a largely male construction worker population. The new program uses construction worker peer educators to promote HIV risk reduction. Findings noted in this report indicate that the peer-educator program reached a higher proportion of workers than the health-communicator program

Australasian emergency nurses\u27 willingness to attend work in a disaster: a survey

Abstract not availablePaul Arbon, Jamie Ranse, Lynette Cusack, Julie Considine, Ramon Z. Shaban, Richard J. Woodman, Laura Bahnisch, Mayumi Kako, Karen Hammad, Belinda Mitchel

Multi-site investigation of strategies for the clinical implementation of CYP2D6 genotyping to guide drug prescribing

PURPOSE: A number of institutions have clinically implemented CYP2D6 genotyping to guide drug prescribing. We compared implementation strategies of early adopters of CYP2D6 testing, barriers faced by both early adopters and institutions in the process of implementing CYP2D6 testing, and approaches taken to overcome these barriers. METHODS: We surveyed eight early adopters of CYP2D6 genotyping and eight institutions in the process of adoption. Data were collected on testing approaches, return of results procedures, applications of genotype results, challenges faced, and lessons learned. RESULTS: Among early adopters, CYP2D6 testing was most commonly ordered to assist with opioid and antidepressant prescribing. Key differences among programs included test ordering and genotyping approaches, result reporting, and clinical decision support. However, all sites tested for copy-number variation and nine common variants, and reported results in the medical record. Most sites provided automatic consultation and had designated personnel to assist with genotype-informed therapy recommendations. Primary challenges were related to stakeholder support, CYP2D6 gene complexity, phenotype assignment, and sustainability. CONCLUSION: There are specific challenges unique to CYP2D6 testing given the complexity of the gene and its relevance to multiple medications. Consensus lessons learned may guide those interested in pursuing similar clinical pharmacogenetic programs

Wearable devices for remote monitoring of hospitalized patients with COVID-19 in Vietnam

Patients with severe COVID-19 disease require monitoring with pulse oximetry as a minimal requirement. In many low- and middle- income countries, this has been challenging due to lack of staff and equipment. Wearable pulse oximeters potentially offer an attractive means to address this need, due to their low cost, battery operability and capacity for remote monitoring. Between July and October 2021, Ho Chi Minh City experienced its first major wave of SARS-CoV-2 infection, leading to an unprecedented demand for monitoring in hospitalized patients. We assess the feasibility of a continuous remote monitoring system for patients with COVID-19 under these circumstances as we implemented 2 different systems using wearable pulse oximeter devices in a stepwise manner across 4 departments