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Alan Kunz-Lomelin,1 Michael Killian,2 Brittany H Eghaneyan,3,* Katherine Sanchez1,* 1School of Social Work, University of Texas at Arlington, Arlington, TX, USA; 2College of Social Work, Florida State University, Tallahassee, FL, USA; 3Department of Social Work, California State University, Fullerton, CA, USA*These authors contributed equally to this workCorrespondence: Alan Kunz-Lomelin, 3825 Hunters Trail, Carrollton, TX, 75007, USA, Tel +1 (972) 358-0575, Email alan.kunzlomelin@mavs.uta.eduPurpose: We report on antidepressant (AD) adherence among Hispanics seeking mental health services in a community primary care clinic in Texas as an ancillary outcome from a National Institutes of Health-funded study that collected data on Hispanic AD adherence over a period of two years (February 2016–February 2018). Adherence to AD medications was measured throughout the year-long trial and compared across various demographic characteristics. Since Hispanic individuals often experience stigma and cultural barriers related to AD treatment, we sought to understand what factors may increase the likelihood of non-adherence in this population.Patients and Methods: This study focused on 69 patients who were prescribed AD medications while receiving treatment through an integrated health care model. Adherence was measured with the Patient Adherence Questionnaire, a validated 2-item questionnaire that asks patients about their medication use (missed medications or dosage changes) over the past week. We looked at patient adherence at two key time points (4-weeks and 13-weeks) and utilized logistic regression to identify factors that may increase or decrease the likelihood of adherence in Hispanic patients at a community primary care clinic.Results: Non-adherence to AD medication was 49.3% at 4-weeks and 57% at 13-weeks post-treatment initiation. Logistic regression analyses revealed that age was the only significant predictor of AD non-adherence. As age increased, the likelihood of adherence increased by 12.2% at 13-weeks post-treatment initiation and by 11.1% at 4-weeks post-treatment initiation.Conclusion: The likelihood of Hispanic patients to adhere to AD therapy increased with the age of the patient. Since primary care is the most likely place to be prescribed an AD for Hispanic patients, further research to better understand adherence is essential. Integrated health care interventions designed to help identify, reduce, or eliminate barriers to adherence and improve cultural understanding may help address issues of non-adherence in primary care settings.Keywords: medication, primary care, mental health, antidepressant adherence, social work

Background/Objectives: Zika virus (ZIKV) infection is associated with life-threatening diseases in humans. To date, there are no available FDA-approved therapies or vaccines for the specific treatment or prevention of ZIKV infection. Variation in the ZIKV envelope protein (Env), along with its complex quaternary structure, presents challenges to synthetic approaches for developing an effective vaccine and broadly neutralizing antibodies (bnAbs). We hypothesized that beta-cyclodextrin (BCD) could be used to uniquely inactivate infectious ZIKV without disruption of Env. Methods: ZIKV was propagated in Vero cells and admixed with BCD. The BCD-treated ZIKV was evaluated for infectivity using immunofluorescence and quantitative RT-PCR (qRT-PCR) assays, for immunoreactivity in Western blots, structural integrity by electron microscopy, and immunogenicity in mice. Results: Here, we show that 200 mM BCD-treated ZIKV is non-infectious in cell culture, remains immunoreactive with an Env-specific antibody, retains its virion shape and size, and elicits the production of immunogen-specific antibodies in immunized mice. Conclusions: These results indicate that BCD can be used to safely inactivate ZIKV, and they provide insights for vaccine and antibody development. [ABSTRACT FROM AUTHOR]

© 2015, Public Library of Science. All rights reserved.Gastrointestinal T lymphocytes are critical for mucosal immunity and HIV pathogenesis, yet little is known about normal T cell numbers and phenotypes in different regions of the gut, or the degree to w

Baptiste Gramont,1 Émilie Chalayer,1,2 Angélique Savall,3 Martin Killian,1 Thomas Celarier,1 Bernard Tardy21Department of Internal Medicine and Geriatrics, CHU, Saint Etienne, France; 2Centre d’Investigation Clinique, Inserm CIC-EC 1408, Saint Etienne, France; 3Department of Education and Research in General Practice, Jean Monnet University, Saint Etienne, FranceBackground: The thromboprophylactic efficacy of graduated compression stockings (GCS) has not yet been demonstrated in acutely ill medical patients, and guidelines vary considerably. Older acutely ill medical patients appear to constitute a distinctive population presenting high risks of both thrombosis and bleeding.Objective: To evaluate the practices and beliefs of a panel of French geriatricians regarding GCS management in acutely ill medical patients aged over 75 years.Methods: A survey was designed to study French geriatric practice concerning GCS use for thromboprophylaxis.Results: A total of 111 geriatricians answered the questionnaire. Among the responders, 46% declared frequent or very frequent prescription of GCS for preventing venous thromboembolism (VTE) in acutely ill, hospitalized medical patients, 54% declaring that they frequently re-evaluated GCS prescription during the patient’s hospitalization. The main reason reported for discontinuing GCS use was patient request. Regarding complications of GCS, 87% of responders declared having already noted adverse effects with the use of GCS, although 80% estimated the risk of complications to be low or very low. In the context considered, the efficacy of wearing GCS was believed to be high or very high for 73% of responders. GCS prescription was judged to be in accordance with evidence-based medicine for 69%.Conclusion: There is a gap between the frequent use of GCS to prevent VTE in older patients presenting an acute medical illness and the availability of data concerning their efficacy, safety, and management by nurses. Prospective trials including clinical and cost effectiveness are needed.Keywords: thromboprophylaxis, mechanical prophylaxis, thrombosis, geriatrics, elderly

Abstract Autophagy, the major mechanism for degrading long-lived intracellular proteins and organelles, is essential for eukaryotic cell homeostasis. Autophagy also defends the cell against invasion by microorganisms and has important roles in innate and adaptive immunity. Increasingly evident is that HIV-1 replication is dependent on select components of autophagy. Fittingly, HIV-1 proteins are able to modulate autophagy to maximize virus production. At the same time, HIV-1 proteins appear to disrupt autophagy in uninfected cells, thereby contributing to CD4+ cell death and HIV-1 pathogenesis. These observations allow for new approaches for the treatment and possibly the prevention of HIV-1 infection. This review focuses on the relationship between autophagy and HIV-1 infection. Discussed is how autophagy plays dual roles in HIV-1 replication and HIV-1 disease progression.

Acquired immune deficiency syndrome (AIDS) was first described 30 years ago in a report from the US Centers for Disease Control. Two years later the causative virus was identified and afterwards named the human immunodeficiency virus (HIV). This article reviews the progress made in the three decades since the recognition of AIDS and the discovery of HIV, with respect to the virus, the infected cell, and the host, as well as directions for future studies.

HIV replication is suppressed in vitro by a CD8(+) cell noncytotoxic antiviral response (CNAR). This activity directly correlates with an asymptomatic clinical state. The objective of this study was to identify the phenotype of CD8(+) cell subsets having strong CNAR activity. CD8(+) cell subset frequencies and CNAR levels were measured for human immunodeficiency virus (HIV)-uninfected individuals and three groups of HIV type 1 (HIV-1)-infected individuals: asymptomatic individuals with low-level viremia (vHIV), antiretroviral-drug-treated subjects with undetectable virus levels (TxHIV), and therapy-naïve aviremic elite controllers (EC). CD8(+) cells from the vHIV individuals exhibited the highest HIV-suppressing activity and had elevated frequencies of CD45RA(-) CD27(+) and PD-1(+) (CD279(+)) cells. Functional assessments of CD8(+) cells sorted into distinct subsets established that maximal CNAR activity was mediated by CD45RA(-) CCR7(-) CD27(+) and PD-1(+) CD8(+) cells. T cell receptor (TCR) repertoire profiles of CD8(+) cell subsets having strong CNAR activity exhibited increased perturbations in comparison to those of inactive subsets. Together, these studies suggest that CNAR is driven by HIV replication and that this antiviral activity is associated with oligoclonally expanded activated CD8(+) cells expressing PD-1 and having a transitional memory cell phenotype. The findings better describe the identity of CD8(+) cells showing CNAR and should facilitate the evaluation of this important immune response in studies of HIV pathogenesis, resistance to infection, and vaccine development.

CD8+ lymphocytes can suppress HIV replication without killing the infected cells. This CD8+ cell noncytotoxic anti-HIV response (CNAR) is associated with a beneficial clinical course.In this longitudinal study of 16 participants in the Options Project at UCSF, we measured the ability of CD8+ lymphocytes to suppress HIV replication in CD4+ cells during primary HIV infection, early antiretroviral therapy, and after treatment.CD8+ lymphocytes from subjects with untreated primary HIV-1 infection strongly suppressed HIV replication. Initiation of antiretroviral therapy during primary HIV-1 infection caused a marked decline in this CNAR. CD8+ cells from these subjects regained anti-HIV activity when early therapy was discontinued. The timing of the appearance of CD8+ cell anti-HIV activity directly correlated with the emergence of detectable virus levels. Maximal CNAR activity coincided with a decay in the kinetics of HIV replication. In addition, peak viral loads during treatment interruption were lower than pre-treatment virus levels (median reduction = 0.8 logs, p = 0.005) and CD4+ T cell counts were maintained for a 24-week period of follow-up.These results suggest that CNAR plays an important role in suppressing HIV replication in the setting of antiretroviral treatment interruption in HIV-infected individuals.

Rapid sequence intubation (RSI) is frequently performed by emergency medical services (EMS). We investigated the relationship between succinylcholine and rocuronium use and time until first laryngoscopy attempt, first-pass success, and Cormack-Lehane (CL) grades. We included adult patients for whom prehospital RSI was attempted from July 2015 through June 2022 in a retrospective, observational study with pre-post analysis. Timing was verified using recorded defibrillator audio in addition to review of continuous ECG, pulse oximetry, and end-tidal carbon dioxide waveforms. Our primary exposure was neuromuscular blocking agent (NMBA) used, either rocuronium or succinylcholine. Our prespecified primary outcome was the first attempt Cormack-Lehane view. Key secondary outcomes were first laryngoscopy attempt success rate, timing from NMBA administration to first attempt, number of attempts, and hypoxemic events. Of 5,179 patients in the EMS airway registry, 1,475 adults received an NMBA while not in cardiac arrest. Cormack-Lehane grades for succinylcholine and rocuronium were similar: grade I (64%, 59% [95% CI 0.64–1.09]), grade II (16%, 21%), grade III (18%, 16%), grade IV (3%, 3%). The median interval from NMBA administration to start of the first attempt was 57 s for succinylcholine and 83 s for rocuronium (mean difference 28 [95% CI 20–36] seconds). First attempt success was 84% for succinylcholine and 83% for rocuronium. Hypoxemic events were present in 25% of succinylcholine cases and 23% of rocuronium cases. Prehospital use of either rocuronium or succinylcholine is associated with similar Cormack-Lehane grades, first-pass success rates, and rates of peri-intubation hypoxemia. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus type 1 (HIV-1) evolves in vivo under selective pressure from CD8(+) T-lymphocyte (CTL) responses, which are in turn determined by host and viral genetic factors, such as restricting major histocompatibility complex molecules and the available viral epitope sequences. However, CTL are derived stochastically through the random gene rearrangements to produce T-cell receptors (TCR), and the relative impact of genetic versus stochastic processes on CTL targeting of HIV and immune-driven viral evolution is unclear. Here we evaluate identical twins infected with HIV-1 as neonates from a common blood transfusion, with subsequently similar environmental exposures, thereby allowing controlled comparisons of CTL targeting and viral evolution. Seventeen years after infection, their CTL targeting of HIV-1 was remarkably similar. In contrast, their overall TCR profiles were highly dissimilar, and a dominant epitope was recognized by distinctly different TCR in each twin. Furthermore, their viral epitopes had diverged, and there was ongoing viral phylogenetic divergence between the twins between 12 and 17 years after infection. These results indicate that while CTL targeting is predominately genetically determined, stochastic influences render the interaction of HIV-1 and host immunity, and therefore viral escape and CTL efficacy, unpredictable.