A model of lymphocryptovirus-associated post-transplant lymphoproliferative disorder in immunosuppressed Mauritian cynomolgus macaques.

Immunocompromised individuals are at risk for developing lymphocryptovirus-associated lymphoproliferative diseases, such as Epstein Barr virus (EBV)-associated B cell lymphomas and post-transplant lymphoproliferative disorder (PTLD). We previously reported development of cynomolgus lymphocryptovirus (CyLCV)-associated PTLD in Mauritian cynomolgus macaques (MCMs) undergoing hematopoietic stem cell transplantation (HSCT), which mirrored EBV-PTLD in transplant patients. Here, we sought to develop a MCM model of lymphocryptovirus-associated lymphoproliferative disease in immunosuppressed MCMs without HSCT.

Immune perturbation following SHIV infection is greater in newborn macaques than in infants.

Transmission of HIV-1 to newborns and infants remains high, with 130,000 new infections in 2022 in resource-limited settings. Half of HIV-infected newborns, if untreated, progress to disease and death within 2 years. While immunologic immaturity likely promotes pathogenesis and poor viral control, little is known about immune damage in newborns and infants.

Viral escape mutations do not account for non-protection from SIVmac239 challenge in RhCMV/SIV vaccinated rhesus macaques.

Simian immunodeficiency virus (SIV) vaccines based upon 68-1 Rhesus Cytomegalovirus (RhCMV) vectors show remarkable protection against pathogenic SIVmac239 challenge. Across multiple independent rhesus macaque (RM) challenge studies, nearly 60% of vaccinated RM show early, complete arrest of SIVmac239 replication after effective challenge, whereas the remainder show progressive infection similar to controls. Here, we performed viral sequencing to determine whether the failure to control viral replication in non-protected RMs is associated with the acquisition of viral escape mutations.

Effect of metabolic status on response to SIV infection and antiretroviral therapy in nonhuman primates.

Current antiretroviral therapy (ART) regimens efficiently limit HIV replication, thereby improving the life expectancy of people living with HIV; however, they also cause metabolic side effects. The ongoing obesity epidemic has resulted in more people with metabolic comorbidities at the time of HIV infection, yet the effect of preexisting metabolic dysregulation on infection sequelae and response to ART is unclear. Here, to investigate the impact of preexisting obesity and insulin resistance on acute infection and subsequent long-term ART, we infected a cohort of lean and obese adult male macaques with SIV and administered ART.

Cytomegalovirus vaccine vector-induced effector memory CD4 + T cells protect cynomolgus macaques from lethal aerosolized heterologous avian influenza challenge.

An influenza vaccine approach that overcomes the problem of viral sequence diversity and provides long-lived heterosubtypic protection is urgently needed to protect against pandemic influenza viruses. Here, to determine if lung-resident effector memory T cells induced by cytomegalovirus (CMV)-vectored vaccines expressing conserved internal influenza antigens could protect against lethal influenza challenge, we immunize Mauritian cynomolgus macaques (MCM) with cynomolgus CMV (CyCMV) vaccines expressing H1N1 1918 influenza M1, NP, and PB1 antigens (CyCMV/Flu), and challenge with heterologous, aerosolized avian H5N1 influenza. All six unvaccinated MCM died by seven days post infection with acute respiratory distress, while 54.

HIV seroconversion among female sex workers: retrospective cohort study from a large-scale HIV prevention and sexual and reproductive health program in Tanzania.

Introduction: In 2016, UNAIDS set ambitious targets to reduce global HIV infections by 75% by 2020 and 90% by 2030, based on the 2.1 million new infections reported in 2010. However, by 2022, new HIV infections had only decreased by 38%, from 2.

Estimating the costs and perceived benefits of oral pre-exposure prophylaxis (PrEP) delivery in ten counties of Kenya: a costing and a contingent valuation study.

Background: Kenya included oral PrEP in the national guidelines as part of combination HIV prevention, and subsequently began providing PrEP to individuals who are at elevated risk of HIV infection in 2017. However, as scale-up continued, there was a recognized gap in knowledge on the cost of delivering oral PrEP. This gap limited the ability of the Government of Kenya to budget for its PrEP scale-up and to evaluate PrEP relative to other HIV prevention strategies.

Whey Protein Supplementation and Type 2 Diabetes Mellitus Risk Factors: An Umbrella Systematic Review of Randomized Controlled Trials.

Emerging research suggests whey protein (WP) supplementation may modify type 2 diabetes mellitus (T2DM) risk factors, including glucose control. As systematic reviews and/or meta-analyses of randomized controlled trials (RCTs) gain importance in nutrition literature, we conducted an umbrella systematic review to chronicle published systematic reviews and/or meta-analyses of RCTs pertinent to WP supplementation and T2DM modifiable risk factors. This review was conducted in accordance with Preferred Reporting Items for Overviews of Reviews standards.

Scholarship of Drug Information and Library Sciences Instruction in North American Pharmacy Education: A Systematic Review of English-Language Research.

Objectives: This study aimed to characterize the scholarship of teaching and learning specific to drug information and library sciences (DILS) in pharmacy education and provide a comprehensive, evidence-based resource for faculty, detailing published practices for content delivery and scholarly research gaps.

Findings: Systematic searches of PubMed, Embase, International Pharmaceutical Abstracts, Educational Resources Information Center, Scopus, Library Literature & Information Science Full Text, and Library, Information Science & Technology Abstracts were conducted from January 1997 through early February 2022. Included studies were published in English, involved DILS content, were specific to pharmacy education, were original research, and were conducted in North America.

PIF4 enhances the expression of genes to promote growth in response to nitrate.

Nitrate supply is fundamental to support shoot growth and crop performance, but the associated increase in stem height exacerbates the risks of lodging and yield losses. Despite their significance for agriculture, the mechanisms involved in the promotion of stem growth by nitrate remain poorly understood. Here, we show that the elongation of the hypocotyl of , used as a model, responds rapidly and persistently to upshifts in nitrate concentration, rather than to the nitrate level itself.

Allogeneic haematopoietic cell transplants as dynamical systems: influence of early-term immune milieu on long-term T-cell recovery.

Objectives: Immune recovery following haematopoietic cell transplantation (HCT) functions as a dynamical system. Reducing the duration of intense immune suppression and augmenting antigen presentation has the potential to optimise T-cell reconstitution, potentially influencing long-term outcomes.

Methods: Based on donor-derived T-cell recovery, 26 patients were adaptively randomised between mycophenolate mofetil (MMF) administered for 30-day post-transplant with filgrastim for cytokine support (MMF30 arm,  = 11), or MMF given for 15 days with sargramostim (MMF15 arm,  = 15).

Allogeneic immunity clears latent virus following allogeneic stem cell transplantation in SIV-infected ART-suppressed macaques.

Allogeneic hematopoietic stem cell transplantation (alloHSCT) from donors lacking C-C chemokine receptor 5 (CCR5) can cure HIV, yet mechanisms remain speculative. To define how alloHSCT mediates HIV cure, we performed MHC-matched alloHSCT in SIV, anti-retroviral therapy (ART)-suppressed Mauritian cynomolgus macaques (MCMs) and demonstrated that allogeneic immunity was the major driver of reservoir clearance, occurring first in peripheral blood, then peripheral lymph nodes, and finally in mesenteric lymph nodes draining the gastrointestinal tract. While allogeneic immunity could extirpate the latent viral reservoir and did so in two alloHSCT-recipient MCMs that remained aviremic >2.

Modulating auxin response stabilizes tomato fruit set.

Fruit formation depends on successful fertilization and is highly sensitive to weather fluctuations that affect pollination. Auxin promotes fruit initiation and growth following fertilization. Class A auxin response factors (Class A ARFs) repress transcription in the absence of auxin and activate transcription in its presence.

Evaluation of References Supporting Hospital Pharmacy Policies.

There is a lack of research evaluating the role of references in hospital policies. The goal of this study was to describe the type of literature used as a reference in medication policies and evaluate the agreement of the policy with evidence-based guidelines. One hundred forty-seven pharmacy owned policies met inclusion criteria; 27.

Meat Consumption and Gut Microbiota: a Scoping Review of Literature and Systematic Review of Randomized Controlled Trials in Adults.

Emerging research indicates the importance of gut microbiota in mediating the relationship between meat intake and human health outcomes. We aimed to assess the state of available scientific literature on meat intake and gut microbiota in humans (PROSPERO, International Prospective Register of Systematic Reviews, CRD42020135649). We first conducted a scoping review to identify observational and interventional studies on this topic.

ATM phosphorylates PP2A subunit A resulting in nuclear export and spatiotemporal regulation of the DNA damage response.

Ataxia telangiectasia mutated (ATM) is a serine-threonine protein kinase and important regulator of the DNA damage response (DDR). One critical ATM target is the structural subunit A (PR65-S401) of protein phosphatase 2A (PP2A), known to regulate diverse cellular processes such as mitosis and cell growth as well as dephosphorylating many proteins during the recovery from the DDR. We generated mouse embryonic fibroblasts expressing PR65-WT, -S401A (cannot be phosphorylated), and -S401D (phospho-mimetic) transgenes.

Poultry Consumption and Human Health: How Much Is Really Known? A Systematically Searched Scoping Review and Research Perspective.

This scoping review was conducted to systematically search and chronicle scientific literature pertinent to poultry intake and human health. The protocol (uploaded to Open Science Framework, https://osf.io/2k7bj/) was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews guidelines.

Health system opportunities and challenges for PrEP implementation in Kenya: A qualitative framework analysis.

Background: As pre-exposure prophylaxis (PrEP) scales up in sub-Saharan Africa, governments and implementers need to understand how to best manage national programs. Kenya's national PrEP program offers an opportunity to review elements of program success within the health system and evaluate the utility of a national implementation framework. We explored health system considerations for PrEP implementation to understand how Kenya's national PrEP implementation priorities align with those of PrEP service providers, peer educators, and program or county managers.

SAUR63 stimulates cell growth at the plasma membrane.

In plants, regulated cell expansion determines organ size and shape. Several members of the family of redundantly acting Small Auxin Up RNA (SAUR) proteins can stimulate plasma membrane (PM) H+-ATPase proton pumping activity by inhibiting PM-associated PP2C.D phosphatases, thereby increasing the PM electrochemical potential, acidifying the apoplast, and stimulating cell expansion.

Cytomegalovirus-vaccine-induced unconventional T cell priming and control of SIV replication is conserved between primate species.

Strain 68-1 rhesus cytomegalovirus expressing simian immunodeficiency virus (SIV) antigens (RhCMV/SIV) primes MHC-E-restricted CD8+ T cells that control SIV replication in 50%-60% of the vaccinated rhesus macaques. Whether this unconventional SIV-specific immunity and protection is unique to rhesus macaques or RhCMV or is intrinsic to CMV remains unknown. Here, using cynomolgus CMV vectors expressing SIV antigens (CyCMV/SIV) and Mauritian cynomolgus macaques, we demonstrate that the induction of MHC-E-restricted CD8+ T cells requires matching CMV to its host species.

Quantitative Phase Imaging: Recent Advances and Expanding Potential in Biomedicine.

Quantitative phase imaging (QPI) is a label-free, wide-field microscopy approach with significant opportunities for biomedical applications. QPI uses the natural phase shift of light as it passes through a transparent object, such as a mammalian cell, to quantify biomass distribution and spatial and temporal changes in biomass. Reported in cell studies more than 60 years ago, ongoing advances in QPI hardware and software are leading to numerous applications in biology, with a dramatic expansion in utility over the past two decades.