Acute HIV Infection in Youth: Protocol for the Adolescent Trials Network 147 (ATN147) Comprehensive Adolescent Research and Engagement Studies (CARES) Study.

Background: Early treatment studies have shown that prompt treatment of HIV with combination antiretroviral therapy (cART) can limit the size of latent viral reservoirs, thereby providing clinical and public health benefits. Studies have demonstrated that adolescents have a greater capacity for immune reconstitution than adults. Nevertheless, adolescents who acquired HIV through sexual transmission have not been included in early treatment studies because of challenges in identification and adherence to cART.

Strategies for incorporating patient-reported outcomes in the care of people with chronic kidney disease (PRO kidney): a protocol for a realist synthesis.

Background: Patient-reported outcomes and experience measures (jointly referred to here as PROs) are internationally recognized as a means for patients to provide information about their quality of life, symptoms, and experiences with care. Although increasingly recognized as key to improving the quality of healthcare at individual (e.g.

The novel lncRNA is pro-neurogenic and mutated in human neurodevelopmental disorders.

Long noncoding RNAs (lncRNAs) have been shown to act as important cell biological regulators including cell fate decisions but are often ignored in human genetics. Combining differential lncRNA expression during neuronal lineage induction with copy number variation morbidity maps of a cohort of children with autism spectrum disorder/intellectual disability versus healthy controls revealed focal genomic mutations affecting several lncRNA candidate loci. Here we find that a t(5:12) chromosomal translocation in a family manifesting neurodevelopmental symptoms disrupts specifically .

Bovine Neonatal Monocytes Display Phenotypic Differences Compared With Adults After Challenge With the Infectious Abortifacient Agent .

The neonatal period represents a window of susceptibility for ruminants given the abundance of infectious challenges in their environment. Maternal transfer of immunity does not occur but post-parturition, however this does not compensate for potential deficits in the cellular compartment. Here we present a cellular and transcriptomic study to investigate if there is an age-related difference in the monocyte response in cattle during intra-cellular protozoan infection.

Variation in metal tolerance associated with population exposure history in Southern toads (Anaxyrus terrestris).

Human activities have radically shaped the global landscape, affecting the structure and function of ecosystems. Habitat loss is one of the most visible changes to the landscape and a primary driver of species declines; however, anthropogenic environmental contamination also threatens population persistence, but is not as readily observed. Aquatic organisms are especially susceptible to chemical perturbations, which can negatively impact survival and fitness related traits.

C5aR1 regulates T follicular helper differentiation and chronic graft-versus-host disease bronchiolitis obliterans.

CD4+ follicular helper T (Tfh) cells are specialized providers of T cell help to B cells and can function as pathogenic mediators of murine antibody-dependent chronic graft-versus-host disease (GvHD). Using a parent→F1 model of lupus-like chronic GvHD, in which Tfh cell and germinal center (GC) B cell differentiation occurs over 14 days, we demonstrate that absence of CD4+ T cell-expressed C5a receptor 1 (C5ar1) or pharmacological C5aR1 blockade abrogated generation/expansion of Tfh cells, GC B cells, and autoantibodies. In a Tfh cell-dependent model of chronic GvHD manifested by bronchiolitis obliterans syndrome (BOS), C5aR1 antagonism initiated in mice with established disease ameliorated BOS and abolished the associated differentiation of Tfh and GC B cells.

IL-17 and IL-22 elicited by a DNA vaccine encoding ROP13 associated with protection against Toxoplasma gondii in BALB/c mice.

Toxoplasma gondii, an intracellular parasitic protozoan, is capable of infecting man and all warm-blooded animals. Cell-mediated immunity is vital in mounting protective responses against T. gondii infection.

The effect of changes to GOLD severity stage on long term morbidity and mortality in COPD.

Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity stage classifies Chronic Obstructive Pulmonary Disease (COPD) into groups based on symptoms, exacerbations and forced expiratory volume in one second (FEV). This allows patients to change to less severe COPD stages, a novel aspect of assessment not previously evaluated. We aimed to investigate the association between temporal changes in GOLD severity stage and outcomes in COPD patients.

The commissioning and validation of Monaco treatment planning system on an Elekta VersaHD linear accelerator.

Accurate beam modeling is essential to help ensure overall accuracy in the radiotherapy process. This study describes our experience with beam model validation of a Monaco treatment planning system on a Versa HD linear accelerator. Data were collected such that Monaco beam models could be generated using three algorithms: collapsed cone (CC) and photon Monte Carlo (MC) for photon beams, and electron Monte Carlo (eMC) for electron beams.

Using Sexual Orientation and Gender Identity to Monitor Disparities in HIV, Sexually Transmitted Infections, and Viral Hepatitis.

Objectives: To quantify sexual orientation and gender identity (SOGI) disparities in incidence of HIV, other sexually transmitted infections (STIs), and viral hepatitis.

Methods: We performed a records-based study of 19 933 patients visiting a federally qualified health center in Los Angeles, California, between November 2016 and October 2017 that examined HIV, STIs, and viral hepatitis incidence proportions. We created multivariable logistic regression models to examine the association between incidence proportions and SOGI among people living with HIV and HIV-negative patients.

Fasciola hepatica, TGF-β and host mimicry: the enemy within.

Helminths parasites undergo developmental changes and migration within their definitive host, in addition to establishing chronic infection. Essential to this is the evasion of host immune responses; the canonical Th2 response is effective at removing parasites resident in the intestine. Conversely, helminths also promote the development of antigen-specific anergy and regulation.

The effect of indapamide vs. bendroflumethiazide for primary hypertension: a systematic review.

The aims of the current review were to compare the efficacy of monotherapy with bendroflumethiazide vs. indapamide on mortality, cardiovascular outcomes, blood pressure, need for intensification of treatment and treatment withdrawal. Two authors independently screened the results of a literature search, assessed the risk of bias and extracted relevant data.

Small-molecule BCL6 inhibitor effectively treats mice with nonsclerodermatous chronic graft-versus-host disease.

Patient outcomes for steroid-dependent or -refractory chronic graft-versus-host diesease (cGVHD) are poor, and only ibrutinib has been US Food and Drug Administration (FDA) approved for this indication. cGVHD is often driven by the germinal center (GC) reaction, in which T follicular helper cells interact with GC B cells to produce antibodies that are associated with disease pathogenesis. The transcriptional corepressor B-cell lymphoma 6 (BCL6) is a member of the Broad-complex, Tramtrack, and Bric-abrac/poxvirus and zinc finger (BTB/POZ) transcription factor family and master regulator of the immune cells in the GC reaction.

Identification of a novel gene fusion in ALT positive osteosarcoma.

The Alternative Lengthening of Telomeres (ALT) pathway stimulates telomere elongation and prevents cellular senescence in approximately 60% of osteosarcoma. While the precise mechanism underlying activation of the ALT pathway is unclear, mutations in the chromatin remodeling protein ATRX, histone chaperone DAXX, and the histone variant H3.3 correlate with ALT status.

The sustainability of Lean in pediatric healthcare: a realist review.

Background: Lean is a quality improvement management system from the Toyota manufacturing industry. Since the early 2000's, Lean has been used as an intervention for healthcare improvement. Lean is intended to reduce costs and improve customer value through continuous improvement.

The Influence of Active Gaming on Cardiorespiratory Fitness in Black and Hispanic Youth.

Background: Youth in the United States have low levels of cardiorespiratory fitness, a risk factor for childhood obesity. Lower levels of physical fitness for black and Hispanic youth contribute to health disparities. In this feasibility study, we examined active video games (AVGs) as a tool to improve fitness and attitudes toward physical activity during early adolescence.

Notch signaling mediated by Delta-like ligands 1 and 4 controls the pathogenesis of chronic GVHD in mice.

Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic cell transplantation (allo-HCT) and remains an area of unmet clinical need with few treatment options available. Notch blockade prevents acute GVHD in multiple mouse models, but the impact of Notch signaling on cGVHD remains unknown. Using genetic and antibody-mediated strategies of Notch inhibition, we investigated the role of Notch signaling in complementary mouse cGVHD models that mimic several aspects of human cGVHD in search of candidate therapeutics.

Submicron Aggregation of Chemically Denatured Monoclonal Antibody.

Isothermal chemical denaturation (ICD) has been widely used to evaluate the conformational stability of therapeutic proteins such as monoclonal antibodies. However, the chemical unfolding pathway and the subsequent aggregation of antibodies are not yet well-understood. In the present work, we conducted a systematic study on an ICD-induced aggregation of a pharmaceutical monoclonal antibody.

Effectiveness of Rotating Shield Brachytherapy for Prostate Cancer Dose Escalation and Urethral Sparing.

Purpose: To compare single-fraction Gd-based rotating shield brachytherapy (RSBT) for prostate cancer with conventional Ir-based high-dose-rate brachytherapy (HDR-BT) in a planning study that radiobiologically accounts for dose rate and relative biological effectiveness. RSBT was used for planning target volume (PTV) dose escalation without increasing urethral dose for monotherapy, or for urethral sparing without decreasing PTV dose as a boost to external beam radiation therapy.

Methods And Materials: Twenty-six patients were studied.

Retraction Note: DDX5 and its associated lncRNA Rmrp modulate T17 cell effector functions.

Change History: This Article has been retracted; see accompanying Retraction. Corrected online 20 January: In this Article, author Frank Rigo was incorrectly listed with a middle initial; this has been corrected in the online versions of the paper.

Primary Renal Carcinoid - A Case Report.

Carcinoid tumours in the abdomen are uncommon, but typically occur in the gastrointestinal tract. Primary renal carcinoid is an extremely rare tumour, poorly described in the literature. We describe an unusual case where an atypical renal mass on imaging led to a preoperative diagnosis of renal carcinoid on imaging guiding biopsy.

LRRK2 is a negative regulator of phagosome maturation in macrophages.

Mutations in the leucine-rich repeat kinase 2 (LRRK2) are associated with Parkinson's disease, chronic inflammation and mycobacterial infections. Although there is evidence supporting the idea that LRRK2 has an immune function, the cellular function of this kinase is still largely unknown. By using genetic, pharmacological and proteomics approaches, we show that LRRK2 kinase activity negatively regulates phagosome maturation via the recruitment of the Class III phosphatidylinositol-3 kinase complex and Rubicon to the phagosome in macrophages.

External validation of ADO, DOSE, COTE and CODEX at predicting death in primary care patients with COPD using standard and machine learning approaches.

Background: Several models for predicting the risk of death in people with chronic obstructive pulmonary disease (COPD) exist but have not undergone large scale validation in primary care. The objective of this study was to externally validate these models using statistical and machine learning approaches.

Methods: We used a primary care COPD cohort identified using data from the UK Clinical Practice Research Datalink.

What Is Lean Management in Health Care? Development of an Operational Definition for a Cochrane Systematic Review.

Industrial improvement approaches such as Lean management are increasingly being adopted in health care. Synthesis is necessary to ensure these approaches are evidence based and requires operationalization of concepts to ensure all relevant studies are included. This article outlines the process utilized to develop an operational definition of Lean in health care.