Hypertension among persons living with HIV/AIDS and its association with HIV-related health factors.

Background: Human Immunodeficiency Virus (HIV) infection remains a public health concern in many countries. The increased life expectancy in the post-Antiretroviral Therapy (ART) era has led to an increased risk of cardiovascular disease and death among Persons Living with HIV (PLHIV). Hypertension remains a significant risk factor for cardiovascular disease among PLHIV.

Association of random and observed urine drug screening with long-term retention in opioid treatment programs.

Background: In the US, opioid treatment providers (OTPs) have wide latitude to perform urine drug screening (UDS) and discharge clients for positive results. OTP clients have identified randomized and directly observed UDS as potentially stigmatizing, but little research has examined the association between UDS modality and retention in OTPs.

Methods: This cross-sectional study uses the 2016-2017 NDATSS wave among OTPs that administered methadone.

Stem cells and pain.

Pain can be defined as an unpleasant sensory and emotional experience caused by either actual or potential tissue damage or even resemble that unpleasant experience. For years, science has sought to find treatment alternatives, with minimal side effects, to relieve pain. However, the currently available pharmacological options on the market show significant adverse events.

Natural history of Ebola virus disease in rhesus monkeys shows viral variant emergence dynamics and tissue-specific host responses.

Ebola virus (EBOV) causes Ebola virus disease (EVD), marked by severe hemorrhagic fever; however, the mechanisms underlying the disease remain unclear. To assess the molecular basis of EVD across time, we performed RNA sequencing on 17 tissues from a natural history study of 21 rhesus monkeys, developing new methods to characterize host-pathogen dynamics. We identified alterations in host gene expression with previously unknown tissue-specific changes, including downregulation of genes related to tissue connectivity.

Single molecule studies of the native hair cell mechanosensory transduction complex.

Hearing and balance rely on the conversion of a mechanical stimulus into an electrical signal, a process known as mechanosensory transduction (MT). In vertebrates, this process is accomplished by an MT complex that is located in hair cells of the inner ear. While the past three decades of research have identified many subunits that are important for MT and revealed interactions between these subunits, the composition and organization of a functional complex remains unknown.

Dynamic stability of Sgt2 enables selective and privileged client handover in a chaperone triad.

Membrane protein biogenesis poses acute challenges to protein homeostasis, and how they are selectively escorted to the target membrane is not well understood. Here we address this question in the guided-entry-of-tail-anchored protein (GET) pathway, in which tail-anchored membrane proteins (TAs) are relayed through an Hsp70-Sgt2-Get3 chaperone triad for targeting to the endoplasmic reticulum. We show that the Hsp70 ATPase cycle and TA substrate drive dimeric Sgt2 from a wide-open conformation to a closed state, in which TAs are protected by both substrate binding domains of Sgt2.

Strategies for enhancing the representation of women in clinical trials: an evidence map.

Background: Equitable sex- and gender-based representation in clinical trials is an essential step to ensuring evidence-based care for women. While multi-institutional actions have led to significant improvements in the inclusion of women in trials, inequity persists in areas like sex-neutral cancers and cardiovascular disease. We sought to identify strategies described or evaluated to boost the inclusion of women in clinical trials.

Criminogenic Needs and Legal Problem Severity Among Legal System Involved Veterans.

Background: Many veterans seeking behavioral health services have history of criminal-legal involvement. Research on criminogenic needs of legal system involved veterans is burgeoning. However, most research has relied on cross-sectional examinations and the vast majority of prior work has focused assessment on just one criminogenic need per study.

Vestibular damage affects the precision and accuracy of navigation in a virtual visual environment.

Vestibular information is available to the brain during navigation, as are the other self-generated (idiothetic) and external (allothetic) sensorimotor cues that contribute to central estimates of position and motion. Rodent studies provide strong evidence that vestibular information contributes to navigation but human studies have been less conclusive. Furthermore, sex-based differences have been described in human navigation studies performed with the head stationary, a situation where dynamic vestibular (and other idiothetic) information is absent, but sex differences in the utilization of vestibular information have not been described.

ChREBP is activated by reductive stress and mediates GCKR-associated metabolic traits.

Common genetic variants in glucokinase regulator (GCKR), which encodes GKRP, a regulator of hepatic glucokinase (GCK), influence multiple metabolic traits in genome-wide association studies (GWASs), making GCKR one of the most pleiotropic GWAS loci in the genome. It is unclear why. Prior work has demonstrated that GCKR influences the hepatic cytosolic NADH/NAD ratio, also referred to as reductive stress.

A role for mutations in and other genes affecting ependymal cells in idiopathic normal pressure hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is an enigmatic neurological disorder that develops after age 60 and is characterized by gait difficulty, dementia, and incontinence. Recently, we reported that heterozygous deletions may cause iNPH. Here, we identify mutations affecting nine additional genes (, ) that are statistically enriched among iNPH patients.

Risk of hepatitis B reactivation in patients with myeloproliferative neoplasms treated with ruxolitinib.

Classical Philadelphia-negative myeloproliferative neoplasms (MPNs), , polycythemia vera, essential thrombocythemia, and primary/secondary myelofibrosis, are clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid cells occurs. MPNs are characterized by mutations in driver genes, the JAK2V617F point mutation being the most commonly detected genetic alteration in these hematological malignancies. Thus, JAK inhibition has emerged as a potential therapeutic strategy in MPNs, with ruxolitinib being the first JAK inhibitor developed, approved, and prescribed in the management of these blood cancers.

NLRP3 Inflammasome Involvement in Heart, Liver, and Lung Diseases-A Lesson from Cytokine Storm Syndrome.

Inflammation and inflammasomes have been proposed as important regulators of the host-microorganism interaction, playing a key role in morbidity and mortality due to the coronavirus disease 2019 (COVID-19) in subjects with chronic conditions and compromised immune system. The inflammasome consists of a multiprotein complex that finely regulates the activation of caspase-1 and the production and secretion of potent pro-inflammatory cytokines such as IL-1β and IL-18. The pyrin containing NOD (nucleotide-binding oligomerization domain) like receptor (NLRP) is a family of intracellular receptors, sensing patterns associated to pathogens or danger signals and NLRP3 inflammasome is the most deeply analyzed for its involvement in the innate and adaptive immune system as well as its contribution to several autoinflammatory and autoimmune diseases.

Brief report on the efficacy of sotorasib in KRAS-Mutated NSCLC patients with brain metastases.

Introduction: Sotorasib has emerged as a treatment option for patients with KRAS-mutated non-small cell lung cancer (NSCLC); however, its effect in patients with brain metastases is not well described. We assessed the intracranial response of sotorasib in a retrospective case series of patients with brain metastases (BMs) at a single institution.

Methods: Patients with KRAS-mutated NSCLC with BMs who received sotorasib at Mass General Brigham Hospitals were included.

Immunotherapy for head and neck cancer: where do we go from here?

Tweetable abstract Immunotherapy for head and neck cancer shows promising new directions - and challenges ahead. What can we learn from recent trials to improve patient selection and optimize combination therapy?

WarpDrive: Improving spatial normalization using manual refinements.

Spatial normalization-the process of mapping subject brain images to an average template brain-has evolved over the last 20+ years into a reliable method that facilitates the comparison of brain imaging results across patients, centers & modalities. While overall successful, sometimes, this automatic process yields suboptimal results, especially when dealing with brains with extensive neurodegeneration and atrophy patterns, or when high accuracy in specific regions is needed. Here we introduce WarpDrive, a novel tool for manual refinements of image alignment after automated registration.

Clinical Utility of SARS-CoV-2 Serological Testing and Defining a Correlate of Protection.

Herein, we review established clinical use cases for SARS-CoV-2 antibody measures, which include diagnosis of recent prior infection, isolating high titer convalescent plasma, diagnosing multisystem inflammatory syndrome in children (MIS-C), and booster dosing in the immunosuppressed and other populations. We then address whether an antibody correlate of protection (CoP) for SARS-CoV-2 has been successfully defined with the following considerations: Antibody responses in the immunocompetent, vaccine type, variants, use of binding antibody tests vs. neutralization tests, and endpoint measures.

Re-Evaluating Human Cytomegalovirus Vaccine Design: Prediction of T Cell Epitopes.

HCMV vaccine development has traditionally focused on viral antigens identified as key targets of neutralizing antibody (NAb) and/or T cell responses in healthy adults with chronic HCMV infection, such as glycoprotein B (gB), the glycoprotein H-anchored pentamer complex (PC), and the unique long 83 (UL83)-encoded phosphoprotein 65 (pp65). However, the protracted absence of a licensed HCMV vaccine that reduces the risk of infection in pregnancy regardless of serostatus warrants a systematic reassessment of assumptions informing vaccine design. To illustrate this imperative, we considered the hypothesis that HCMV proteins detected as targets of T cell responses may contain important vaccine antigens.

Eat to Treat: The Methods and Assessments of a Culinary Medicine Seminar for Future Physicians and Practicing Clinicians.

Nutrition-associated chronic disease is an epidemic in the United States (US), yet most medical schools lack adequate nutrition education. We developed a six-session culinary medicine (CM) seminar entitled "Eat to Treat: A Nutrition Course for Future Clinicians" that teaches culinary skills, nutrition science, and counseling techniques to improve clinical nutrition management. The seminar was offered in-person to first-year medical students in a medical school-based teaching kitchen from 2017 to 2019.

c-Abl Phosphorylates MFN2 to Regulate Mitochondrial Morphology in Cells under Endoplasmic Reticulum and Oxidative Stress, Impacting Cell Survival and Neurodegeneration.

The endoplasmic reticulum is a subcellular organelle key in the control of synthesis, folding, and sorting of proteins. Under endoplasmic reticulum stress, an adaptative unfolded protein response is activated; however, if this activation is prolonged, cells can undergo cell death, in part due to oxidative stress and mitochondrial fragmentation. Here, we report that endoplasmic reticulum stress activates c-Abl tyrosine kinase, inducing its translocation to mitochondria.