Resistance mutations that distinguish HIV-1 envelopes with discordant VRC01 phenotypes from multi-lineage infections in the HVTN703/HPTN081 trial: implications for cross-resistance.

The Antibody Mediated Prevention (AMP) trials showed that passively infused VRC01, a broadly neutralizing antibody (bNAb) targeting the CD4 binding site (CD4bs) on the HIV-1 envelope protein (Env), protected against neutralization-sensitive viruses. We identified six individuals from the VRC01 treatment arm with multi-lineage breakthrough HIV-1 infections from HVTN703, where one variant was sensitive to VRC01 (IC < 25 ug/mL) but another was resistant. By comparing Env sequences of resistant and sensitive clones from each participant, we identified sites predicted to affect VRC01 neutralization and assessed the effect of their reversion in the VRC01-resistant clone on neutralization sensitivity.

Argonaute proteins regulate the timing of the spermatogenic transcriptional program.

Argonaute proteins are best known for their role in microRNA-mediated post-transcriptional gene silencing. Here, we show that AGO3 and AGO4, but not AGO2, localize to the sex chromatin of pachytene spermatocytes where they are required for transcriptional silencing of XY-linked genes, known as Meiotic Sex Chromosome Inactivation (MSCI). Using an mouse, we show that AGO3 and AGO4 are key regulators of spermatogenesis, orchestrating expression of meiosis-related genes during prophase I while maintaining silencing of spermiogenesis genes.

Running-Associated Swollen Hands (RASH): Post Ambulatory Swollen Hands (POTASH) in a Man Who Completed a Half Marathon.

A 64-year-old man participated in a 13.1-mile half marathon in San Diego, CA on April 23, 2023. The ambient temperature when he started the race was 54°F, which increased to 64°F on his completing the race 3 hours and 58 minutes later.

Increasing SGLT-2 inhibitor prescribing through an integrated case-finding algorithm guided interdisciplinary intervention.

Background: Use of sodium-glucose cotransporter 2 inhibitors (SGLT-2 inhibitors) falls short of their cardiorenal protective benefits. Patient and provider-level barriers hinder the adoption of these life-saving medications. Innovative practices to provide primary care providers (PCPs) with added clinical-decision support via a dedicated remote interdisciplinary diabetes rounds (IDRs) team could promote SGLT-2 inhibitor selection.

Forensic Dermatology Expert Analytical Report: A New Frontier of Forensic Medicine.

Specialists in forensic medicine assist in crime scene investigations. The forensic medicine experts include anthropologists, ballistic analysts, entomologists, odontologists, and osteologists. The experts are usually not at the crime scene; they provide an evaluation of evidence that is sent to them.

Mitochondrial-derived microproteins: from discovery to function.

Given the uniqueness of the mitochondria, and the fact that they have their own genome, mitochondrial-derived microproteins (MDPs) are similar to, but different from, nuclear-encoded microproteins. The discovery of an increasing number of microproteins from this organelle and the importance of mitochondria to cellular and organismal health make it a priority to study this novel class of proteins in search of possible therapeutic targets and cures. In this review, we discuss the history of MDP discovery, describe the function of each MDP, and conclude with future goals and techniques to help discover more MDPs.

Treatment-Resistant Chromoblastomycosis Successfully Managed With Surgical Excision.

Chromoblastomycosis is an uncommon, chronic granulomatous fungal infection of the skin and subcutaneous tissue. Chromoblastomycosis is most commonly caused by the traumatic inoculation of dematiaceous (pigmented) fungi, most commonly species,  species, and species. Chromoblastomycosis usually affects agricultural workers in tropical and subtropical climates.

High Omega-3, Low Omega-6 Diet With Fish Oil for Men With Prostate Cancer on Active Surveillance: The CAPFISH-3 Randomized Clinical Trial.

Purpose: Men on active surveillance (AS) for prostate cancer are extremely interested in dietary changes or supplements to prevent progression of their disease. We sought to determine whether a high omega-3, low omega-6 fatty acid diet with fish oil capsules (D + FO) decreases proliferation (Ki-67) in prostate biopsies in men with prostate cancer on AS over a 1-year time period.

Methods: In this phase II, prospective randomized trial, men (N = 100) with grade group 1 or 2 prostate cancer who elected AS were randomly assigned to the D + FO or a control group.

Perspectives on non-emergent neonatal intensive care unit to pediatric intensive care unit care transfers in the United States.

Background: There is a substantial population of long-stay patients who non-emergently transfer directly from the neonatal intensive care unit (NICU) to the pediatric intensive care unit (PICU) without an interim discharge home. These infants are often medically complex and have higher mortality relative to NICU or PICU-only admissions. Given an absence of data surrounding practice patterns for non-emergent NICU to PICU transfers, we hypothesized that we would encounter a broad spectrum of current practices and a high proportion of dissatisfaction with current processes.

Discovery and functional analysis of a novel ALPK1 variant in ROSAH syndrome.

Retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and migraine headache (ROSAH) syndrome is an autosomal dominant disorder and to date is known to be caused by either the Thr237Met or Tyr254Cys variant in the protein kinase ALPK1. Here, we identify a family in which ROSAH syndrome is caused by a novel variant in which Ser277 is changed to Phe. All six patients examined display ocular inflammation and optic nerve elevation, four have retinal degeneration and four are registered blind.

Epitope tagging with genome editing in mice reveals that the proton channel OTOP1 is apically localized and not restricted to Type III "sour" taste receptor cells.

The gustatory system allows animals to assess the nutritive value and safety of foods prior to ingestion. The first step in gustation is the interaction of taste stimuli with one or more specific sensory receptors, that are generally believed to be present on the apical surface of the taste receptor cells. However, this assertion is rarely tested.

Diseases caused by altered specificity of a protein kinase for its allosteric activators.

Protein kinases regulate many intracellular processes, and their dysregulation causes cancers and other diseases. This review focuses on the atypical alpha-kinase 1 (ALPK1), which is activated in mammalian cells by nucleoside diphosphate heptoses (ADP-heptose, UDP-heptose, and CDP-heptose) produced by microbial pathogens but not by mammalian cells. Mutations in human ALPK1 cause ROSAH syndrome and spiradenoma, which result from an alteration in its specificity for nucleoside diphosphate heptoses, causing aberrant activation by mammalian nucleoside diphosphate sugars without microbial infection.

MOTS-c modulates skeletal muscle function by directly binding and activating CK2.

MOTS-c is a mitochondrial microprotein that improves metabolism. Here, we demonstrate CK2 is a direct and functional target of MOTS-c. MOTS-c directly binds to CK2 and activates it in cell-free systems.

How to optimize and evaluate diversity in gynecologic cancer clinical trials: statements from the GCIG Barcelona Meeting.

Findings from clinical trials have led to advancement of care for patients with gynecologic malignancies. However, restrictive inclusion of patients into trials has been widely criticized for inadequate representation of the real-world population. Ideally, patients enrolled in clinical trials should represent a broader population to enhance external validity and facilitate translation of outcomes across all relevant groups.

Leptin-activated hypothalamic BNC2 neurons acutely suppress food intake.

Leptin is an adipose tissue hormone that maintains homeostatic control of adipose tissue mass by regulating the activity of specific neural populations controlling appetite and metabolism. Leptin regulates food intake by inhibiting orexigenic agouti-related protein (AGRP) neurons and activating anorexigenic pro-opiomelanocortin (POMC) neurons. However, whereas AGRP neurons regulate food intake on a rapid time scale, acute activation of POMC neurons has only a minimal effect.

Editors and Journals: Part III-" (Who Is In Charge)?".

Judging whether an editor is good at the job is essential; however, this task may be difficult or even impossible. Several factors are involved, many of which are beyond the control of an editor. We examined some of such situations, which are as follows: (1) Reviewer's abuse of privileged information, in which a reviewer or an associate, who is likely to be a competitor, directs members of their laboratory to rapidly replicate the data and submit the resulting paper in the same or another journal while delaying publication of the submitted paper; (2) defective micromanagement by a stakeholder or owner, such as failure to order paper for the publication of a journal; (3) penny-wise dollar-foolish mismanagement by the owner, such as limiting the figures allowed to an absurdly low number in a dermatology journal (we have a visual specialty); (4) factional abuse, such as when members of a society use a gimmick to exercise outsized influence to effect a change in journal's content, and (5) " (who is in charge)?," in which changes in the governance of an ownership society or publisher affect quality of the journal.

Cutaneous Basal Cell Carcinoma In Situ: A Review of the World Literature.

Cutaneous basal cell carcinoma (BCC) in situ is a recently recognized subtype of the skin neoplasm in which the abnormal cells are confined to the epidermis. BCC in situ of the skin was previously referred to as a superficial BCC. A review of the world literature has revealed 10 cutaneous BCCs in situ that have been described in nine patients but likely reflect a more general phenomenon.

Impact of Shaking EDTA, Citrate, or MgSO Tubes on Platelet Count Results.

: In EDTA-induced pseudothrombopenia, citrate or MgSO are recommended for platelet counting. Pre-analytical conditions are poorly defined for tubes containing MgSO or citrate. In this study, we analyzed the impact of agitation of these tubes on platelet counts.