Pre-Exposure Prophylaxis for HIV: Bioethical, Clinical, and Epidemiological Considerations.

Public health authorities are broadly promoting a strategy known as pre-exposure prophylaxis (PrEP) for the prevention of human immunodeficiency virus (HIV) transmission in the context of high-risk sexual activity and injection drug use. However, there are several limitations to this strategy that are underrecognized. This article reviews the primary literature supporting the use of PrEP and explores the unintended consequences associated with its use.

COVID-19 and myocardial injury: Targeting elevated biomarkers for potential novel therapies.

Background: The prevalence of COVID-19 as the primary diagnosis among hospitalized patients with myocardial injury has increased during the pandemic and targeting elevated oxidant stress and inflammatory biomarkers may offer a potential role for novel therapies to improve outcomes.

Methods: At a single VA Medical Center from January 1 through December 31, 2021, troponin assays from patients being evaluated in the Emergency Room for consideration of admission were analyzed and peak levels from each patient were considered abnormal if exceeding the Upper Reference Limit (URL). Among admitted patients with an elevated troponin level, ICD-10 diagnoses were categorized, biomarker elevations were recorded, and independent predictors of death in patients with COVID-19 were determined at a median of 6-months following admission.

Roadmap to safety: a single center study of evidence-informed approach to placenta accreta spectrum.

Objective: To assess the impact of an evidence-informed protocol for management of placenta accreta spectrum (PAS).

Methods: This was a retrospective cohort study of patients who underwent cesarean hysterectomy (c-hyst) for suspected PAS from 2012 to 2022 at a single tertiary care center. Perioperative outcomes were compared pre- and post-implementation of a standardized Multidisciplinary Approach to the Placenta Service (MAPS) protocol, which incorporates evidence-informed perioperative interventions including preoperative imaging and group case review.

Development of obstetric anesthesia core competencies for USA residency programs through a Delphi process.

Purpose: The standard for anesthesia residency training in the USA mainly relies on the Accreditation Council for Graduate Medical Education (ACGME) Outcome Project, a framework that lacks specific directives for subspecialties including obstetric anesthesia. We aimed to identify core competencies in obstetric anesthesiology that can be adapted to different residency training programs to help improve the quality of training and accountability of the institutions within the USA.

Methods: We identified a preliminary list of competencies from review of existing competency-based obstetric anesthesia training curricula and practice guidelines.

Inadequate Niacin Intake Disrupts Growth and Retinol Homeostasis Resulting in Higher Liver and Lower Serum Retinol Concentrations in Male Rats.

Background: Niacin-derived nicotinamide adenine dinucleotide is an essential cofactor for many dehydrogenase enzymes involved in vitamin A (VA) metabolism. Several countries with high prevalence of VA deficiency rely on maize, a poor source of available niacin, as a dietary staple.

Objectives: This study evaluated the interaction of dietary niacin on VA homeostasis using male Sprague-Dawley rats, aged 21 d (baseline body weight 88.

Anesthesia Considerations for Placenta Accreta Spectrum.

Anesthesiologists are critical members of the multidisciplinary team managing patients with suspected placenta accreta spectrum (PAS). Preoperatively, anesthesiologists provide predelivery consultation for patients with suspected PAS where anesthetic modality and invasive monitor placement is discussed. Additionally, anesthesiologists carefully assess patient and surgical risk factors to choose an anesthetic plan and to prepare for massive intraoperative hemorrhage.

ssPINE: Probabilistic Algorithm for Automated Chemical Shift Assignment of Solid-State NMR Data from Complex Protein Systems.

The heightened dipolar interactions in solids render solid-state NMR (ssNMR) spectra more difficult to interpret than solution NMR spectra. On the other hand, ssNMR does not suffer from severe molecular weight limitations like solution NMR. In recent years, ssNMR has undergone rapid technological developments that have enabled structure-function studies of increasingly larger biomolecules, including membrane proteins.

POKY software tools encapsulating assignment strategies for solution and solid-state protein NMR data.

NMR spectroscopy provides structural and functional information about biomolecules and their complexes. The complexity of these systems can make the NMR data difficult to interpret, particularly for newer users of NMR technology, who may have limited understanding of the tools available and how they are used. To alleviate this problem, we have created software based on standardized workflows for both solution and solid-state NMR spectroscopy of proteins.

Placental Findings in Pregnancies Complicated by Maternal Cardiovascular Disease.

Background: The incidence of pregnancy in women with cardiovascular disease (CVD) has increased, yet little is known about placental pathology in these women.

Objectives: The objectives of this study were to describe placental pathology in pregnancies complicated by maternal CVD and to compare findings among categories of maternal CVD.

Methods: A retrospective, single-center study was conducted.

Placenta Accreta Spectrum Disorders: Knowledge Gaps in Anesthesia Care.

Placenta accreta spectrum (PAS) disorder is a potentially life-threatening condition that can occur during pregnancy. PAS puts pregnant individuals at a very high risk of major blood loss, hysterectomy, and intensive care unit admission. These patients should receive care in a center with multidisciplinary experience and expertise in managing PAS disorder.

Coordination of Di-Acetylated Histone Ligands by the ATAD2 Bromodomain.

The ATPase Family, AAA domain-containing protein 2 (ATAD2) bromodomain (BRD) has a canonical bromodomain structure consisting of four α-helices. ATAD2 functions as a co-activator of the androgen and estrogen receptors as well as the MYC and E2F transcription factors. ATAD2 also functions during DNA replication, recognizing newly synthesized histones.

iPick: Multiprocessing software for integrated NMR signal detection and validation.

Peak picking is a critical step in biomolecular NMR spectroscopy. The program, iPick, presented here provides a scripting tool and a graphical user interface (GUI), which allow the user to perform interactive and intuitive peak picking and validation. The click-and-run GUI requires no computer programming skills, while the scripting tool can be used by more advanced users to customize the application.

The Protein Data Bank Archive.

Protein Data Bank is the single worldwide archive of experimentally determined macromolecular structure data. Established in 1971 as the first open access data resource in biology, the PDB archive is managed by the worldwide Protein Data Bank (wwPDB) consortium which has four partners-the RCSB Protein Data Bank (RCSB PDB; rcsb.org), the Protein Data Bank Japan (PDBj; pdbj.

Performance assessment of intravenous catheters for massive transfusion: A pragmatic in vitro study.

Background: Rapid infusion of warmed blood products is the cornerstone of trauma resuscitation and treatment of surgical and obstetric massive hemorrhage. Integral to optimizing this delivery is selection of an intravenous (IV) catheter and use of a rapid infusion device (RID). We investigated which IV catheter and RID system enabled the greatest infusion rate of blood products and the governing catheter characteristics.

The BRPF1 bromodomain is a molecular reader of di-acetyllysine.

Bromodomain-containing proteins are often part of chromatin-modifying complexes, and their activity can lead to altered expression of genes that drive cancer, inflammation and neurological disorders in humans. Bromodomain-PHD finger protein 1 (BRPF1) is part of the MOZ (monocytic leukemic zinc-finger protein) HAT (histone acetyltransferase) complex, which is associated with chromosomal translocations known to contribute to the development of acute myeloid leukemia (AML). BRPF1 contains a unique combination of chromatin reader domains including two plant homeodomain (PHD) fingers separated by a zinc knuckle (PZP domain), a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain.

Structural Insights into the Recognition of Mono- and Diacetylated Histones by the ATAD2B Bromodomain.

Bromodomains exhibit preferences for specific patterns of post-translational modifications on core and variant histone proteins. We examined the ligand specificity of the ATAD2B bromodomain and compared it to its closely related paralogue in ATAD2. We show that the ATAD2B bromodomain recognizes mono- and diacetyllysine modifications on histones H4 and H2A.

CHESPA/CHESCA-SPARKY: automated NMR data analysis plugins for SPARKY to map protein allostery.

Motivation: Correlated Nuclear Magnetic Resonance (NMR) chemical shift changes identified through the CHEmical Shift Projection Analysis (CHESPA) and CHEmical Shift Covariance Analysis (CHESCA) reveal pathways of allosteric transitions in biological macromolecules. To address the need for an automated platform that implements CHESPA and CHESCA and integrates them with other NMR analysis software packages, we introduce here integrated plugins for NMRFAM-SPARKY that implement the seamless detection and visualization of allosteric networks.

Availability And Implementation: CHESCA-SPARKY and CHESPA-SPARKY are available in the latest version of NMRFAM-SPARKY from the National Magnetic Resonance Facility at Madison (http://pine.

Uncovering a membrane-distal conformation of KRAS available to recruit RAF to the plasma membrane.

The small GTPase KRAS is localized at the plasma membrane where it functions as a molecular switch, coupling extracellular growth factor stimulation to intracellular signaling networks. In this process, KRAS recruits effectors, such as RAF kinase, to the plasma membrane where they are activated by a series of complex molecular steps. Defining the membrane-bound state of KRAS is fundamental to understanding the activation of RAF kinase and in evaluating novel therapeutic opportunities for the inhibition of oncogenic KRAS-mediated signaling.

Probabilistic identification of saccharide moieties in biomolecules and their protein complexes.

The chemical composition of saccharide complexes underlies their biomedical activities as biomarkers for cardiometabolic disease, various types of cancer, and other conditions. However, because these molecules may undergo major structural modifications, distinguishing between compounds of saccharide and non-saccharide origin becomes a challenging computational problem that hinders the aggregation of information about their bioactive moieties. We have developed an algorithm and software package called "Cheminformatics Tool for Probabilistic Identification of Carbohydrates" (CTPIC) that analyzes the covalent structure of a compound to yield a probabilistic measure for distinguishing saccharides and saccharide-derivatives from non-saccharides.

Fragment screening targeting Ebola virus nucleoprotein C-terminal domain identifies lead candidates.

The Ebola Virus is a causative agent of viral hemorrhagic fever outbreaks and a potential global health risk. The outbreak in West Africa (2013-2016) led to 11,000+ deaths and 30,000+ Ebola infected individuals. The current outbreak in the Democratic Republic of Congo (DRC) with 3000+ confirmed cases and 2000+ deaths attributed to Ebola virus infections provides a reminder that innovative countermeasures are still needed.