Comparative Efficacy of Semaglutide Versus Liraglutide or Efinopegdutide on Weight Loss in Obese Patients: A Systematic Review and Meta-Analysis.

Glucagon-like peptide-1 agonists (GLP-1 RAs) have produced substantial weight loss effects in type 2 diabetes mellitus (T2DM) cohorts, but these effects have not been thoroughly studied in patients with obesity and without diabetes. This review aimed to analyze direct comparative studies for semaglutide versus other GLP-1 RA (liraglutide and efinopegdutide) in facilitating weight loss and evaluating adverse events in patients with obesity. A systematic search following the guidelines established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was performed in PubMed, Embase, and Cochrane Library for direct comparative studies comparing semaglutide with other GLP-1 RA on weight loss in patients with obesity.

Long-term hypoxia modulates depolarization activation of BK currents in fetal sheep middle cerebral arterial myocytes.

Introduction: Previous evidence indicates that gestational hypoxia disrupts cerebrovascular development, increasing the risk of intracranial hemorrhage and stroke in the newborn. Due to the role of cytosolic Ca in regulating vascular smooth muscle (VSM) tone and fetal cerebrovascular blood flow, understanding Ca signals can offer insight into the pathophysiological disruptions taking place in hypoxia-related perinatal cerebrovascular disease. This study aimed to determine the extent to which gestational hypoxia disrupts local Ca sparks and whole-cell Ca signals and coupling with BK channel activity.

What Changed? Variables Associated With the General Surgery Match.

Introduction: Between 1994 and 2014, despite an increase in applicants, successful matches into general surgery (GS) decreased by 13%. We aim to (1) understand the trends in competitiveness for a GS residency, and ascertain the associations between (2) geographical distribution and (3) research experiences on matching.

Methods: National Resident Matching Program data (2013-2022) were analyzed for (1) annual positions and matches, (2) United States Medical Licensing Examination scores, and (3) research experiences.

eIF1 and eIF5 dynamically control translation start site fidelity.

Translation initiation defines the identity of a synthesized protein through selection of a translation start site on a messenger RNA. This process is essential to well-controlled protein synthesis, modulated by stress responses, and dysregulated in many human diseases. The eukaryotic initiation factors eIF1 and eIF5 interact with the initiator methionyl-tRNA on the 40S ribosomal subunit to coordinate start site selection.

Where Will I Go? Relative Location of Physical Medicine and Rehabilitation Residencies Compared With Medical Schools Among Recent Residents.

Physical medicine and rehabilitation has rapidly been garnering interest as health care increases the emphasis on rehabilitation and management for acute and chronic diseases. This study analyzes recent geographical trends of physical medicine and rehabilitation residents via physical medicine and rehabilitation residents from 2019 to 2023, which were identified from publicly available data. The relative distribution from medical school to residency, medical school to preliminary program, and preliminary program to residency were analyzed.

The effectiveness of vaccination on the COVID-19 epidemic in California.

Background: The COVID-19 pandemic has caused overwhelming morbidity, mortality, and hospitalization worldwide, including in the state of California. Vaccination efforts have been an important measure in curtailing the adverse outcomes of COVID-19.

Methods: To quantify the effectiveness of COVID-19 vaccinations in California, we conducted a retrospective cohort study investigating how vaccination has impacted the extent of COVID-19 contraction, hospitalizations, and death totals.

N-methyladenosine in 5' UTR does not promote translation initiation.

The most abundant N-methyladenosine (mA) modification on mRNAs is installed non-stoichiometrically across transcripts, with 5' untranslated regions (5' UTRs) being the least conductive. 5' UTRs are essential for translation initiation, yet the molecular mechanisms orchestrated by mA remain poorly understood. Here, we combined structural, biochemical, and single-molecule approaches and show that at the most common position, a single mA does not affect translation yields, the kinetics of translation initiation complex assembly, or start codon recognition both under permissive growth and following exposure to oxidative stress.

COVID-19 Vaccine Acceptance in Pregnant Women in the United States: A Systematic Review and Meta-Analysis.

Pregnant women are vulnerable to Coronavirus Disease 2019 (COVID-19) complications, yet may hesitate to get vaccinated. It is important to identify racial/ethnic and other individual characteristics associated with COVID-19 vaccine acceptance in the United States during pregnancy. We searched PubMed, Embase, and Web of Science for articles published through January 2023 for keywords/terms related to immunization, COVID-19, and pregnancy, and performed a systematic review and meta-analysis to examine characteristics associated with vaccine acceptance.

tRNA shape is an identity element for an archaeal pyrrolysyl-tRNA synthetase from the human gut.

Protein translation is orchestrated through tRNA aminoacylation and ribosomal elongation. Among the highly conserved structure of tRNAs, they have distinguishing features which promote interaction with their cognate aminoacyl tRNA synthetase (aaRS). These key features are referred to as identity elements.

Protecting human subjects participating in research.

Objectives: Institutions conducting research involving human subjects establish institutional review boards (IRBs) and/or human research protection programs to protect human research subjects. Our objectives were to develop performance metrics to measure human research subject protections and to assess how well IRBs and human research protection programs are protecting human research subjects.

Methods: A set of five performance metrics for measuring human research subject protections was developed and data were collected through annual audits of informed consent documents and human research protocols at 107 Department of Veterans Affairs research facilities from 2010 through 2021.

Universal features of Nsp1-mediated translational shutdown by coronaviruses.

Nonstructural protein 1 (Nsp1) produced by coronaviruses inhibits host protein synthesis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Nsp1 C-terminal domain was shown to bind the ribosomal mRNA channel to inhibit translation, but it is unclear whether this mechanism is broadly used by coronaviruses, whether the Nsp1 N-terminal domain binds the ribosome, or how Nsp1 allows viral RNAs to be translated. Here, we investigated Nsp1 from SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), and Bat-Hp-CoV coronaviruses using structural, biophysical, and biochemical experiments, revealing a conserved role for the C-terminal domain.

Partial spontaneous intersubunit rotations in pretranslocation ribosomes.

The two main steps of translation, peptidyl transfer, and translocation are accompanied by counterclockwise and clockwise rotations of the large and small ribosomal subunits with respect to each other. Upon peptidyl transfer, the small ribosomal subunit rotates counterclockwise relative to the large subunit, placing the ribosome into the rotated conformation. Simultaneously, tRNAs move into the hybrid conformation, and the L1 stalk moves inward toward the P-site tRNA.

Impact of California Statute on Naloxone Availability and Opioid Overdose Rates.

Introduction: Ensuring that people at risk of overdosing on opioids have easy access to naloxone is an essential part of the fight against the opioid crisis. This study evaluates the impact of the 2016 California law (CA AB1535) permitting pharmacies to dispense this life-saving medication without a physician's prescription.

Methods: California counties were categorized on the basis of population density (rural, suburban, urban), rate of opioid-related deaths by population density (high, medium, low), and rate of opioid prescriptions by population density (high, medium, low).

Real-time detection of human telomerase DNA synthesis by multiplexed single-molecule FRET.

Genomic stability in proliferating cells critically depends on telomere maintenance by telomerase reverse transcriptase. Here we report the development and proof-of-concept results of a single-molecule approach to monitor the catalytic activity of human telomerase in real time and with single-nucleotide resolution. Using zero-mode waveguides and multicolor FRET, we recorded the processive addition of multiple telomeric repeats to individual DNA primers.

Universal features of Nsp1-mediated translational shutdown by coronaviruses.

Nonstructural protein 1 (Nsp1) produced by coronaviruses shuts down host protein synthesis in infected cells. The C-terminal domain of SARS-CoV-2 Nsp1 was shown to bind to the small ribosomal subunit to inhibit translation, but it is not clear whether this mechanism is broadly used by coronaviruses, whether the N-terminal domain of Nsp1 binds the ribosome, or how Nsp1 specifically permits translation of viral mRNAs. Here, we investigated Nsp1 from three representative - SARS-CoV-2, MERS-CoV, and Bat-Hp-CoV - using structural, biophysical, and biochemical assays.

Pressure pushes tRNA into excited conformational states.

Conformational dynamics play essential roles in RNA function. However, detailed structural characterization of excited states of RNA remains challenging. Here, we apply high hydrostatic pressure (HP) to populate excited conformational states of tRNA, and structurally characterize them using a combination of HP 2D-NMR, HP-SAXS (HP-small-angle X-ray scattering), and computational modeling.

HIV-1 5'-Leader Mutations in Plasma Viruses Before and After the Development of Reverse Transcriptase Inhibitor-Resistance Mutations.

Background: HIV-1 RT initiation depends on interaction between viral 5'-leader RNA, RT, and host tRNA3. We therefore sought to identify co-evolutionary changes between the 5'-leader and RT in viruses developing RT-inhibitor resistance mutations.

Methods: We sequenced 5'-leader positions 37-356 of paired plasma virus samples from 29 individuals developing the NRTI-resistance mutation M184V, 19 developing an NNRTI-resistance mutation, and 32 untreated controls.

Improved Workflow for Analysis of Vascular Myocyte Time-Series and Line-Scan Ca Imaging Datasets.

Intracellular Ca signals are key for the regulation of cellular processes ranging from myocyte contraction, hormonal secretion, neural transmission, cellular metabolism, transcriptional regulation, and cell proliferation. Measurement of cellular Ca is routinely performed using fluorescence microscopy with biological indicators. Analysis of deterministic signals is reasonably straightforward as relevant data can be discriminated based on the timing of cellular responses.

Dynamics of release factor recycling during translation termination in bacteria.

In bacteria, release of newly synthesized proteins from ribosomes during translation termination is catalyzed by class-I release factors (RFs) RF1 or RF2, reading UAA and UAG or UAA and UGA codons, respectively. Class-I RFs are recycled from the post-termination ribosome by a class-II RF, the GTPase RF3, which accelerates ribosome intersubunit rotation and class-I RF dissociation. How conformational states of the ribosome are coupled to the binding and dissociation of the RFs remains unclear and the importance of ribosome-catalyzed guanine nucleotide exchange on RF3 for RF3 recycling in vivo has been disputed.