Trochlear Morphological Changes in Skeletally Immature Patients Across Consecutive MRI Studies.

Background: Trochlear dysplasia is a consistent risk factor for recurrent patellofemoral instability (PFI), but there is limited understanding of how the trochlea develops during growth. The aim of this study was to evaluate serial magnetic resonance imaging (MRI) studies performed in skeletally immature patients with and without PFI to characterize changes in trochlear anatomy over time.

Hypothesis: PFI leads to progressive worsening of trochlear dysplasia over time.

Partial Avulsion Patterns in the Pediatric Humeral Medial Epicondyle.

Background: The anterior oblique bundle of the medial ulnar collateral ligament (UCL) inserts on the anteroinferior aspect of the humeral medial epicondyle, while the flexor pronator mass (FPM) originates superficial and proximal to the UCL. With valgus stress, these distinct footprints may produce injury patterns that affect only focal areas of the medial epicondyle.

Hypothesis: The proximal UCL can act on the medial epicondyle either in isolation or in conjunction with the FPM to form partial avulsion fracture patterns within the pediatric medial epicondyle, and the predominant pattern involves only the proximal UCL footprint.

A biophysical basis for the spreading behavior and limited diffusion of Xist.

Xist RNA initiates X inactivation as it spreads in cis across the chromosome. Here, we reveal a biophysical basis for its cis-limited diffusion. Xist RNA and HNRNPK together drive a liquid-liquid phase separation (LLPS) that encapsulates the chromosome.

Efficacy of Fruit Extract in Hangover Mitigation: Double-Blind Randomized Clinical Evaluation.

The fruit of Thunb. (HD) is renowned for its medicinal properties and is rich in bioactive compounds, traditionally used in East Asian medicine as a natural antidote for alcohol intoxication. A randomized, double-blind, crossover, placebo (PLA)-controlled clinical trial was conducted to compare the effects of beverages containing 0.

Clinical Evaluation of Extract Combinations for Effective Hangover Relief in Humans.

Alcohol consumption is associated with both short- and long-term adverse effects, including hangover symptoms. The objective of this study was to examine the potential benefits of traditional beverages containing a combination of extract (HD) with either extract (HDPB) or glutathione yeast extract (HDGB) in abbreviating alcohol intoxication and mitigating hangover symptoms. A total of 25 participants between the ages of 19 and 40 who had previously experienced a hangover were evaluated in a randomized, double-blind, crossover, placebo (PLA)-controlled clinical trial.

Dosage compensation of transposable elements in mammals.

In mammals, X-linked dosage compensation involves two processes: X-chromosome inactivation (XCI) to balance X chromosome dosage between males and females, and hyperactivation of the remaining X chromosome (Xa-hyperactivation) to achieve X-autosome balance in both sexes. Studies of both processes have largely focused on coding genes and have not accounted for transposable elements (TEs) which comprise 50% of the X-chromosome, despite TEs being suspected to have numerous epigenetic functions. This oversight is due in part to the technical challenge of capturing repeat RNAs, bioinformatically aligning them, and determining allelic origin.

Protocol for capturing a full transcriptome from single preimplantation embryos using So-Smart-seq.

Strand-optimized Smart-seq (So-Smart-seq) can capture a comprehensive transcriptome from low-input samples. This technique detects both polyadenylated and non-polyadenylated RNAs, inclusive of repetitive RNAs, while excluding highly abundant ribosomal RNAs. So-Smart-seq preserves strand information and minimizes 5' to 3' coverage bias.

Real-world evaluation of an evidence-based telemental health program for PTSD symptoms.

Blended care therapy (BCT), which augments live, video-based psychotherapy sessions with asynchronous digital tools, has the potential to increase access to evidence-based treatments for posttraumatic stress disorder (PTSD). However, its effectiveness in diverse, real-world settings is not well-understood. This evaluation aimed to assess clinical outcomes of a BCT program for PTSD symptoms.

Protocol for mapping RNA G-quadruplex for chromatin-bound RNA using d-rG4-seq.

Here, we present a protocol for using d-rG4-seq, a technique for mapping RNA G-quadruplex (rG4) for chromatin-bound RNA. We describe steps for identifying in vivo rG4 structures based on differential sensitivity of rG4 to dimethyl sulfate (DMS) modification, folding in the presence of monovalent cations, K+ versus Li+, and reverse transcriptase (RT) readthrough when folded. We then detail procedures for isolating RNA from the chromatin-bound fractions to enrich for epigenetic regulators and comparing in vitro versus in vivo profiles.

BTK regulates microglial function and neuroinflammation in human stem cell models and mouse models of multiple sclerosis.

Neuroinflammation in the central nervous system (CNS), driven largely by resident phagocytes, has been proposed as a significant contributor to disability accumulation in multiple sclerosis (MS) but has not been addressed therapeutically. Bruton's tyrosine kinase (BTK) is expressed in both B-lymphocytes and innate immune cells, including microglia, where its role is poorly understood. BTK inhibition may provide therapeutic benefit within the CNS by targeting adaptive and innate immunity-mediated disease progression in MS.

State of Practice on Transcranial MR-Guided Focused Ultrasound: A Report from the ASNR Standards and Guidelines Committee and ACR Commission on Neuroradiology Workgroup.

Transcranial focused ultrasound (FUS) is a versatile, MR-guided, incisionless intervention with diagnostic and therapeutic applications for neurologic and psychiatric diseases. It is currently FDA-approved as a thermoablative treatment of essential tremor and Parkinson disease. However, other applications of FUS including BBB opening for diagnostic and therapeutic applications, sonodynamic therapy, histotripsy, and low-intensity focused ultrasound neuromodulation are all in clinical trials.

Antibiotic Treatment for 7 versus 14 Days in Patients with Bloodstream Infections.

Background: Bloodstream infections are associated with substantial morbidity and mortality. Early, appropriate antibiotic therapy is important, but the duration of treatment is uncertain.

Methods: In a multicenter, noninferiority trial, we randomly assigned hospitalized patients (including patients in the intensive care unit [ICU]) who had bloodstream infection to receive antibiotic treatment for 7 days or 14 days.

Routine Spironolactone in Acute Myocardial Infarction.

Background: Mineralocorticoid receptor antagonists have been shown to reduce mortality in patients after myocardial infarction with congestive heart failure. Whether routine use of spironolactone is beneficial after myocardial infarction is uncertain.

Methods: In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients with myocardial infarction who had undergone percutaneous coronary intervention to receive either spironolactone or placebo and either colchicine or placebo.

In vivo models of subclonal oncogenesis and dependency in hematopoietic malignancy.

Cancer evolution is a multifaceted process leading to dysregulation of cellular expansion and differentiation through somatic mutations and epigenetic dysfunction. Clonal expansion and evolution is driven by cell-intrinsic and -extrinsic selective pressures, which can be captured with increasing resolution by single-cell and bulk DNA sequencing. Despite the extensive genomic alterations revealed in profiling studies, there remain limited experimental systems to model and perturb evolutionary processes.

Regulatory review of benefits and risks of preventing infant RSV disease through maternal immunization.

In August 2023, FDA approved Abrysvo for active immunization of pregnant individuals at 32 through 36 weeks gestational age to prevent lower respiratory tract disease (LRTD), including severe LRTD, caused by respiratory syncytial virus (RSV) in infants from birth through 6 months of age. A pragmatic approach to narrow the interval of use of Abrysvo in pregnant individuals balanced benefits of vaccine effectiveness against potential risks to infant and mother.

Global Comparison of COVID-19 Vaccination Rates among Psoriasis Patients.

(1) Background: The purpose of this study is to compare the rate of COVID-19 vaccination among psoriasis patients internationally and to correlate it with their treatment regimens. (2) Methods: We conducted a cross-sectional study from January 2021 to October 2022 among adults in the United States (US), Chile, China, Switzerland, and Singapore using the Global Healthcare Study on Psoriasis survey. (3) Results: A total of 310 psoriasis patients in the US (98), Chile (32), China (80), Switzerland (39), and Singapore (61) were surveyed.

Malformations of Cortical Development: Updated Imaging Review.

Malformations of cortical development (MCD) are structural anomalies that disrupt the normal process of cortical development. Patients with these anomalies frequently present with seizures, developmental delay, neurologic deficits, and cognitive impairment, resulting in a wide spectrum of neurologic outcomes. The severity and type of malformation, in addition to the genetic pathways of brain development involved, contribute to the observed variability.

PRC2-RNA interactions: Viewpoint from YongWoo Lee and Jeannie T. Lee.

Here, we expound on the view that Xist RNA directly controls Polycomb repressive complex 2 (PRC2) recruitment, off-loading to chromatin, catalytic activity, and eviction from chromatin. RNA-PRC2 interactions also control RNA polymerase II transcription pausing. Dynamic RNA folding determines PRC2 activity.

Senescence Rejuvenation through Reduction in Mitochondrial Reactive Oxygen Species Generation by Extract: In Vitro Evidence.

Oxidative stress caused by reactive oxygen species (ROS) is one of the major causes of senescence. Strategies to reduce ROS are known to be important factors in reversing senescence, but effective strategies have not been found. In this study, we screened substances commonly used as cosmetic additives to find substances with antioxidant effects.

Areal specializations in the morpho-electric and transcriptomic properties of primate layer 5 extratelencephalic projection neurons.

Large-scale analysis of single-cell gene expression has revealed transcriptomically defined cell subclasses present throughout the primate neocortex with gene expression profiles that differ depending upon neocortical region. Here, we test whether the interareal differences in gene expression translate to regional specializations in the physiology and morphology of infragranular glutamatergic neurons by performing Patch-seq experiments in brain slices from the temporal cortex (TCx) and motor cortex (MCx) of the macaque. We confirm that transcriptomically defined extratelencephalically projecting neurons of layer 5 (L5 ET neurons) include retrogradely labeled corticospinal neurons in the MCx and find multiple physiological properties and ion channel genes that distinguish L5 ET from non-ET neurons in both areas.