Decreasing miR-433-3p activity in the osteoblast lineage blunts glucocorticoid-mediated bone loss.

Glucocorticoid excess causes bone loss due to decreased bone formation and increased bone resorption; miR-433-3p is a miRNA that negatively regulates bone formation in male mice by targeting Runx2 as well as RNAs involved in Wnt, protein kinase A and endogenous glucocorticoid signaling. To examine the impact of miR-433-3p on glucocorticoid-mediated bone loss, transgenic mice expressing a miR-433-3p tough decoy inhibitor in the osteoblast lineage were administered prednisolone via slow-release pellets. Bone loss was greater in control mice treated with prednisolone compared with miR-433-3p tough decoy mice due to higher osteoclast activity in the controls.

The association between physician sex and patient outcomes: a systematic review and meta-analysis.

Background: Some prior studies have found that patients treated by female physicians may experience better outcomes, as well as lower healthcare costs than those treated by male physicians. Physician-patient sex concordance may also contribute to better patient outcomes. However, other studies have not identified a significant difference.

Real-world outcomes of first-line maintenance niraparib monotherapy in patients with epithelial ovarian cancer.

Aims: To assess real-world progression-free survival (rwPFS) and time to next treatment (rwTTNT) among patients with epithelial ovarian cancer (EOC) who received first-line maintenance (1LM) niraparib monotherapy.

Patients & Methods: In this US-nationwide, electronic health record-derived, deidentified database study, eligible patients with EOC initiated 1LM niraparib monotherapy (1 January 2017-1 December 2022) following first-line platinum-based chemotherapy. Median rwPFS and rwTTNT were estimated with Kaplan-Meier methodology overall and in a homologous recombination-deficient (HRd) subgroup (further stratified as wild-type [wt] or -mutated [m]).

Emotional Health of Transgender Youth 24 Months After Initiating Gender-Affirming Hormone Therapy.

Purpose: Limited data exist about the emotional health of transgender youth, either before or after initiation of gender-affirming hormone (GAH). The objectives were: (1) Investigate and verify the factor structure of the National Institutes of Health Toolbox Emotional Battery (NIHTB-EB) among trans and non-binary (TNB) youth; (2) Examine changes in emotional health over 24 months of GAH treatment; and (3) Examine the extent to which changes in emotional health were associated with improved appearance congruence (AC).

Methods: Study respondents were from Trans Youth Care - United States (TYCUS) study, an observational, prospective, longitudinal study of adolescents initiating GAH enrolled between 2016 and 2019.

Genetic Variants Associated with the Biochemical Response to Vitamin D3 in the Multi-Ethnic Study of Atherosclerosis.

Context: The response to treatment with vitamin D varies between patients.

Objective: To identify genetic variants associated with the biochemical response to vitamin D3 supplementation.

Design: Randomized placebo-controlled trial conducted between 2017 and 2019.

Hand dominance shift during sleep in sexsomnia: a clue to pathophysiology?

Study Objectives: To elucidate whether awake handedness in sexsomnia is retained during sleep to uncover potential clues about the underlying neurophysiologic mechanisms.

Methods: Participants' and observers' self-reported handedness during sexsomnia events.

Results: Case 1: A 22 y/o right-handed female with an eight-year history of nocturnal sleep-related masturbatory behavior (SMB) involving the left hand (LH) exclusively.

Cytotoxic T-Lymphocyte-Associated Protein 4 Fused to a Modified Fragment of IgG1 Reduces Muscle Fiber Damage in a Model of Duchenne Muscular Dystrophy by Attenuating Proinflammatory Gene Expression in Myeloid Lineage Cells.

Duchenne muscular dystrophy (DMD) is a lethal, muscle-wasting, genetic disease that is greatly amplified by an immune response to the diseased muscles. The mdx mouse model of DMD was used to test whether the pathology can be reduced by treatments with a cytotoxic T-lymphocyte-associated protein 4 fused to a modified fragment of IgG1 (CTLA4-Ig) fusion protein that blocks costimulatory signals required for activation of T cells. CTLA4-Ig treatments reduced mdx sarcolemma lesions and reduced the numbers of activated T cells, macrophages, and antigen-presenting cells in mdx muscle and reduced macrophage invasion into muscle fibers.

Intra-arterial tenecteplase after successful endovascular recanalisation in patients with acute posterior circulation arterial occlusion (ATTENTION-IA): multicentre randomised controlled trial.

Objective: To assess whether intra-arterial tenecteplase administered after successful endovascular recanalisation improves outcomes in patients with acute arterial occlusion of the posterior circulation.

Design: Multicentre randomised controlled trial.

Setting: 31 hospitals in China, 24 January 2023 to 24 August 2023.

Percutaneous Mechanical Aspiration for Infective Endocarditis: Proceedings From an Inaugural Multidisciplinary Summit and Comprehensive Review.

The clinical presentation and epidemiology of infective endocarditis (IE) have evolved over time. While the cornerstones of IE treatment remain antimicrobial therapy and surgery, percutaneous mechanical aspiration (PMA) has emerged as an option for carefully selected patients as a complementary modality, based on retrospective data, case series, and expert experience. In this comprehensive review, we summarize the proceedings from an inaugural summit dedicated to the discussion of PMA in the global management of IE, consisting of experts across multiple disciplines from diverse geographic regions and care environments.

Results from a phase 1b study of telisotuzumab vedotin in combination with osimertinib in patients with c-Met protein-overexpressing, EGFR-mutated locally advanced/metastatic non-small cell lung cancer (NSCLC) after progression on prior osimertinib.

Background: Osimertinib is the standard first-line treatment for advanced epidermal growth factor receptor (EGFR)-mutated NSCLC. However, treatment resistance is inevitable and increased c-Met protein expression correlates with resistance. Telisotuzumab vedotin (Teliso-V) is an antibody-drug conjugate that targets c-Met protein overexpression.

Intra-Arterial Tenecteplase Following Endovascular Reperfusion for Large Vessel Occlusion Acute Ischemic Stroke: The POST-TNK Randomized Clinical Trial.

Importance: The impact of adjunctive intra-arterial tenecteplase administration following near-complete to complete reperfusion by endovascular thrombectomy (EVT) for acute ischemic stroke is unknown.

Objective: To assess the efficacy and adverse events of adjunctive intra-arterial tenecteplase in patients with large vessel occlusion stroke who had achieved near-complete to complete reperfusion (defined as a score on the expanded Thrombolysis in Cerebral Infarction [eTICI] scale of 2c to 3) after EVT.

Design, Setting, And Participants: Investigator-initiated, randomized, open-label, blinded outcome assessment trial implemented at 34 hospitals in China among 540 patients with stroke due to proximal intracranial large vessel occlusion within 24 hours of the time they were last known to be well, with an eTICI score of 2c to 3 after EVT, and without prior intravenous thrombolysis.

Intra-Arterial Urokinase After Endovascular Reperfusion for Acute Ischemic Stroke: The POST-UK Randomized Clinical Trial.

Importance: Persisting or new thrombi in the distal arteries and the microcirculation have been reported to limit the benefits of successful endovascular thrombectomy for patients with acute ischemic stroke. It remains uncertain whether intra-arterial thrombolysis by urokinase following near-complete to complete reperfusion by thrombectomy improves outcomes among patients with ischemic stroke due to large vessel occlusion.

Objective: To assess the efficacy and adverse events of intra-arterial urokinase after near-complete to complete reperfusion by thrombectomy for acute ischemic stroke due to large vessel occlusion.

Effect of information awareness on attitudes toward human papillomavirus vaccination intentions in Japan.

Background: The Human Papillomavirus (HPV) vaccination rate among Japanese high school girls remains critically low, reflecting ongoing public apprehension and misinformation. This study explores the relationship between information presentation and attitudes toward HPV vaccination in Japan.

Methods: We conducted a web-based survey of female high school students aged 15 to 16 and mothers of daughters of similar age across Japan.

Physical Intimate Partner Violence Among Women Experiencing Homelessness Before and During Pregnancy.

Intimate partner violence (IPV) and homelessness can have devastating health consequences for pregnant women. Using the Pregnancy Risk Assessment Monitoring System, we assessed differences in the association of physical IPV before and/or during pregnancy with adverse health outcomes between women experiencing homelessness (WEH) and domiciled women. Among 186,891 respondents, representing an estimated 11,489,161 women, 27.

Assessing the Risk of Sexually Transmitted Infections among Men who have Sex with Men in San Francisco during COVID-19: A Socio-ecological Analysis.

Background: Men who have sex with men (MSM) are disproportionately affected by sexually transmitted infections, a disparity that has only worsened in recent years. During the COVID-19 pandemic, an overall increasing trend remained.

Methods: We utilized data from the MSM cycle of the National HIV Behavioral Surveillance (NHBS) study in San Francisco, California, conducted from June 2021 through December 2021, to identify socio-ecological disruptions during the COVID-19 pandemic that were associated with sexually transmitted infections.

Deep learning model to identify and validate hypotension endotypes in surgical and critically ill patients.

Background: Hypotension is associated with organ injury and death in surgical and critically ill patients. In clinical practice, treating hypotension remains challenging because it can be caused by various underlying haemodynamic alterations. We aimed to identify and independently validate endotypes of hypotension in big datasets of surgical and critically ill patients using unsupervised deep learning.

Carbohydrate Ingestion Eliminates Hypoglycemia & Improves Endurance Exercise Performance in Triathletes Adapted to Very Low & High Carbohydrate Isocaloric Diets.

Very-low-carbohydrate diets (LCHF; <50g/day) have been debated for their potential to lower pre-exercise muscle and liver glycogen stores and metabolic efficiency, risking premature fatigue. It is also hypothesized that carbohydrate ingestion during prolonged exercise delays fatigue by increasing carbohydrate oxidation, thereby sparing muscle glycogen. Leveraging a randomized crossover design, we evaluated performance during strenuous time-to-exhaustion (70%⩒O) tests in trained triathletes following 6-week high-carbohydrate (HCLF, 380g/day) or very-low-carbohydrate (LCHF, 40g/day) diets to determine (i) if adoption of the LCHF diet impairs time-to-exhaustion performance, (ii) whether carbohydrate ingestion (10g/hour) 6-12x lower than current CHO fuelling recommendations during low glycogen availability (>15-hour pre-exercise overnight fast and/or LCHF diet) improves time-to-exhaustion by preventing exercise-induced hypoglycemia (EIH; <3.

Automated quantification of anterior chamber cells using swept-source anterior segment optical coherence tomography.

Purpose: To validate automated counts of presumed anterior chamber (AC) cells in eyes with histories of uveitis involving the anterior segment using swept-source (SS) anterior segment optical coherence tomography (AS-OCT) against manual counts and compare automated counts against Standardized Uveitis Nomenclature (SUN) criteria.

Methods: Eyes were imaged with the ANTERION SS AS-OCT device (Heidelberg Engineering). A fully automated custom algorithm quantified the number of hyper-reflective foci (HRF) in line-scan images.

Lebrikizumab decreases type 2 inflammatory biomarker levels in patients with asthma: data from randomized phase 3 trials (LAVOLTA I and II).

Aim: Lebrikizumab is an interleukin (IL)-13 inhibitor that specifically blocks IL-13 signaling. Here, we report the effects of lebrikizumab on asthma serum biomarkers in 2 phase 3 clinical studies.

Methods: LAVOLTA I and LAVOLTA II are replicate, double-blind, placebo-controlled trials with 52-week placebo-controlled treatment periods that evaluated lebrikizumab 37.

Regulation of mutant huntingtin mitochondrial toxicity by phosphomimetic mutations within its N-terminal region.

Huntington's disease (HD), a neurodegenerative disease, affects approximately 30,000 people in the United States, with 200,000 more at risk. Mitochondrial dysfunction caused by mutant huntingtin (mHTT) drives early HD pathophysiology. mHTT binds the translocase of mitochondrial inner membrane (TIM23) complex, inhibiting mitochondrial protein import and altering the mitochondrial proteome.