Pharmacokinetic interaction assessment of an HIV broadly neutralizing monoclonal antibody VRC07-523LS: a cross-protocol analysis of three phase 1 trials in people without HIV.

VRC07-523LS is a safe and well-tolerated monoclonal antibody (mAb) targeting the CD4 binding site on the HIV envelope (Env) trimer. Efficacy of VRC07-523LS, in combination with mAbs targeting other HIV epitopes, will be evaluated in upcoming trials to prevent HIV acquisition in adults. However, differences in the pharmacokinetics (PK) of VRC07-523LS when administered alone vs.

Maternal and infant outcomes of pregnancy after kidney transplantation: a retrospective cohort study.

Purpose: To investigate the effect of postoperative pregnancy on maternal-infant outcomes and transplanted kidney function in kidney transplantation (KT) recipients.

Methods: Our study included 104 KT recipients and 104 non-KT women who delivered at four hospitals affiliated with Zhejiang University School of Medicine from December 2015 to November 2023.

Results: In the KT group, kidney function showed a downward trend after delivery, and most patients recovered normal kidney function within 6 months postpartum.

Sleeve Gastrectomy Versus Semaglutide for Weight Loss in a Severely Obese Minority Cohort: A Propensity-Matched Study.

Background: The rising obesity rates in the USA have led to a surge in various weight loss treatments. Glucagon-like peptide-1 (GLP-1) analogues have shown promise in reducing weight but primarily studied in Caucasian populations. Sleeve gastrectomy (SG) has already proven successful weight loss outcomes.

Safety, tolerability, pharmacokinetics, and neutralisation activities of the anti-HIV-1 monoclonal antibody PGT121.414.LS administered alone and in combination with VRC07-523LS in adults without HIV in the USA (HVTN 136/HPTN 092): a first-in-human, open-label, randomised controlled phase 1 trial.

Background: Multiple broadly neutralising monoclonal antibodies (mAbs) are in development for HIV-1 prevention. The aim of this trial was to test the PGT121.414.

MicroRNA-33 regulates the synaptic plasticity-related gene ARC in temporal lobe epilepsy.

This study aimed to elucidate the expression patterns of miR-33 and ARC in both a rat model of temporal lobe epilepsy (TLE) and human TLE patients, to explore the role of miR-33 in epilepsy onset through its regulation of ARC expression in the hippocampus. Our findings, supported by a Dual-Luciferase reporter assay, suggest that miR-33 can bind to the 3' UTR region of ARC. We observed that miR-33 levels were reduced at 1 hour and 60 days post-seizure, while ARC expression notably increased at these time points.

The role of hypertension in the relationship between leisure screen time, physical activity and migraine: a 2-sample Mendelian randomization study.

Background: The relationship between lifestyle and migraine is complex, as it remains uncertain which specific lifestyle factors play the most prominent role in the development of migraine, or which modifiable metabolic traits serve as mediators in establishing causality.

Methods: Independent genetic variants strongly associated with 20 lifestyle factors were selected as instrumental variables from corresponding genome-wide association studies (GWASs). Summary-level data for migraine were obtained from the FinnGen consortium (18,477 cases and 287,837 controls) as a discovery set and the GWAS meta-analysis data (26,052 cases and 487,214 controls) as a replication set.

Impact of LS Mutation on Pharmacokinetics of Preventive HIV Broadly Neutralizing Monoclonal Antibodies: A Cross-Protocol Analysis of 16 Clinical Trials in People without HIV.

Monoclonal antibodies are commonly engineered with an introduction of Met428Leu and Asn434Ser, known as the LS mutation, in the fragment crystallizable region to improve pharmacokinetic profiles. The LS mutation delays antibody clearance by enhancing binding affinity to the neonatal fragment crystallizable receptor found on endothelial cells. To characterize the LS mutation for monoclonal antibodies targeting HIV, we compared pharmacokinetic parameters between parental versus LS variants for five pairs of anti-HIV immunoglobin G1 monoclonal antibodies (VRC01/LS/VRC07-523LS, 3BNC117/LS, PGDM1400/LS PGT121/LS, 10-1074/LS), analyzing data from 16 clinical trials of 583 participants without HIV.

Effects of Narrative Exposure Therapy for Treating Depressive and Anxious Disorders: A Systematic Review and Meta-Analysis.

Objective: Narrative exposure therapy (NET) has been used in various contexts for the treatment of the effects of trauma, with promising results in clinical trials. However, its effects on anxiety and depression are still unclear. The present study is a systematic review and meta-analysis of the effects of NET on depression and anxiety.

" Challenges to Antiretroviral Therapy Adherence in Kampala, Uganda.

The aim of this study wasto advance knowledge of the social, geographical, and economic complexities faced by people on cART and to understand how they navigate treatment adherence within the urban context of Kampala, Uganda.Semi-structured interviews (n=30) were conducted with individuals receiving HIV treatment from the Joint Clinical Research Centre (JCRC) in Kampala. The thematic analysis of the interview transcripts was conducted in NVivo, with direct quotations from the transcripts used to illustrate key themes.

Impact of Opera on Resilience and Thriving in Serious Mental Illness: Pilot Evaluation of The Center Cannot Hold Part 2 and Resilience Workshop.

There are few studies of impacts of arts on recovery in schizphrenia, on audience mood and social connection. We developed a pilot evaluation of opera performances in a university setting on Elyn Saks' journey from psychosis, teaching law and falling in love, coupled with pre-opera workshop on approaches to resilience. Using surveys, primary outcomes were pre and post affect (PANAS-X positive, negative; visual "affect grid" touchscreen for affective valence and arousal) and social connectedness with secondary outcomes of increasing understanding, reducing stigma and willingness to socialize or serve persons with mental illness.

Robustness to Spurious Correlations Improves Semantic Out-of-Distribution Detection.

Methods which utilize the outputs or feature representations of predictive models have emerged as promising approaches for out-of-distribution (ood) detection of image inputs. However, these methods struggle to detect ood inputs that share nuisance values (e.g.

Low pulse pressure and high serum complement C1q are risk factors for hemodialysis headache: A case-control study.

Background And Objective: Hemodialysis headache (HDH) is a common complication of dialysis that negatively affects the patient's quality of life. The etiology and triggering factors of HDH are not fully understood. This study aims to assess the prevalence and characteristics of HDH among patients undergoing hemodialysis across multiple centers in China.

Adults on pre-exposure prophylaxis (tenofovir-emtricitabine) have faster clearance of anti-HIV monoclonal antibody VRC01.

Broadly neutralizing monoclonal antibodies (mAbs) are being developed for HIV-1 prevention. Hence, these mAbs and licensed oral pre-exposure prophylaxis (PrEP) (tenofovir-emtricitabine) can be concomitantly administered in clinical trials. In 48 US participants (men and transgender persons who have sex with men) who received the HIV-1 mAb VRC01 and remained HIV-free in an antibody-mediated-prevention trial (ClinicalTrials.

The Role of Circadian Rhythm in Neurological Diseases: A Translational Perspective.

Intrinsic biological clocks drive the circadian rhythm, which coordinates the physiological and pathophysiological processes in the body. Recently, a bidirectional relationship between circadian rhythms and several neurological diseases has been reported. Neurological diseases can lead to the disruption of circadian homeostasis, thereby increasing disease severity.

Safety, tolerability, pharmacokinetics, and immunological activity of dual-combinations and triple-combinations of anti-HIV monoclonal antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS administered intravenously to HIV-uninfected adults: a phase 1 randomised trial.

Background: Preclinical and clinical studies suggest that combinations of broadly neutralising antibodies (bnAbs) targeting different HIV envelope epitopes might be required for sufficient prevention of infection. We aimed to evaluate the dual and triple anti-HIV bnAb combinations of PGDM1400 (V2 Apex), PGT121 (V3 glycan), 10-1074 (V3 glycan), and VRC07-523LS (CD4 binding site).

Methods: In this phase 1 trial (HVTN 130/HPTN 089), adults without HIV were randomly assigned (1:1:1) to three dual-bnAb treatment groups simultaneously, or the triple-bnAb group, receiving 20 mg/kg of each antibody administered intravenously at four centres in the USA.

Virtual versus In-Person Ophthalmology Interviews: Perceptions of U.S. Ophthalmology Fellowship Applicants in 2022-2023.

 Despite easing restrictions on social distancing and travel since the beginning of coronavirus disease 2019 pandemic, virtual interviews remain a widely used format for ophthalmology fellowship interviews. This study aims to evaluate the relative benefits and drawbacks of in-person versus virtual interviews during a cycle where both formats were prevalent.  A prospective cross-sectional study surveyed all fellowship applicants (  = 311) who applied to Wills Eye Hospital and Bascom Palmer Eye Institute during the 2022 to 2023 application cycle.

Aryl hydrocarbon receptors improve migraine-like pain behaviors in rats through the regulation of regulatory T cell/T-helper 17 cell-related homeostasis.

Objective: To investigate the effect of the aryl hydrocarbon receptor (AHR)/regulatory T cell (Treg)/T-helper 17 (Th17) cell pathway on the pathogenesis of migraine.

Background: Migraine is a disabling neurovascular disease that imposes an enormous burden on both individuals and society. The pathophysiological mechanisms of migraine remain controversial.

Clinical and Demographic Factors Associated With COVID-19, Severe COVID-19, and SARS-CoV-2 Infection in Adults: A Secondary Cross-Protocol Analysis of 4 Randomized Clinical Trials.

Importance: Current data identifying COVID-19 risk factors lack standardized outcomes and insufficiently control for confounders.

Objective: To identify risk factors associated with COVID-19, severe COVID-19, and SARS-CoV-2 infection.

Design, Setting, And Participants: This secondary cross-protocol analysis included 4 multicenter, international, randomized, blinded, placebo-controlled, COVID-19 vaccine efficacy trials with harmonized protocols established by the COVID-19 Prevention Network.

Pharmacokinetic serum concentrations of VRC01 correlate with prevention of HIV-1 acquisition.

Background: The phase 2b proof-of-concept Antibody Mediated Prevention (AMP) trials showed that VRC01, an anti-HIV-1 broadly neutralising antibody (bnAb), prevented acquisition of HIV-1 sensitive to VRC01. To inform future study design and dosing regimen selection of candidate bnAbs, we investigated the association of VRC01 serum concentration with HIV-1 acquisition using AMP trial data.

Methods: The case-control sample included 107 VRC01 recipients who acquired HIV-1 and 82 VRC01 recipients who remained without HIV-1 during the study.

PACAP6-38 improves nitroglycerin-induced central sensitization by modulating synaptic plasticity at the trigeminal nucleus caudalis in a male rat model of chronic migraine.

Aims: Chronic migraine (CM) is a common neurological disorder with complex pathogenesis. Evidence suggests that pituitary adenylate cyclase-activating peptide (PACAP) induces migraine-like attacks and may be potential a new target for migraine treatment, but the therapeutic results of targeting PACAP and its receptors are not uniform. Therefore, the aim of this study was to investigate the regulatory effect of PACAP type I receptor (PAC1R) antagonist, PACAP6-38, on nitroglycerin (NTG)-induced central sensitization in a CM model.

2-Deoxyglucose alleviates migraine-related behaviors by modulating microglial inflammatory factors in experimental model of migraine.

Background: Targeting metabolic pathways has emerged as a new migraine treatment strategy as researchers realize the critical role metabolism plays in migraine. Activated inflammatory cells undergo metabolic reprogramming and rely on glycolysis to function. The objective of this study was to investigate the glycolysis changes in the experimental model of migraine and the effect of glycolysis inhibitor 2-Deoxy-D-glucose (2-DG) in the pathophysiology of migraine.

Burden of Common Neurologic Diseases in Asian Countries, 1990-2019: An Analysis for the Global Burden of Disease Study 2019.

Background And Objectives: Based on the Global Burden of Diseases, Injuries, and Risk Factors (GBD) study, neurologic disorders are a major cause of morbidity and mortality worldwide. However, there has been no comprehensive assessment of neurologic disorders in Asia. Data from the GBD 1990-2019 study were investigated to provide new details for neurologic disorders in Asia.

Inhibiting PAC1 receptor internalization and endosomal ERK pathway activation may ameliorate hyperalgesia in a chronic migraine rat model.

Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multipotent neuropeptide widely distributed in the trigeminovascular system (TVS) and higher brain regions. At present, the underlying mechanism of PACAP/PACAP type1 (PAC1) receptor in migraine generation remains unclear.

Methods: The rat model of chronic migraine (CM) was established by repeated intraperitoneal injection of nitroglycerin (NTG).