Acceptability of a dapivirine levonorgestrel vaginal ring in two Phase 1 trials (MTN-030/IPM 041 and MTN-044/IPM 053/CCN019): Implications for multipurpose prevention technology development.

End-user feedback early in product development is important for optimizing multipurpose prevention technologies for HIV and pregnancy prevention. We evaluated the acceptability of the 90-day dapivirine levonorgestrel ring (DPV-LNG ring) used for 14 days compared to a dapivirine-only ring (DVR-200mg) in MTN-030/IPM 041 (n = 23), and when used for 90 days cyclically or continuously in MTN-044/IPM 053/CCN019 (n = 25). We enrolled healthy, non-pregnant, HIV-negative women aged 18-45 in Pittsburgh, PA and Birmingham, AL (MTN-030 only).

Implementation of a data-driven quality improvement program in primary care for patients with coronary heart disease: a mixed methods evaluation of acceptability, satisfaction, barriers and enablers.

Background The study aimed to understand the acceptability, satisfaction, uptake, utility and feasibility of a quality improvement (QI) intervention to improve care for coronary heart disease (CHD) patients in Australian primary care practices and identify barriers and enablers, including the impact of COVID-19. Methods Within the QUality improvement for Effectiveness of care for people Living with heart disease (QUEL) study, 26 Australian primary care practices, supported by five Primary Health Networks (PHN) participated in a 1-year QI intervention (November 2019 - November 2020). Data were collected from practices and PHNs staff via surveys and semi-structured interviews.

Ketamine Infusion for Complex Regional Pain Syndrome Treatment: A Narrative Review.

Purpose Of Review: Complex Regional Pain Syndrome (CRPS) is a neuropathic pain disorder characterized by pain disproportionate to the inciting event that is constant for an extended duration. Numerous treatment options for this condition have been explored with unsatisfactory results in many cases. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist typically used as an anesthetic and analgesic, presents a promising potential treatment for CRPS in patients who fail to respond to traditional therapies.

Optical Coherence Tomography Angiography in Patients With the Boston Keratoprosthesis Type 1.

Purpose: To report on optical coherence tomography angiography (OCTA) in patients with a type 1 Boston keratoprosthesis (KPro) and determine its feasibility through assessment of imaging artifacts.

Methods: KPro and non-KPro subjects were matched for age, gender, and glaucoma diagnosis. OCTA images of the peripapillary optic nerve were obtained, reviewed by 2 readers masked to the diagnosis for artifacts and usability, and used for microvascular measurements.

Optimizing Exposure Measures in Large-Scale Household Air Pollution Studies: Results from the Multicountry HAPIN Trial.

Repeated measurements of household air pollution may provide better estimates of average exposure but can add to costs and participant burden. In a randomized trial of gas versus biomass cookstoves in four countries, we took supplemental personal 24-h measurements on a 10% subsample for mothers and infants, interspersed between protocol samples. Mothers had up to five postrandomization protocol measurements over 16 months, while infants had three measurements over one year.

Exposure Contrasts of Women Aged 40-79 Years during the Household Air Pollution Intervention Network Randomized Controlled Trial.

Exposure to household air pollution has been linked to adverse health outcomes among women aged 40-79. Little is known about how shifting from biomass cooking to a cleaner fuel like liquefied petroleum gas (LPG) could impact exposures for this population. We report 24-h exposures to particulate matter (PM), black carbon (BC), and carbon monoxide (CO) among women aged 40 to <80 years participating in the Household Air Pollution Intervention Network trial.

Investigating eating architecture and the impact of the precision of recorded eating time: a cross-sectional study.

Background: The precision of recorded eating times directly affects the estimation of eating architecture i.e. size, timing, and frequency of eating.

Changes and persistence in heart rate variability before and during social stress: A comparison of individuals with and without social anxiety disorder.

Individuals with social anxiety disorder (SAD) experience significant and persistent fear of social situations as they anticipate rejection, scrutiny, and embarrassment. Given that physiological reactions to social situations may shape emotional experience in SAD, understanding psychophysiological changes operating in SAD may be important to address this potentially key perpetuating factor. This study compared the patterns of change (via contrasts of estimated marginal means) and persistence (via autoregressive models) of two indices of heart rate variability (HRV; Root Mean Square of Successive Differences between normal heartbeats, and High-Frequency absolute units) as physiological measures of emotion regulation, between individuals with SAD (n = 94) and without (n = 59) using the Trier Social Stress Test phases (TSST).

Treatment efficacy prediction of focused ultrasound therapies using multi-parametric magnetic resonance imaging.

Magnetic resonance guided focused ultrasound (MRgFUS) is one of the most attractive emerging minimally invasive procedures for breast cancer, which induces localized hyperthermia, resulting in tumor cell death. Accurately assessing the post-ablation viability of all treated tumor tissue and surrounding margins immediately after MRgFUS thermal therapy residual tumor tissue is essential for evaluating treatment efficacy. While both thermal and vascular MRI-derived biomarkers are currently used to assess treatment efficacy, currently, no adequately accurate methods exist for the in vivo determination of tissue viability during treatment.

Association of Pre- and Postinjury Mental Health With Long-term Clinical and Financial Outcomes.

Background: As increased attention is placed on optimizing long-term outcomes of trauma patients by addressing mental health, little is known regarding the interplay of pre- and postinjury mental health on long-term financial and functional outcomes.

Methods: Patients from 19 Level 1 and 2 trauma centers took part in serial surveys 1 to 24 months postdischarge. Preinjury mental health diagnoses were identified using trauma registry data and postinjury mental health symptoms from survey data.

Pacific Northwest native plants and native cultivars, part I: pollinator visitation.

Planting native flora is a popular conservation strategy for pollinators. When searching for native plants, consumers may encounter cultivars of native plants, which can have different phenotypic traits than plants found in wild populations ("wild-type native plants"). Previous research evaluating pollinator visitation to wild-type native plants and native cultivars has yielded mixed results, in terms of whether their visitation rates are similar or distinct.

Combinations of substances contributing to death among overdose decedents in Maryland (2020-2021).

Background: In 2020, Maryland had the fourth-highest opioid overdose mortality rate in the USA. We describe substances identified in postmortem toxicology screening and designated as cause of death (COD) for overdose decedents in Maryland, including specific combinations of substances designated as COD.

Methods: We performed a retrospective analysis of N=5442 adult overdose decedents (ie, manner of death unintentional or undetermined) in Maryland between January 2020 and December 2021.

Cell state-dependent allelic effects and contextual Mendelian randomization analysis for human brain phenotypes.

Gene expression quantitative trait loci are widely used to infer relationships between genes and central nervous system (CNS) phenotypes; however, the effect of brain disease on these inferences is unclear. Using 2,348,438 single-nuclei profiles from 391 disease-case and control brains, we report 13,939 genes whose expression correlated with genetic variation, of which 16.7-40.

Optimizing Exclusion Criteria for Clinical Trials of Persistent Lyme Disease Using Real-World Data.

Background/objectives: Although eligibility criteria for clinical trials significantly impact study outcomes, these criteria are often established without scientific justification, leading to delayed recruitment, small sample sizes, and limited study generalizability. Persistent Lyme disease (PLD) presents unique challenges due to symptom variability, inconsistent treatment responses, and the lack of reliable biomarkers, underscoring the need for scientifically justified eligibility criteria.

Objective: This study examines the effects of commonly used enrollment criteria on sample yield in PLD clinical trials using real-world data (RWD) from the MyLymeData patient registry.

A Rare Case of Congenital Buccal Lipoblastoma in a Term Neonate.

A lipoblastoma is a benign tumor of adipocytes originating from embryonic white fat and occurs in the pediatric population. Congenital lipoblastomas, however, are rare, and the incidence of these tumors in neonates is unknown. Due to their rare presentation, congenital oral lipoblastomas can, firstly, pose diagnostic challenges for the pediatrician and must be differentiated from the more commonly seen oral lesions in the newborn and other rare malignant growths.

A phase I study of temsirolimus in combination with metformin in patients with advanced or recurrent endometrial cancer.

Introduction: Molecular alterations in the PI3K/AKT and Ras/Raf/MEK/ERK pathways are frequently observed in patients with endometrial cancers. However, mTOR inhibitors, such as temsirolimus, have modest clinical benefits. In addition to inducing metabolic changes in cells, metformin activates AMPK, which in turn inhibits the mTOR pathway.

Bile acid synthesis impedes tumor-specific T cell responses during liver cancer.

The metabolic landscape of cancer greatly influences antitumor immunity, yet it remains unclear how organ-specific metabolites in the tumor microenvironment influence immunosurveillance. We found that accumulation of primary conjugated and secondary bile acids (BAs) are metabolic features of human hepatocellular carcinoma and experimental liver cancer models. Inhibiting conjugated BA synthesis in hepatocytes through deletion of the BA-conjugating enzyme bile acid-CoA:amino acid -acyltransferase (BAAT) enhanced tumor-specific T cell responses, reduced tumor growth, and sensitized tumors to anti-programmed cell death protein 1 (anti-PD-1) immunotherapy.

Outcomes of Immunotherapy Treatment in Sinonasal Mucosal Melanoma.

Background: Sinonasal mucosal melanoma has poor survival despite multimodality treatment. While the impact of immunotherapy (IT) on metastatic cutaneous melanoma is well-defined, there are relatively little data on sinonasal mucosal melanoma.

Objective: We sought to define immunotherapy outcomes in patients with sinonasal mucosal melanoma.

The inductive effect does not explain electron density in haloacetates: are our textbooks wrong?

The inductive effect is a central concept in chemistry and is often exemplified by the p values of acetic acid derivatives. The reduction in p is canonically attributed to the reduction in the electron density of the carboxylate group through the inductive effect. However, wave functional theory calculations presented herein reveal that the charge density of the carboxylate group is not explained by the inductive effect.

Impact of Social Determinants of Health on Pre-exposure Prophylaxis Care for HIV Prevention.

Background: HIV continues to disproportionately impact men who have sex with men (MSM) in the United States (US). Pre-exposure prophylaxis (PrEP) is effective, but disparities persist. Limited studies have conducted systematic evaluations of social determinants of health (SDOH) and their effects on PrEP persistence among MSM.

Attitudes toward scale-up of an Intensive Combination Approach to Rollback the Epidemic in Nigerian adolescents (iCARE) intervention for youth in Nigeria: results of a mixed methods early-implementation study.

Background: Youth living with HIV (YLH) are disproportionately impacted by HIV with poor outcomes along the entire HIV care continuum. In a 2020-2022 pilot study, iCARE Nigeria, successfully tested a combination intervention incorporating mobile health technology and peer navigation to: 1) improve testing and linkage to HIV care for young men, especially young men who have sex with men (YMSM) and 2) improve medication adherence and treatment outcomes for YLH. The intervention was scaled up to 5 sites in 3 Nigerian cities.

The effects of social loss and isolation on partner odor investigation and dopamine and oxytocin receptor expression in female prairie voles.

In humans, grief is characterized by intense sadness, intrusive thoughts of the deceased, and intense longing for reunion with the deceased. Human fMRI studies show hyperactivity in emotional pain and motivational centers of the brain when an individual is reminded of a deceased attachment figure, but the molecular underpinnings of these changes in activity are unknown. Prairie voles (Microtus ochrogaster), which establish lifelong social bonds between breeding pairs, also display distress and motivational shifts during periods of prolonged social loss, providing a model to investigate these behavioral and molecular changes at a mechanistic level.

Priorities for research on improving health behaviours for optimal mental health of Australian university students: A twin-panel Delphi study.

Issue Addressed: University students are at risk of poor health behaviours which negatively affect mental health and wellbeing. Informing the implementation of appropriate strategies to support Australian university students' health and wellbeing, requires quality evidence. This study aimed to identify research priorities for improving health behaviours to optimise mental health of Australian university students.

Decoding the Torsional Dynamics of Main-Chain Atoms Within CαNN Motif Facilitating Specific Anion Recognition.

The structural plasticity of proteins at the molecular level is largely dictated by backbone torsion angles, which play a critical role in ligand recognition and binding. To establish the anion-induced cooperative arrangement of the main-chain (mc) torsion, herein, we analyzed a set of naturally occurring CαNN motifs as "static models" for their anion-binding competence through docking and molecular dynamics simulations and decoded its torsion angle influenced mc-driven anion recognition potential. By comparing a pool of 20 distinct sets of CαNN motif with identical sequences in their "anion bound/present, aP" and "anion free/absent, aA" versions, we could discern that there exists a positive correlation between the "difference of anion residence time (ΔR)" and "difference among the main-chain torsion angle" of the aP and aA population.

Unraveling the elongating bovine conceptus microenvironment: identification of gene transcripts and proteins along the conceptus-maternal interface in cattle.

The bovine conceptus elongates near Day 16 of development and releases interferon-tau (IFNT), disrupting the endometrial luteolytic mechanism to sustain luteal P4 and pregnancy. Conceptus factors other than IFNT modify local endometrial activities to support pregnancy; however, the microenvironment is largely uncharacterized. We utilized a bovine conceptus-endometrial culture system to elucidate the microenvironment in the form of RNA and protein.