Gender and Race Differences in Rates of PTSD Service Connection: Results From a Nationally Representative Panel of OEF/OIF/OND Veterans.

Background: Department of Veterans Affairs disability benefits for post-traumatic stress disorder (PTSD), also known as "service connection," have been shown to reduce homelessness and poverty, increase mental health engagement, and improve clinical outcomes. However, gender and race disparities in PTSD service connection have been described in Vietnam and post-Vietnam era Veterans.

Methods: Post-traumatic stress disorder service connection outcomes were assessed in a nationally representative, randomly selected, gender-stratified, prospective panel of 960 Veterans who served during Operations Enduring Freedom, Iraqi Freedom, and New Dawn.

Next generation bioelectronic medicine: making the case for non-invasive closed-loop autonomic neuromodulation.

The field of bioelectronic medicine has advanced rapidly from rudimentary electrical therapies to cutting-edge closed-loop systems that integrate real-time physiological monitoring with adaptive neuromodulation. Early innovations, such as cardiac pacemakers and deep brain stimulation, paved the way for these sophisticated technologies. This review traces the historical and technological progression of bioelectronic medicine, culminating in the emerging potential of closed-loop devices for multiple disorders of the brain and body.

N-Branched Tricyclic Guanidines as Novel Melanocortin-3 Receptor Agonists and Melanocortin-4 Receptor Antagonists.

The melanocortin receptors are a class of centrally and peripherally expressed G protein-coupled receptors, of which the MC3R and MC4R subtypes are implicated in the regulation of appetite and energy homeostasis and can serve as potential therapeutic targets for disorders such as obesity and cachexia. An unbiased high-throughput mixture-based library screen was implemented to identify novel ligands with an emphasis on the identification of nanomolar-potent agonists of the mouse melanocortin-3 receptor. This screen yielded the discovery of an N-branched tricyclic guanidine scaffold (TPI2408) that contained three nanomolar potent mMC3R agonists and additional compounds that possessed antagonism for the mMC4R.

Why do people in the U.S. pay more for Bouillabaisse than Kaeng Som? Experimental tests of how cuisine and authenticity affect the value of food.

The average prices of foods vary across cuisines but do these differences reflect the value people assign to different cuisines or how much they are willing to pay? Across four preregistered randomized experiments (total N=1,083), we manipulated the cuisine-of-origin (French, Thai) and authenticity (low, high) descriptions for analogous dishes across cuisines (e.g., two seafood stews: French bouillabaisse and Thai kaeng som) and restaurant review pages in Studies 2-4.

Site-specific plan-view (S)TEM sample preparation from thin films using a dual-beam FIB-SEM.

To fully evaluate the atomic structure, and associated properties of materials using transmission electron microscopy, examination of samples from three non-collinear orientations is needed. This is particularly challenging for thin films and nanoscale devices built on substrates due to limitations with plan-view sample preparation. In this work, a new method for preparation of high-quality, site-specific, plan-view TEM samples from thin-films grown on substrates, is presented and discussed.

Situating the salience and parietal memory networks in the context of multiple parallel distributed networks using precision functional mapping.

Brain networks serving higher cognitive functions are widely distributed across frontal and posterior association zones. Two exceptions have been the parietal memory network (PMN) and salience network (SAL), which are typically restricted to posterior (e.g.

Functional variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are associated with increased risk of colorectal cancer.

Background: Individuals with cystic fibrosis (CF; a recessive disorder) have an increased risk of colorectal cancer (CRC). Evidence suggests individuals with a single CFTR variant may also have increased CRC risk.

Methods: Using population-based studies (GECCO, CORECT, CCFR, and ARIC; 53 785 CRC cases and 58 010 controls), we tested for an association between the most common CFTR variant (Phe508del) and CRC risk.

A Phase II Trial of Onapristone and Fulvestrant for Patients With ER+ and HER2- Metastatic Breast Cancer.

Background: The SMILE study is a multi-institutional phase II clinical trial to determine the efficacy and safety of an antiprogestin, onapristone, in combination with fulvestrant as second-line therapy for patients with ER+, PgR+/-, HER2- metastatic breast cancer. This study was terminated early and herein, we report patient characteristics, and outcomes.

Methods: Eligibility criteria included disease progression on ≥2 lines of prior therapy, ECOG performance status ≤ 2, measurable disease per RECIST 1.

Guidance on the assessment of the functionality of biomaterials for periodontal tissue regeneration: Methodologies and testing procedures.

Innovative biomaterials and tissue engineering strategies show great promise in regenerating periodontal tissues. This guidance provides an overview and detailed recommendations for evaluating the biological functionality of these new biomaterials in vitro, focusing on mineralization, immunomodulatory effects, cellular differentiation, and angiogenesis. Additionally, it discusses the use of in vivo experimental models that mimic periodontitis and scrutinizes methods such as osteogenic differentiation, immunomodulation, and anti-inflammatory responses to assess the effectiveness of these biomaterials in promoting periodontal tissue reconstruction.

Metabolically Stable Adenylation Inhibitors of Biotin Protein Ligase as Antibacterial Agents.

The antibacterial agent Bio-AMS is metabolized in vivo through hydrolysis of the central acyl-sulfamide linker leading to high clearance and release of a moderately cytotoxic metabolite . Herein, we disclose analogues designed to prevent the metabolism of the central acyl-sulfamide moiety through steric hindrance or attenuation of the acyl-sulfamide electrophilicity. was identified as a metabolically stable analogue with a single-digit nanomolar dissociation constant for biotin protein ligase (BPL) and minimum inhibitory concentrations (MICs) against and ranging from 0.

Rapid (≤25 °C) cycloisomerization of anhydride-tethered triynes to benzynes - origin of a remarkable anhydride linker-induced rate enhancement.

The hexadehydro-Diels-Alder (HDDA) reaction is a cycloisomerization between a conjugated diyne and a tethered diynophile that generates -benzyne derivatives. Considerable fundamental understanding of aryne reactivity has resulted from this body of research. The multi-yne cycloisomerization substrate is typically pre-formed and the (rate-limiting) closure of this diyne/diynophile pair to produce the isomeric benzyne generally requires thermal input, often requiring reaction temperatures of >100 °C and times of 16-48 h to achieve near-full conversion.

Centering historically minoritized populations to design effective messages about an evidence-based policy to advance social equity.

Researchers have raised concerns that messages describing racial disparities in social outcomes can reduce or polarize support for public policies to address inequality. We questioned this assumption by testing the impact of carefully crafted messages about child tax credit (CTC) expansion. We conducted two randomized message trials, study 1 using Prolific's nonprobability panel ( = 1,402) and study 2 using SSRS's Opinion Panel, a web-based probability sample of US adults ( = 4,483).

Genome-wide association study of urinary cadmium levels in current smokers from the multiethnic cohort study.

Background: Cadmium (Cd), classified as an International Agency for Research on Cancer (IARC) Group 1 human carcinogen, is present in cigarette smoke. Recent studies have illustrated the potential role of genetics in influencing Cd biomarker levels.

Methods: We conducted a genome-wide association study (GWAS) of urinary Cd levels in 1977 current smokers from the Multiethnic Cohort Study, comprising participants from five different racial and ethnic groups.

Oxidative stress suppresses internal carotid artery dilation to hypercapnia in healthy older adults.

: Cerebrovascular disease and dementia risk increases with age and lifetime risk is greater in women. Cerebrovascular dysfunction likely precedes cerebrovascular disease and dementia but the mechanisms are incompletely understood. We hypothesized that oxidative stress mediates cerebrovascular dysfunction with human aging.

PEGylation Improves the Therapeutic Index of Dexamethasone To Treat Acute Respiratory Distress Syndrome with Obesity Background in Mouse.

With increasing prevalence globally, obesity presents unique challenges to the clinical management of other diseases. In the case of acute respiratory distress syndrome (ARDS), glucocorticoid therapy (e.g.

Recommended Opioid Receptor Tool Compounds: Comparative for Receptor Selectivity Profiles and for Pharmacological Antinociceptive Profiles.

Opioid agonist ligands bind opioid receptors and stimulate downstream signaling cascades for various biological processes including pain and reward. Historically, before cloning the receptors, muscle contraction assays using isolated organ tissues were used followed by radiolabel ligand binding assays on native tissues. Upon cloning of the opioid G protein-coupled receptors (GPCRs), cell assays using transfected opioid receptor DNA plasmids became the standard practice including S-GTPγS functional and cAMP based assays.

A Case of Atraumatic Splenic Rupture Due to T-Cell/Histiocyte-Rich Large B-Cell Lymphoma and a Potential Role for Massive Transfusion Protocol.

Splenic rupture leads to massive hemorrhage and requires immediate surgical intervention. Splenic rupture results from trauma or from underlying disease processes. Lymphoma is a rare cause of atraumatic splenic rupture (ASR) with high mortality rates.

CAR-T therapy toxicities: the importance of macrophages in their development and possible targets for their management.

CAR-T cell therapies have risen to prominence over the last decade, and their indications are increasing with several products approved as early as second line in Large B Cell non-Hodgkin Lymphomas. Their major toxicities are the cytokine release syndrome (CRS) and the Immune-effector Cell Associated Neurotoxicity Syndrome (ICANS). These entities involve a hyperinflammatory cascade which is amplified through the mononuclear phagocytic system (MPS).

Trends in Osteoporosis Drug Therapy Receipt Among Commercial and Medicare Advantage Enrollees in the United States, 2011-2022.

Context: A national assessment of osteoporosis drug therapy (ODT) use can inform the extent of underdiagnosis and undertreatment of osteoporosis.

Objective: The aim was to describe trends in ODT use by age, sex, fragility fracture, and documented osteoporosis.

Methods: This was a retrospective analysis of patient-quarter observations for adults aged ≥50 years with commercial or Medicare Advantage health insurance in the OptumLabs Data Warehouse between 2011 and 2022.

The role of cancer cell-released extracellular vesicles: have we become closer to cancer pain treatment?

The effective management of cancer pain continues to be a challenge because of our limited understanding of cancer pain mechanisms and, in particular, how cancer cells interact with neurons to produce pain. In a study published in , Inyang used a mouse model of human papillomavirus (HPV1)-induced oropharyngeal squamous cell carcinoma to show a role for cancer cell-derived extracellular vesicles (cancer sEVs) in cancer pain. They found that inhibiting the release of sEVs reduced spontaneous and evoked pain behaviors, and that pain produced by sEVs is due to activation of TRPV1 channels.

Contextualizing the Upper Paleolithic of the Armenian Highlands: New data from Solak-1, central Armenia.

As a potential corridor connecting Southwest Asia with western and northern Europe, the Armenian Highlands and southern Caucasus hold great potential for increasing our understanding of Upper Paleolithic behavioral and cultural variability. However, given the dearth of Upper Paleolithic sites, we lack the data necessary to answer basic questions regarding the timing and nature of the Upper Paleolithic in this region. Solak-1 is an open-air site located along the upper Hrazdan Valley (1635 m above sea level) in central Armenia.

Structural insights into binding-site access and ligand recognition by human ABCB1.

ABCB1 is a broad-spectrum efflux pump central to cellular drug handling and multidrug resistance in humans. However, how it is able to recognize and transport a wide range of diverse substrates remains poorly understood. Here we present cryo-EM structures of lipid-embedded human ABCB1 in conformationally distinct apo-, substrate-bound, inhibitor-bound, and nucleotide-trapped states at 3.

Distinct computational mechanisms of uncertainty processing explain opposing exploratory behaviors in anxiety and apathy.

Background: Decision-making in uncertain environments can lead to varied outcomes, and how we process those outcomes may depend on our emotional state. Understanding how individuals interpret the sources of uncertainty is crucial for understanding adaptive behavior and mental well-being. Uncertainty can be broadly categorized into two components: volatility and stochasticity.

Influence of Photoemission Geometry on Timing and Efficiency in 4D Ultrafast Electron Microscopy.

Broader adoption of 4D ultrafast electron microscopy (UEM) for the study of chemical, materials, and quantum systems is being driven by development of new instruments as well as continuous improvement and characterization of existing technologies. Perhaps owing to the still-high barrier to entry, the full range of capabilities of laser-driven 4D UEM instruments has yet to be established, particularly when operated at extremely low beam currents (~fA). Accordingly, with an eye on beam stability, we have conducted particle tracing simulations of unconventional off-axis photoemission geometries in a UEM equipped with a thermionic-emission gun.

Norditerpene natural products from subterranean fungi with anti-parasitic activity.

is a common, waterborne gastrointestinal parasite that causes diarrheal disease worldwide. Currently there are no effective therapeutics to treat cryptosporidiosis in at-risk populations. Since natural products are a known source of anti-parasitic compounds, we screened a library of extracts and pure natural product compounds isolated from bacteria and fungi collected from subterranean environments for activity against .