Epidemiology of Metastatic Castration-Resistant Prostate Cancer in Veterans Nationwide.

Background: There is limited research on the burden and outcomes of patients diagnosed with metastatic castration-resistant prostate cancer (mCRPC), which may result in limited understanding of the disease and lead to suboptimal disease management. Using a validated algorithm to identify mCRPC disease onset, this study offers the first comprehensive description of mCRPC among veterans nationwide.

Methods: The study used data from the Veterans Health Administration's Corporate Data Warehouse.

Case Report: Adverse reaction to butorphanol in a Collie homozygous for the () mutation.

Certain dog breeds, particularly herding breeds like Collies, are predisposed to drug sensitivity due to the (previously known as ) mutation, which disrupts P-glycoprotein (P-gp) function. This mutation impairs drug efflux at the blood-brain barrier, leading to increased susceptibility to neurotoxic effects. While adverse reactions to P-gp substrate drugs such as macrocyclic lactones and chemotherapeutics are well documented, opioid sensitivity remains poorly understood.

Design of a Continuous GAA-Producing Probiotic as a Potential Mitigator of the Effects of Sleep Deprivation.

Creatine is a popular athletic supplement that has also been shown to improve cognitive performance upon sleep deprivation. However, it is rapidly cleared from the gastrointestinal tract a few hours after consumption. Toward providing a persistent creatine dose, we engineered the human probiotic Nissle (EcN) to produce guanidinoacetic acid (GAA), which is converted to creatine in the liver.

Incidence of benign prostatic hyperplasia in testicular cancer survivors in the Veteran's affairs health system.

Introduction: Testosterone and prostatic inflammation have been postulated to influence the development of benign prostatic hyperplasia (BPH). Our study aims to evaluate the incidence of BPH in Testicular Cancer (TCa) survivors, focusing on its association with chemotherapy and post TCa diagnosed hypogonadism.

Methods: We conducted a retrospective cohort analysis of US veterans diagnosed with TCa between 1990 and 2021, using the Veterans affairs database.

Metabolic Syndrome Among Testicular Cancer Survivors: Long-Term Follow-Up of the Veterans Affairs Health System.

Background: The 5-year survival rate for patients with testicular germ cell tumors (TC) is excellent. However, these survivors are at an increased risk for metabolic syndrome (MetS), a significant source of morbidity and precursor to cardiovascular disease. This study investigates the incidence of MetS in TC survivors compared to matched controls.

Osteoporosis Amongst Testicular Cancer Survivors: Long Term Follow-Up of the Veterans Affairs Health System.

Introduction: Testicular cancer (TC) is the most common malignancy among young males and is associated with cure rates over 95%. However, the long-term health implications of treatments, such as the risk of osteoporosis, remain inadequately understood. This study aims to explore the incidence of osteoporosis in TC survivors and associated risk factors.

Incorporating Structured and Unstructured Data Sources to Identify and Characterize Hereditary Cancer Testing Among Veterans With Metastatic Castration-Resistant Prostate Cancer.

Purpose: This study introduces an integrated approach using structured and unstructured data from an electronic health record to identify and characterize patient utilization of hereditary cancer genetic testing among patients with metastatic castration-resistant prostate cancer (mCRPC). Secondary objectives were to describe factors associated with the receipt of testing.

Methods: This retrospective cohort study included a cohort of Veterans diagnosed with mCRPC from January 2016 to December 2021.

Evaluation of an indirect Na1.7 inhibitor as adjunctive analgesic in burn-related neuropathic pain in a cat.

Burn-related neuropathic pain (BRNP) can arise following burn-induced nerve damage, affects approximately 6% of burned human patients and can result in chronic pain. Although widely studied in humans, data on BRNP or its treatment in animals is lacking. A 4-year-old domestic shorthair cat was presented with an infected, non-healing wound suspected to be a caustic burn.

Neuropeptide Y and Pain: Insights from Brain Research.

Neuropeptide Y (NPY) is a highly conserved neuropeptide with widespread distribution in the central nervous system and diverse physiological functions. While extensively studied for its inhibitory effects on pain at the spinal cord level, its role in pain modulation within the brain remains less clear. This review aims to summarize the complex landscape of supraspinal NPY signaling in pain processing.

Incidence of Erectile Dysfunction and Testosterone Deficiency in Testicular Cancer Survivors.

Purpose: The aim of this project was to characterize the incidence of men's health disorders, specifically focusing on the incidence of erectile dysfunction (ED) and testosterone deficiency (TD) in a large, nationwide study of testicular cancer (TC) survivors treated in a centralized health care system.

Materials And Methods: We conducted a retrospective cohort study of US veterans diagnosed with TC from 1990 to 2021. These veterans were compared with an age-matched and race-matched control group of US veterans without a diagnosis of TC.

Redefining Candidates for Deintensification in Locoregionally Advanced P16+ Oropharyngeal Cancer Based on Relative Risk.

Purpose: Randomized trials have found that patients with locoregionally advanced p16+ oropharyngeal squamous cell carcinoma (OPSCC) do not benefit from treatment deintensification, even among favorable risk groups. Although various methods have been used to identify candidates for treatment deintensification, the optimal approach is unknown.

Methods And Materials: We conducted a multi-institutional cohort study of 444 patients with previously untreated p16+ OPSCC undergoing definitive radiation therapy with or without systemic therapy between 2009 and 2022.

Uncoupling the CRMP2-Ca2.2 Interaction Reduces Pain-Like Behavior in a Preclinical Joint-Pain Model.

Osteoarthritis (OA) represents a significant pain challenge globally, as current treatments are limited and come with substantial and adverse side effects. Voltage-gated calcium channels have proved to be pharmacologically effective targets, with multiple Food and Drug Administration-approved Ca2.2 modulators available for the treatment of pain.

A deoxyviolacein-based transposon insertion vector for pigmented tracer studies.

Pigments provide a simple means to rapidly visually ascertain the quantities or presence of specific microbes in a complex community. The selection of pigment-producing colonies that are simple to differentiate from common colony phenotypes provides a high degree of certainty for the identity of pigment-tagged strains. Successful employment of pigment production is dependent on various intrinsic factors related to proper levels of gene expression and pigment production that are not always easy to predict and vary within each microbe.

Mouse models of non-dystrophic and dystrophic myotonia exhibit nociplastic pain-like behaviors.

Pain is a prominent and debilitating symptom in myotonic disorders, including myotonia congenita and myotonic dystrophy type 1 (DM1). Although patients frequently report chronic pain, its underlying mechanisms remain poorly defined. In both disorders, impaired chloride conductance through voltage-gated CLC-1 chloride channels in skeletal muscle disrupts membrane repolarization, leading to delayed relaxation and persistent muscle hyperexcitability.

Trust your gut: Establishing confidence in gastrointestinal models - An overview of the state of the science and contexts of use.

The webinar series and workshop titled “Trust Your Gut: Establishing Confidence in Gastrointestinal Models – An Overview of the State of the Science and Contexts of Use” was co-organized by NICEATM, NIEHS, FDA, EPA, CPSC, DoD, and the Johns Hopkins Center for Alternatives to Animal Testing (CAAT) and hosted at the National Institutes of Health in Bethesda, MD, USA on October 11-12, 2023. New approach methods (NAMs) for assessing issues of gastrointestinal tract (GIT)- related toxicity offer promise in addressing some of the limitations associated with animal-based assessments. GIT NAMs vary in complexity, from two-dimensional monolayer cell line-based systems to sophisticated 3-dimensional organoid systems derived from human primary cells.

Uncoupling the CRMP2-Ca2.2 interaction reduces pain-like behavior in a preclinical osteoarthritis model.

Osteoarthritis (OA) represents a significant pain challenge globally, as current treatments are limited and come with substantial and adverse side effects. Voltage-gated calcium channels have proved to be pharmacologically effective targets, with multiple FDA-approved Ca2.2 modulators available for the treatment of pain.

Multimodal illumination platform for 3D single-molecule super-resolution imaging throughout mammalian cells.

Single-molecule super-resolution imaging is instrumental in investigating cellular architecture and organization at the nanoscale. Achieving precise 3D nanometric localization when imaging structures throughout mammalian cells, which can be multiple microns thick, requires careful selection of the illumination scheme in order to optimize the fluorescence signal to background ratio (SBR). Thus, an optical platform that combines different wide-field illumination schemes for target-specific SBR optimization would facilitate more precise 3D nanoscale studies of a wide range of cellular structures.

Parabrachial Calca neurons drive nociplasticity.

Pain that persists beyond the time required for tissue healing and pain that arises in the absence of tissue injury, collectively referred to as nociplastic pain, are poorly understood phenomena mediated by plasticity within the central nervous system. The parabrachial nucleus (PBN) is a hub that relays aversive sensory information and appears to play a role in nociplasticity. Here, by preventing PBN Calca neurons from releasing neurotransmitters, we demonstrate that activation of Calca neurons is necessary for the manifestation and maintenance of chronic pain.

Adrenal-Permissive Germline HSD3B1 Allele and Prostate Cancer Outcomes.

Importance: The adrenal androgen-metabolizing 3β-hydroxysteroid dehydrogenase-1 enzyme, encoded by the HSD3B1 gene, catalyzes the rate-limiting step necessary for synthesizing nontesticular testosterone and dihydrotestosterone production. The common adrenal-permissive HSD3B1(1245C) allele is responsible for encoding the 3β-HSD1 protein with decreased susceptibility to degradation resulting in higher extragonadal androgen synthesis. Retrospective studies have suggested an association of the HSD3B1 adrenal-permissive homozygous genotype with androgen deprivation therapy resistance in prostate cancer.

A parabrachial hub for the prioritization of survival behavior.

Long-term sustained pain in the absence of acute physical injury is a prominent feature of chronic pain conditions. While neurons responding to noxious stimuli have been identified, understanding the signals that persist without ongoing painful stimuli remains a challenge. Using an ethological approach based on the prioritization of adaptive survival behaviors, we determined that neuropeptide Y (NPY) signaling from multiple sources converges on parabrachial neurons expressing the NPY Y1 receptor to reduce sustained pain responses.

Multimodal illumination platform for 3D single-molecule super-resolution imaging throughout mammalian cells.

Single-molecule super-resolution imaging is instrumental for investigating cellular architecture and organization at the nanoscale. Achieving precise 3D nanometric localization when imaging structures throughout mammalian cells, which can be multiple microns thick, requires careful selection of the illumination scheme in order to optimize the fluorescence signal to background ratio (SBR). Thus, an optical platform that combines different wide-field illumination schemes for target-specific SBR optimization would facilitate more precise, 3D nanoscale studies of a wide range of cellular structures.