Revisiting Injectable Estrogen Dosing Recommendations for Gender-Affirming Hormone Therapy.

Injectable estrogens are options for gender-affirming hormone therapy per guidelines, which suggest intramuscular dosages of 5-30 mg every 2 weeks or 2-10 mg weekly with estradiol cypionate or valerate interchangeably. Data among transgender and gender-diverse patients are limited due to local unavailability and concerns around laboratory assay variability and estradiol (E2) level fluctuation. We note a concerning trend where patients are prescribed high-dose injections based on the guidelines leading to serum E2 levels well above the range recommended in the same guidelines.

Updates on the MR safety guidelines - Essentials for radiologists.

Magnetic Resonance Imaging (MRI) is a sophisticated diagnostic tool that utilizes the magnetic properties of biological tissue to generate detailed images of internal structures without the use of ionizing radiation. Despite its benefits in providing high-contrast images of soft tissues, the strong magnetic fields used in MRI present a unique safety challenge. Increasing MRI-related accidents and the prevalence of patients with metallic implants in recent years underscore the critical need for stringent MR safety protocols.

Bone Health ECHO Case Report: Significant Elevation in Bone Turnover Markers and Progression of Vertebral Fractures After Denosumab Discontinuation Followed by a PTH-Analog.

Bone Health ECHO (Extension for Community Healthcare Outcomes) is a virtual community of practice, where healthcare professionals have met via videoconferencing weekly since 2015. This model of learning is focused on short didactics and the presentation of real but de-identified patient cases followed by highly interactive discussions. These are often clinical situations with diagnostic and therapeutic dilemmas that are not readily addressed by randomized placebo-controlled clinical trials and clinical practice guidelines.

A descriptive examination of rurality in the Environmental influences on Child Health Outcomes Cohort: Implications, illustrations, and future directions.

Purpose: The Environmental influences on Child Health Outcomes (ECHO) Cohort has enrolled over 60,000 children to examine how early environmental factors (broadly defined) are associated with key child health outcomes. The ECHO Cohort may be well-positioned to contribute to our understanding of rural environments and contexts, which has implications for rural health disparities research. The present study examined the outcome of child obesity to not only illustrate the suitability of ECHO Cohort data for these purposes but also determine how various definitions of rural and urban populations impact the presentation of findings and their interpretation.

Rare variants in cardiomyopathy genes predispose to cardiac injury in severe COVID-19 patients of African or Hispanic ancestry.

In one of the earliest reports from China during COVID-19, it was noted that over 20% of patients hospitalized with the disease had significant elevations of troponin, a marker of myocardial tissue damage, that put them at a higher risk. In a hypothesis-independent whole exome sequencing (WES) study in hospitalized COVID-19 patients of diverse ancestry, we observed putative enrichment in pathogenic variants in genes known to be involved in the pathogenesis of cardiomyopathy. This observation led us to hypothesize that the observed high morbidity and mortality in these patients might be due to the presence of rare genetic factors that had previously been silent but became relevant as a consequence of the severe stress inflicted by an infection with SARS-CoV-2.

Acetylation of proximal cysteine-lysine pairs by alcohol metabolism.

Alcohol consumption induces hepatocyte damage through complex processes involving oxidative stress and disrupted metabolism. These factors alter proteomic and epigenetic marks, including alcohol-induced protein acetylation, which is a key post-translational modification (PTM) that regulates hepatic metabolism and is associated with the pathogenesis of alcohol-associated liver disease (ALD). Recent evidence suggests lysine acetylation occurs when a proximal cysteine residue is within ∼15 Å of a lysine residue, referred to as a cysteine-lysine (Cys-Lys) pair.

Feasibility of newborn screening for pyridoxine-dependent epilepsy.

Background: Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is a developmental epileptic encephalopathy historically characterized by seizures that are resistant to antiseizure medications. Treatment with pyridoxine and lysine reduction therapies are associated with seizure control and improved developmental outcomes. In rare circumstances, patients have died prior to diagnosis and treatment with pyridoxine, and many patients are diagnosed after six months of age when lysine reduction therapies have limited efficacy.

The Role of Beta-Hydroxybutyrate in Mitigating the Inflammatory and Metabolic Consequences of Uric Acid.

Uric acid (UA), a metabolite of purine and fructose metabolism, is linked to inflammation and metabolic disorders, including gout and cardiovascular disease. Its pro-inflammatory effects are largely driven by the activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, leading to increased cytokine production. Beta-hydroxybutyrate (BHB), a ketone produced during fasting or carbohydrate restriction, has been shown to reduce inflammation.

Metabolic Aging as an Increased Risk for Chronic Obstructive Pulmonary Disease.

Background/objectives: Both aging and chronic obstructive pulmonary disease (COPD) are strongly associated with changes in the metabolome; however, it is unknown whether there are common aging/COPD metabolomic signatures and if accelerated aging is associated with COPD.

Methods: Plasma from 5704 subjects from the Genetic Epidemiology of COPD study (COPDGene) and 2449 subjects from Subpopulations and intermediate outcome measures in COPD study (SPIROMICS) were profiled using the Metabolon global metabolomics platform (1013 annotated metabolites). Post-bronchodilator spirometry measures of airflow obstruction (forced expiratory volume at one second (FEV)/forced vital capacity (FVC) < 0.

A Pharmacokinetic/Toxicodynamic Model of Cisplatin Nephrotoxicity Using the Kidney Injury Molecule-1 Biomarker.

Cisplatin is a platinum-based chemotherapeutic that causes acute kidney injury in over 30% of patients. The aim of this study was to develop a population pharmacokinetic/toxicodynamic (PKTD) model of cisplatin-induced kidney injury that incorporated plasma total platinum and urinary kidney injury molecule-1 (KIM-1) concentrations. Cancer patients receiving their first or second round of cisplatin-containing chemotherapy (n=39) were prospectively randomized to a 5-HT antagonist (5-HTA) antiemetic (ondansetron, granisetron, or palonosetron) and had blood and urine collected over 10 days.

SHAPE: A visual computing pipeline for interactive landmarking of 3D photograms and patient reporting for assessing craniosynostosis.

3D photogrammetry is a cost-effective, non-invasive imaging modality that does not require the use of ionizing radiation or sedation. Therefore, it is specifically valuable in pediatrics and is used to support the diagnosis and longitudinal study of craniofacial developmental pathologies such as craniosynostosis - the premature fusion of one or more cranial sutures resulting in local cranial growth restrictions and cranial malformations. Analysis of 3D photogrammetry requires the identification of craniofacial landmarks to segment the head surface and compute metrics to quantify anomalies.

Impact of an Online Group-Coaching Program on Ambulatory Faculty Physician Well-Being: A Randomized Trial.

Background: Physician burnout contributes to distress, turnover, and poor patient outcomes. Evidence suggests individual professional coaching may mitigate burnout but is costly and time intensive. Group coaching evidence is lacking.

Time to Therapy May Not Impact Diagnosis Upstaging in Patients Referred for Management of Luminal Gastrointestinal Neoplasia.

Background: The COVID-19 pandemic dramatically impacted endoscopy practice. Recommendations were to postpone elective cases, including procedures for removal of luminal neoplasia. This provided a natural experiment to evaluate outcomes related to these decisions and the impact of time to procedure on change in histology.

MIRO2 promotes cancer invasion and metastasis via MYO9B suppression of RhoA activity.

Metastasis to vital organs remains the leading cause of cancer-related deaths, emphasizing an urgent need for actionable targets in advanced-stage cancer. The role of mitochondrial Rho GTPase 2 (MIRO2) in prostate cancer growth was recently reported; however, whether MIRO2 is important for additional steps in the metastatic cascade is unknown. Here, we show that knockdown of MIRO2 ubiquitously reduces tumor cell invasion in vitro and suppresses metastatic burden in prostate and breast cancer mouse models.

Defining Midwifery-Led Care in the United States Using Concept Analysis.

National health policy initiatives recommend increased integration of midwifery care in the United States to improve care quality and reduce maternal health disparities. However, the service models through which midwives provide midwifery care and produce quality outcomes are poorly understood. Midwifery-led care is a service model frequently associated with improved outcomes compared with other models.

Release your inhibitions: The cell biology of GABAergic postsynaptic plasticity.

GABAergic synaptic inhibition controls circuit function by regulating neuronal plasticity, excitability, and firing. To achieve these goals, inhibitory synapses themselves undergo several forms of plasticity via diverse mechanisms, strengthening and weakening phasic inhibition in response to numerous activity-induced stimuli. These mechanisms include changing the number and arrangement of functional GABARs within the inhibitory postsynaptic domain (iPSD), which can profoundly regulate inhibitory synapse strength.

Trends in Demographic Characteristics and Risk Factors among Individuals with Syphilis in Colorado from 2011-2020.

Background: Identify opportunities to improve syphilis screening by describing changes in patient characteristics and risk factors among individuals with syphilis and by comparing cases with and without an indication for syphilis screening.

Methods: This retrospective cohort study used Colorado public health surveillance data to identify 8,326 syphilis diagnoses from 2011-2020. Demographics, clinical characteristics, and risk factors were compared across 2-year groups and between individuals with and without an indication for screening.

What Motivates Older Sedentary People Living With HIV in the United States to Participate in an Exercise Trial? A Qualitative Study.

Although exercise supports the physical function and health of older people living with HIV (PLWH), less than half of PLWH globally achieve recommended levels of activity. A qualitative descriptive design was used to determine what motivates sedentary PLWH, 50 years and older, to participate in an exercise trial. Interviews were conducted with PLWH who participated in an exercise trial (n = 30) and PLWH who declined enrollment in the same exercise trial (n = 4).

Flexibility and resilience in equity-centered research: lessons learned conducting a randomized controlled trial of a family-based substance use prevention program for American Indian families.

Meaningful and effective community engagement lies at the core of equity-centered research, which is a powerful tool for addressing health disparities in American Indian (AI) communities. It is essential for centering Indigenous wisdom as a source of solutions and disrupting Western-centric perspectives and inequitable and exclusionary research practices. This paper reports on lessons learned implementing an effectiveness trial of the Thiwáhe Glúwaš'akapi program (TG) program (translated as "sacred home in which families are made strong")-a family-based substance use prevention program-in a post-pandemic era with an American Indian reservation community that has confronted extreme challenges.

Anticancer Effect of C19-Position Substituted Geldanamycin Derivatives Targeting NRF2-NQO1-activated Esophageal Squamous Cell Carcinoma.

In esophageal squamous cell carcinoma, genetic activation of NRF2 increases resistance to chemotherapy and radiotherapy, which results in a significantly worse prognosis for patients. Therefore NRF2-activated cancers create an urgent clinical need to identify new therapeutic options. In this context, we previously identified the geldanamycin family of HSP90 inhibitors, which includes 17DMAG, to be synthetic lethal with NRF2 activity.

Hyperglycemia Inhibits AAA Expansion: Examining the Role of Lysyl Oxidase.

Abdominal aortic aneurysm (AAA) is a common, progressive and potentially fatal dilation of the most distal aortic segment. Multiple studies with longitudinal follow-up of AAA have identified markedly slower progression among patients affected with diabetes. Understanding the molecular pathway responsible for the growth inhibition could have implications for therapy in nondiabetic AAA patients.

BRD4 inhibition rewires cardiac macrophages toward a protective phenotype marked by low MHC class II expression.

Bromodomain and extra-terminal domain (BET) proteins, including BRD4, bind acetylated chromatin and co-activate gene transcription. A BET inhibitor, JQ1, prevents and reverses pathological cardiac remodeling in preclinical models of heart failure. However, the underlying cellular mechanisms by which JQ1 improves cardiac structure and function remain poorly defined.