Pulmonary hypertension in infancy: a reversible cause.

A term, healthy infant presented with respiratory distress and severe pulmonary hypertension (PH). With an unclear aetiology and the intent to decrease right ventricular afterload, pulmonary vasodilators were initiated. Follow-up imaging revealed a supravalvular mitral ring as the cause of the PH which resolved after surgical resection of the membrane.

The Moreton Lecture Series: The Renin-Angiotensin-Aldosterone System-Physiology, Pathophysiology, and Pharmacological Inhibition.

The renin-angiotensin-aldosterone system (RAAS) is a complex regulator comprising hormones, proteins, and enzymes. The discovery of the RAAS and its pharmacological manipulation has been essential in the management of cardiovascular diseases, including hypertension. Beyond the benefits of hypertension, RAAS inhibition has implications for heart failure, atherosclerotic disease, and kidney disease.

Basic Science and Pathogenesis.

Background: Tauopathies are a group of neurological disorders including Alzheimer's disease that involve progressive neurodegeneration, behavioral deficits, and aberrant tau accumulation. While the molecular mechanisms that regulate the progression of the tauopathy are not fully elucidated, there is evidence to suggest that accumulation of nuclear DNA damage, particularly nuclear DNA double-strand breaks (DNA DSBs), contribute to the progression of neurodegeneration. In our present work, we investigated the relationship between DNA DSB accumulation and neuroinflammation in the brains of AD patients and a mouse model of tauopathy.

PeerPub: A Device for Concurrent Operant Oral Self-Administration by Multiple Rats.

The social environment has long been recognized to play an important role in substance use, which is often modeled in rodents using operant conditioning. However, most operant chambers only accommodate one rodent at a time. We present PeerPub - a unique social operant chamber.

MiR-675 Inhibits Primary Ovarian Tumor Growth and Metastasis by Suppressing EMT and TGFβ Signaling.

MicroRNAs (miRNAs) can function as either tumor suppressors or oncogenes. This study explores the role of miR-675 in ovarian cancer (OC) using OC cell lines and an orthotopic mouse model. We demonstrate that miR-675 expression inhibits primary tumor growth and metastasis by targeting TGFβ1, suppressing epithelial to mesenchymal transition (EMT), and attenuating the TGFβ signaling pathway.

Inclined distance running at iso-efficient speeds: Effect on joint work.

Runners often reduce their pace during inclined running to maintain a constant metabolic workload, known as iso-efficiency speed (a speed-incline combination with the same metabolic intensity as level running). This study investigates changes in lower extremity (LE) joint work profiles when running on an incline at iso-efficiency speed. Eleven collegiate distance runners completed a treadmill running task under three conditions (0%, 4%, and 8% incline).

Role of exosomes in dental and craniofacial regeneration - A review.

Background: The treatment of congenital deformities, traumatic injuries, infectious diseases, and tumors in the craniomaxillofacial (CMF) region is complex due to the intricate nature of the tissues involved. Conventional treatments such as bone grafts and cell transplantation face limitations, including the need for multiple surgeries, complications, and safety concerns.

Objective: This paper aims to provide a comprehensive analysis of the role of exosomes (EXOs) in CMF and dental tissue regeneration and to explore their potential applications in regenerative dental medicine.

Proton Pump Inhibitor Use and Incident Cardiovascular Disease in Older Postmenopausal Women.

Background: Epidemiological studies have been inconsistent regarding an association between proton pump inhibitor (PPI) use and risk of primary cardiovascular disease (CVD) events.

Methods: We studied 85,189 postmenopausal women (mean age 63 years at baseline) without known CVD at enrollment into the Women's Health Initiative Observational Study (1993-1998). PPI use was determined from medication inventories at baseline and Year-3.

Improving Sickle Cell Patient Appointment Compliance in a Hospital-based Pediatric Ophthalmology Clinic.

This quality improvement initiative aimed to reduce the no-show rate at a hospital-based tertiary sickle cell ophthalmology clinic. Missed appointments place a significant burden on the healthcare system, resulting in prolonged waiting times and underutilized clinical resources that impact the quality of care provided. Individuals with sickle cell disease commonly require multiple appointments to address the myriads of comorbidities associated with their disease.

Association of COMT rs4680 Genotype With Chronic Neuropathic Pain Experience in Patients With Sickle Cell Disease.

Purpose: The pain experience of patients with sickle cell disease (SCD) frequently consists of episodes of acute exacerbation. However, recent studies suggest that many patients who suffer from SCD have symptoms of chronic neuropathic pain. Additional research is needed to determine what role genotype plays in the patient's pain phenotype experience in SCD.

Resazurin dye is an in vivo sensor of kidney tubular function.

Glomerular filtration rate (GFR) is the main functional index of kidney health and disease. Currently, no methods are available to directly measure tubular mass and function. Here, we report a serendipitous finding that the in vitro cell viability dye resazurin can be used in mice as an exogenous sensor of tubular function.

Familial Alzheimer's disease mutations in amyloid precursor protein impair calcineurin signaling to NMDA receptors.

Familial Alzheimer's disease (FAD) is frequently associated with mutations in the amyloid precursor protein (APP), which are thought to lead to cognitive deficits by impairing NMDA receptor (NMDAR)-dependent forms of synaptic plasticity. Given the reliance of synaptic plasticity on NMDAR-mediated Ca entry, shaping of NMDAR activity by APP and/or its disease-causing variants could provide a basis for understanding synaptic plasticity impairments associated with FAD. A region of APP (residues 639-644 within APP695) processed by the γ-secretase complex, which generates amyloid β (Aβ) peptides, is a hotspot for FAD mutations.

Male and female behavioral variability and morphine response in C57BL/6J, DBA/2J, and their BXD progeny following chronic stress exposure.

Drug addiction is a multifactorial syndrome in which genetic predispositions and exposure to environmental stressors constitute major risk factors for the early onset, escalation, and relapse of addictive behaviors. While it is well known that stress plays a key role in drug addiction, the genetic factors that make certain individuals particularly sensitive to stress and, thereby, more vulnerable to becoming addicted are unknown. In an effort to test a complex set of gene x environment interactions-specifically gene x chronic stress-here we leveraged a systems genetics resource: BXD recombinant inbred mice (BXD5, BXD8, BXD14, BXD22, BXD29, and BXD32) and their parental mouse lines, C57BL/6J and DBA/2J.

UPJE: Most pharmacy law educators have heard of it, but support remains divided.

Background: Most states require pharmacists to successfully pass the Multistate Pharmacy Jurisprudence Examination (MPJE) required by the National Association of Boards of Pharmacy (NABP) to obtain licensure as a pharmacist, though pass rates for the MPJE have declined in recent years. Meanwhile, NABP is pursing efforts to standardize the exam with the emergent Uniform Pharmacy Jurisprudence Examination (UPJE).

Objective: This study aimed to describe the current thinking of pharmacy law educators across the US on the UPJE.

Transcriptomic resources for Bagrada hilaris (Burmeister), a widespread invasive pest of Brassicales.

The bagrada bug, Bagrada hilaris (Burmeister), is an emerging agricultural pest in the Americas, threatening agricultural production in the southwestern United States, Mexico and Chile, as well as in the Old World (including Africa, South Asia and, more recently, Mediterranean areas of Europe). Substantive transcriptomic sequence resources for this damaging species would be beneficial towards understanding its capacity for developing insecticide resistance, identifying viruses that may be present throughout its population and identifying genes differentially expressed across life stages that could be exploited for biomolecular pesticide formulations. This study establishes B.

Orthopaedic Provider Coding Trends After 2021 Changes to the Current Procedural Terminology Evaluation and Management Coding Guidelines: A Retrospective Cohort Study.

Background: The goal of this study was to determine changes in orthopaedic coding practices between December 2020 and January 2021 after training providers on the 2021 Current Procedural Terminology Evaluation and Management (E&M) Centers for Medicare and Medicaid Services guideline changes.

Methods: Outpatient encounters in December 2020, January 2021, December 2021, and January 2023 were grouped by provider and E&M code level. The codes used for established patients were 99211, 99212, 99213, 99214, and 99215, ordered from low to high-complexity visits.

Urothelial carcinoma in situ with "early papillary formation" vs "lateral spread/shoulder lesion" of prior high-grade noninvasive papillary urothelial carcinoma: A survey of pathologist and urologist interpretations.

Objectives: Urothelial carcinoma in situ (CIS) with early papillary formation is terminology sometimes used to suggest incipient high-grade papillary urothelial carcinoma (PUC) but may lead to confusion between true CIS and lateral flat spread of PUC.

Methods: It remains unclear how pathologists and urologists interpret this scenario, so a survey was circulated to 68 pathologists (group 1 = 28 academic genitourinary pathologists; group 2 = 17 pathologists with a self-reported genitourinary focus; group 3 = 23 pathologists self-reported as not genitourinary specialists) and 32 urologists.

Results: Regarding atypical urothelial lesions that appear mainly flat but contain possible papillae, group 3 was more likely to label this as CIS compared with groups 1 and 2 (35% for group 3 vs 13% for groups 1 and 2), while groups 1 and 2 more often adopted another descriptive diagnosis, such as "CIS with early papillary features" (38% for groups 1 and 2 vs 13% for group 3).

Insulin secretion, sensitivity, and clearance in normoglycemic Black and White adults with parental type 2 diabetes: association with incident dysglycemia.

Introduction: Ethnic disparities in the prevalence and pathophysiology of type 2 diabetes are well documented, but prospective data on insulin dynamics vis-à-vis pre-diabetes/early dysglycemia risk in diverse populations are scant.

Research Design And Methods: We analyzed insulin secretion, sensitivity, and clearance among participants in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study. The POP-ABC study followed initially normoglycemic offspring of parents with type 2 diabetes for 5.

Poststroke hyperglycemia dysregulates cap-dependent translation in neural cells.

Aims: Post stroke hyperglycemia has been shown to deter functional recovery. Earlier findings have indicated the cap-dependent translation regulator 4E-BP1 is detrimentally upregulated in hyperglycemic conditions. The present study aims to test the hypothesis that hyperglycemic ischemic reperfusion injury (I/R) affects normal protein translation poststroke.

Analgesic Effect of Oxytocin in Alcohol-Dependent Male and Female Rats.

Introduction: Chronic alcohol exposure in humans and rodents causes tolerance to the analgesic effects of alcohol, and enhances pain sensitivity during alcohol withdrawal (i.e., hyperalgesia).

Genome-wide CRISPR screen identifies AraC-Dauno-Eto (ADE) response modulators that predicts outcome in pediatric AML.

Cytarabine, daunorubicin, and etoposide (ADE) have been the standard backbone of induction chemotherapy regimens for acute myeloid leukemia (AML) patients for over five decades. However, chemoresistance is still a major concern, and a significant proportion of AML becomes resistant to ADE treatment leading to relapse and poor survival. Therefore, there is a significant need to identify mechanisms mediating drug resistance to overcome chemoresistance.

JUMPlib: Integrative Search Tool Combining Fragment Ion Indexing with Comprehensive TMT Spectral Libraries.

The identification of peptides is a cornerstone of mass spectrometry-based proteomics. Spectral library-based algorithms are well-established methods to enhance the identification efficiency of peptides during database searches in proteomics. However, these algorithms are not specifically tailored for tandem mass tag (TMT)-based proteomics due to the lack of high-quality TMT spectral libraries.

Long-read epigenomic diagnosis and prognosis of Acute Myeloid Leukemia.

Acute Myeloid Leukemia (AML) is an aggressive cancer with dismal outcomes, vast subtype heterogeneity, and suboptimal risk stratification. In this study, we harmonized DNA methylation data from 3,314 patients across 11 cohorts to develop the Acute Leukemia Methylome Atlas (ALMA) of diagnostic relevance that predicted 27 WHO 2022 acute leukemia subtypes with an overall accuracy of 96.3% in discovery and 90.

ALSUntangled #77: Psilocybin.

ALSUntangled reviews alternate and off-label treatments prompted by patient interest. Here, we review psilocybin, a chemical derived from mushrooms and belonging in the category of drugs known as psychedelics. Psilocybin has plausible mechanisms for slowing ALS progression because of its ability to cross the blood brain barrier and effect neurogenesis and inflammation.