Activation of Gs signaling in mouse enteroendocrine K cells greatly improves obesity- and diabetes-related metabolic deficits.

Following a meal, glucagon-like peptide 1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP), the 2 major incretins promoting insulin release, are secreted from specialized enteroendocrine cells (L and K cells, respectively). Although GIP is the dominant incretin in humans, the detailed molecular mechanisms governing its release remain to be explored. GIP secretion is regulated by the activity of G protein-coupled receptors (GPCRs) expressed by K cells.

Patient and navigator experiences with the opioid use disorder treatment system in Philadelphia, PA.

Background: In 2022, 1413 people in Philadelphia died of an unintentional drug overdose. Addressing the complex challenges within the opioid use disorder (OUD) treatment system requires a comprehensive grasp of multiple system-level siloes from the perspective of patients who are accessing services and certified recovery specialists. Identifying facilitators and barriers to treatment entry and retention are critical.

Scarce perinatal social support for women with OUD: Opportunities for doula services.

Problem: Persons with opioid use disorder (OUD) often lack social support, which is associated with improved recovery outcomes.

Background: In the last two decades, the rate of opioid use disorder (OUD) among pregnant people has quadrupled.

Question: This study aimed to describe the prenatal and postpartum social support networks and needs of persons with OUD and assess perceived acceptability of community-based social supports such as doulas.

Ocular findings in Jansen metaphyseal chondrodysplasia.

Jansen metaphyseal chondrodysplasia (JMC) is an ultra-rare disorder caused by germline heterozygous variants resulting in constitutive activation of parathyroid hormone type 1 receptor. A description of ocular manifestations of the disease is lacking. Six patients with JMC underwent a detailed ophthalmic evaluation, spectral-domain optical coherence tomography (OCT), visual field testing, and craniofacial CT scans.

Intra-islet α-cell Gs signaling promotes glucagon release.

Glucagon, a hormone released from pancreatic α-cells, is critical for maintaining euglycemia and plays a key role in the pathophysiology of diabetes. To stimulate the development of new classes of therapeutic agents targeting glucagon release, key α-cell signaling pathways that regulate glucagon secretion need to be identified. Here, we focused on the potential importance of α-cell G signaling on modulating α-cell function.

The ric-8b protein (resistance to inhibitors of cholinesterase 8b) is key to preserving contractile function in the adult heart.

Resistance to inhibitors of cholinesterases (ric-8 proteins) are involved in modulating G-protein function, but little is known of their potential physiological importance in the heart. In the present study, we assessed the role of resistance to inhibitors of cholinesterase 8b (Ric-8b) in determining cardiac contractile function. We developed a murine model in which it was possible to conditionally delete ric-8b in cardiac tissue in the adult animal after the addition of tamoxifen.

Technology use among the nation's medical examiner and coroner offices: Data from the 2018 Census of Medical Examiner and Coroner Offices.

Technology uses among medical examiner and coroner (MEC) offices in the United States are not well characterized, yet technology is essential to job-performing duties. Resources, operational infrastructure, and MECs' policies and procedures that affect technology use should be better understood. MEC offices need access to technologies like internet, case management systems (CMSs), databases, and advanced imaging to perform their basic duties.

Gsα Regulates Macrophage Foam Cell Formation During Atherosclerosis.

Background: Many cardiovascular pathologies are induced by signaling through G-protein-coupled receptors via Gsα (G protein stimulatory α subunit) proteins. However, the specific cellular mechanisms that are driven by Gsα and contribute to the development of atherosclerosis remain unclear.

Methods: High-throughput screening involving data from single-cell and bulk sequencing were used to explore the expression of Gsα in atherosclerosis.

A human obesity-associated MC4R mutation with defective Gq/11α signaling leads to hyperphagia in mice.

Melanocortin 4 receptor (MC4R) mutations are the most common cause of human monogenic obesity and are associated with hyperphagia and increased linear growth. While MC4R is known to activate Gsα/cAMP signaling, a substantial proportion of obesity-associated MC4R mutations do not affect MC4R/Gsα signaling. To further explore the role of specific MC4R signaling pathways in the regulation of energy balance, we examined the signaling properties of one such mutant, MC4R (F51L), as well as the metabolic consequences of MC4RF51L mutation in mice.

Invasive Testing for Preoperative Localization of Parathyroid Tumors.

Context: The identification of parathyroid tumor(s) in patients with persistent/recurrent primary hyperparathyroidism (PHPT) is critical for a successful reoperative surgery. If noninvasive studies (ultrasound, computed tomography, magnetic resonance imaging, sestamibi) fail to conclusively localize the tumor, invasive procedures (arteriography and selective venous sampling) are performed.

Objective: To describe our experience with invasive studies for parathyroid tumor localization and provide follow-up data on selective arterial hypocalcemic stimulation with central venous sampling, a technique developed at our center.

Harm reduction in undergraduate and graduate medical education: a systematic scoping review.

Background: Substance use increasingly contributes to early morbidity and mortality, which necessitates greater preparation of the healthcare workforce to mitigate its harm. The purpose of this systematic scoping review is to: 1) review published curricula on harm reduction for substance use implemented by undergraduate (UME) and graduate medical education (GME) in the United States and Canada, 2) develop a framework to describe a comprehensive approach to harm reduction medical education, and 3) propose additional content topics for future consideration.

Methods: PubMed, Scopus, ERIC: Education Resources Information Center (Ovid), and MedEdPORTAL were searched.

A Knock-In Mouse Model of the Variant p.Y392S Develops Normal Parathyroid Glands.

Context: The glial cells missing 2 () gene functions as a transcription factor that is essential for parathyroid gland development, and variants in this gene have been associated with 2 parathyroid diseases: isolated hypoparathyroidism in patients with homozygous germline inactivating variants and primary hyperparathyroidism in patients with heterozygous germline activating variants. A recurrent germline activating missense variant of , p.Y394S, has been reported in patients with familial primary hyperparathyroidism.

Bricks and mortar of well-being: exploring the housing-health connection.

Housing is a determinant of health. Increasing housing costs and worsening housing conditions have impacted populations worldwide. This Editorial aims to examine the dynamic connection between housing and health and the role of public health in addressing this relationship for a Collection launched at BMC Public Health on Housing as a determinant of health and well-being.

Transference.

The article presents a view of transference from the early versions of transference by Classical/Structural analysts, through a variety of analytic positions that extend and implicitly question the concept of transference. After looking at Brenner and Bird's transference positions, we trace the beginning of relational analysis as articulated by Gill. The differences among several subsequent relational positions are then explicated.

Crosstalk between corepressor NRIP1 and cAMP signaling on adipocyte thermogenic programming.

Objectives: Nuclear receptor interacting protein 1 (NRIP1) suppresses energy expenditure via repression of nuclear receptors, and its depletion markedly elevates uncoupled respiration in mouse and human adipocytes. We tested whether NRIP1 deficient adipocytes implanted into obese mice would enhance whole body metabolism. Since β-adrenergic signaling through cAMP strongly promotes adipocyte thermogenesis, we tested whether the effects of NRIP1 knock-out (NRIP1KO) require the cAMP pathway.

Spatializing stigma-power: Mental health impacts of spatial stigma in a legally-excluded settlement in Mumbai, India.

In disadvantaged neighborhoods such as informal settlements (or "slums" in the Indian context), infrastructural deficits and social conditions have been associated with residents' poor mental health. Within social determinants of health framework, spatial stigma, or negative portrayal and stereotyping of particular neighborhoods, has been identified as a contributor to health deficits, but remains under-examined in public health research and may adversely impact the mental health of slum residents through pathways including disinvestment in infrastructure, internalization, weakened community relations, and discrimination. Based on analyses of individual interviews (n = 40) and focus groups (n = 6) in Kaula Bandar (KB), an informal settlement in Mumbai with a previously described high rate of probable common mental disorders (CMD), this study investigates the association between spatial stigma and mental health.

GPCR Binding and JNK3 Activation by Arrestin-3 Have Different Structural Requirements.

Arrestins bind active phosphorylated G protein-coupled receptors (GPCRs). Among the four mammalian subtypes, only arrestin-3 facilitates the activation of JNK3 in cells. In available structures, Lys-295 in the lariat loop of arrestin-3 and its homologue Lys-294 in arrestin-2 directly interact with the activator-attached phosphates.

Phenotypic Profiling and Molecular Mechanisms in Hyperparathyroidism-jaw Tumor Syndrome.

Context: Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a heritable form of primary hyperparathyroidism caused by germline inactivating mutations in CDC73 encoding parafibromin and is associated with an increased risk of parathyroid cancer. There is little evidence to guide the management of patients with the disease.

Objective: (1) Characterize the natural history of HPT-JT, (2) correlate genotype and histology of parathyroid tumors with parafibromin immunostaining, (3) understand molecular changes downstream to CDC73 loss.

Blood-based Proteomic Signatures Associated With MEN1-related Duodenopancreatic Neuroendocrine Tumor Progression.

Purpose: Patients with multiple endocrine neoplasia type 1 (MEN1) are predisposed to develop duodenopancreatic neuroendocrine tumors (dpNETs), and metastatic dpNET is the primary cause of disease-related mortality. Presently, there is a paucity of prognostic factors that can reliably identify patients with MEN1-related dpNETS who are at high risk of distant metastasis. In the current study, we aimed to establish novel circulating molecular protein signatures associated with disease progression.

Long-Term Outcomes of Parathyroid Autografts in Primary Hyperparathyroidism.

Context: Autologous implantation of parathyroid tissue is frequently utilized after parathyroidectomy in patients with heritable forms of primary hyperparathyroidism (PHPT). Data on long-term functional outcome of these grafts is sparse.

Objective: To investigate long-term outcomes of parathyroid autografts.

Mice With RIP-Cre-mediated Deletion of the Long Noncoding RNA Show Normal Pancreatic Islets and Enlarged Pituitary.

Context: Maternally expressed gene 3 () is a long noncoding RNA (lncRNA) that has been implicated as a tumor suppressor.

Objective: The expression of RNA is downregulated in various human tumors, including pituitary adenoma and pancreatic islet tumors due to gene deletion or DNA hypermethylation. Mouse models with conventional germline deletion of have shown that is essential for perinatal or postnatal development and survival.

Improving Research on Racial Disparities in Access to Medications to Treat Opioid Use Disorders.

Objectives: The aims of the study are to review the current research on the association between access to medications for opioid use disorders (MOUD) and race, to identify gaps in research methods, and to propose new approaches to end racialized disparities in access to MOUD.

Methods: We conducted a literature review of English language peer-reviewed published literature from 2010 to 2021 to identify research studies examining the association between race and use of, or access to, MOUD.

Results: We reviewed 21 studies related to access to MOUD for Black and White populations.

Functional Role of Arrestin-1 Residues Interacting with Unphosphorylated Rhodopsin Elements.

Arrestin-1, or visual arrestin, exhibits an exquisite selectivity for light-activated phosphorylated rhodopsin (P-Rh*) over its other functional forms. That selectivity is believed to be mediated by two well-established structural elements in the arrestin-1 molecule, the activation sensor detecting the active conformation of rhodopsin and the phosphorylation sensor responsive to the rhodopsin phosphorylation, which only active phosphorylated rhodopsin can engage simultaneously. However, in the crystal structure of the arrestin-1-rhodopsin complex there are arrestin-1 residues located close to rhodopsin, which do not belong to either sensor.