Outcomes after medical treatment for primary aldosteronism: an international consensus and analysis of treatment response in an international cohort.

Background: Primary aldosteronism can be treated medically but there is no standardised method to evaluate treatment outcomes. We aimed to develop criteria for assessing the outcomes of targeted medical treatment of primary aldosteronism, analyse outcomes across an international cohort, and identify factors associated with a complete treatment response.

Methods: An international panel of 31 primary aldosteronism experts used the Delphi method to reach consensus on the definition of complete, partial, or absent biochemical and clinical outcomes of medical treatment of primary aldosteronism.

Exploring the Predictive Role of 11-Oxyandrogens in Diagnosing Polycystic Ovary Syndrome.

Context: Hyperandrogenism is a hallmark of polycystic ovary syndrome (PCOS), yet the androgen(s) responsible remain ambiguous. Recent studies have suggested that 11-oxygenated C steroids (11-oxyandrogens), specifically 11-ketotestosterone, may be a good marker for hyperandrogenism in PCOS.

Objective: To investigate the utility of 11-oxyandrogens to differentiate women with and without PCOS relative to classical androgens.

The Subcutaneous Adipose Microenvironment as a Determinant of Body Fat Development in Polycystic Ovary Syndrome.

Context: Adipose steroid metabolism modifies body fat development in polycystic ovary syndrome (PCOS).

Objective: To determine whether subcutaneous (SC) abdominal adipose aldo-keto reductase 1C3 (AKR1C3; a marker of testosterone generation) is increased in normal-weight women with PCOS vs age- and body mass index (BMI)-matched normoandrogenic ovulatory women (controls) and is related to SC abdominal adipose activator protein-1 (AP-1; a marker of adipocyte differentiation) and/or androgen receptor (AR) protein expression in predicting fat accretion.

Design: Prospective cohort study.

Non-canonical Wnt signaling triggered by WNT2B drives adrenal aldosterone production.

The steroid hormone aldosterone, produced by the zona glomerulosa (zG) of the adrenal gland, is a master regulator of plasma electrolytes and blood pressure. While aldosterone control by the renin-angiotensin system is well understood, other key regulatory factors have remained elusive. Here, we replicated a prior association between a non-coding variant in and an increased risk of primary aldosteronism, a prevalent and debilitating disease caused by excessive aldosterone production.

Lung Cancer: New Directions in Senior Patients Assessment.

Age is but one significant prognostic factor in lung cancer, influencing survival, treatment response, and outcomes. This narrative review synthesizes findings from searches of 11 leading databases of research studies, systematic reviews, book chapters, and clinical trial reports on lung cancer in senior patients, with a focus on geriatric assessment as well as biomarkers. Key prognostic factors for lung cancer in seniors include biological age, functional capability, physical and psychological comorbidities, frailty, nutrition, status, and biomarkers like DNA methylation age.

The Tuberculosis Drug Candidate SQ109 and Its Analogs Have Multistage Activity against .

Toward repositioning the antitubercular clinical candidate SQ109 as an antimalarial, analogs were investigated for structure-activity relationships for activity against asexual blood stages of the human malaria parasite pathogenic forms, as well as transmissible, sexual stage gametocytes. We show that equipotent activity (IC) in the 100-300 nM range could be attained for both asexual and sexual stages, with the activity of most compounds retained against a multidrug-resistant strain. The multistage activity profile relies on high lipophilicity ascribed to the adamantane headgroup, and antiplasmodial activity is critically dependent on the diamine linker.

Memantine Inhibits Calcium-Permeable AMPA Receptors.

Memantine is an US Food and Drug Administration (FDA) approved drug that selectively inhibits NMDA-subtype ionotropic glutamate receptors (NMDARs) for treatment of dementia and Alzheimer's. NMDARs enable calcium influx into neurons and are critical for normal brain function. However, increasing evidence shows that calcium influx in neurological diseases is augmented by calcium-permeable AMPA-subtype ionotropic glutamate receptors (AMPARs).

Aspects of Occlusal Recordings Performed with the T-Scan System and with the Medit Intraoral Scanner.

Introduction: Dental occlusion refers to the static and dynamic relationships that are established between the teeth of the two arches and is an important factor in the homeostasis of the dento-maxillary system. The objective of the present study was to compare two digital occlusal analysis systems: the T-Scan III system and the Medit I600 intraoral scanner.

Materials And Methods: The study was carried out on 20 students from the Faculty of Dental Medicine Craiova, whose dental occlusion was assessed with the T-Scan III system and with the Medit I600 intraoral scanner.

Facile Access to Solifenacin Impurity K: One-Step Synthesis and an HPLC-MS Method for Its Determination.

Solifenacin (SFC) is a potent muscarinic antagonist that effectively reduces bladder muscle contraction, thereby alleviating symptoms such as frequency of micturition and urgency. Oxidation of SFC leads to the formation of impurities like Impurity K. Effective analysis and control of this impurity is crucial for ensuring compliance with regulatory standards and safeguarding patient health.

Human Gonads Do Not Contribute to the Circulating Pool of 11-Oxygenated Androgens.

Context: Androstenedione (A4) and testosterone (T) are produced by both the adrenal glands and the gonads. The adrenal enzyme 11β-hydroxylase (CYP11B1) executes the final step in cortisol synthesis; CYP11B1 also uses A4 and T as substrates, generating 11-hydroxyandrostenedione and 11-hydroxytestosterone, respectively. It has been suggested that CYP11B1 is expressed in the gonads, yet the circulating levels of all 11-oxygenated androgens (11-oxyandrogens) are similar in males and females of reproductive ages, despite enormous differences in T.

An in Vitro triple screen model for human mineralocorticoid receptor activity.

The mineralocorticoid receptor (MR, NR3C2) mediates ion and water homeostasis in epithelial cells of the distal nephron and other tissues. Aldosterone, the prototypical mineralocorticoid, regulates electrolyte and fluid balance. Cortisol binds to MR with equal affinity to aldosterone, but many MR-expressing tissues inactivate cortisol to cortisone via 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2).

Control of Physiologic Glucose Homeostasis via the Hypothalamic Modulation of Gluconeogenic Substrate Availability.

The brain augments glucose production during fasting, but the mechanisms are poorly understood. Here, we show that -expressing neurons in the ventromedial hypothalamic nucleus (VMN cells) prevent low blood glucose during fasting through sympathetic nervous system (SNS)-mediated augmentation of adipose tissue lipolysis and substrate release. Activating VMN neurons mobilized gluconeogenic substrates without altering glycogenolysis or gluconeogenic enzyme expression.

Abiraterone in Classic Congenital Adrenal Hyperplasia: Results of Medical Therapy Before Adrenalectomy.

We present the case of a 20-year-old woman with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, with uncontrolled hyperandrogenemia despite supraphysiological glucocorticoid therapy. We used abiraterone acetate, an inhibitor of the 17-hydroxylase/17,20-lyase enzyme, to suppress adrenal androgen synthesis and allow physiological glucocorticoid and mineralocorticoid therapy, as a proof-of-concept, before proceeding to bilateral adrenalectomy. We report the patient's clinical course, the changes in adrenal steroids, and the immunohistochemistry of the adrenals.

The Spectrum of Dysregulated Aldosterone Production: An International Human Physiology Study.

Context: Primary aldosteronism is a form of low-renin hypertension characterized by dysregulated aldosterone production.

Objective: To investigate the contributions of renin-independent aldosteronism and ACTH-mediated aldosteronism in individuals with a low-renin phenotype representing the entire continuum of blood pressure.

Design/participants: Human physiology study of 348 participants with a low-renin phenotype with severe and/or resistant hypertension, hypertension with hypokalemia, elevated blood pressure and stage I/II hypertension, and normal blood pressure.

Evaluation of a Best-Practice Advisory for Primary Aldosteronism Screening.

Importance: Primary aldosteronism (PA) is a common cause of secondary hypertension and an independent risk factor for cardiovascular morbidity and mortality. Fewer than 2% to 4% of patients at risk are evaluated for PA.

Objective: To develop and evaluate an electronic health record best-practice advisory (BPA) that assists with PA screening.

Multifocal, Asymmetric Bilateral Primary Aldosteronism Cannot be Excluded by Strong Adrenal Vein Sampling Lateralization: An International Retrospective Cohort Study.

Background: Primary aldosteronism (PA) has been broadly dichotomized into unilateral and bilateral forms. Adrenal vein sampling (AVS) lateralization indices (LI) ≥2 to 4 are the standard-of-care to recommend unilateral adrenalectomy for presumed unilateral PA. We aimed to assess the rates and characteristics of residual PA after AVS-guided adrenalectomy.

Preventing Dementia-A Cross-Sectional Study of Outpatients in a Tertiary Internal Medicine Department.

Dementia is a significant health problem worldwide, being the seventh leading cause of death (2,382,000 deaths worldwide in 2016). Recent data suggest there are several modifiable risk factors that, if addressed, can decrease dementia risk. Several national dementia screening programs exist; however, limited-income countries do not have the means to implement such measures.

Management of Anastomotic Leakage after Low Anterior Rectal Resections with Total Mesorectal Excision - A Retrospective Study.

This study sought to investigate the diagnostic procedures, treatment modalities, and consequences of anastomotic leakage (AL) in low anterior resection rectal cancer patients. A retrospective analysis was conducted on 186 patients consecutively admitted and treated in the 1st Department of Surgery in Craiova, between January 2018 and June 2022, all of whom had undergone surgical interventions for adenocarcinoma of the rectum. Among this cohort, 106 patients who had undergone scheduled low and ultralow anterior rectal resections with total mesorectal excision were selected for further analysis.

Soluble epoxide hydrolase-targeting PROTAC activates AMPK and inhibits endoplasmic reticulum stress.

Soluble epoxide hydrolase (sEH) is a drug target with the potential for therapeutic utility in the areas of inflammation, neurodegenerative disease, chronic pain, and diabetes, among others. Proteolysis-targeting chimeras (PROTACs) molecules offer new opportunities for targeting sEH, due to its capacity to induce its degradation. Here, we describe that the new ALT-PG2, a PROTAC that degrades sEH protein in the human hepatic Huh-7 cell line, in isolated mouse primary hepatocytes, and in the liver of mice.

The Increase in Childhood Obesity and Its Association with Hypertension during Pandemics.

There has been a major ongoing health impact of the COVID-19 pandemic on children's lives, including lifestyle and overall health. Enforcement of prevention measures, such as school closures and social distancing, has significantly affected children's daily routines and activities. This perspective manuscript aims to explore the rise in childhood obesity and its association with hypertension during pandemics.

Factors Associated with Burnout in Medical Staff: A Look Back at the Role of the COVID-19 Pandemic.

Unlabelled: Despite the significant consequences for medical practice and public health, burnout in healthcare workers remains underestimated. Pandemic periods have increased the reactivity to stress by favoring some changes whose influence are still felt.

Purpose: This study aims to identify opportune factors during pandemic periods that predispose medical personnel to burnout and the differences between medical staff which worked with COVID-19 patients and those who did not work with COVID-19 patients.

Somatic SLC30A1 mutations altering zinc transporter ZnT1 cause aldosterone-producing adenomas and primary aldosteronism.

Primary aldosteronism (PA) is the most common form of endocrine hypertension and is characterized by inappropriately elevated aldosterone production via a renin-independent mechanism. Driver somatic mutations for aldosterone excess have been found in approximately 90% of aldosterone-producing adenomas (APAs). Other causes of lateralized adrenal PA include aldosterone-producing nodules (APNs).