Measurement of 11-dehydrocorticosterone in mice, rats and songbirds: Effects of age, sex and stress.

Glucocorticoids (GCs) are secreted into the blood by the adrenal glands and are also locally-produced by organs such as the lymphoid organs (bone marrow, thymus, and spleen). Corticosterone is the primary circulating GC in many species, including mice, rats and birds. Within lymphoid organs, corticosterone can be locally produced from the inactive metabolite, 11-dehydrocorticosterone (DHC).

18-Oxocortisol Synthesis in Aldosterone-Producing Adrenocortical Adenoma and Significance of KCNJ5 Mutation Status.

Peripheral 18-oxocortisol (18oxoF) level could contribute to the detection of aldosterone-producing adenoma (APA) in patients with primary aldosteronism. However, peripheral 18oxoF varies among such patients, which is a big drawback concerning its clinical application. We studied 48 cases of APA, 35 harboring KCNJ5 mutation, to clarify the significance of clinical and pathological parameters about peripheral 18oxoF.

Cardiomyocyte glucocorticoid and mineralocorticoid receptors directly and antagonistically regulate heart disease in mice.

Stress is increasingly associated with heart dysfunction and is linked to higher mortality rates in patients with cardiometabolic disease. Glucocorticoids are primary stress hormones that regulate homeostasis through two nuclear receptors, the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), both of which are present in cardiomyocytes. To examine the specific and coordinated roles that these receptors play in mediating the direct effects of stress on the heart, we generated mice with cardiomyocyte-specific deletion of GR (cardioGRKO), MR (cardioMRKO), or both GR and MR (cardioGRMRdKO).

Current strategies for therapeutic drug delivery after traumatic CNS injury.

Therapeutic strategies for traumatic injuries in the central nervous system (CNS) are largely limited to the efficiency of drug delivery. Despite the disrupted blood-CNS barrier during the early phase after injury, the drug administration faces a variety of obstacles derived from homeostatic imbalance at the injury site. In the late phase after CNS injury, the restoration of the blood-CNS barrier integrity varies depending on the injury severity resulting in inconsistent delivery of therapeutics.

Expression of aldosterone synthase CYP11B2 was inversely correlated with longevity.

Immunohistochemistry of human aldosterone synthase (CYP11B2) has revealed that most of aldosterone is autonomously produced in aldosterone-producing cell clusters (APCCs) beneath the capsule of adult adrenals rather than physiologically in the zona glomerulosa (ZG). APCCs have been occasionally found to harbor a somatic mutation of ion channel/pump genes, and number and size of APCCs increase with age until 50 years old. Herein, the objective of the study was to examine APCC development in 106 autopsied adrenals from 85 elderly individuals who died at ages from 50 to 103 years.

Central expression of synaptophysin and synaptoporin in nociceptive afferent subtypes in the dorsal horn.

Central sprouting of nociceptive afferents in response to neural injury enhances excitability of nociceptive pathways in the central nervous system, often causing pain. A reliable quantification of central projections of afferent subtypes and their synaptic terminations is essential for understanding neural plasticity in any pathological condition. We previously characterized central projections of cutaneous nociceptive A and C fibers, selectively labeled with cholera toxin subunit B (CTB) and Isolectin B4 (IB4) respectively, and found that they expressed a general synaptic molecule, synaptophysin, largely depending on afferent subtypes (A vs.

Genetic Characteristics of Aldosterone-Producing Adenomas in Blacks.

Somatic mutations have been identified in aldosterone-producing adenomas (APAs) in genes that include KCNJ5, ATP1A1, ATP2B3, and CACNA1D. Based on independent studies, there appears to be racial differences in the prevalence of somatic KCNJ5 mutations, particularly between East Asians and Europeans. Despite the high cardiovascular disease mortality of blacks, there have been no studies focusing on somatic mutations in APAs in this population.

Integrating comprehensive hepatitis C virus care within a residential substance use disorder treatment program.

Background And Aims: Although central to the hepatitis C virus (HCV) epidemic, many patients with both substance use disorders (SUD) and HCV have difficultly engaging in treatment for either condition. To facilitate HCV care in Veterans with active SUD, a comprehensive HCV screening, education, referral, and treatment program was integrated into a VA residential SUD treatment program.

Methods: Evaluation of HCV screening, education, referral, and treatment initiative among admissions to a residential SUD treatment program from December 2014 to April 2018.

Prostate Cancer Screening Guidelines for African American Veterans: A New Perspective.

Background: Prostate cancer is the most common form of cancer, other than skin cancers, in American men and the second leading cause of cancer deaths. In 2012, the US Preventative Task Force recommended against the prostate specific antigen-based screening for prostate cancer, regardless of race or age, due to overtreatment of low-risk disease and lack of impact on disease outcomes. In African-American men, however, the incidence of prostate cancer is almost 60% higher and the mortality rate is two- to three-times greater than that of Caucasian men.

Tumor Cell Subtypes Based on the Intracellular Hormonal Activity in KCNJ5-Mutated Aldosterone-Producing Adenoma.

Aldosterone-producing adenomas (APAs) harbor marked intratumoral heterogeneity in terms of morphology, steroidogenesis, and genetics. However, an association of biological significance of morphologically identified tumor cell subtypes and genotypes is virtually unknown. KCNJ5 mutation is most frequently detected and generally considered a curable phenotype by adrenalectomy.

A cognitive processing therapy-based treatment program for veterans diagnosed with co-occurring posttraumatic stress disorder and substance use disorder: The relationship between trauma-related cognitions and outcomes of a 6-week treatment program.

Dysfunctional trauma-related cognitions are important in the emergence and maintenance of posttraumatic stress disorder (PTSD) and the modification of such cognitions is a proposed mechanism of trauma treatment. However, the authors are not aware of any research examining trauma-related cognitions as a treatment mechanism in a sample of individuals with comorbid PTSD and substance use disorder (SUD). Accordingly, the present study sought to address this gap in the literature and examined the relationship between trauma-related cognitions and treatment outcomes within a sample of seventy-two veterans diagnosed with PTSD and SUD.

Racial disparities in tumor features and outcomes of patients with squamous cell carcinoma of the tonsil.

Objective: To identify differences in 3-year overall survival (OS) and disease-free survival (DFS) based on race in patients with tonsillar squamous cell carcinoma.

Methods: We retrospectively analyzed 80 patients with squamous cell carcinoma of the tonsil treated between 2006 and 2015. Overall survival and DFS curves comparing white and black patients were generated using the Kaplan-Meier method.

Immunohistopathology and Steroid Profiles Associated With Biochemical Outcomes After Adrenalectomy for Unilateral Primary Aldosteronism.

Unilateral primary aldosteronism (PA) is the most common surgically curable form of hypertension that must be accurately differentiated from bilateral PA for therapeutic management (surgical versus medical). Adrenalectomy results in biochemical cure (complete biochemical success) in almost all patients diagnosed with unilateral PA; the remaining patients with partial or absent biochemical success comprise those with persisting aldosteronism who were misdiagnosed as unilateral PA preoperatively. To identify determinants of postsurgical biochemical outcomes, we compared the adrenal histopathology and the peripheral venous steroid profiles of patients with partial and absent or complete biochemical success after adrenalectomy for unilateral PA.

The Biology of Normal Zona Glomerulosa and Aldosterone-Producing Adenoma: Pathological Implications.

The identification of several germline and somatic ion channel mutations in aldosterone-producing adenomas (APAs) and detection of cell clusters that can be responsible for excess aldosterone production, as well as the isolation of autoantibodies activating the angiotensin II type 1 receptor, have rapidly advanced the understanding of the biology of primary aldosteronism (PA), particularly that of APA. Hence, the main purpose of this review is to discuss how discoveries of the last decade could affect histopathology analysis and clinical practice. The structural remodeling through development and aging of the human adrenal cortex, particularly of the zona glomerulosa, and the complex regulation of aldosterone, with emphasis on the concepts of zonation and channelopathies, will be addressed.

Social Support Moderates Effects of Natural Disaster Exposure on Depression and Posttraumatic Stress Disorder Symptoms: Effects for Displaced and Nondisplaced Residents.

Social support is a known protective factor against the negative psychological impact of natural disasters. Most past research has examined how the effects of exposure to traumatic events influences whether someone meets diagnostic criteria for depression and posttraumatic stress disorder (PTSD); it has also suggested sequelae of disaster exposure depends on whether survivors are displaced from their homes. To capture the full range of the psychological impact of natural disasters, we examined the buffering effects of social support on depressive symptoms and cluster-specific PTSD symptoms, with consideration of displacement status.

Impairment of Thyroid Function in Critically Ill Patients in the Intensive Care Units.

Unexplained hypotension in the intensive care unit is commonly attributed to volume depletion, cardiorespiratory failure, sepsis, or relative adrenal insufficiency. In these acute conditions, thyroid hormone levels measured in blood, serum or plasma are often altered and solely attributed to critical illness. We report a series of 3 critically ill patients with prolonged respiratory failure, suppressed mental status and unexplained hypotension.

Targeted surgical parathyroidectomy in end-stage renal disease patients and long-term metabolic control: A single-center experience in the current era.

Background: The long-term results of surgical parathyroidectomy (PTX) in end-stage renal disease (ESRD) patients are less well known in the modern era of newer activated vitamin-D analogs, calcimimetics and intraoperative monitoring of parathyroid hormone (PTH).

Methods: We performed a retrospective chart review of all ESRD patients undergoing PTX at the University of Mississippi Medical Center between January 2005 and August 2011, with follow-up data as available up to 4 years. All PTXs were performed with intraoperative second-generation PTH monitoring and targeted gland size reduction.

Measuring Adherence to Hepatitis C Direct-Acting Antiviral Medications: Using the VAS in an HCV Treatment Clinic.

Objectives: To implement the widespread treatment of hepatitis C virus (HCV), validated self-report measures to assess medication adherence are needed for monitoring patients who are prescribed HCV direct-acting antivirals (DAAs). The Visual Analog Scale (VAS) is an efficient and well-validated tool for measuring adherence to antiretrovirals in human immunodeficiency virus populations. This study compared VAS scores with pill counts and serum levels of HCV RNA in a sample of HCV-infected veterans prescribed DAAs.

Purkinje Cell Protein 4 Expression Is Associated With DNA Methylation Status in Aldosterone-Producing Adenoma.

Context: Aldosterone production is stimulated by activation of calcium signaling in aldosterone-producing adenomas (APAs), and epigenetic factors such as DNA methylation may be associated with the expression of genes involved in aldosterone regulation.

Objective: Our aim was to investigate the DNA methylation of genes related to calcium signaling cascades in APAs and the association of mutations in genes linked to APAs with DNA methylation levels.

Methods: Nonfunctioning adrenocortical adenoma (n = 12) and APA (n = 35) samples were analyzed.

Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing Adenoma.

Primary aldosteronism is the most frequent cause of secondary hypertension and is associated with increased morbidity and mortality compared with hypertensive controls. The central diagnostic challenge is the differentiation between bilateral and unilateral disease, which determines treatment options. Bilateral adrenal venous sampling, currently recommended for differential diagnosis, is an invasive procedure with several drawbacks, making it desirable to develop novel noninvasive diagnostic tools.

Disordered CYP11B2 Expression in Primary Aldosteronism.

Primary aldosteronism is the most common type of secondary hypertension affecting 6-10% of patients with primary hypertension. PA is mainly caused by unilateral hyperaldosteronism due to an aldosterone-producing adenoma, unilateral hyperplasia with or without micronodules or bilateral zona glomerulosa hyperplasias with or without macro or micronodules. The development of antibodies against the terminal enzyme of aldosterone biosynthesis (CYP11B2) has permitted the further characterization of normal adrenals and resected adrenals from patients with primary aldosteronism.

Implementing Video to Home to Increase Access to Evidence-Based Psychotherapy for Rural Veterans.

This clinical demonstration project used facilitation to implement VA Video to Home (VTH) to deliver evidence-based psychotherapies to underserved rural Veterans, to increase access to mental health care. Participants were Veterans seeking mental health treatment at "Sonny" Montgomery Veterans Affairs Medical Center in Jackson, MS, and/or its six community-based outpatient clinics. Measures included patient encounter and demographic data, patient and provider interviews, reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) factors, measures of fidelity to manualized evidence-based psychotherapies (EBPs), and qualitative interviews.

United States Registered Nurse Workforce Report Card and Shortage Forecast: A Revisit.

This is a reevaluation of registered nurse (RN) supply and demand from 2016 to 2030 using a previously published work forecast model and grading methodology with more recent workforce data. There will be a shortage of 154 018 RNs by 2020 and 510 394 RNs by 2030; the South and West regions will have higher shortage ratios than Northeast and Midwest regions. This reflects a nearly 50% overall improvement when compared with the authors' prior study, and the low-performing states have improved from 18 "D" and 12 "F" grades as published earlier to 13 "D" and 1 "F" in this study.