Effects of interleukin-1 receptor antagonism in women with polycystic ovary syndrome-the FertIL trial.

Introduction: Chronic low-grade inflammation might contribute to hyperandrogenemia and metabolic complications in polycystic ovary syndrome (PCOS). The proinflammatory cytokine interleukin (IL)-1 stimulates androgen production from ovarian cells, whereas blockade of the IL-1 pathway improves cardiometabolic health. We aimed to investigate whether blocking the IL-1 pathway ameliorates hyperandrogenemia in patients with PCOS.

A multimodal aftercare intervention improves the outcome after kidney transplantation - results of the KTx360° aftercare program using claims data.

Background: The after-care treatment project KTx360° aimed to reduce graft failure and mortality after kidney transplantation (KTx).

Methods: The study was conducted in the study centers Hannover, Erlangen and Hannoversch Muenden from May 2017 to October 2020 under the trial registration ISRCTN29416382. The program provided a multimodal aftercare program including specialized case management, telemedicine support, psychological and exercise assessments, and interventions.

5α-reduction of epitestosterone is catalysed by human SRD5A1 and SRD5A2 and increases androgen receptor transactivation.

Epitestosterone is a stereoisomer of the active androgen testosterone and its circulating concentrations are similar to those of testosterone in women and children. However, its biological function and pathways of metabolism remain unknown. The structural similarity to testosterone suggests a potential function in the modulation of androgen receptor signalling.

Inhibition of the glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 drives concurrent 11-oxygenated androgen excess.

Aldo-keto reductase 1C3 (AKR1C3) is a key enzyme in the activation of both classic and 11-oxygenated androgens. In adipose tissue, AKR1C3 is co-expressed with 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1), which catalyzes not only the local activation of glucocorticoids but also the inactivation of 11-oxygenated androgens, and thus has the potential to counteract AKR1C3. Using a combination of in vitro assays and in silico modeling we show that HSD11B1 attenuates the biosynthesis of the potent 11-oxygenated androgen, 11-ketotestosterone (11KT), by AKR1C3.

PATHway: Intervention optimization of a prevention program for adolescents at-risk for depression in the primary care setting.

With as many as 13% of adolescents diagnosed with depressive disorders each year, prevention of depressive disorders has become a key priority for the National Institute of Mental Health (NIMH). Currently, we have no widely available interventions to prevent these disorders. To address this need, we developed a multi-health system collaboration to develop and evaluate the primary care based technology "behavioral vaccine," Competent Adulthood Transition with Cognitive-Behavioral Humanistic and Interpersonal Therapy (CATCH-IT).

The glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 catalyzes the activation of testosterone.

Testosterone biosynthesis from its precursor androstenedione is thought to be exclusively catalysed by the 17β-hydroxysteroid dehydrogenases-HSD17B3 in testes, and AKR1C3 in the ovary, adrenal and peripheral tissues. Here we show for the first time that the glucocorticoid activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) can also catalyse the 17β-reduction of androstenedione to testosterone, using a combination of in vitro enzyme kinetic assays, mathematical modelling, and molecular docking analysis. Furthermore, we show that co-expression of HSD11B1 and AKR1C3 increases testosterone production several-fold compared to the rate observed with AKR1C3 only, and that HSD11B1 is likely to contribute significantly to testosterone production in peripheral tissues.

Race/Ethnicity Modifies the Relationship Between Diet Quality at the Home- and Individual-Levels and Weight Status Among African American and Hispanic/Latinx Households With Preschool-Age Children.

Higher obesity prevalence and poorer diet quality disproportionately impacting groups based on income and race/ethnicity may be partially attributed to the home food environment. This study examined home- and individual-level diet quality with weight status among racially/ethnically diverse households. This cross-sectional study included African American (AA) and Hispanic/Latinx (H/L) households with preschool-age children ( = 97).

Exploring the Effects of a Mediterranean Diet and Weight Loss on the Gut Microbiome and Cognitive Performance in Older, African American Obese Adults: A Post Hoc Analysis.

African American adults have a higher prevalence of Alzheimer's dementia (AD) than non-Hispanic Whites. The impact of a Mediterranean Diet (Med Diet) and intentional weight loss (IWL) on the gut microbiome may alter AD risk. A post hoc analysis of the Building Research in Diet and Cognition (BRIDGE) trial was performed to determine whether participation in an 8-month Med Diet lifestyle intervention with ( = 35) or without IWL ( = 31) was associated with changes in gut microbiota structure, abundance, and function and whether these changes were related to changes in cognitive performance.

Tissue Glucocorticoid Metabolism in Adrenal Insufficiency: A Prospective Study of Dual-release Hydrocortisone Therapy.

Background: Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy.

Architecture of androgen receptor pathways amplifying glucagon-like peptide-1 insulinotropic action in male pancreatic β cells.

Male mice lacking the androgen receptor (AR) in pancreatic β cells exhibit blunted glucose-stimulated insulin secretion (GSIS), leading to hyperglycemia. Testosterone activates an extranuclear AR in β cells to amplify glucagon-like peptide-1 (GLP-1) insulinotropic action. Here, we examined the architecture of AR targets that regulate GLP-1 insulinotropic action in male β cells.

Comparing the gut microbiome of obese, African American, older adults with and without mild cognitive impairment.

Those with mild cognitive impairment (MCI), a precursor to dementia, have a gut microbiome distinct from healthy individuals, but this has only been shown in healthy individuals, not in those exhibiting several risk factors for dementia. Using amplicon 16S rRNA gene sequencing in a case-control study of 60 older (ages 55-76), obese, predominately female, African American adults, those with MCI (cases) had different gut microbiota profiles than controls. While microbial community diversity was similar between cases and controls, the abundances of specific microbial taxa weren't, such as Parabacteroides distasonis (lower in cases) and Dialister invisus (higher in cases).

Design of the Building Research in CRC prevention (BRIDGE-CRC) trial: a 6-month, parallel group Mediterranean diet and weight loss randomized controlled lifestyle intervention targeting the bile acid-gut microbiome axis to reduce colorectal cancer risk among African American/Black adults with obesity.

Background: Among all racial/ethnic groups, people who identify as African American/Blacks have the second highest colorectal cancer (CRC) incidence in the USA. This disparity may exist because African American/Blacks, compared to other racial/ethnic groups, have a higher prevalence of risk factors for CRC, including obesity, low fiber consumption, and higher intakes of fat and animal protein. One unexplored, underlying mechanism of this relationship is the bile acid-gut microbiome axis.

Classic and 11-oxygenated androgens in serum and saliva across adulthood: a cross-sectional study analyzing the impact of age, body mass index, and diurnal and menstrual cycle variation.

Objective: 11-oxygenated androgens significantly contribute to the circulating androgen pool. Understanding the physiological variation of 11-oxygenated androgens and their determinants is essential for clinical interpretation, for example, in androgen excess conditions. We quantified classic and 11-oxygenated androgens in serum and saliva across the adult age and body mass index (BMI) range, also analyzing diurnal and menstrual cycle-dependent variation.

Effect of Mediterranean diet and Mediterranean diet plus calorie restriction on cognition, lifestyle, and cardiometabolic health: A randomized clinical trial.

A Mediterranean diet and intentional weight loss each positively affect cognitive functioning. Combining both could produce synergistic effects on cognition. The purpose of this study is to compare a Mediterranean diet lifestyle intervention with and without caloric restriction versus control on cognition, lifestyle, and cardiometabolic disease.

Multi-steroid profiling by UHPLC-MS/MS with post-column infusion of ammonium fluoride.

Background: Multi-steroid profiling is a powerful analytical tool that simultaneously quantifies steroids from different biosynthetic pathways. Here we present an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay for the profiling of 23 steroids using post-column infusion of ammonium fluoride.

Methods: Following liquid-liquid extraction, steroids were chromatographically separated over 5 min using a Phenomenex Luna Omega C column and a water (0.

Prevalence of Mental Disorders in a German Kidney Transplant Population: Results of a KTx360°-Substudy.

In patients after kidney transplantation (KTx) an increased rate of affective and anxiety disorders has been observed. Repeatedly, a relationship between mental health issues and increased morbidity and mortality in KTx recipients has been reported. However, information on the prevalence of mental disorders in KTx patients is scarce.

Validation of a self-report home food availability checklist against in-home food inventories conducted in low-income Black/African American and Hispanic/Latinx households with preschool-age children.

Home food availability (HFA) checklists can be completed by self-report to assess the home food environment. Checklists developed for Black/African American (B/AA) and Hispanic/Latinx (H/L) households are seldom validated against objective approaches such as exhaustive in-home food inventories. This study validated a self-report HFA checklist developed for B/AA and H/L households (n = 97) against researcher-completed HFA checklists verified by exhaustive in-home food inventories.

Adapting to the COVID-19 pandemic on Building Research in Diet and Cognition (BRIDGE) trial.

Background: The COVID-19 pandemic has altered the research landscape for clinical trials, requiring thoughtful consideration regarding how to handle the risks and benefits of continuing them.

Design: This brief report describes the experience of adapting the Building Research in Diet and Cognition (BRIDGE) study, a randomized clinical trial examining the effects of the Mediterranean diet, with and without weight loss, on cognitive functioning in 185 older obese African American adults during the COVID-19 pandemic.

Measurement: The University of Illinois at Chicago (UIC) developed an expedited amendment process for research shifting to remote data collection.

Chemokine/Cytokine Levels Correlate with Organ Involvement in PR3-ANCA-Associated Vasculitis.

Background: ANCA-associated vasculitis (AAV) is a rare small vessel disease characterized by multi-organ involvement. Biomarkers that can measure specific organ involvement are missing. Here, we ask whether certain circulating cytokines and chemokines correlate with renal involvement and if distinct cytokine/chemokine patterns can differentiate between renal, ear/nose/throat, joints, and lung involvement of AAV.

Adapting to the impact of the COVID-19 pandemic on a randomized controlled trial examining lifestyle behaviors on cognitive functioning in obese African American adults: Building Research in Diet and Cognition (BRIDGE).

. The COVID-19 pandemic has significantly altered the research landscape for clinical trials, requiring thoughtful consideration regarding how to handle the risks and benefits of continuing them. .

Organ integration in kidney transplant patients - Results of a KTx360° substudy.

Objective: Organ transplantation is the treatment of choice for patients with end-stage organ disease. From early on, the psychological perspective on integrating the organ has been of interest. As quantitative studies on organ integration are scarce, we aimed at evaluating this aspect in a large sample of kidney transplant (KTx) recipients.

Association of diet quality and physical function among overweight and obese primarily African American older adults with lower extremity osteoarthritis.

Background: Strategies to reduce osteoarthritis (OA) symptoms and increase physical function in persons with lower extremity (LE) OA is a public health priority.

Objective: To examine associations between diet quality and measures of physical function among overweight and obese older adults with self-reported LE OA.

Methods: 413 overweight and obese primarily African American adults ≥60 years old with LE OA were assessed.

Building research in diet and cognition (BRIDGE): Baseline characteristics of older obese African American adults in a randomized controlled trial to examine the effect of the Mediterranean diet with and without weight loss on cognitive functioning.

In the United States, >5.4 million people age 65 and older are affected by cognitive impairment and dementia, including Alzheimer's disease. African Americans are more likely than non-Hispanic whites to suffer from these disorders.