Loss-of-function genomic variants highlight potential therapeutic targets for cardiovascular disease.

Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses of participants in the HUNT Study in Norway (n = 69,479) to search for protein-altering variants with beneficial impact on quantitative blood traits related to cardiovascular disease, but without detrimental impact on liver function. We identify 76 (11 previously unreported) presumed causal protein-altering variants associated with one or more CVD- or liver-related blood traits.

The subcortical basis of outcome and cognitive impairment in TBI: A longitudinal cohort study.

Objective: To understand how, biologically, the acute event of traumatic brain injury gives rise to a long-term disease, we address the relationship between evolving cortical and subcortical brain damage and measures of functional outcome and cognitive functioning at 6 months after injury.

Methods: For this longitudinal analysis, clinical and MRI data were collected in a tertiary neurointensive care setting in a continuous sample of 157 patients surviving moderate to severe traumatic brain injury between 2000 and 2018. For each patient, we collected T1- and T2-weighted MRI data acutely and at the 6-month follow-up, as well as acute measures of injury severity (Glasgow Coma Scale), follow-up measures of functional impairment (Glasgow Outcome Scale-extended), and, in a subset of patients, neuropsychological measures of attention, executive functions, and episodic memory.

3-Year effect of weight loss via severe versus moderate energy restriction on body composition among postmenopausal women with obesity - the TEMPO Diet Trial.

Unlabelled: We have previously shown that a severely energy-restricted diet leads to greater loss of weight, fat, lean mass and bone mineral density (BMD) at 12 months in postmenopausal women with obesity than a moderately energy-restricted diet. We now aim to evaluate whether these effects are sustained longer term (ie, at 36 months). 101 postmenopausal women were randomized to either 12 months of moderate (25 to 35%) energy restriction with a food-based diet (moderate intervention), or 4 months of severe (65 to 75%) energy restriction with a total meal replacement diet followed by moderate energy restriction for 8 months (severe intervention).

Interleukin-2 drives cortisol secretion in an age-, dose-, and body composition-dependent way.

Background: Interleukin-2 (IL-2), one of the proinflammatory cytokines, is used in the treatment of certain malignancies. In some studies, transient increases in cortisol and ACTH secretion occurred. Thus, this agent may be used as an experimental probe of adrenal cortisol secretion.

FIB-4 stage of liver fibrosis is associated with incident heart failure with preserved, but not reduced, ejection fraction among people with and without HIV or hepatitis C.

Background: Liver fibrosis, is independently associated with incident heart failure (HF). Investigating the association between liver fibrosis and type of HF, specifically HF with reduced ejection fraction (EF; HFrEF) or HF with preserved ejection fraction (HFpEF), may provide mechanistic insight into this association. We sought to determine the association between liver fibrosis score (FIB-4) and type of HF, and to assess whether HIV or hepatitis C status modified this association.

Cost-Effectiveness Analysis of Four Common Diagnostic Methods for Clostridioides difficile Infection.

Background: No studies have evaluated the cost-effectiveness of single and two-step different diagnostic test strategies for Clostridioides difficile infection (CDI), including direct and indirect costs.

Objective: To evaluate the cost-effectiveness of commonly available diagnostic tests for CDI including nucleic acid amplification testing (NAAT) alone, glutamate dehydrogenase followed by enzyme immunoassay for toxin (GDH/EIA), GDH then NAAT (GDH/NAAT), and NAAT then EIA (NAAT/EIA).

Design: Decision tree model from the US societal perspective with inputs derived from the literature.

Age and time-of-day differences in the hypothalamo-pituitary-testicular, and adrenal, response to total overnight sleep deprivation.

Study Objectives: In young men, sleep restriction decreases testosterone (Te) and increases afternoon cortisol (F), leading to anabolic-catabolic imbalance, insulin resistance, and other andrological health consequences. Age-related differences in the hypothalamo-pituitary-testicular/adrenal response to sleep restriction could expose older individuals to greater or lesser risk. We aimed to evaluate and compare the 24-h and time-of-day effect of sleep restriction on F, luteinizing hormone (LH), and Te in young and older men.

Cross-talk between miR-29c and transforming growth factor-β3 is mediated by an epigenetic mechanism in leiomyoma.

Objective: To determine the expression of miR-29c and its target gene transforming growth factor-β3 (TGF-β3) in leiomyoma and the mechanisms of their reciprocal regulation.

Design: Experimental study.

Setting: Academic research laboratory.

Dynamic Interactions Between LH and Testosterone in Healthy Community-Dwelling Men: Impact of Age and Body Composition.

Background: Aging is associated with diminished testosterone (Te) secretion, which may be attributed to Leydig cell dysfunction, decreased pituitary stimulation, and altered Te feedback.

Objective: To study all regulatory nodes-gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and Leydig cell-in the same cohort of healthy men.

Study Design: This was a placebo-controlled, blinded, prospectively randomized cross-over study in 40 men, age range 19 to 73 years, and body mass index (BMI) range 20 to 34.

Effect of Weight Loss via Severe vs Moderate Energy Restriction on Lean Mass and Body Composition Among Postmenopausal Women With Obesity: The TEMPO Diet Randomized Clinical Trial.

Importance: Severely energy-restricted diets are the most effective dietary obesity treatment. However, there are concerns regarding potential adverse effects on body composition.

Objective: To compare the long-term effects of weight loss via severe vs moderate energy restriction on lean mass and other aspects of body composition.

HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype.

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.

Menopausal Estrogen-Alone Therapy and Health Outcomes in Women With and Without Bilateral Oophorectomy: A Randomized Trial.

Background: Whether health outcomes of menopausal estrogen therapy differ between women with and without bilateral salpingo-oophorectomy (BSO) is unknown.

Objective: To examine estrogen therapy outcomes by BSO status, with additional stratification by 10-year age groups.

Design: Subgroup analyses of the randomized Women's Health Initiative Estrogen-Alone Trial.

Functional Brain Hyperactivations Are Linked to an Electrophysiological Measure of Slow Interhemispheric Transfer Time after Pediatric Moderate/Severe Traumatic Brain Injury.

Increased task-related blood oxygen level dependent (BOLD) activation is commonly observed in functional magnetic resonance imaging (fMRI) studies of moderate/severe traumatic brain injury (msTBI), but the functional relevance of these hyperactivations and how they are linked to more direct measures of neuronal function remain largely unknown. Here, we investigated how working memory load (WML)-dependent BOLD activation was related to an electrophysiological measure of interhemispheric transfer time (IHTT) in a sample of 18 msTBI patients and 26 demographically matched controls from the UCLA RAPBI (Recovery after Pediatric Brain Injury) study. In the context of highly similar fMRI task performance, a subgroup of TBI patients with slow IHTT had greater BOLD activation with higher WML than both healthy control children and a subgroup of msTBI patients with normal IHTT.

Semen and reproductive hormone parameters in fertile men with and without varicocele.

Although varicoceles are a widely accepted identifiable male factor in infertile couples, the benefit of varicocele repair in improving pregnancy and live birth rates remains uncertain. The Study for Future Families obtained semen and reproductive hormone samples from US men whose partners were currently pregnant. In our analysis cohort of 709 men, a varicocele was detected by clinical examination in 56 (8%) of men.

Stem Cells from a Female Rat Model of Type 2 Diabetes/Obesity and Stress Urinary Incontinence Are Damaged by In Vitro Exposure to its Dyslipidemic Serum, Predicting Inadequate Repair Capacity In Vivo.

Female stress urinary incontinence (FSUI) is prevalent in women with type 2 diabetes/obesity (T2D/O), and treatment is not optimal. Autograph stem cell therapy surprisingly has poor efficacy. In the male rat model of T2D/O, it was demonstrated that epigenetic changes, triggered by long-term exposure to the dyslipidemic milieu, led to abnormal global transcriptional signatures (GTS) of genes and microRNAs (miR), and impaired the repair capacity of muscle-derived stem cells (MDSC).

Neuromyelitis optica spectrum disorder: Patient experience and quality of life.

Objective: To gain insights into NMOSD disease impact, which may negatively affect QoL of patients, their families, and social network.

Methods: The current study used validated instruments to assess physical, emotional, and socioeconomic burden of NMOSD on QoL among 193 patients.

Results: A majority of patients reported an initial diagnosis of a disease other than NMOSD.

Coronary artery calcium testing: A call for universal coverage.

Heart attacks kill more Americans than all cancers combined. Fatal heart attack victims have no symptoms until minutes before they die, hence early detection of high-risk asymptomatic individuals is needed. Even though heart attacks kill and cost more than cancers, as a nation we spend over 20 times more on screening for asymptomatic cancer than for asymptomatic atherosclerotic cardiovascular disease (ASCVD), the underlying cause of heart attacks.

Clinically Meaningful Change in Sexual Desire in the Psychosexual Daily Questionnaire in Older Men from the TTrials.

Background: A recent study of older men participating in the Testosterone Trials (TTrials) defined a clinically meaningful change in the Psychosexual Daily Questionnaire (PDQ) question 4 in hypogonadal men age ≥65 years. This study defines clinically meaningful change in the same population for sexual desire assessed by PDQ question 1.

Aim: To determine a clinically meaningful change in the answers to question 1 of the PDQ in hypogonadal older men.

A Clinical Perspective of Sleep and Andrological Health: Assessment, Treatment Considerations, and Future Research.

Context: Sleep that is insufficient, misaligned, or disrupted causes hypersomnolence and neuropsychological deficits, adversely affects cardiometabolic health, and is increasingly recognized to impair other biological processes that lead to conditions important to men, such as hypogonadism, erectile dysfunction, and infertility.

Evidence Acquisition: Literature review from 1970 to December 2018.

Evidence Synthesis: High-quality and complementary epidemiological and interventional studies establish that abnormal sleep is associated with increased mortality, hypertension, and other cardiometabolic disorders (insufficient, disrupted, and misaligned sleep), as well as reduced fecundity and total sperm count (insufficient sleep), erectile dysfunction (disrupted sleep), and low testosterone (both).

Buccally absorbed vs intravenous prochlorperazine for treatment of migraines headaches.

Objective: To compare the efficacy of buccally absorbed prochlorperazine (BAP) to intravenous prochlorperazine (IVP) for the abortive treatment of migraine headaches.

Methods: Randomized double-blind trial. Eighty subjects aged 18-65 presenting with migraines to the ED of a safety-net, urban hospital.

Combined nestorone-testosterone gel suppresses serum gonadotropins to concentrations associated with effective hormonal contraception in men.

Background: Novel male-based contraceptives are needed to broaden family planning choices. A progestin, Nestorone (Nes) gel, plus a testosterone (T) gel suppresses sperm concentrations to levels associated with effective contraception in normal men. However, administration of two gels on different parts of the body daily is impractical.

Exercise Training in Patients With Non-Small Cell Lung Cancer During In-Hospital Chemotherapy Treatment: A RANDOMIZED CONTROLLED TRIAL.

Purpose: The aim of this study was to perform a randomized trial to assess the impact of exercise training in patients with non-small cell lung cancer during chemotherapy on several outcomes in comparison to a control group (CG).

Methods: The exercise training group (ETG) consisted of 20 patients and the CG consisted of 10 patients. In the ETG, a 4-wk in-hospital exercise training program was performed in 2-wk cycles interspersed with consecutive rounds of chemotherapy with cytostatic drugs.

Associations Between Obstructive Sleep Apnea and Measures of Arterial Stiffness.

Study Objectives: The aim of this study was to determine whether severity measures of obstructive sleep apnea (OSA) are associated with arterial stiffness and central blood pressure (two important cardiovascular risk factors) in a large group of patients with OSA.

Methods: Baseline data from six studies on OSA in which arterial stiffness and central aortic blood pressure measures were determined using applanation tonometry were pooled. Associations between measures of arterial stiffness (heart rate corrected augmentation index [AI75]), central aortic blood pressure (central systolic pressure [CSP] and heart rate corrected central augmentation pressure [CAP75]) and measures of OSA severity were explored using stepwise regression modelling.