Heart field origin of great vessel precursors relies on nkx2.5-mediated vasculogenesis

The pharyngeal arch arteries (PAAs) are transient embryonic blood vessels that make indispensable contributions to the carotid arteries and great vessels of the heart, including the aorta and pulmonary artery1, 2. During embryogenesis, the PAAs appear in a craniocaudal sequence to connect pre-existing segments of the primitive circulation after de novo vasculogenic assembly from angioblast precursors3, 4. Despite the unique spatiotemporal characteristics of PAA development, the embryonic origins of PAA angioblasts and the genetic factors regulating their emergence remain unknown. Here, we identify the embryonic source of PAA endothelium as nkx2.5+ progenitors in lateral plate mesoderm long considered to adopt cell fates within the heart exclusively5, 6. Further, we report that PAA endothelial differentiation relies on Nkx2.5, a canonical cardiac transcription factor not previously implicated in blood vessel formation. Together, these studies reveal the heart field origin of PAA endothelium and attribute a novel vasculogenic function to the cardiac transcription factor nkx2.5 during great vessel precursor development

Predictors of sexual dysfunction incidence and remission in men

Introduction. The progress and determinants of sexual dysfunction in middle-aged and elderly men remain unclear. Aim. To describe the incidence or remission and biopsychosocial predictors of erectile dysfunction (ED) and low sexual desire (SD). Main Outcome Measures. Erectile function (International Index of Erectile Function) and sexual desire (Sexual Desire Inventory 2) were assessed at follow-up. Sociodemographic, lifestyle, and health-related factors were examined in multivariate models of ED and low SD. Methods. Data were collected from 810 randomly selected men residing in northern and western Adelaide, Australia, and aged 35–80 years at baseline, who made clinic visits 5 years apart. Results. At baseline, 23.2% (n = 123) of men had ED. ED incidence and remission were observed in 31.7% (n = 179) and 29.0% (n = 71) of eligible men, respectively. At baseline, 19.2% (n = 165) had low solitary sexual desire, and 6.0% (n = 50) had low dyadic sexual desire; incidence of low sexual desire occurred in 17.6% (n = 83) (solitary) and 8.3% (n = 51) (dyadic), while remission occurred in 15.4% (n = 68) (solitary) and 22.6% (n = 40) (dyadic) of men. In the final regression models, predictors of incident ED were higher age, lower income, higher abdominal fat mass, low alcohol intake, higher risk of obstructive sleep apnea (OSA) risk, voiding lower urinary tract symptoms (LUTS), depression, and diabetes. Predictors of ED remission were lower age, current employment, and absence of voiding LUTS, angina, diabetes, and dyslipidemia. Predictors of low dyadic SD incidence included higher age, never having been married, widowhood, being unemployed, being retired, insufficient physical activity, and low alcohol intake. Predictors of low dyadic SD remission were being married, not being widowed, higher income, lower abdominal fat mass, lower OSA risk, and higher plasma testosterone. Predictors of low solitary SD included never having been married, being unemployed, low alcohol intake, lower testosterone, storage LUTS, and hypertension. Predictors of low solitary SD remission were being married, being employed, higher income, higher physical activity, moderate alcohol intake, and depression. Conclusions. Sexual dysfunction in aging men is a dynamic disorder whose incidence and remission are predicted by a range of modifiable risk factors

Testosterone and modifiable risk factors associated with diabetes in men

Results: Diabetes prevalence was positively associated with age groups 45–54 years (2.8 [1.4, 5.8]), 55–64 years (3.9 [1.9, 8.3]) and ≥65 years (4.0 [1.8, 8.9]), lowest income group (1.8 [1.0, 3.4]), ex-smoker (1.8 [1.2, 2.9]), lowest (3.2 [1.9, 5.5]) and middle (1.9 [1.1, 3.4]) alcohol tertiles, cardiovascular disease (1.9 [1.2, 2.8]), metabolic syndrome (4.0 [2.6, 6.1]), and lowest plasma total testosterone tertile (1.8 [1.1, 3.0]), but negatively associated with middle (0.5 [0.3, 0.8]) and highest (0.4 [0.3, 0.7]) sugar intake tertiles, arthritis (0.6 [0.3, 1.0]), and elevated LDL cholesterol (0.5 [0.3, 0.8]); ORs showed an inverted ‘U’ shape for middle and highest voiding lower urinary tract symptoms tertiles. Body composition, muscle strength, and cardio-metabolic factors partially explained the association between low plasma total testosterone and diabetes. Conclusions: Plasma total testosterone was inversely and independently associated with diabetes prevalence, that might have been partially explained by several modifiable risk factors.

Elucidating the Biological Mechanisms Linking Depressive Symptoms With Type 2 Diabetes in Men: The Longitudinal Effects of Inflammation, Microvascular Dysfunction, and Testosterone

Objective: This prospective cohort study sought to examine key biological measures linking depressive symptoms with Type 2 diabetes, specifically inflammation, microvascular dysfunction, and androgens.Methods: A cohort of 688 men without diabetes who were 35 years or older were followed up for 5 years. Venous interleukin-6, high-sensitivity C-reactive protein, sE-selectin, endogenous total testosterone, fasting glucose, and glycated hemoglobin (HbA1c) were quantified at baseline and 5 years later. Depressive symptoms were assessed using the Beck Depression Inventory-I, and men were categorized into persistent, remitted, incident, and nondepressed groups (reference). Logistic regression was used to determine odds ratios (ORs) for diabetes adjusted for propensity score calculated from 18 established risk factors.Results: Diabetes developed in 112 men (16.3% of sample). Persistent depressive symptoms were associated with diabetes (adjusted OR = 2.45, 95% confidence interval [CI] = 1.16–5.20, p = .019). Baseline testosterone (OR = 0.43, 95% CI = 0.22–0.81, p = .01) and follow-up testosterone (OR = 0.51, 95% CI = 0.31–0.84, p = .008) were inversely associated with Type 2 diabetes. Annualized HbA1c was positively associated with annualized change in cognitive Beck Depression Inventory symptoms (β = 0.14, p = .001) and inversely associated with annualized change in testosterone (β = −0.10, p = .014). Annualized change in fasting glucose was associated with sE-selectin (β = 0.12, p Conclusions: The findings suggest that lower endogenous total testosterone levels and persistent depressive symptoms were associated with Type 2 diabetes risk and HbA1c in men over a 5-year period

Lower urinary tract symptoms, depression, anxiety and systemic inflammatory factors in men : a population-based cohort study

The relationship between lower urinary tract symptoms (LUTS) and common mental health disorders such as depression and anxiety in men remains unclear. Inflammation has recently been identified as an independent risk factor for LUTS and depression [1, 2]. This study aims to assess the association between depression, anxiety and LUTS, and the moderating influence of systemic inflammation, in the presence of other biopsychosocial confounders