Metabolic effects of testosterone added to intensive lifestyle intervention in older men with obesity and hypogonadism.

BACKGROUND: Whether testosterone replacement therapy (TRT) conveys additional cardiometabolic benefit to an intensive lifestyle therapy (LT) in older men with obesity and hypogonadism remains unclear. OBJECTIVE: To determine whether TRT augments the effect of LT on metabolic outcomes in older men with obesity and hypogonadism. DESIGN: Secondary analysis of a randomized, double-blind, placebo-controlled trial. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: 83 older (age ≥ 65 years) men with obesity (BMI ≥ 30 kg/m2) and persistently low AM testosterone (< 10.4 nmol/L) associated with frailty. INTERVENTIONS: LT (weight management and exercise training) plus either testosterone (LT+TRT) or placebo (LT+Pbo) for six months. OUTCOME MEASURES: Primary outcome was change in glycated hemoglobin (HbA1c). Secondary outcomes included changes in other glucometabolic and lipid profile components, liver enzymes, inflammatory markers, adipokines; subcutaneous, visceral, intramuscular, and hepatic fat; blood pressure, and metabolic syndrome score. RESULTS: HbA1c decreased similarly in LT+TRT and LT+Pbo groups (-0.5% vs. -0.6%, respectively; p= 0.35). While TRT showed no synergistic effect with LT on ameliorating secondary outcomes, it eliminated the augmentative effect of LT on high-density lipoprotein cholesterol concentration (5.4 ± 1.0 mg/dL in LT+Pbo group vs. 0.2 ± 1.1 mg/dL in LT+TRT group, p= 0.01) and adiponectin levels (-408 ± 489 ng/mL in TRT+LT group vs 1832 ± 468 ng/mL in LT+Pbo group, p= 0.02). CONCLUSION: In older men with obesity and hypogonadism, adding TRT for six months to LT does not result in further improved cardiometabolic profiles, and could potentially blunt some of the metabolic benefits induced by LT.

Music as a Therapy to Alleviate Anxiety During Inpatient Rehabilitation for Stroke.

PURPOSE: The aim of the study was to determine if listening to music may reduce anxiety experienced by stroke patients during acute rehabilitation. DESIGN: A prospective, nonblinded, randomized study in an inpatient rehabilitation setting. METHODS: Fifty participants were randomized into two groups: (1) 1 hour of music (intervention) or (2) no music (control). All participants completed pretest anxiety and depression screening and 44 completed the posttest anxiety screening. Differences between groups were determined using chi-square and t tests. FINDINGS: After listening to music for 1 hour, participants who completed the posttest (n = 44) reported significantly less anxiety (p < .0001) compared to before the intervention. The control group showed no difference in their pre- and posttest anxiety scores (p = .84). No differences were determined among age, gender, or diagnostic groups. CONCLUSIONS: These findings demonstrate that music intervention may help lessen anxiety in rehabilitation patients poststroke. CLINICAL RELEVANCE: Offering musical intervention to stroke patients in rehabilitation may lessen symptoms of anxiety.

Gun ownership and social gun culture.

We assessed gun ownership rates in 2013 across the USA and the association between exposure to a social gun culture and gun ownership. We used data from a nationally representative sample of 4000 US adults, from 50 states and District of Columbia, aged >18 years to assess gun ownership and social gun culture performed in October 2013. State-level firearm policy information was obtained from the Brady Law Center and Injury Prevention and Control Center. One-third of Americans reported owning a gun, ranging from 5.2% in Delaware to 61.7% in Alaska. Gun ownership was 2.25-times greater among those reporting social gun culture (PR=2.25, 95% CI 2.02 to 2.52) than those who did not. In conclusion, we found strong association between social gun culture and gun ownership. Gun cultures may need to be considered for public health strategies that aim to change gun ownership in the USA.

Serotonergic systems in the balance: CRHR1 and CRHR2 differentially control stress-induced serotonin synthesis.

Anxiety and affective disorders are often associated with hypercortisolism and dysfunctional serotonergic systems, including increased expression of TPH2, the gene encoding the rate-limiting enzyme of neuronal serotonin synthesis. We previously reported that chronic glucocorticoid exposure is anxiogenic and increases rat Tph2 mRNA expression, but it was still unclear if this also translates to increased TPH2 protein levels and in vivo activity of the enzyme. Here, we found that adult male rats treated with corticosterone (CORT, 100 µg/ml) via the drinking water for 21 days indeed show increased TPH2 protein expression in the dorsal and ventral part of the dorsal raphe nucleus (DRD, DRV) during the light phase, abolishing the enzyme's diurnal rhythm. In a second study, we systemically blocked the conversion of 5-hydroxytryptophan (5-HTP) to serotonin immediately before rats treated with CORT or vehicle were either exposed to 30 min acoustic startle stress or home cage control conditions. This allowed us to measure 5-HTP accumulation as a direct readout of basal versus stress-induced in vivo TPH2 activity. As expected, basal TPH2 activity was elevated in the DRD, DRV and MnR of CORT-treated rats. In response to stress, a multitude of serotonergic systems reacted with increased TPH2 activity, but the stress-, anxiety-, and learned helplessness-related dorsal and caudal DR (DRD/DRC) displayed stress-induced increases in TPH2 activity only after chronic CORT-treatment. To address the mechanisms underlying this region-specific CORT-dependent sensitization, we stereotaxically implanted CORT-treated rats with cannulae targeting the DR, and pharmacologically blocked either corticotropin-releasing hormone receptor type 1 (CRHR1) or type 2 (CRHR2) 10 min prior to acoustic startle stress. CRHR2 blockade prevented stress-induced increases of TPH2 activity within the DRD/DRC, while blockade of CRHR1 potentiated stress-induced TPH2 activity in the entire DR. Stress-induced TPH2 activity in the DRD/DRC furthermore predicted TPH2 activity in the amygdala and in the caudal pontine reticular nucleus (PnC), while serotonin synthesis in the PnC was strongly correlated with the maximum startle response. Our data demonstrate that chronically elevated glucocorticoids sensitize stress- and anxiety-related serotonergic systems, and for the first time reveal competing roles of CRHR1 and CRHR2 on stress-induced in vivo serotonin synthesis.

Race and ethnicity, neighborhood poverty and pediatric firearm hospitalizations in the United States.

PURPOSE: To better understand the effects of race and/or ethnicity and neighborhood poverty on pediatric firearm injuries in the United States, we compared overall and intent-specific firearm hospitalizations (FH) with those of pedestrian motor vehicle crash hospitalizations (PMVH). METHODS: We used Nationwide Inpatient Sample data (1998-2011) among 0-15 year-olds in a 1:1 case-case study; 4725 FH and 4725 PMVH matched by age, year, and region. RESULTS: Risk of FH versus PMVH was 64% higher among black children, Odds ratio (OR) = 1.64, 95% confidence interval (95% CI) = 1.44-1.87, as compared to white children (P < .0001); this risk did not vary by neighborhood poverty (P interaction = .52). Risk of homicide FH versus PMVH was 842% higher among black (OR = 8.42, 95% CI = 6.27-11.3), 452% higher among Hispanics (OR = 4.52, 95% CI = 3.33-6.13) and 233% higher among other race (OR = 2.33, 95% CI = 1.52-3.59) compared to white children. There was a lower risk for unintentional FH among black OR = 0.73, 95% CI = 0.62-0.87, Hispanics (OR = 0.60, 95% CI = 0.49-0.74), and other (OR = 0.63, 95% CI = 0.47-0.83) compared to whites. These intent-specific risks attributed to race did not vary by neighborhood affluence. CONCLUSIONS: Black children were at greater likelihood of FH compared to white children regardless of neighborhood economic status. Minority children had an increased likelihood of intentional FH and a decreased likelihood of unintentional FH as compared to white children irrespective of neighborhood income.

State-specific, racial and ethnic heterogeneity in trends of firearm-related fatality rates in the USA from 2000 to 2010.

OBJECTIVES: To document overall, racial, ethnic and intent-specific spatiotemporal trends of firearm-related fatality rates (FRF rates) in the USA. DESIGN: Cross-sectional study per year from 2000 to 2010. SETTING USA PARTICIPANTS: Aggregate count of all people in the USA from 2000 to 2010. OUTCOME MEASURES: Data from the Web-based Injury Statistics Query and Reporting System from 2000 to 2010 was used to determine annual FRF rates per 100,000 and by states, race, ethnicity and intent. RESULTS: The average national 11-year FRF rate was 10.21/100,000, from 3.02 in Hawaii to 18.62 in Louisiana: 60% of states had higher than national rates and 41 states showed no temporal change. The average national FRF rates among African-Americans and Caucasians were 18.51 and 9.05/100,000 and among Hispanics and non-Hispanics were 7.13 and 10.13/100,000; Hispanics had a decreasing change of -0.18, p trend<0.0001. In states with increasing trends (Florida and Massachusetts), Caucasians and non-Hispanics drove the rise; while in states with decreasing trends (California, North Carolina, Arizona, Nevada, New York, Illinois, Maryland), Hispanics and African-Americans drove the fall. The average national FRF rates due to homicides (4.1/100,000) and suicides (5.8/100,000) remained constant, but varied between states. CONCLUSIONS: Endemic national FRF rates mask a wide variation in time trends between states. FRF rates were twice as high in African-Americans than Caucasians but decreased among Hispanics. Efforts to identify state-specific best practices can contribute to changes in national FRF rates that remain high.