Intensity-dependent reductions in resting blood pressure following short-term isometric exercise training

To reduce resting blood pressure, a minimum isometric exercise training (IET) intensity has been suggested, but this is not known for short-term IET programmes. We therefore compared the effects of moderate- and low-intensity IET programmes on resting blood pressure. Forty normotensive participants (22.3 ± 3.4 years; 69.5 ± 15.5 kg; 170.2 ± 8.7 cm) were randomly assigned to groups of differing training intensities [20%EMGpeak (~23%MVC, maximum voluntary contraction, or 30%EMGpeak (~34%MVC)] or control group; 3 weeks of IET at 30%EMGpeak resulted in significant reductions in resting mean arterial pressure (e.g. −3.9 ± 1.0 mmHg, P 0.05). Moreover, after pooling all female versus male participants, IET induced a 6.9-mmHg reduction in systolic blood pressure in female participants, but only a 1.5-mmHg reduction in systolic blood pressure in male participants, although the difference was not significant. An IET intensity between 20%EMGpeak and 30%EMGpeak is sufficient to elicit significant resting blood pressure reductions in a short-term training period (3 weeks). In addition, sexual dimorphism may exist in the magnitude of reductions, but further work is required to confirm this possibility, which could be important in understanding the mechanisms responsible

Neonatal Androgenization Exacerbates Alcohol-Induced Liver Injury in Adult Rats, an Effect Abrogated by Estrogen

Alcoholic liver disease (ALD) affects millions of people worldwide and is a major cause of morbidity and mortality. However, fewer than 10% of heavy drinkers progress to later stages of injury, suggesting other factors in ALD development, including environmental exposures and genetics. Females display greater susceptibility to the early damaging effects of ethanol. Estrogen (E2) and ethanol metabolizing enzymes (cytochrome P450, CYP450) are implicated in sex differences of ALD. Sex steroid hormones are developmentally regulated by the hypothalamic-pituitary-gonadal (HPG) axis, which controls sex-specific cycling of gonadal steroid production and expression of hepatic enzymes. The aim of this study was to determine if early postnatal inhibition of adult cyclic E2 alters ethanol metabolizing enzyme expression contributing to the development of ALD in adulthood. An androgenized rat model was used to inhibit cyclic E2 production. Control females (Ctrl), androgenized females (Andro) and Andro females with E2 implants were administered either an ethanol or isocalorically-matched control Lieber-DeCarli diet for four weeks and liver injury and CYP450 expression assessed. Androgenization exacerbated the deleterious effects of ethanol demonstrated by increased steatosis, lipid peroxidation, profibrotic gene expression and decreased antioxidant defenses compared to Ctrl. Additionally, CYP2E1 expression was down-regulated in Andro animals on both diets. No change was observed in CYP1A2 protein expression. Further, continuous exogenous administration of E2 to Andro in adulthood attenuated these effects, suggesting that E2 has protective effects in the androgenized animal. Therefore, early postnatal inhibition of cyclic E2 modulates development and progression of ALD in adulthood

Association Between the Affordable Care Act and Emergency Department Visits for Psychiatric Disease

Introduction: Emergency department (ED) utilization for psychiatric disease is increasing, and a lack of health insurance has been identified as a potential cause of preventable or avoidable ED use. Through the Affordable Care Act (ACA), more uninsured individuals gained health insurance; however, the effects of increased health insurance coverage on ED utilization for psychiatric disease have not been examined.Methods: We performed a longitudinal, cross-sectional analysis of data from the Nationwide Emergency Department Sample, the largest all-payer ED database in the US, which contains data on over 25 million ED visits each year. We examined ED utilization for psychiatric disease as the primary reason for visit among adults aged 18-64. We compared the proportion of ED visits with a psychiatric diagnosis during post-ACA years (2011-2016) to pre-ACA (2009) using logistic regression adjusted for age, gender, payer, and hospital region.Results: The proportion of ED visits with psychiatric diagnosis increased from pre-ACA (4.9%) to post-ACA years (ranging from 5.0-5.5%). There was a significant difference in the proportion of ED visits with a psychiatric diagnosis when comparing each post-ACA year with pre-ACA, with adjusted odds ratios ranging from 1.01-1.09. Among ED visits with a psychiatric diagnosis, the most common age group was 26-49 years, and patients were more likely to be male than female and to have visited urban rather than rural hospitals. During post-ACA years (2014-2016), private and uninsured payers decreased, Medicaid payers increased, and Medicare payers increased in 2014 and decreased in 2015-2016 compared to pre-ACA.Conclusion: With the ACA more people gained health insurance, yet ED visits for psychiatric disease continued to increase. These results suggest that increasing access to health insurance alone is not sufficient to reduce ED utilization for patients with a psychiatric disease.&nbsp

Differential Expression of Inflammatory Cytokines and Stress Genes in Male and Female Mice in Response to a Lipopolysaccharide Challenge.

Sex plays a key role in an individual's immune response against pathogenic challenges such that females fare better when infected with certain pathogens. It is thought that sex hormones impact gene expression in immune cells and lead to sexually dimorphic responses to pathogens. We predicted that, in the presence of E. coli gram-negative lipopolysaccharide (LPS), there would be a sexually dimorphic response in proinflammatory cytokine production and acute phase stress gene expression and that these responses might vary among different mouse strains and times in a pattern opposite to that of body temperature associated with LPS-induced shock.Interleukin-6 (IL-6), macrophage inflammatory protein-Iβ (MIP-1β), tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) as well as beta-fibrinogen (Fgb) and metallothionein-1 (Mt-1) mRNA expression were measured at four time points (0, 2, 4 and 7 hours) after injection of E. coli LPS in mice from three inbred strains.Statistical analysis using analyses of variance (ANOVAs) showed that the levels of the all six traits changed over time, generally peaking at 2 hours after LPS injection. Mt-1, Fgb, and IL-6 showed differences among strains, although these were time-specific. Sexual dimorphism was seen for Fgb and IL6, and was most pronounced at the latest time period (7 hours) where male levels exceeded those for females. Trends for all six cytokine/gene expression traits were negatively correlated with those for body temperatures.The higher levels of expression of Fgb and IL6 in males compared with females are consistent with the greater vulnerability of males to infection and subsequent inflammation. Temperature appears to be a useful proxy for mortality in endotoxic shock, but sexual dimorphism in cytokine and stress gene expression levels may persist after an LPS challenge even if temperatures in the two sexes are similar and have begun to stabilize

Effect of strain on the expression of metallothionein-1 in mice.

<p>Expression of Mt-1, a stress gene expressed in the liver, as compared to the control gene, Actb, following amplification with quantitative real time PCR. (Mean ± SEM) Mt-1 data was transformed by raising all values to 0.4. A. At 0 hours, a significant difference between BALB/c mice and C57BL/6 mice was observed. Neither was significantly different from CD1 mice in terms of Mt-1 expression. B. At 4 hours, a significant difference was observed from baseline levels for all strains. At this time, the levels were slightly higher for all three strains than the levels observed at 0 hours. F = 3.06; d.f. = 6,00; *P = 0.0 Means with different superscripts within time points are significantly different.</p

Effect of sex and strain on the expression of IL-6.

<p>Expression of serum IL-6, a proinflammatory cytokine, tested using quantitative ELISAs. (Mean ± SEM) IL-6 data was transformed by raising all values to 0.3. At 0 hours, a significant difference was observed, with any difference in sex or strain being dependent on the other variable. At 7 hours, a significant difference was observed, with any difference in sex or strain being dependent on the other variable. Differing letters indicate significance. P < 0.05.</p

Beta-fibrinogen expression over time in three strains.

<p>Expression of Fgb mRNA as compared to control Actb mRNA following amplification of both genes with quantitative real time PCR. (Mean ± SEM) Fgb data was transformed by raising all values to 0.2. A. There was a significant strain by time interaction (<i>F</i> = 5.55; d.f. = 6, 91; <i>P</i> < 0.0001), with post-hoc tests showing differences in expression levels between BALB/c and B6 mice at 7 hours, and between BL6 and both other strains at 4 hours B. There was also a sex by time interaction (<i>F</i> = 6.73; d.f. = 3, 91; <i>P</i> = 0.0004)), with higher expression levels in males compared with females at the 2 hour and especially the 7 hour time periods, but the reverse at the 4 hour time period. Means with different superscripts are significantly different. P < 0.05.</p

Body temperature changes over time following LPS exposure.

<p>Following a non-lethal dosage of 5mg/kg of LPS, mice were tested over a 9-hour time period for changes in body temperature. (Mean ± SEM) These were plotted by sex and strain. A. A significant difference in temperature was observed between male and female BALB/c mice at 3 hours and at 4 hours following LPS injection. B. A significant difference in temperature was observed between male and female CD1 mice at 2 hours, but not at any other time points measured. C. A significant difference was observed between male and female C57BL/6 mice at 4 and 5 hours following LPS injection. *P < 0.05.</p