The efficacy of isometric resistance training utilizing handgrip exercise for blood pressure management: A randomized trial.

INTRODUCTION: Hypertension is a major risk factor contributing to cardiovascular disease, which is the number one cause of deaths worldwide. Although antihypertensive medications are effective at controlling blood pressure, current first-line treatment for hypertension is nonpharmacological lifestyle modifications. Recent studies indicate that isometric resistance training (IRT) may also be effective for assisting with blood pressure management. The aim of this study was to determine the efficacy of IRT for blood pressure management and the suitability of a low-intensity working control group. METHODS: Forty hypertensive individuals, aged between 36 and 65 years, conducted IRT for 8 weeks. Participants were randomized into 2 groups, working at an intensity of either 5% or 30% of their maximum voluntary contraction. Participants performed 4 × 2 minute isometric handgrip exercises with their nondominant hand, each separated by a 3-minute rest period, 3 days a week. RESULTS: Blood pressure measurements were conducted at baseline and at the end of the protocol using a Finometer. Eight weeks of isometric resistance training resulted in a 7-mmHg reduction of resting systolic blood pressure (SBP) (136 ±â€Š12 to 129 ±â€Š15; P = 0.04) in the 30% group. Reductions of 4 mmHg were also seen in mean arterial pressure (MAP) (100 ±â€Š8 to 96 ±â€Š11; P = 0.04) in the 30% group. There were no statistically significant reductions in diastolic blood pressure for the 30% group, or any of the data for the 5% group. CONCLUSION: Isometric resistance training conducted using handgrip exercise at 30% of maximum voluntary contraction significantly reduced SBP and MAP. A lack of reduction in blood pressure in the 5% group indicates that a low-intensity group may be suitable as a working control for future studies.

The relationship between positive psychological characteristics and longer telomeres.

OBJECTIVE: Longer telomeres are associated with better health and longevity. This research investigated the relationship between positive psychological dispositional traits and telomere length. Positive traits examined were typical high positive affect, typical low negative affect, life satisfaction, trait mindfulness, trait emotional intelligence, general self-efficacy and optimism. DESIGN AND MEASURES: One hundred and twenty women and men, with a mean age of 40.92, completed measures of positive characteristics and provided samples for telomere length analysis. RESULTS: Together the positive dispositional characteristics explained significant variance in telomere length, R = .40. Among the individual characteristics, greater optimism and higher emotional intelligence were associated with longer telomeres after adjustment for age and gender and the association between optimism and telomere length remained significant after adjusting for age and gender as well as the other positive characteristics, with a partial correlation r of .30. CONCLUSION: These results in conjunction with previous research findings provide a platform for further exploration of biological pathways connecting positive characteristics such as optimism to telomere length and investigation of the impact of increasing a characteristic such as optimism on telomere functioning.

Proteomic and Microscopic Strategies towards the Analysis of the Cytoskeletal Networks in Major Neuropsychiatric Disorders.

Mental health disorders have become worldwide health priorities. It is estimated that in the next 20 years they will account for a 16 trillion United State dollars (US$) loss. Up to now, the underlying pathophysiology of psychiatric disorders remains elusive. Altered cytoskeleton proteins expression that may influence the assembly, organization and maintenance of cytoskeletal integrity has been reported in major depressive disorders, schizophrenia and to some extent bipolar disorders. The use of quantitative proteomics, dynamic microscopy and super-resolution microscopy to investigate disease-specific protein signatures holds great promise to improve our understanding of these disorders. In this review, we present the currently available quantitative proteomic approaches use in neurology, gel-based, stable isotope-labelling and label-free methodologies and evaluate their strengths and limitations. We also reported on enrichment/subfractionation methods that target the cytoskeleton associated proteins and discuss the need of alternative methods for further characterization of the neurocytoskeletal proteome. Finally, we present live cell imaging approaches and emerging dynamic microscopy technology that will provide the tools necessary to investigate protein interactions and their dynamics in the whole cells. While these areas of research are still in their infancy, they offer huge potential towards the understanding of the neuronal network stability and its modification across neuropsychiatric disorders.

An update on the interaction between the serotonin transporter promoter variant (5-HTTLPR), stress and depression, plus an exploration of non-confirming findings.

In the three years since the most recent meta-analysis of the association between the serotonin transported promoter polymorphism (5-HTTLPR), stress and the development of depression, another 27 studies have been published on this issue, which is an increase of 50% more studies than were previously reviewed. In addition, previous findings of inconsistency of results across studies argued for further exploration of this relationship. From the 81 studies identified to June 2013, the significant relationship between the short form of the 5-HTTLPR was confirmed (p=.0000009), which is stronger than the relationship reported in the most recent meta-analysis in 2011. However, nearly 26% of the 81 studies reviewed failed to show any significant association between the 5-HTTLPR, stress and depression, and four studies found opposite results to those expected. Examination of the methodologies of all studies failed to indicate any flaws in the opposite or unequivocal studies, and the latter had larger sample sizes than those studies which supported the expected association, arguing that the null results were not an outcome of insufficient statistical power. The need to consider aspects of samples and measures of depression, particularly the presence of subtypes of depression in future research is discussed.

Susceptibility of Candida albicans biofilms to azithromycin, tigecycline and vancomycin and the interaction between tigecycline and antifungals.

Despite growing data on antimicrobial lock therapy (ALT) in treating bacterial catheter-related bloodstream infections (CR-BSIs), ALT has not been established as a treatment option for CR-BSI caused by Candida albicans. Based on our finding that high-dose doxycycline exhibited antifungal activity against mature C. albicans biofilms, we evaluated additional antibacterial agents with Gram-positive activity [azithromycin, tigecycline (TIG) and vancomycin]. After screening these antibiotics, it was found that TIG had substantial antifungal activity against mature C. albicans biofilms. Therefore, TIG was assayed alone and in combination with fluconazole (FLC), amphotericin B (AmB) or caspofungin (CAS). TIG at 2048 µg/mL resulted in a >50% reduction in the growth of planktonic C. albicans cells. TIG inhibited the formation of biofilms from 128 µg/mL. Against mature biofilms, 2048 µg/mL TIG reduced metabolic activity by 84.2%. Furthermore, addition of 512 µg/mL TIG to FLC at all concentrations tested provided additional reduction in the metabolic activity of mature biofilms. However, this was not superior to 512 µg/mL TIG alone. TIG at 512 µg/mL increased the antifungal effect of lower concentrations of AmB (0.03125-0.25 µg/mL), but at 0.03125 µg/mL and 0.0625 µg/mL this effect was not superior to 512 µg/mL TIG alone. TIG inhibited the antifungal effect of higher concentrations of AmB (≥ 2 µg/mL). TIG at 512 µg/mL inhibited the antifungal activity of CAS at lower concentrations (0.25-8 µg/mL). These data indicate that high-dose TIG is highly active in vitro against planktonic cells, forming biofilms and mature biofilms of C. albicans.

Deletion of the C-terminus of polynucleotide phosphorylase increases twitching motility, a virulence characteristic of the anaerobic bacterial pathogen Dichelobacter nodosus.

The Gram-negative anaerobe Dichelobacter nodosus is the causative agent of footrot in sheep. Different strains of D. nodosus cause disease of differing severities, ranging from benign to virulent. Virulent strains have greater twitching motility and secrete proteases that are more thermostable than those secreted by benign strains. We have identified polynucleotide phosphorylase (PNPase) as a putative virulence regulator and have proposed that PNPase expression is modulated by the adjacent integration of genetic elements. In this study, we compared PNPase activity in three virulent and four benign strains of D. nodosus and found that PNPase activity is lower in virulent strains. We disrupted the pnpA gene in three benign D. nodosus strains and two virulent strains and showed that deletion of the S1 domain of PNPase reduced catalytic activity. In all but one case, deletion of the PNPase S1 domain had no effect on the thermostability of extracellular proteases. However, this deletion resulted in an increase in twitching motility in benign, but not in virulent strains. Reconstruction of the pnpA gene in two mutant benign strains reduced twitching motility to the parental level. These results support the hypothesis that PNPase is a virulence repressor in benign strains of D. nodosus.

Candida albicans PEP12 is required for biofilm integrity and in vivo virulence.

To investigate the role of the prevacuolar secretion pathway in biofilm formation and virulence in Candida albicans, we cloned and analyzed the C. albicans homolog of the Saccharomyces cerevisiae prevacuolar trafficking gene PEP12. C. albicans PEP12 encodes a deduced t-SNARE that is 28% identical to S. cerevisiae Pep12p, and plasmids bearing C. albicans PEP12 complemented the abnormal vacuolar morphology and temperature-sensitive growth of an S. cerevisiae pep12 null mutant. The C. albicans pep12 Delta null mutant was defective in endocytosis and vacuolar acidification and accumulated 40- to 60-nm cytoplasmic vesicles near the plasma membrane. Secretory defects included increased extracellular proteolytic activity and absent lipolytic activity. The pep12Delta null mutant was more sensitive to cell wall stresses and antifungal agents than the isogenic complemented strain or the control strain DAY185. Notably, the biofilm formed by the pep12Delta mutant was reduced in overall mass and fragmented completely upon the slightest disturbance. The pep12Delta mutant was markedly reduced in virulence in an in vitro macrophage infection model and an in vivo mouse model of disseminated candidiasis. These results suggest that C. albicans PEP12 plays a key role in biofilm integrity and in vivo virulence.