The relationship of high-intensity cross-training with arterial stiffness

Background Central arterial stiffness is a cardiovascular risk factor that can be readily affected through engagement in physical exercise training, with resistance and aerobic exercise having disparate affects. Despite the growing popularity of high-intensity cross-training (HICT), little is currently known about the effects of this mixed modality exercise stimulus on arterial stiffness. Therefore, the purpose of this study was to characterize the arterial stiffness of habitual HICT participants vs. aerobically active and sedentary controls using a cross-sectional design. Methods A total of 30 participants were recruited: 10 middle-aged long-term participants of HICT (CrossFit) and 20 age, sex, and height matched controls (10 recreationally active, 10 sedentary). Central and peripheral pulse wave velocities were measured for the carotid-femoral and femoral-dorsalis pedis arterial segments. Aerobic fitness (maximal oxygen uptake, VO2max) was measured and typical exercise participation rates were self-reported for each group. Results HICT participants manifested central pulse wave velocity (PWV) (5.3 ± 1.0 m/s, mean ± SD) and VO2max (43 ± 6 mL/kg/min) values nearly identical to active controls. Both active groups had significantly better values than sedentary controls (7.1 ± 1.0 m/s, p ≤ 0.001; and 32 ± 7 mL/kg/min, p = 0.01). No differences were observed in peripheral PWV between groups. Conclusion Habitual participation in HICT exercise was not associated with increased central nor peripheral arterial stiffness. Long-term HICT participants presented with similar fitness and arterial stiffness as compared with participants who practiced traditional aerobic exercise. Compared to sedentary living, HICT may offer musculoskeletal and cardiovascular health benefits without negatively impacting arterial stiffness

Saccharomyces cerevisiae Rad9 Acts as a Mec1 Adaptor to Allow Rad53 Activation

SummaryBackground: The DNA damage checkpoint is a protein kinase-based signaling system that detects and signals physical alterations in DNA. Despite having identified many components of this signaling cascade, the exact mechanisms by which checkpoint kinases are activated after DNA damage, as well as the role of the checkpoint mediators, remain poorly understood.Results: To elucidate the mechanisms that underlie the MEC1 and RAD9-dependent activation of Rad53, the Saccharomyces cerevisiae ortholog of Chk2, we mapped and characterized in vivo phosphorylation sites present on Rad53 after DNA damage by mass spectrometry. We find that Rad53 requires for its activation multisite phosphorylation on a number of typical and atypical Mec1 phosphorylation sites, thus confirming that Rad53 is a direct target of Mec1, the mammalian ATR homolog. Moreover, by using biochemical reconstitution experiments, we demonstrate that efficient and direct phosphorylation of Rad53 by Mec1 is only observed in the presence of purified Rad9, the archetypal checkpoint mediator. We find that the stimulatory activity of Rad9 requires a phospho- and FHA-dependent interaction with Rad53, which allows Rad53 to be recognized as a substrate for Mec1.Conclusions: Our results indicate that Rad9 acts as a bona fide signaling adaptor that enables Rad53 phosphorylation by Mec1. Given the high degree of conservation of checkpoint signaling in eukaryotes, we propose that one of the critical functions of checkpoint mediators such as MDC1, 53BP1, or Brca1 is to act as PIKK adaptors during the DNA damage response

BRCA1 and BRCA2 mutation predictions using the BOADICEA and BRCAPRO models and penetrance estimation in high-risk French-Canadian families.

INTRODUCTION: Several genetic risk models for breast and ovarian cancer have been developed, but their applicability to specific populations has not been evaluated. We used data from French-Canadian families to evaluate the mutation predictions given by the BRCAPRO and BOADICEA models. We also used this data set to estimate the age-specific risks for breast and ovarian cancer in BRCA1 and BRCA2 mutation carriers. METHODS: A total of 195 families with multiple affected individuals with breast or ovarian cancer were recruited through the INHERIT (INterdisciplinary HEalth Research International Team on BReast CAncer susceptibility) BRCAs research program. Observed BRCA1 and BRCA2 mutation status was compared with predicted carrier probabilities under the BOADICEA and BRCAPRO models. The models were assessed using Brier scores, attributes diagrams and receiver operating characteristic curves. Log relative risks for breast and ovarian cancer in mutation carriers versus population risks were estimated by maximum likelihood, using a modified segregation analysis implemented in the computer program MENDEL. Twenty-five families were eligible for inclusion in the BRCA1 penetrance analysis and 27 families were eligible for the BRCA2 penetrance analysis. RESULTS: The BOADICEA model predicted accurately the number of BRCA1 and BRCA2 mutations for the various groups of families, and was found to discriminate well at the individual level between carriers and noncarriers. BRCAPRO over-predicted the number of mutations in almost all groups of families, in particular the number of BRCA1 mutations. It significantly overestimated the carrier frequency for high predicted probabilities. However, it discriminated well between carriers and noncarriers. Receiver operating characteristic (ROC) curves indicate similar sensitivity and specificity for BRCAPRO and BOADICEA. The estimated risks for breast and ovarian cancer in BRCA1 and BRCA2 mutation carriers were consistent with previously published estimates. CONCLUSION: The BOADICEA model predicts accurately the carrier probabilities in French-Canadian families and may be used for counselling in this population. None of the penetrance estimates was significantly different from previous estimates, suggesting that previous estimates may be appropriate for counselling in this population.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Invasive pulmonary aspergillosis in chronic obstructive pulmonary disease: an emerging fungal pathogen

ABSTRACTAcute invasive pulmonary aspergillosis occurs predominantly in immunocompromised hosts, with increasing numbers of cases of invasive aspergillosis among patients with chronic obstructive pulmonary disease (COPD) being reported. Among 13 cases of invasive aspergillosis diagnosed in COPD patients admitted to the intensive care unit with acute respiratory distress, the only risk factor for invasive fungal infection was corticosteroid treatment. Invasive aspergillosis should be suspected in COPD patients receiving steroid treatment who have extensive pulmonary infiltrates. Survival depends on rapid diagnosis and early appropriate treatment. A decrease or interruption of steroid treatment should be considered as part of the overall therapeutic strategy

Possible common central pathway for resistin and insulin in regulating food intake.

Aim: Adipose tissue has been the object of intense research in the field of obesity and diabetes diseases in the last decade. Examination of adipocyte-secreted peptides led to the identification of a unique polypeptide, resistin (RSTN), which has been suggested as a link between obesity and diabetes. RSTN plays a clearly documented role in blocking insulin (INS)-induced hypoglycaemia. As brain injection of INS affects feeding behaviour, we studied the possible interaction between INS and RSTN in food-deprived rats, measuring effects on food intake. In addition, we examined how RSTN might affect neuropeptide Y (NPY)-induced feeding, as studies have shown that rat RSTN can interfere with the NPY system. Methods: Overnight food-deprived rats were injected into the third brain ventricle (3V) with either INS (10 or 20 mUI), RSTN (0.1–0.4 nmol/rat), or saline before access to food. Another group of rats was injected into the 3V with RSTN alone, NPY alone or RSTN plus NPY. Their food intake and body weight were measured. Results: Our results confirm the hypophagic effect of RSTN on food deprivation-induced food intake, and more importantly, show that RSTN neither potentiates nor blocks the effects of INS on food intake, but does reduce the hyperphagic effect of NPY. Conclusion:  The observation that RSTN does not modify feeding INS-induced hypophagia, but does influence NPY-induced feeding, points to the possibility that RSTN may be involved in control of food intake through an NPY-ergic mechanism as INS