Associations of objectively measured sedentary behavior,light activity,and markers of cardiometabolic health in young women

Purpose

To investigate the associations among objectively measured sedentary behavior, light physical activity, and markers of cardiometabolic health in young women.

Methods

Cardiovascular disease risk factors, homeostasis model assessment for insulin resistance (HOMA-IR), lipid accumulation product, and inflammatory markers were measured in 50 young, adult women. Accelerometers were worn over 7 days to assess sedentary time (<150 counts min^?1), light physical activity (150–2,689 counts min^?1), and moderate-to-vigorous physical activity (MVPA; ≥2,690 counts min^?1). Multivariate regression examined independent associations of sedentary behavior and light physical activity with cardiometabolic health. Covariates included MVPA, cardiorespiratory fitness (VO_2peak) and body mass, and body composition.

Results

Sedentary behavior was associated with triglycerides (p = 0.03) and lipid accumulation product (p = 0.02) independent of MVPA. These associations were attenuated by VO_2peak and body mass or body composition (p ≥ 0.05). Light physical activity was independently associated with triglycerides and lipid accumulation product after adjustment for all covariates (p < 0.05). The association between light physical activity and HOMA-IR was independent of MVPA (p = 0.02) but was attenuated by VO_2peak and body mass or body composition (p > 0.05).

Conclusions

Sedentary behavior and light physical activity were independently associated with markers of cardiometabolic health in young, adult women. Our data suggest that VO_2peak and body composition may be important mediators of these associations. Decreasing sedentary behavior and increasing light physical activity may be important for maintaining cardiometabolic health in young, adult women.     

Long-term male-specific chronic pain via telomere- and p53‑mediated spinal cord cellular senescence

Mice with experimental nerve damage can display long‑lasting neuropathic pain behavior. We show here that 4 months and later after nerve injury, male but not female mice displayed telomere length (TL) reduction and p53‑mediated cellular senescence in the spinal cord, resulting in maintenance of pain and associated with decreased lifespan. Nerve injury increased the number of p53‑positive spinal cord neurons, astrocytes, and microglia, but only in microglia was the increase male‑specific, matching a robust sex specificity of TL reduction in this cell type, which has been previously implicated in male‑specific pain processing. Pain hypersensitivity was reversed by repeated intrathecal administration of a p53‑specific senolytic peptide, only in male mice and only many months after injury. Analysis of UK Biobank data revealed sex-specific relevance of this pathway in humans, featuring male‑specific genetic association of the human p53 locus (TP53) with chronic pain and a male-specific effect of chronic pain on mortality. Our findings demonstrate the existence of a biological mechanism maintaining pain behavior, at least in males, occurring much later than the time span of virtually all extant preclinical studies.     

Pulmonary endothelium as a site of synthesis and storage of interleukin-6 in experimental congestive heart failure

BACKGROUND: Pulmonary endothelium is an early upstream hemodynamic target of left ventricular dysfunction. Interleukin 6 (IL-6) is a pro-inflammatory cytokine reported to increase in congestive heart failure (CHF) patients. AIMS: We sought to determine the origin of IL-6, IL-6 receptor (IL-6R) and gp130 in experimental CHF. METHODS: We used rats with coronary artery ligation as an experimental model of either compensated or decompensated heart failure. Lung and aorta samples were analysed by RT-PCR, ELISA and immunohistochemistry for IL-6 and its receptors. RESULTS: IL-6 mRNA expression increased in the lung of rats with decompensated heart failure and was positively correlated with infarct severity whereas IL-6R mRNA decreased in the lung of myocardial infarction rats and gp130 mRNA remained unchanged. In contrast, there were no changes in IL-6 mRNA expression in the aorta and left ventricular myocardium. IL-6 peptide content as determined by ELISA and Western Blot in lung tissue was 2-fold higher in decompensated heart failure as compared to control rats. These data were confirmed by immunohistochemistry showing a preferential endothelial localization of IL-6 in the CHF lung. IL-6 peptide was also present in the pleural effusion of decompensated heart failure and was positively correlated with IL-6 mRNA expression in the lungs of decompensated HF rats. Pulmonary IL-6 overexpression was associated with nuclear translocation of NF-kappaB and cytosolic degradation of IkappaB. CONCLUSION: Dysfunctional pulmonary endothelium is a source of synthesis and storage of IL-6 in an experimental model of CHF.     

Age effects on basic symptoms in the community: A route to gain new insight into the neurodevelopment of psychosis?

European Archives of Psychiatry and Clinical Neuroscience - Reports of limited clinical significance of attenuated psychotic symptoms before age 15/16 indicate an important role of neurodevelopment...     

Tractostorm: The what,why, and how of tractography dissection reproducibility

Investigative studies of white matter (WM) brain structures using diffusion MRI (dMRI) tractography frequently require manual WM bundle segmentation, often called “virtual dissection.” Human errors and personal decisions make these manual segmentations hard to reproduce, which have not yet been quantified by the dMRI community. It is our opinion that if the field of dMRI tractography wants to be taken seriously as a widespread clinical tool, it is imperative to harmonize WM bundle segmentations and develop protocols aimed to be used in clinical settings. The EADC‐ADNI Harmonized Hippocampal Protocol achieved such standardization through a series of steps that must be reproduced for every WM bundle. This article is an observation of the problematic. A specific bundle segmentation protocol was used in order to provide a real‐life example, but the contribution of this article is to discuss the need for reproducibility and standardized protocol, as for any measurement tool. This study required the participation of 11 experts and 13 nonexperts in neuroanatomy and “virtual dissection” across various laboratories and hospitals. Intra‐rater agreement (Dice score) was approximately 0.77, while inter‐rater was approximately 0.65. The protocol provided to participants was not necessarily optimal, but its design mimics, in essence, what will be required in future protocols. Reporting tractometry results such as average fractional anisotropy, volume or streamline count of a particular bundle without a sufficient reproducibility score could make the analysis and interpretations more difficult. Coordinated efforts by the diffusion MRI tractography community are needed to quantify and account for reproducibility of WM bundle extraction protocols in this era of open and collaborative science.     

Traditional and new composite endpoints in heart failure clinical trials: facilitating comprehensive efficacy assessments and improving trial efficiency

Composite endpoints are commonly used as the primary measure of efficacy in heart failure clinical trials to assess the overall treatment effect and to increase the efficiency of trials. Clinical trials still must enrol large numbers of patients to accrue a sufficient number of outcome events and have adequate power to draw conclusions about the efficacy and safety of new treatments for heart failure. Additionally, the societal and health system perspectives on heart failure have raised interest in ascertaining the effects of therapy on outcomes such as repeat hospitalization and the patient's burden of disease. Thus, novel methods for using composite endpoints in clinical trials (e.g. clinical status composite endpoints, recurrent event analyses) are being applied in current and planned trials. Endpoints that measure functional status or reflect the patient experience are important but used cautiously because heart failure treatments may improve function yet have adverse effects on mortality. This paper discusses the use of traditional and new composite endpoints, identifies qualities of robust composites, and outlines opportunities for future research.     

Oral sildenafil as a treatment option for lymphatic malformations in PIK3CA‐related tissue overgrowth syndromes

Patients with extensive lymphatic malformations associated with tissue overgrowth syndromes (such as Klippel‐Trenaunay syndrome and CLOVES) often pose a therapeutic challenge for physicians. In recent years, it has been suggested that oral sildenafil therapy might be used to treat congenital lymphatic malformations. However, this possible new therapy has not yet been used in patients with lymphatic malformations associated with tissue overgrowth syndromes. A 30‐year‐old man with extensive capillary‐lymphatic malformations of the right leg and thorax, and a tissue overgrowth syndrome caused by a somatic mutation in the PIK3CA gene, was treated with oral sildenafil due to symptoms of pain, dyspnea, and functional impairment. Several weeks after the start of the treatment, the patient reported softening of the lymphatic malformation and a significant improvement of his symptoms and physical condition. So far, sildenafil is still considered a last resort in the treatment of complex treatment‐resistant lymphatic malformations. With this case report, we demonstrate that sildenafil could also be an alternative treatment option for lymphatic malformations in patients with syndromes belonging to the PIK3CA‐related overgrowth spectrum.