Physical activity ameliorates cardiovascular health in elderly subjects: the functional role of the Beta adrenergic system.

Aging is a complex process characterized by a gradual decline in organ functional reserves, which eventually reduces the ability to maintain homeostasis. An exquisite feature of elderly subjects, which constitute a growing proportion of the world population, is the high prevalence of cardiovascular disorders, which negatively affect both the quality of life and the life expectancy. It is widely acknowledged that physical activity represents one of the foremost interventions capable in reducing the health burden of cardiovascular disease. Interestingly, the benefits of moderate-intensity physical activity have been established both in young and elderly subjects. Herein we provide a systematic and updated appraisal of the literature exploring the pathophysiological mechanisms evoked by physical activity in the elderly, focusing on the functional role of the β adrenergic system

Erratum: The Non-Coding RNA Journal Club: Highlights on Recent Papers-4. Non-Coding RNA 2016, 2, 9.

Please note that in the published editorial [1], affiliations 1, and 8 contained errors.[...]

The Potential of Biomimetics Design in the Development of Impact Resistant Material

Ballistic impact resistance is an essential quality for materials to be used in protective shields. In this case, biomimetics design approach was used to improve the existing design of shield by finding solution from nature. Principles were extracted from biological models, such as fish scale, nacre and mantis shrimp, to improve the impact resistance of the shield. These models indicated that a multi-layered material structure shows superior impact resistance properties in case the stiffness of outer layers is much higher than that of inner layers and layer thickness is increased from outer towards inner layers. To verify this statement, materials with carbon fibre reinforced epoxy (CFRP) as the exterior layers and polycarbonate (PC) as the interior ones were designed and numerically analysed. Also pure polycarbonate samples were analysed for comparison purposes. The results showed that biomimetically designed composites had higher ballistic limit velocity than the control specimens for same target thickness

Enhanced GRK2 expression and desensitization of betaAR vasodilatation in hypertensive patients.

Increased levels of G protein coupled receptor kinase GRK2 appear to participate in hypertension presumably through the desensitization of beta adrenergic receptors (betaARs) that mediate vasodilatation. There are contrasting data on the occurrence of betaAR desensitization in the vasculature, we therefore investigated betaAR vasodilatation and desensitization in normotensives and in hypertensive humans. In blood lymphocytes, we assessed betaAR signaling and GRK2 expression and found betaAR signaling alterations and, consistent with desensitization, ncreased GRK2 levels in hypertensives. We studied in vivo vasodilatation to the betaAR agonist isoproterenol (ISO) injected in the brachia artery in control conditions and during the concomitant infusion of heparin, a known in vitro nonspecific GRK inhibitor. ISO induced a dose-dependent vasorelaxation that was attenuated in hypertensives indicating a loss of betaAR signaling. Intra-arterial infusion of heparin nhibited lymphocyte GRK2 activity and prevented desensitization of betaAR vasodilatation in normotensives. In hypertensives, heparin restored vasodilatation to ISO, to levels observed in normotensives. Our results suggest that betaAR desensitization does indeed occur at the vascular levels in vivo, and that heparin by acting as a GRK inhibitor prevents this in normotensives and restores impaired betaAR vasodilation in hypertensives. We conclude that desensitization participates to impaired betaAR vasodilation in hypertension

Honey bee pollen in meagre (Argyrosomus regius) juvenile diets: Effects on growth, diet digestibility, intestinal traits, and biochemical markers related to health and stress

This research aimed to evaluate the effects of the inclusion of honey bee pollen (HBP) in meagre (Argyrosoumus regius) juveniles’ diets on growth performance, diet digestibility, intestinal morphology, and immunohistochemistry. Furthermore, stress-related molecular markers and biochemical blood profile of fish were evaluated, together with mineral trace and toxic element concentration in pollen and diets. Specimens of meagre (360) of 3.34 ± 0.14 g initial body weight, were randomly allocated to twelve 500 L circular tanks (30 fish per tank). Four diets were formulated: a control diet and three experimental diets with 1%, 2.5%, and 4% of HBP inclusion. All the growth parameters and crude protein and ether extract digestibility coefficients were negatively linearly affected by increased HBP inclusion (p < 0.0001). Histology of medium intestine showed slight signs of alterations in group HPB1 and HPB2.5 compared to control. Fish from HBP4 group showed severe alterations at the intestinal mucosa level. Immunohistochemical detection of TNF-α in the medium intestine showed the presence of TNF-α+ cells in the lamina propria, which resulted in accordance with the increased level of the TNF-α protein detected by immunoblotting in the liver. This stress situation was confirmed by the increased hepatic level of HSP70 (p < 0.05) in fish fed the HBP4 diet and by the linear decrease of total serum protein levels in HBP-containing diets (p < 0.0001). These negative effects can be related to the ultrastructure of the bee pollen grain walls, which make the bioactive substances unavailable and can irritate the intestine of a carnivorous fish such as meagre

Caregiver Stigma and Burden in Memory Disorders: An Evaluation of the Effects of Caregiver Type and Gender

Despite considerable gains in public awareness of dementia, dementia patients and their caregivers continue to be stigmatized. Previous work has explored stigma and burden among adult children of persons with dementia in Israel, but no similar data exist for spousal caregivers or caregivers in general in the United States. This study examines the differences in stigma and burden experienced by spousal and adult child caregivers and male and female caregivers of persons with dementia. Eighty-two caregivers were given the Zarit Burden Inventory Short Form (ZBI) and the Caregiver Section of the Family Stigma in Alzheimer’s Disease Scale (FS-ADS-C). Scores on the FS-ADS-C and ZBI were positively correlated (rs=.51, p<.001). Female caregivers reported experiencing more stigma on the FS-ADS-C (t(80) = −4.37, p<.001) and more burden on the ZBI (t(80) = −2.68, p=.009) compared to male caregivers, and adult child caregivers reported experiencing more stigma on the FS-ADS-C (t(30.8) = −2.22, p=.034) and more burden on the ZBI (t(80) = −2.65, p=.010) than spousal caregivers. These results reinforce the importance of support for caregivers, particularly adult child and female caregivers who may experience higher levels of stigma and burden

Vesicle miR-195 derived from endothelial cells inhibits expression of serotonin transporter in vessel smooth muscle cells

Serotonin or 5-hydroxytryptamine (5-HT) has been shown to be essential in lots of physiological and pathological processes. It is well known that 5-HT and 5-HT transporter (5-HTT) play important roles in the pulmonary artery in pulmonary hypertension. However, little is known about the function of 5-HTT in other arteries. In this study we found that the expression of 5-HTT was elevated in injured carotid arteries and over-expression of 5-HTT induced proliferation of smooth muscle cells (SMCs); however, this phenotype could be reversed by knocking-down of 5-HTT or endothelial cells conditional medium (EC-CM). A 5-HTT inhibitor, fluoxetine, treated animals also exhibited reduced restenosis after injury. We identified that miR-195 was packaged in the extracellular vesicles from EC-CM. We further confirmed that extracellular vesicles could transfer miR-195 from ECs to SMCs to inhibit the expression of 5-HTT in SMCs and the proliferation of SMCs. These results provide the first evidence that ECs communicate with SMCs via micro-RNA195 in the regulation of the proliferation of SMCs through 5-HTT, which will contribute to a better understanding of communications between ECs and SMCs via micro-RNA. Our findings suggest a potential target for the control of vessel restenosis

AKT participates in endothelial dysfunction in hypertension.

In hypertension, reduced nitric oxide production and blunted endothelial vasorelaxation are observed. It was recently reported that AKT phosphorylates and activates endothelial nitric oxide synthase and that impaired kinase activity may be involved in endothelial dysfunction.To identify the physiological role of the kinase in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), we used adenoviral vectors to transfer the human AKT1 gene selectively to the common carotid endothelium. In vitro, endothelial vasorelaxations to acetylcholine, isoproterenol, and insulin were blunted in control carotids from SHR compared with WKY rats, and human AKT1 overexpression corrected these responses. Similarly, blood flow assessed in vivo by Doppler ultrasound was reduced in SHR compared with WKY carotids and normalized after AKT1 gene transfer. In primary cultured endothelial cells, we evaluated AKT phosphorylation, activity, and compartmentalization and observed a mislocalization of the kinase in SHR.We conclude that AKT participates in the settings of endothelial dysfunction in SHR rats by impaired membrane localization. Our data suggest that AKT is involved in endothelium dysfunction in hypertension

Discordance in glycemic categories and regression to normality at baseline in 10,000 people in a Type 2 diabetes prevention trial

The world diabetes population quadrupled between 1980 and 2014 to 422 million and the enormous impact of Type 2 diabetes is recognised by the recent creation of national Type 2 diabetes prevention programmes. There is uncertainty about how to correctly risk stratify people for entry into prevention programmes, how combinations of multiple ‘at high risk’ glycemic categories predict outcome, and how the large recently defined ‘at risk’ population based on an elevated glycosylated haemoglobin (HbA1c) should be managed. We identified all 141,973 people at highest risk of diabetes in our population, and screened 10,000 of these with paired fasting plasma glucose and HbA1c for randomisation into a very large Type 2 diabetes prevention trial. Baseline discordance rate between highest risk categories was 45.6 %, and 21.3 - 37.0 % of highest risk glycaemic categories regressed to normality between paired baseline measurements (median 40 days apart). Accurate risk stratification using both fasting plasma glucose and HbA1c data, the use of paired baseline data, and awareness of diagnostic imprecision at diagnostic thresholds would avoid substantial overestimation of the true risk of Type 2 diabetes and the potential benefits (or otherwise) of intervention, in high risk subjects entering prevention trials and programmes

Cholinergic enhancement of brain activation in mild cognitive impairment during episodic memory encoding

Objective: To determine the physiological impact of treatment with donepezil (Aricept) on neural circuitry supporting episodic memory encoding in patients with amnestic mild cognitive impairment (MCI) using functional magnetic resonance imaging (fMRI). Methods: Eighteen patients with MCI and 20 age-matched healthy controls (HC) were scanned twice while performing an event-related verbal episodic encoding task. MCI participants were scanned before treatment and after approximately 3 months on donepezil; HCwere untreated but rescanned at the same interval.Voxel-level analyses assessed treatment effects on activation profiles in MCI patients relative to retest changes in non-treated HC. Changes in task-related connectivity in medial temporal circuitry were also evaluated, as were associations between brain activation, task-related functional connectivity, task performance, and clinical measures of cognition. Results: At baseline, the MCI group showed reduced activation during encoding relative to HC in the right medial temporal lobe (MTL; hippocampal/parahippocampal) and additional regions, as well as attenuated task-related deactivation, relative to rest, in a medial parietal lobe cluster. After treatment, the MCI group showed normalized MTL activation and improved parietal deactivation. These changes were associated with cognitive performance. After treatment, the MCI group also demonstrated increased task-related functional connectivity from the right MTL cluster seed region to a network of other sites including the basal nucleus/caudate and bilateral frontal lobes. Increased functional connectivity was associated with improved task performance. Conclusion: Pharmacologic enhancement of cholinergic function in amnestic MCI is associated with changes in brain activation and functional connectivity during episodic memory processing which are in turn related to increased cognitive performance. fMRI is a promising biomarker for assessing treatment related changes in brain function