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Much of the population is now faced with an enormous burden of age-associated chronic diseases. Recent discoveries in geroscience indicate that healthspan in model organisms such as mice can be manipulated by targeting cellular senescence, a hallmark mechanism of aging, defined as an irreversible proliferative arrest that occurs when cells experience oncogenic or other diverse forms of damage. Senescent cells and their pro-inflammatory secretome have emerged as contributors to age-related tissue dysfunction and morbidity. Cellular senescence has causal roles in mediating osteoporosis, frailty, cardiovascular diseases, osteoarthritis, pulmonary fibrosis, renal diseases, neurodegenerative diseases, hepatic steatosis, and metabolic dysfunction. Therapeutically targeting senescent cells in mice can prevent, delay, or alleviate each of these conditions. Therefore, senotherapeutic approaches, including senolytics and senomorphics, that either selectively eliminate senescent cells or interfere with their ability to promote tissue dysfunction, are gaining momentum as potential realistic strategies to abrogate human senescence to thereby compress morbidity and extend healthspan.

Miller, RM, Freitas, EDS, Heishman, AD, Koziol, KJ, Galletti, BAR, Kaur, J, and Bemben, MG. Test-retest reliability between free weight and machine-based movement velocities. J Strength Cond Res 34(2): 440-444, 2020-Several devices are available to measure muscular power through velocity measurement, including the Tendo FitroDyne. The ability for such devices to produce consistent results is still questioned, and the reproducibility of measurement between free weight and machine exercise has yet to be examined. Therefore, the aim of this investigation was to determine the test-retest reliability for barbell velocity during the bench press (BP) and weight velocity during the 2 leg press (2LP) for loads corresponding to 20-80% of 1 repetition maximum (1RM). Forty recreationally active individuals (22.6 ± 2.5 years; 175.9 ± 10.8 cm; and 76.2 ± 13.2 kg) with a 1RM BP and 2LP of 66.8 ± 32.4 kg and 189.5 ± 49 kg, respectively, volunteered for this study. Subjects completed 1 familiarization visit preceding 3 testing visits, which encompassed 1RM determination and 2 days of velocity testing. Forty-eight hours after 1RM testing, the subjects performed 1 repetition at 20, 30, 40, 50, 60, 70, and 80% of their 1RM for each exercise in randomized order. Subjects returned to the laboratory 1 week later to perform the velocity assessment again in randomized order. Intraclass correlation coefficient (ICC2,1) and relative SEM for the BP and 2LP ranged from 0.56 to 0.98 (3-18.1%) and 0.78 to 0.98 (2.8-7.2%), respectively, and no mean differences were observed between trials. The results suggest high reliability for BP velocity between 30 and 60% 1RM and moderate reliability at 20, 70, and 80% 1RM, while the 2LP displayed high to excellent reliability from 20 to 80% 1RM. Cumulatively, machine-based exercise displayed greater reproducibility; however, additional machine exercises need to be examined to bolster this conclusion.

ObjectivesResponding to pandemics is challenging in pluralistic health systems. This study assesses COVID-19 knowledge and case management of informal providers (IPs), trained practitioners of Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homeopathy (AYUSH) and Bachelor of Medicine, Bachelor of Surgery (MBBS) medical doctors providing primary care services in rural Bihar, India.DesignThis was a cross-sectional study of primary care providers conducted via telephone between 1 and 15 July 2020.SettingPrimary care providers from 224 villages in 34 districts across Bihar, India.Participants452 IPs, 57 AYUSH practitioners and 38 doctors (including 23 government doctors) were interviewed from a census of 1138 primary care providers used by community members that could be reached by telephone.Primary outcome measure(s)Providers were interviewed using a structured questionnaire with choice-based answers to gather information on (1) change in patient care seeking, (2) source of COVID-19 information, (3) knowledge on COVID-19 spread, symptoms and methods for prevention and (4) clinical management of COVID-19.ResultsDuring the early days of the COVID-19 pandemic, 72% of providers reported a decrease in patient visits. Most IPs and other private primary care providers reported receiving no COVID-19 related engagement with government or civil society agencies. For them, the principal source of COVID-19 information was television and newspapers. IPs had reasonably good knowledge of typical COVID-19 symptoms and prevention, and at levels similar to doctors. However, there was low stated compliance among IPs (16%) and qualified primary care providers (15% of MBBS doctors and 12% of AYUSH practitioners) with all WHO recommended management practices for suspect COVID-19 cases. Nearly half of IPs and other providers intended to treat COVID-19 suspects without referral.ConclusionsPoor management practices of COVID-19 suspects by rural primary care providers weakens government pandemic control efforts. Government action of providing information to IPs, as well as engaging them in contact tracing or public health messaging can strengthen pandemic control efforts.

Introduction: All psychiatric disorders exhibit excitotoxicity, mitochondrial dysfunction, inflammation, oxidative stress, and neural damage as their common characteristic. The endogenous nuclear f...

Ischemia/reperfusion (I/R) is one of the common reasons for acute kidney injury (AKI) and we need to develop effective therapies for treating AKI. We investigated the role of fenofibrate against I/R-induced AKI and associated hepatic dysfunction in rats. In male wistar albino rats, renal pedicle occlusion for 40 min and 24 h reperfusion resulted in AKI. I/R-induced AKI was demonstrated by measuring serum creatinine, creatinine clearance, urea, uric acid, potassium, fractional excretion of sodium and urinary microproteins. Oxidative stress in rat kidneys was quantified by assaying superoxide anion generation, thiobarbituric acid reactive substances, and reduced glutathione levels. AKI-induced hepatic damage was quantified by assaying serum aminotransferases, alkaline phosphatase and bilirubin levels. Moreover, serum cholesterol, high density lipoprotein and triglycerides were quantified. Hematoxylin-eosin staining of renal and hepatic tissues was done and the kidney and liver injury scores were determined. Immunohistology of endothelial nitric oxide synthase (eNOS) was done in rat kidneys. Fenofibrate was administered for 1 week before subjecting rats to AKI. In separate group, the nitric oxide synthase inhibitor, L-nitroarginine methyl ester (L-NAME) was administered prior to fenofibrate treatment. In I/R group, significant alteration in the serum/urine parameters indicated AKI and hepatic dysfunction along with marked increase in kidney and liver injury scores. Treatment with fenofibrate attenuated AKI and associated hepatic dysfunction. Moreover, I/R-induced decrease in renal eNOS expression was abrogated by fenofibrate. Pre-treatment with L-NAME abolished fenofibrate mediated reno- and hepato-protective effects. In conclusion, fenofibrate attenuates I/R-induced AKI and associated hepatic dysfunction putatively through modulation of eNOS expression.

PURPOSE OF REVIEW. Senescent cells are now known to accumulate in multiple tissues with aging and through their inflammation (the senescence-associated secretory phenotype, SASP), contribute to aging and chronic diseases. Here we review the roles of senescent osteocytes in the context of bone loss. RECENT FINDINGS. Numerous studies have established that senescent osteocytes accumulate in the bone microenvironment with aging in mice and in humans. Moreover, at least in mice, elimination of senescent cells results in attenuation of age-related bone loss. Osteocyte senescence also occurs in response to other cellular stressors, including radiotherapy, chemotherapy, and metabolic dysfunction where it appears to mediate skeletal deterioration. SUMMARY. Osteocyte senescence is linked to bone loss associated with aging and other conditions. Senescent osteocytes are potential therapeutic targets to alleviate skeletal dysfunction. Additional studies better defining the underlying mechanisms as well as translating these exciting findings from mouse models to humans are needed.

Maximal muscular power is achieved at lower percentages of maximal strength (1RM); however, this notion has not been elucidated based on sex or training status. Therefore, the purpose of this investigation was to examine the influence of sex and training status on maximal power production. Sixty men and women (resistance trained or untrained) completed 1RM testing for the two-leg press (2LP) and bench press (BP). Participants then returned to perform single repetitions at 20, 30, 40, 50, 60, 70 and 80% of their 1RM to determine muscular power. Factorial analyses determined significant interactions (training status by sex by intensity) for the BP (F=35.6, p

To systematically analyze shape and size of soluble irreversible aggregates and the effect of aggregate formation on viscosity. Online light scattering, refractive index and viscosity detectors attached to HPLC (Viscotek®) were used to study aggregation, molecular weight and intrinsic viscosity of bovine serum albumin (BSA). Irreversible aggregates were generated by heat stress. Bulk viscosity was measured by an oscillating piston viscometer. As BSA was heated at a higher concentration or for a longer time, the relative contribution, molecular weight and intrinsic viscosity of aggregate species increased. Molecular shape was evaluated from intrinsic viscosity values, and aggregates were estimated to be more asymmetric than monomer species. The presence of aggregates resulted in an increase in bulk viscosity when relative contribution of very high molecular weight species exceeded 10%. For model system and conditions studied, generation of higher order aggregate species was concluded to be associated with an increase in molecular asymmetry. Elevated viscosity in the presence of aggregated species points to molecular asymmetry being a critical parameter affecting solution viscosity of BSA.

Vitamin D deficiency/insufficiency has been primarily associated with skeletal disorders, however, since vitamin D receptors are found on multiple types of cells, there is also a link to increased chronic disease risk and all-cause mortality. The aim of this study was to examine whether deficient/insufficient vitamin D levels are associated with risk factors of chronic diseases and cognitive dysfunction in 50 to 70 year old adults. Participants completed the health status, three-day dietary record and vitamin D food frequency, sun exposure, and international physical activity questionnaires. Cognitive function of the participants was assessed using the Automated Neuropsychological Assessment Metrics while body composition (percent body fat, android/gynoid ratio) was assessed using Dual Energy X-ray Absorptiometry. Applanation tonometry was used to obtain pressure wave forms at the radial artery to examine arterial stiffness and central pressures. A fasting blood draw was taken to measure vitamin D, blood lipid and glucose levels. Fifty percent of the participants (36/72) were vitamin D deficient/insufficient. Individuals in the low physical activity (PA) group had lower serum vitamin D concentration compared to those in the high PA group (p = 0.04). Moreover, serum vitamin D levels were negatively related to risk factors of chronic diseases, blood glucose (r = &minus, 0.38, p = 0.01), triglycerides (r = &minus, 0.27, p = 0.02), and android/gynoid ratio (r = &minus, 0.32, p = 0.01). Deficient/insufficient vitamin D levels are linked to the risk factors of chronic diseases in men and women aged 50 to 70 years.

Intraventricular hemorrhage (IVH) is a common complication of prematurity in infants born at 23–28 weeks of gestation. Survivors exhibit impaired growth of the cerebral cortex and neurodevelopmental sequeale, but the underlying mechanism(s) are obscure. Previously, we have shown that neocortical neurogenesis continues until at least 28 gestational weeks. This renders the prematurely born infants vulnerable to impaired neurogenesis. Here, we hypothesized that neurogenesis is impaired by IVH, and that signaling through GSK3β, a critical intracellular kinase regulated by Wnt and other pathways, mediates this effect. These hypotheses were tested observationally in autopsy specimens from premature infants, and experimentally in a premature rabbit IVH model. Significantly, in premature infants with IVH, the number of neurogenic cortical progenitor cells was reduced compared with infants without IVH, indicating acutely decreased neurogenesis. This finding was corroborated in the rabbit IVH model, which further demonstrated reduction of upper layer cortical neurons after longer survival. Both the acute reduction of neurogenic progenitors, and the subsequent decrease of upper layer neurons, were rescued by treatment with AR-A014418, a specific inhibitor of GSK3β. Together, these results indicate that IVH impairs late stages of cortical neurogenesis, and suggest that treatment with GSK3β inhibitors may enhance neurodevelopment in premature infants with IVH.

This study determined the time course for changes in muscle swelling and plasma volume following high (HI) and low-intensity resistance exercise with blood-flow restriction (LI-BFR). Ten male participants (22.1±3.0 yrs) completed three experimental conditions: high-intensity exercise (HI - 80% of 1RM), low-intensity exercise with BFR (LI-BFR –20% of 1RM, and 160 mmHg of BFR), and control (CON – no exercise or BFR). Muscle cross-sectional area (mCSA), muscle thickness, thigh circumference, and percentage change in plasma volume (PV%∆) were measured. mCSA was significantly greater than rest values at 15 min post-exercise (p

Benign paroxysmal positional vertigo (BPPV) is the most common peripheral vestibular disorder, accounting for 20% of all vertigo cases. Idiopathic BPPV is most common between the ages of 50 and 70, although the condition is found in all age groups. This study was conducted in our institute on 90 patients who presented to the outpatient department with history of vertigo and were diagnosed with BPPV via a positive Dix Hallpike test. Patients were randomnly placed in three groups of 30 each. Patients in Group A were treated with Epleys manoeuvre alone, in Group B were treated with Epleys Manouvre followed by oral Betahistine and patients in Group C were treated with Betahistine alone. All the patients were followed up after 1 week and 4 weeks following treatment. In our study we found that patients responded better when they were treated with Epleys Manouvre with Betahistine with less relapse and recurrence. Treatment with Epleys manouvre resulted in early improvement of symptoms. It was found in our study that Betahistine as a sole modality of treatment of vertigo in BPPV can be preferred in patients who are unfit to undergo canal repositioning manouvres.

IntroductionPoor access to quality healthcare is one of the most important reasons of high maternal and neonatal mortality in India, particularly in poorer states like Bihar. India has implemented initiatives to promote institutional maternal deliveries. It is important to ensure that health facilities are adequately equipped and staffed to provide quality care for mothers and newborns.MethodsWe conducted a cross-sectional study of 190 primary health centres (PHCs) and 36 district hospitals (DHs) across all districts in Bihar to assess the readiness of facilities to provide quality maternal and neonatal care. Infrastructure, equipment and supplies and staffing were assessed using the WHO service availability and readiness assessment and Indian public health standard guidelines. Additionally, we used household survey data to assess the quality of care reported by mothers delivering at study facilities.ResultsPHCs and DHs were found to have 61% and 67% of the mandated structural components to provide maternal and neonatal care, on average, respectively. DHs were, on average, slightly better equipped in terms of infrastructure, equipment and supplies by comparison to PHCs. DHs were found to be inadequately prepared to provide neonatal care. Lack of recommended handwashing stations and bins at both DHs and PHCs suggested low levels of hygiene. Only half of the essential drugs were available in both DHs and PHCs. While no association was revealed between structural capacity and patient-reported quality of care, adequacy of staffing was positively associated with the quality of care in DHs.ConclusionExamining all DHs and a representative sample of PHCs in Bihar, this study revealed the gaps in structural components that need to be filled to provide quality care to mothers and newborns. Access to quality care is essential if progress in reducing maternal and neonatal mortality is to be achieved in this high-burden state.