No effect of five days of bed rest or short-term resistance exercise prehabilitation on markers of skeletal muscle mitochondrial content and dynamics in older adults

Bed rest (BR) results in significant impairments in skeletal muscle metabolism. Mitochondrial metabolism is reportedly highly sensitive to disuse, with dysregulated fission-fusion events and impaired oxidative function previously reported. The effects of clinically relevant short-term BR (≤5 days) on mitochondrial protein expression are presently unclear, as are the effects of exercise prehabilitation as a potential counteractive intervention. The present study examined the effects of a 5-day period of BR and short-term resistance exercise prehabilitation (ST-REP) on mitochondrial-protein content. Ten older men (71 ± 4 years) underwent 5 days of BR, completing four sessions of high-volume unilateral resistance exercise prehabilitation over 7 days beforehand. Muscle biopsies were obtained from the vastus lateralis in the non-exercised control and exercised legs, both pre- and post-prehabilitation and pre- and post-BR, to determine changes in citrate synthase enzyme activity and the expression of key proteins in the mitochondrial electron transport chain and molecular regulators of fission-fusion dynamics, biosynthesis, and mitophagy. We observed no significant effect of either BR or ST-REP on citrate synthase protein content, enzyme activity, or ETC complex I-V protein content. Moreover, we observed no significant changes in markers of mitochondrial fission and fusion (p-DRP1S616, p-DRP1S637, p-DRP1S616/S637 ratio, p-MFFS146, Mitofillin, OPA1, or MFN2 (p > 0.05 for all). Finally, we observed no differences in markers of biosynthesis (p-AMPKT172, p-ACCS79, PGC1a, TFAM) or mitophagy-related signaling (ULK-1, BNIP3/NIX, LC3B I/II) (p > 0.05 for all). In contrast to previous longer-term periods of musculoskeletal disuse (i.e., 7–14 days), a clinically relevant, 5-day period of BR resulted in no significant perturbation in muscle mitochondrial protein signaling in healthy older adults, with no effect of ST-REP in the week prior to BR. Accordingly, disuse-induced muscle atrophy may precede alterations in mitochondrial content

Circulating mediators of inflammation and immune activation in AIDS-related non-Hodgkin lymphoma

Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-related malignancy in developed countries. An elevated risk of developing NHL persists among HIV-infected individuals in comparison to the general population despite the advent of effective antiretroviral therapy. The mechanisms underlying the development of AIDS-related NHL (A-NHL) are not fully understood, but likely involve persistent B-cell activation and inflammation. Methods: This was a nested case-control study within the ongoing prospective Multicenter AIDS Cohort Study (MACS). Cases included 47 HIV-positive male subjects diagnosed with high-grade B-cell NHL. Controls were matched to each case from among participating HIV-positive males who did not develop any malignancy. Matching criteria included time HIV+ or since AIDS diagnosis, age, race and CD4+ cell count. Sera were tested for 161 serum biomarkers using multiplexed beadbased immunoassays. Results: A subset of 17 biomarkers, including cytokines, chemokines, acute phase proteins, tissue remodeling agents and bone metabolic mediators was identified to be significantly altered in A-NHL cases in comparison to controls. Many of the biomarkers included in this subset were positively correlated with HIV viral load. A pathway analysis of our results revealed an extensive network of interactions between current and previously identified biomarkers. Conclusions: These findings support the current hypothesis that A-NHL develops in the context of persistent immune stimulation and inflammation. Further analysis of the biomarkers identified in this report should enhance our ability to diagnose, monitor and treat this disease. © 2014 Nolen et al

Permanent vascular access in patients with end-stage renal disease, Brazil

OBJECTIVE: To assess factors associated with the establishment of permanent vascular access for patients with end-stage renal disease. METHODS: Cross-sectional study conducted in a nationally representative sample of Brazilian end-stage renal disease patients in dialysis and transplant centers during 2007. The sample comprised only patients who received hemodialysis as a primary therapy modality and reported the type of vascular access for their primary hemodialysis treatment (N=2,276). Data were from the TRS Project - "Economic and Epidemiologic Evaluation of Modalities of Renal Replacement Therapy in Brazil". Multiple logistic regression analysis was used to assess factors associated with the establishment of permanent vascular access in these patients. RESULTS: About 30% of the patients studied had an arteriovenous vascular access. The following factors were associated with a lower likelihood of having an arteriovenous vascular access as a primary type of access: time of hemodialysis start since the diagnosis of chronic renal failure < 1 year; shorter dialysis therapy; having no private health insurance; living in the central-western, northeastern and southeastern regions of Brazil; and living in the northern region plus having no private health insurance. In the final model there was found a positive association between the outcome and pre-dialysis care and no were association with socioeconomic and comorbidity variables. CONCLUSIONS: The study results showed that the focus should on pre-dialysis care to increase the establishment of an arteriovenous vascular access before starting hemodialysis in Brazil

Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)

Background: Risk factors for severe COVID-19 include older age, male sex, obesity, black or Asian ethnicity and underlying medical conditions. Whether these factors also influence susceptibility to developing COVID-19 is uncertain. Methods: We undertook a prospective, population-based cohort study (COVIDENCE UK) from 1 May 2020 to 5 February 2021. Baseline information on potential risk factors was captured by an online questionnaire. Monthly follow-up questionnaires captured incident COVID-19. We used logistic regression models to estimate multivariable-adjusted ORs (aORs) for associations between potential risk factors and odds of COVID-19. Results: We recorded 446 incident cases of COVID-19 in 15 227 participants (2.9%). Increased odds of developing COVID-19 were independently associated with Asian/Asian British versus white ethnicity (aOR 2.28, 95% CI 1.33 to 3.91), household overcrowding (aOR per additional 0.5 people/bedroom 1.26, 1.11 to 1.43), any versus no visits to/from other households in previous week (aOR 1.31, 1.06 to 1.62), number of visits to indoor public places (aOR per extra visit per week 1.05, 1.02 to 1.09), frontline occupation excluding health/social care versus no frontline occupation (aOR 1.49, 1.12 to 1.98) and raised body mass index (BMI) (aOR 1.50 (1.19 to 1.89) for BMI 25.0–30.0 kg/m2 and 1.39 (1.06 to 1.84) for BMI >30.0 kg/m2 versus BMI <25.0 kg/m2). Atopic disease was independently associated with decreased odds (aOR 0.75, 0.59 to 0.97). No independent associations were seen for age, sex, other medical conditions, diet or micronutrient supplement use. Conclusions: After rigorous adjustment for factors influencing exposure to SARS-CoV-2, Asian/Asian British ethnicity and raised BMI were associated with increased odds of developing COVID-19, while atopic disease was associated with decreased odds. Trial registration number: ClinicalTrials.gov Registry (NCT04330599)

Adrenocorticotropic Hormone Suppresses Gonadotropin-Stimulated Estradiol Release from Zebrafish Ovarian Follicles

While stress is known to impact reproductive performance, the pathways involved are not entirely understood. Corticosteroid effects on the functioning of the hypothalamus-pituitary-gonadal axis are thought to be a key aspect of stress-mediated reproductive dysfunction. A vital component of the stress response is the pituitary secretion of adrenocorticotropic hormone (ACTH), which binds to the melanocortin 2 receptor (MC2R) in the adrenal glands and activates cortisol biosynthesis. We recently reported MC2R mRNA abundance in fish gonads leading to the hypothesis that ACTH may be directly involved in gonadal steroid modulation. Using zebrafish (Danio rerio) ovarian follicles, we tested the hypothesis that acute ACTH stimulation modulates cortisol and estradiol (E2) secretion. ACTH neither affected cortisol nor unstimulated E2 release from ovarian follicles. However, ACTH suppressed human chorionic gonadotropin (hCG)-stimulated E2 secretion in a dose-related manner, with a maximum decrease of 62% observed at 1 I.U. ACTH mL−1. This effect of ACTH on E2 release was not observed in the presence of either 8-bromo-cAMP or forskolin, suggesting that the mechanism(s) involved in steroid attenuation was upstream of adenylyl cyclase activation. Overall, our results suggest that a stress-induced rise in plasma ACTH levels may initiate a rapid down-regulation of acute stimulated E2 biosynthesis in the zebrafish ovary, underscoring a novel physiological role for this pituitary peptide in modulating reproductive activity

Computed tomography segmental calcium score (SCS) to predict stenosis severity of calcified coronary lesions

To estimate the probability of ≥50 % coronary stenoses based on computed tomography (CT) segmental calcium score (SCS) and clinical factors. The Institutional Review Board approved the study. A training sample of 201 patients underwent CT calcium scoring and conventional coronary angiography (CCA). All patients consented to undergo CT before CCA after being informed of the additional radiation dose. SCS and calcification morphology were assessed in individual coronary segments. We explored the predictive value of patient’s symptoms, clinical history, SCS and calcification morphology. We developed a prediction model in the training sample based on these variables then tested it in an independent test sample. The odds ratio (OR) for ≥50 % coronary stenosis was 1.8-fold greater (p = 0.006) in patients with typical chest pain, twofold (p = 0.014) greater in patients with acute coronary syndromes, twofold greater (p < 0.001) in patients with prior myocardial infarction. Spotty calcifications had an OR for ≥50 % stenosis 2.3-fold (p < 0.001) greater than the absence of calcifications, wide calcifications 2.7-fold (p < 0.001) greater, diffuse calcifications 4.6-fold (p < 0.001) greater. In middle segments, each unit of SCS had an OR 1.2-fold (p < 0.001) greater than in distal segments; in proximal segments the OR was 1.1-fold greater (p = 0.021). The ROC curve area of the prediction model was 0.795 (0.95 confidence interval 0.602–0.843). Validation in a test sample of 201 independent patients showed consistent diagnostic performance. In conjunction with calcification morphology, anatomical location, patient’s symptoms and clinical history, SCS can be helpful to estimate the probability of ≥50 % coronary stenosis

Evidence for Shared Cognitive Processing of Pitch in Music and Language

Language and music epitomize the complex representational and computational capacities of the human mind. Strikingly similar in their structural and expressive features, a longstanding question is whether the perceptual and cognitive mechanisms underlying these abilities are shared or distinct – either from each other or from other mental processes. One prominent feature shared between language and music is signal encoding using pitch, conveying pragmatics and semantics in language and melody in music. We investigated how pitch processing is shared between language and music by measuring consistency in individual differences in pitch perception across language, music, and three control conditions intended to assess basic sensory and domain-general cognitive processes. Individuals’ pitch perception abilities in language and music were most strongly related, even after accounting for performance in all control conditions. These results provide behavioral evidence, based on patterns of individual differences, that is consistent with the hypothesis that cognitive mechanisms for pitch processing may be shared between language and music.National Science Foundation (U.S.). Graduate Research Fellowship ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Grant 5K99HD057522

The effects of progressive resistance training combined with a whey-protein drink and vitamin D supplementation on glycaemic control, body composition and cardiometabolic risk factors in older adults with type 2 diabetes: study protocol for a randomized controlled trial

Background - While physical activity, energy restriction and weight loss are the cornerstone of type 2 diabetes management, less emphasis is placed on optimizing skeletal muscle mass. As muscle is the largest mass of insulin-sensitive tissue and the predominant reservoir for glucose disposal, there is a need to develop safe and effective evidence-based, lifestyle management strategies that optimize muscle mass as well as improve glycaemic control and cardiometabolic risk factors in people with this disease, particularly older adults who experience accelerated muscle loss. Methods/Design - Using a two-arm randomized controlled trial, this 6-month study builds upon the community-based progressive resistance training (PRT) programme Lift for Life® to evaluate whether ingestion of a whey-protein drink combined with vitamin D supplementation can enhance the effects of PRT on glycaemic control, body composition and cardiometabolic health in older adults with type 2 diabetes. Approximately 200 adults aged 50 to 75 years with type 2 diabetes, treated with either diet alone or oral hypoglycaemic agents (not insulin), will be recruited. All participants will be asked to participate in a structured, supervised PRT programme based on the Lift for Life® programme structure, and randomly allocated to receive a whey-protein drink (20 g daily of whey-protein plus 20 g after each PRT session) plus vitamin D supplements (2000 IU/day), or no additional powder and supplements. The primary outcome measures to be collected at baseline, 3 and 6 months will be glycated haemoglobin (HbA1c) and insulin sensitivity (homeostatic model assessment). Secondary outcomes will include changes in: muscle mass, size and intramuscular fat; fat mass; muscle strength and function; blood pressure; levels of lipids, adipokines and inflammatory markers, serum insulin-like growth factor-1 and 25-hydroxyvitamin D; renal function; diabetes medication; health-related quality of life, and cognitive function. Discussion - The findings from this study will provide new evidence on whether increased dietary protein achieved through the ingestion of a whey-protein drink combined with vitamin D supplementation can enhance the effects of PRT on glycaemic control, muscle mass and size, and cardiometabolic risk factors in older adults with type 2 diabetes

A Multifaceted Analysis of Immune-Endocrine-Metabolic Alterations in Patients with Pulmonary Tuberculosis

Our study investigated the circulating levels of factors involved in immune-inflammatory-endocrine-metabolic responses in patients with tuberculosis with the aim of uncovering a relation between certain immune and hormonal patterns, their clinical status and in vitro immune response. The concentration of leptin, adiponectin, IL-6, IL-1β, ghrelin, C-reactive protein (CRP), cortisol and dehydroepiandrosterone (DHEA), and the in vitro immune response (lymphoproliferation and IFN-γ production) was evaluated in 53 patients with active untreated tuberculosis, 27 household contacts and 25 healthy controls, without significant age- or sex-related differences. Patients had a lower body mass index (BMI), reduced levels of leptin and DHEA, and increased concentrations of CRP, IL-6, cortisol, IL-1β and nearly significant adiponectin values than household contacts and controls. Within tuberculosis patients the BMI and leptin levels were positively correlated and decreased with increasing disease severity, whereas higher concentrations of IL-6, CRP, IL-1β, cortisol, and ghrelin were seen in cases with moderate to severe tuberculosis. Household contacts had lower DHEA and higher IL-6 levels than controls. Group classification by means of discriminant analysis and the k-nearest neighbor method showed that tuberculosis patients were clearly different from the other groups, having higher levels of CRP and lower DHEA concentration and BMI. Furthermore, plasma leptin levels were positively associated with the basal in vitro IFN-γ production and the ConA-driven proliferation of cells from tuberculosis patients. Present alterations in the communication between the neuro-endocrine and immune systems in tuberculosis may contribute to disease worsening