Erythropoietin Treatment Enhances Muscle Mitochondrial Capacity in Humans

Erythropoietin (Epo) treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo) treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over 8 weeks with oral iron (100 mg) supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate, and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS) was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from 92 ± 5 to 113 ± 7 pmol·s−1·mg−1) and ETS (107 ± 4 to 143 ± 14 pmol·s−1·mg−1, p < 0.05), demonstrating that Epo treatment induces an upregulation of OXPHOS and ETS in human skeletal muscle

Quality of recovery after total hip and knee arthroplasty in South Africa : a national prospective observational cohort study

BACKGROUND: Encouraged by the widespread adoption of enhanced recovery protocols (ERPs) for elective total hip and knee arthroplasty (THA/TKA) in high-income countries, our nationwide multidisciplinary research group first performed a Delphi study to establish the framework for a unified ERP for THA/TKA in South Africa. The objectives of this second phase of changing practice were to document quality of patient recovery, record patient characteristics and audit standard perioperative practice. METHODS: From May to December 2018, nine South African public hospitals conducted a 10-week prospective observational study of patients undergoing THA/TKA. The primary outcome was ‘days alive and at home up to 30 days after surgery’ (DAH30) as a patient-centred measure of quality of recovery incorporating early death, hospital length of stay (LOS), discharge destination and readmission during the first 30 days after surgery. Preoperative patient characteristics and perioperative care were documented to audit practice. RESULTS: Twenty-one (10.1%) out of 207 enrolled patients had their surgery cancelled or postponed resulting in 186 study patients. No fatalities were recorded, median LOS was 4 (inter-quartile-range (IQR), 3–5) days and 30-day readmission rate was 3.8%, leading to a median DAH30 of 26 (25–27) days. Forty patients (21.5%) had pre-existing anaemia and 24 (12.9%) were morbidly obese. In the preoperative period, standard care involved assessment in an optimisation clinic, multidisciplinary education and full-body antiseptic wash for 67 (36.2%), 74 (40.0%) and 55 (30.1%) patients, respectively. On the first postoperative day, out-of-bed mobilisation was achieved by 69 (38.1%) patients while multimodal analgesic regimens (paracetamol and Non-Steroid-Anti-Inflammatory-Drugs) were administered to 29 patients (16.0%). CONCLUSION: Quality of recovery measured by a median DAH30 of 26 days justifies performance of THA/TKA in South African public hospitals. That said, perioperative practice, including optimisation of modifiable risk factors, lacked standardisation suggesting that quality of patient care and postoperative recovery may improve with implementation of ERP principles. Notwithstanding the limited resources available, we anticipate that a change of practice for THA/TKA is feasible if ‘buy-in’ from the involved multidisciplinary units is obtained in the next phase of our nationwide ERP initiative.http://www.biomedcentral.com/bmcmusculoskeletdisordpm2021AnaesthesiologyOrthopaedic SurgeryPhysiotherap

Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata

Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.Peer reviewe

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele