Multimodal cell atlas of the ageing human skeletal muscle.

Muscle atrophy and functional decline (sarcopenia) are common manifestations of frailty and are critical contributors to morbidity and mortality in older people1. Deciphering the molecular mechanisms underlying sarcopenia has major implications for understanding human ageing2. Yet, progress has been slow, partly due to the difficulties of characterizing skeletal muscle niche heterogeneity (whereby myofibres are the most abundant) and obtaining well-characterized human samples3,4. Here we generate a single-cell/single-nucleus transcriptomic and chromatin accessibility map of human limb skeletal muscles encompassing over 387,000 cells/nuclei from individuals aged 15 to 99 years with distinct fitness and frailty levels. We describe how cell populations change during ageing, including the emergence of new populations in older people, and the cell-specific and multicellular network features (at the transcriptomic and epigenetic levels) associated with these changes. On the basis of cross-comparison with genetic data, we also identify key elements of chromatin architecture that mark susceptibility to sarcopenia. Our study provides a basis for identifying targets in the skeletal muscle that are amenable to medical, pharmacological and lifestyle interventions in late life.

A new Acanthotetilla sponge from the Southwest Atlantic (Tetillidae, Spirophorina, Tetractinellida, Demospongiae), with an updated discussion on the diversity, distribution and morphologic characters of Acanthotetilla spp.

Acanthotetilla is a genus of tetillid sponges diagnosed by the presence of medium-sized, heavily spined oxeas, which are known as megacanthoxeas (or simply acanthoxeas). Currently, seven species are known worldwide: three from the Western Atlantic (A. gorgonosclera, A. rocasensis and A. walteri), three from the Western Indian (A. hemisphaerica, A. enigmatica and A. seychellensis) and one from the Western Pacific (A. celebensis). A megacanthoxea-bearing specimen was obtained from the Fernando de Noronha Archipelago, Southwest Atlantic, in 2016. It is described here as a new Acanthotetilla, namely, A. noronhensis sp. nov. This new species has two categories of megacanthoxeas, like A. celebensis from Celebes/Sulawesi Sea, Indonesia. However, the former differs from the latter, as well as from other congeners, by the combination of endolithic habit and spiculation. Acanthotetilla noronhensis sp. nov. is known on the basis of a single specimen from a large collection of sponges from Fernando de Noronha. Besides, the species was not found in other sponge collections from different areas of Brazil, including oceanic areas. Thus, the new species has probably a low abundance and restricted distribution, alike all other known Acanthotetilla species, aside A. celebensis, which (regardless its low abundance) occurs in a large sector of the western Pacific. Despite A. noronhensis sp. nov. and A. celebensis being separated by a wide geographic distance, the unique occurrence of two categories of megacanthoxeas might suggest closer phylogenetic relationship and biogeographic history as well. A wider discussion on the diversity, distribution and morphologic characters of Acanthotetilla spp. is supplied in this study. A comparative taxonomic table and a taxonomic identification key to Acanthotetilla spp. is supplied as well.

Identical sequences, different behaviors: Protein diversity captured at the single-molecule level.

The classical "one sequence, one structure, one function" paradigm has shaped much of our intuition of how proteins work inside the cell. Partially due to the insight provided by bulk biochemical assays, individual biomolecules are often assumed to behave as identical entities, and their characterization relies on ensemble averages that flatten any conformational diversity into a unique phenotype. While the emergence of single-molecule techniques opened the gates to interrogating individual molecules, technical shortcomings typically limit the duration of these measurements, which precludes a complete characterization of an individual protein and, hence, capturing the heterogeneity among molecular populations. Here, we introduce an ultrastable magnetic tweezers design, which enables us to measure the folding dynamics of a single protein during several uninterrupted days with high temporal and spatial resolution. Thanks to this instrumental development, we fully characterize the nanomechanics of two proteins with a very distinct force response, the talin R3IVVI domain and protein L. Days-long recordings on the same protein individual accumulate thousands of folding transitions with submicrosecond resolution, allowing us to reconstruct their free energy landscapes and describe how they evolve with force. By mapping the nanomechanical identity of many different protein individuals, we directly capture their molecular diversity as a quantifiable dispersion on their force response and folding kinetics. By significantly expanding the measurable timescales, our instrumental development offers a tool for profiling individual molecules, opening the gates to directly characterizing biomolecular heterogeneity.

Increased femoral anteversion in females with anterior knee pain relates to both the neck and the shaft of the femur.

INTRODUCTION: Increased femoral anteversion (FAV) can have many clinical manifestations, including anterior knee pain (AKP). To our knowledge, no studies have measured the location of FAV in a cohort of female AKP patients. The objective of this research is to determine whether the increased FAV in AKP females originates above the lesser trochanter, below the lesser trochanter or at both levels. MATERIALS AND METHODS: Thrity-seven consecutive AKP female patients (n = 66 femurs) were recruited prospectively. There were 17 patients (n = 26 femurs; mean age of 28 years) in whom the suspicion for the increased FAV of the femur was based on the clinical examination (pathological group-PG). The control group (CG) consisted of 20 patients (n = 40 femurs; mean age of 29 years) in whom there was no increased FAV from the clinical standpoint. All of them underwent a torsional computed tomography of the lower limbs. FAV was measured according to Murphy´s method. A segmental analysis of FAV was performed using the lesser trochanter as a landmark. RESULTS: Significant differences in the total FAV (18.7 ± 5.52 vs. 42.46 ± 6.33; p < 0.001), the neck version (54.88 ± 9.64 vs. 64.27 ± 11.25; p = 0.0006) and the diaphysis version (- 36.17 ± 8.93 vs. - 21.81 ± 11.73; p < 0.001) were observed between the CG and the PG. The difference in the diaphyseal angle between CG and PG accounts for 60% of the total difference between healthy and pathological groups, while the difference between both groups in the angle of the neck accounts for 40%. CONCLUSION: In chronic AKP female patients with increased FAV, the two segments of the femur contribute to the total FAV, with a different pattern among patients and controls, being the compensation mechanism of the diaphysis much lower in the pathological femurs than in the controls.

Case Report: A prenatal diagnosis of osteogenesis imperfecta in a patient with a novel pathogenic variant in COL1A2.

Osteogenesis imperfecta is considered a rare genetic condition which is characterized by bone fragility. In 85% of cases, it is caused by mutations in COL1A1 and COL1A2 genes which are essential to produce type I collagen. We report the case of a female neonate delivered to a 27-year-old women at San Bartolomé Teaching Hospital with a family history of clavicle fracture. A prenatal control with ultrasound was performed to the mother at 29 weeks. A fetus with altered morphology and multiple fractures was found. Therefore, a prenatal diagnosis of osteogenesis imperfecta was performed. The neonate was born with a respiratory distress syndrome and an acyanotic congenital heart disease. Therefore, she remained in NICU until her death. We highlight the importance of prenatal diagnosis, genetic counseling and a multidisciplinary evaluation in this type of pathologies and report a new probably pathogenic variant in the COL1A2 gene detected by exomic sequencing in amniotic fluid.

Central sensitization negatively influences the level of disability in female patients with anterior knee pain.

PURPOSE: To define the prevalence of Central Sensitization (CS) in patients with Anterior Knee Pain (AKP) and determine whether there is an association between CS and the magnitude of pain, disability, quality-of-life and psychological impairment. METHODS: The data of a total of 44 AKP female patients with a mean age of 27.7 years (15-50) recruited consecutively from hospital outpatient knee clinics were prospectively included in this study. The patients had no antecedents of knee trauma or surgery and no history of injury or disease of the nervous system. There were also 50 healthy female controls with a mean age of 26.1 years (16-46). CS was evaluated using the Central Sensitization Inventory (CSI). Quality-of-life was evaluated using the EuroQoL-5D questionnaire. Self-reporting of clinical pain intensity was obtained using the Visual Analogue Scale. The Kujala Knee Scale and IKDC form were used to evaluate disability. Anxiety and depression were evaluated using the Hospital Anxiety and Depression Subscale (HAD). Kinesiophobia was measured with the Tampa Scale for Kinesiophobia (TSK-11) and catastrophizing by means of the Pain Catastrophizing Scale (PCS). RESULTS: Sixteen AKP patients (36%), and 2 (4%) of the healthy controls presented with central sensitization (p < 0.01). AKP patients with CS have a greater degree of disability based on the Kujala Scale and higher levels of anxiety and depression than AKP patients without CS. The score of AKP patients in the CSI correlated weakly with disability and quality of life and moderately with anxiety and depression. However, no association was seen between CSI score and pain intensity, nor with catastrophizing and kinesiophobia. A multivariate logistic regression analysis showed that only depression was statistically significant in the prediction of the presence of CS (odds ratio 1.45; 95% CI 1.07 to 1.96). CONCLUSIONS: AKP patients have a significantly higher prevalence of CS in comparison with what has been reported for the general population. This finding suggests the presence of altered pain modulation in a subgroup of AKP patients. LEVEL OF EVIDENCE: Level III.

Predictive value of texture analysis on lumbar MRI in patients with chronic low back pain.

PURPOSE: The aim of this study was to determine whether MRI texture analysis could predict the prognosis of patients with non-specific chronic low back pain. METHODS: A prospective observational study was conducted on 100 patients with non-specific chronic low back pain, who underwent a conventional MRI, followed by rehabilitation treatment, and revisited after 6 months. Sociodemographic variables, numeric pain scale (NPS) value, and the degree of disability as measured by the Roland-Morris disability questionnaire (RMDQ), were collected. The MRI analysis included segmentation of regions of interest (vertebral endplates and intervertebral disks from L3-L4 to L5-S1, paravertebral musculature at the L4-L5 space) to extract texture variables (PyRadiomics software). The classification random forest algorithm was applied to identify individuals who would improve less than 30% in the NPS or would score more than 4 in the RMDQ at the end of the follow-up. Sensitivity, specificity, and the area under the ROC curve were calculated. RESULTS: The final series included 94 patients. The predictive model for classifying patients whose pain did not improve by 30% or more offered a sensitivity of 0.86, specificity 0.57, and area under the ROC curve 0.71. The predictive model for classifying patients with a RMDQ score 4 or more offered a sensitivity of 0.83, specificity of 0.20, and area under the ROC curve of 0.52. CONCLUSION: The texture analysis of lumbar MRI could help identify patients who are more likely to improve their non-specific chronic low back pain through rehabilitation programs, allowing a personalized therapeutic plan to be established.

AMOC decline and recovery in a warmer climate.

This study presents novel insight into the mechanisms of Atlantic Meridional Overturning Circulation (AMOC) reduction and its recovery under a warmer climate scenario. An one-thousand-year-long numerical simulation of a global coupled ocean-ice-atmosphere climate model, subjected to a stationary atmospheric radiative forcing, depict a coherent picture of the Arctic sea ice melting as a trigger for the initial AMOC reduction, along with decreases in the northward fluxes of salt and heat. Further atmospheric-driven ocean processes contribute to an erosion of the stable stratification of the fresher, yet colder waters in the surface layers of the North Atlantic, contributing to the recovery of a permanently altered AMOC.

Primary human hepatocytes-laden scaffolds for the treatment of acute liver failure.

Cell-based liver therapies based on retrieving and steadying failed metabolic function(s) for acute and chronic diseases could be a valuable substitute for liver transplants, even though they are limited by the low engraftment capability and reduced functional quality of primary human hepatocytes (PHH). In this paper we propose the use of gelatin-hyaluronic acid (Gel-HA) scaffolds seeded with PHH for the treatment of liver failure. We first optimized the composition using Gel-HA hydrogels, looking for the mechanical properties closer to the human liver and determining HepG2 cells functionality. Gel-HA scaffolds with interconnected porosity (pore size 102 µm) were prepared and used for PHH culture and evaluation of key hepatic functions. PHH cultured in Gel-HA scaffolds exhibited increased albumin and urea secretion and metabolic capacity (CYP and UGT activity levels) compared to standard monolayer cultures. The transplant of the scaffold containing PHH led to an improvement in liver function (transaminase levels, necrosis) and ameliorated damage in a mouse model of acetaminophen (APAP)-induced liver failure. The study provided a mechanistic understanding of APAP-induced liver injury and the impact of transplantation by analyzing cytokine production and oxidative stress induction to find suitable biomarkers of cell therapy effectiveness.

Miastenia gravis. Actualización diagnóstica y terapéutica / Myasthenia gravis. Update on diagnosis and therapy

La miastenia gravis es una enfermedad autoinmune causada por la presencia de anticuerpos específicos dirigidos a diferentes componentes postsinápticos de la unión neuromuscular, y clínicamente se caracteriza por la presencia de debilidad muscular fatigable. En la etiopatogenia juega un papel central el timo, y los autoanticuerpos patogénicos más frecuentemente detectados están dirigidos al receptor de la acetilcolina. El incremento en el conocimiento de los componentes inmunológicos de la unión neuromuscular en las últimas dos décadas ha sido fundamental para identificar nuevos anticuerpos patogénicos, reducir el porcentaje de pacientes con miastenia seronegativa y proponer una clasificación de los pacientes en subgrupos con interés clínico-terapéutico. Además, en los últimos años hemos asistido al desarrollo de nuevos fármacos destinados al tratamiento de los pacientes con miastenia que muestran refractariedad al tratamiento inmunosupresor convencional (AU)

Myasthenia gravis is an autoimmune disease caused by the presence of specific antibodies targeting different postsynaptic components of the neuromuscular junction, and is clinically characterized by the presence of fatigueable muscle weakness. In the etiopathogenesis plays a central role the thymus and the most frequently detected pathogenic autoantibodies are targeted to the acetylcholine receptor. The increase in the knowledge of the immunological components of the neuromuscular junction in the last two decades has been fundamental to identify new pathogenic antibodies, reduce the percentage of patients with seronegative myasthenia, and propose a classification of patients into subgroups with clinical-therapeutic interest. In addition, in recent years, new drugs have been developed for the treatment of patients with myasthenia gravis that are refractory to conventional immunosuppressive treatment (AU)

Checklist, diversity descriptors and selected descriptions of a highly diverse intertidal sponge (Porifera) assemblage at Costa do Descobrimento (Bahia, Brazil).

Costa do Descobrimento is located in southern Bahia, Brazil, and only 22 species of sponges (Porifera) were known from the area until now, despite its important reef formations. In the present study, we report a checklist of the sponges of Costa do Descobrimento and their distribution in the studied reefs, with several species illustrated in life. We also describe nine new sponge records for this region, some of which are new records for Brazil, or new records of species previously only poorly known. We present alpha and beta diversity indices and compare the sponge assemblage of the sampled locations. Four reefs were considered: two fringing reefs (Arraial D'Ajuda-AA and Coroa Vermelha / Mutá-CVM) and two offshore Municipal Marine Park "Parque Municipal Marinho- (P.M.M. Coroa Alta-CA and P.M.M. Recife de Fora-RF). A total of 229 specimens were collected (224 Demospongiae, 2 Homoscleromorpha and 3 Calcarea). These were classified in 101 morphotypes. Studied materials included representatives of 15 orders, 34 families and 48 genera. The richest orders are Haplosclerida (29 spp.), Poecilosclerida (15 spp.) and Tetractinellida (11 spp.). The richest families were Chalinidae (24 spp.), Clionaidae (7 spp.) and Mycalidae and Suberitidae (6 spp. each). The richest genus is, by far, Haliclona (20 spp.). Only 13 species were shared among all four reefs surveyed, namely Amphimedon viridis, Cinachyrella alloclada, C. apion, Cladocroce caelum, Cliona varians, Dysidea robusta, Mycale (Naviculina) diversisigmata, Niphates erecta, Spirastrella hartmani, Tedania (Tedania) ignis, Terpios fugax, Tethya bitylastra and T. maza. The reefs with the highest richness were CA and CVM, and the lowest richness was observed in RF. The most similar reefs in terms of species composition were CA and CVM, while AA and RF were more dissimilar to the previous reefs, but also from each other. While the difference among CA, CVM and AA was mainly explained by species turnover, RF differed from the previous based on its lower richness (nestedness component). Even though CA and CVM were the richest reefs, AA presented the highest number of exclusive species, highlighting the uniqueness of this reef, and urging the inclusion of local beachrock fringing reefs in a more holistic conservation strategy at Costa do Descobrimento.

[Myasthenia gravis. Update on diagnosis and therapy]. / Miastenia gravis. Actualización diagnóstica y terapéutica.

Myasthenia gravis is an autoimmune disease caused by the presence of specific antibodies targeting different postsynaptic components of the neuromuscular junction, and is clinically characterized by the presence of fatigueable muscle weakness. In the etiopathogenesis plays a central role the thymus and the most frequently detected pathogenic autoantibodies are targeted to the acetylcholine receptor. The increase in the knowledge of the immunological components of the neuromuscular junction in the last two decades has been fundamental to identify new pathogenic antibodies, reduce the percentage of patients with seronegative myasthenia, and propose a classification of patients into subgroups with clinical-therapeutic interest. In addition, in recent years, new drugs have been developed for the treatment of patients with myasthenia gravis that are refractory to conventional immunosuppressive treatment.

Microbiome diversity from sponges biogeographically distributed between South America and Antarctica.

Sponges from South America and Antarctica are evolutionarily closely related. Specific symbiont signatures that could differentiate these two geographic regions are unknown. This study aimed to investigate the microbiome diversity of sponges from South America and Antarctica. In total 71 sponge specimens were analyzed (Antarctica: N = 59, 13 different species; South America: N = 12, 6 different species). Illumina 16S rRNA sequences were generated (2.88 million sequences; 40K ± 29K/sample). The most abundant symbionts were heterotrophic (94.8 %) and belonged mainly to Proteobacteria and Bacteroidota. EC94 was the most abundant symbiont and dominated the microbiome of some species (70-87 %), comprising at least 10 phylogroups. Each of the EC94 phylogroups was specific to one genus or species of sponge. Furthermore, South America sponges had higher abundance of photosynthetic microorganisms (2.3 %) and sponges from Antarctica, the highest abundance of chemosynthetic (5.5 %). Sponge symbionts may contribute to the function of their hosts. The unique features from each of these two regions (e.g., light, temperature, and nutrients) possibly stimulate distinct microbiome diversity from sponges biogeographically distributed across continents.

Critically Ill Patients with Renal Hyperfiltration: Optimizing Antibiotic Dose.

Renal hyperfiltration (RHF) is a prevalent phenomenon in critically ill patients characterized by augmented renal clearance (ARC) and increased of elimination of renally eliminated medications. Multiple risk factors had been described and potential mechanisms may contribute to the occurrence of this condition. RHF and ARC are associated with the risk of suboptimal exposure to antibiotics increasing the risk of treatment failure and unfavorable patient outcomes. The current review discusses the available evidence related to the RHF phenomenon, including definition, epidemiology, risk factors, pathophysiology, pharmacokinetic variability, and considerations for optimizing the dosage of antibiotics in critically ill patients.

Has Arthroscopic Meniscectomy Use Changed in Response to the Evidence? A Large-database Study From Spain.

BACKGROUND: Several randomized clinical trials on the treatment of meniscal tears have shown that surgery is not superior to nonoperative treatment in middle-aged and older adults. However, clinical practice has not changed consistently worldwide in response to this evidence, and arthroscopic meniscectomy remains one of the most frequently performed operations. QUESTIONS/PURPOSES: (1) How has the use of arthroscopic meniscectomy changed in Spain between 2003 and 2018, particularly in middle-aged (35 to 59 years) and older patients (over 60 years) relative to younger patients? (2) How have surgical volumes changed across different healthcare areas in the same health system? (3) How has the proportion of outpatient versus inpatient arthroscopic procedures changed over time? METHODS: Data on all 420,228 arthroscopic meniscectomies performed in Spain between 2003 and 2018 were obtained through the Atlas of Variations in Medical Practice project (these years were chosen because data in that atlas for 2002 and 2019 were incomplete). This database has been promoted by the Spanish Health Ministry since 2002, and it collects basic information on all admissions to public and public-private partnership hospitals. The Spanish population of 2003 was used to calculate age- and sex-standardized rates of interventions per 10,000 inhabitants and year. To assess the change in standardized rates among the age groups over the study period, a linear regression analysis was used. Standard small-area variation statistics were used to analyze variation among healthcare areas. Data on outpatient surgery and length of stay for inpatient procedures were also included. RESULTS: The standardized rate of arthroscopic meniscectomy in Spain in 2003 was 4.8 procedures per 10,000 population (95% CI 3.9 to 5.6), while in 2018, there were 6.3 procedures per 10,000 population (95% CI 5.4 to 7.3), which represents an increase of 33%. Standardized rates increased slightly in the age group < 35 years (0.06 interventions per 10,000 inhabitants per year [95% CI 0.05 to 0.08]), whereas they increased more markedly in the age groups of 35 to 59 years (0.14 interventions per 10,000 inhabitants per year [95% CI 0.11 to 0.17]) and in those 60 years and older (0.13 interventions per 10,000 inhabitants per year [95% CI 0.09 to 0.17]). The variability among healthcare areas in the meniscectomy rate progressively decreased from 2003 to 2018. In 2003, 32% (6544 of 20,384) of knee arthroscopies were performed on an outpatient basis, while in 2018, these accounted for 67% (19,573 of 29,430). CONCLUSION: We observed a progressive increase in arthroscopic meniscectomies in Spain; this procedure was more prevalent in older patients presumed to have degenerative pathologic findings. This increase occurred despite increasing high-level evidence of a lack of the additional benefit of meniscectomy over other less-invasive treatments in middle-aged and older people. Our study highlights the need for action in health systems with the use of financial, regulatory, or incentive strategies to reduce the use of low-value procedures, as well as interventions to disseminate the available evidence to clinicians and patients. Research is needed to identify the barriers that are preventing the reversal of interventions that high-quality evidence shows are ineffective. LEVEL OF EVIDENCE: Level III, therapeutic study.

16 Years (2006-2021) of Surface Ozone Measurements in Córdoba (Southern Spain): Trends and the Impact of the COVID-19 Lockdown.

Surface ozone concentrations (O3) during the period 2006-2021 are analysed at Córdoba city (southern Iberian Peninsula) in suburban and urban sampling sites. The aims are to present the levels and temporal variations, to explore trends and to quantity the variation in O3 concentrations in the context of the COVID-19 lockdown. The O3 means are higher in the suburban station (62 µg m-3 and 51.3 µg m-3), being the information level threshold only exceeded twice during this period. The daily evolution shows a maximum at about 17:00 UTC, whereas the minimum is reached at about 9:00 UTC, with higher levels in the suburban station. The seasonal evolution of this daily cycle also presents monthly differences in shape and intensity between stations. The trends are analysed by means of daily averages and daily 5th and 95th percentiles, and they show a similar increase in all of these parameters, with special emphasis on the daily P95 concentrations, with 0.27 µg m-3 year-1 and 0.24 µg m-3 year-1. Finally, the impact of the COVID-19 lockdown shows a decline in O3 concentrations over 10%.

Consensus guide on prophylactic gonadectomy in different sex development.

The risk of suffering from gonadal germ cell tumors (GCT) is increased in some patients with different sexual development (DSD), mainly in those with Y chromosome material. This risk, however, varies considerably depending on a multitude of factors that make the decision for prophylactic gonadectomy extremely difficult. In order to make informed recommendations on the convenience of this procedure in cases where there is potential for malignancy, this consensus guide evaluates the latest clinical evidence, which is generally low, and updates the existing knowledge in this field.

Glucose 6-P Dehydrogenase-An Antioxidant Enzyme with Regulatory Functions in Skeletal Muscle during Exercise.

Hypomorphic Glucose 6-P dehydrogenase (G6PD) alleles, which cause G6PD deficiency, affect around one in twenty people worldwide. The high incidence of G6PD deficiency may reflect an evolutionary adaptation to the widespread prevalence of malaria, as G6PD-deficient red blood cells (RBCs) are hostile to the malaria parasites that infect humans. Although medical interest in this enzyme deficiency has been mainly focused on RBCs, more recent evidence suggests that there are broader implications for G6PD deficiency in health, including in skeletal muscle diseases. G6PD catalyzes the rate-limiting step in the pentose phosphate pathway (PPP), which provides the precursors of nucleotide synthesis for DNA replication as well as reduced nicotinamide adenine dinucleotide phosphate (NADPH). NADPH is involved in the detoxification of cellular reactive oxygen species (ROS) and de novo lipid synthesis. An association between increased PPP activity and the stimulation of cell growth has been reported in different tissues including the skeletal muscle, liver, and kidney. PPP activity is increased in skeletal muscle during embryogenesis, denervation, ischemia, mechanical overload, the injection of myonecrotic agents, and physical exercise. In fact, the highest relative increase in the activity of skeletal muscle enzymes after one bout of exhaustive exercise is that of G6PD, suggesting that the activation of the PPP occurs in skeletal muscle to provide substrates for muscle repair. The age-associated loss in muscle mass and strength leads to a decrease in G6PD activity and protein content in skeletal muscle. G6PD overexpression in Drosophila Melanogaster and mice protects against metabolic stress, oxidative damage, and age-associated functional decline, and results in an extended median lifespan. This review discusses whether the well-known positive effects of exercise training in skeletal muscle are mediated through an increase in G6PD.

Frailty and Hospitalization Burden in Patients With Chronic Heart Failure.

Frailty is associated with increased mortality and hospitalizations in patients with heart failure (HF). However, there is little evidence regarding the burden of morbidity. In this study, we aimed to assess the association between frailty and recurrent all-cause HF hospitalizations in patients with stable chronic HF. This was an observational and prospective study that enrolled HF outpatients followed in a specialized HF unit of a single tertiary care center from 2017 to 2019. Frailty was assessed by Fried criteria. Robustness, prefrailty, and frailty were defined as 0, 1 to 2, and ≥3, respectively. The independent association between frailty status and recurrent hospitalizations was assessed through Famoye's bivariate Poisson regression model, and risk estimates were expressed as incidence rate ratios (IRR). A total of 277 patients were included. The mean age was 74 ± 10 years, 118 were women (42.6%), and 131 patients (47.3%) had left ventricular ejection fraction ≥50. According to Fried's score 61 patients (22%) were robust, 95 patients (34%) were prefrail, and 121 patients (44%) were frail. After a median follow-up of 2.21 (1.6 to 2.8) years, 52 patients (19%) died. We registered 348 all-cause hospitalizations in 144 patients (52%) and 178 HF hospitalizations in 108 patients (39%). Compared with robust patients, frailty was associated with a higher risk of all-cause and HF recurrent hospitalizations in multivariable analysis (IRR 2.01, 95% confidence interval 1.14 to 3.57, p = 0.017 and IRR 2.25, 95% confidence interval 1.16-4.36, p = 0.016, respectively). In conclusion, in patients with chronic HF, frailty identifies patients with an increased risk of total and recurrent all-cause and HF hospitalizations.

Bending oxygen saturation index and risk of worsening heart failure events in chronic heart failure.

AIMS: Bendopnea is a clinical symptom of advanced heart failure with uncertain prognostic value. We aimed to evaluate whether bendopnea and the change in oxygen saturation when bending forward (bending oxygen saturation index [BOSI]) are associated with adverse outcomes in ambulatory chronic heart failure (CHF) patients. METHODS AND RESULTS: We prospectively evaluated 440 subjects with symptomatic CHF. BOSI was defined as the difference between sitting and bending oxygen saturation (SpO2 ). The endpoint was the total number of worsening heart failure (WHF) events (heart failure hospitalization or urgent heart failure visit requiring parenteral diuretic therapy). The mean age was 74 ± 10 years, 257 (58.6%) were male, and 226 (51.4%) had a left ventricular ejection fraction <50%. Bendopnea was present in 94 (21.4%) patients, and 120 (27.3%) patients had a BOSI ≥-3%. The agreement between BOSI ≥-3% and bendopnea was moderate (Gwet's AC 0.482, p < 0.001). At a median (p25%-p75%) follow-up of 2.17 years (0.88-3.16), we registered 441 WHF events in 148 patients. After multivariable adjustment, BOSI was independently associated with the risk for total WHF episodes (overall, p < 0.001). Compared to improvement/no change in SpO2 when bending (BOSI 0%), those with BOSI ≥-3% showed an increased risk of WHF events (incidence rate ratio [IRR] 2.16, 95% confidence interval [CI] 1.67-2.79; p < 0.001). In contrast, bendopnea was not associated with the risk of total WHF episodes (IRR 1.04, 95% CI 0.83-1.31; p = 0.705). CONCLUSIONS: In ambulatory and stable CHF patients, BOSI ≥-3% and not bendopnea was independently associated with an increased risk of total (first and recurrent) WHF episodes. Awareness of SpO2 while assessing bendopnea may be a useful tool for predicting heart failure decompensations.