299 research outputs found

    The Stat3-Fam3a axis promotes muscle stem cell myogenic lineage progression by inducing mitochondrial respiration.

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    Metabolic reprogramming is an active regulator of stem cell fate choices, and successful stem cell differentiation in different compartments requires the induction of oxidative phosphorylation. However, the mechanisms that promote mitochondrial respiration during stem cell differentiation are poorly understood. Here we demonstrate that Stat3 promotes muscle stem cell myogenic lineage progression by stimulating mitochondrial respiration in mice. We identify Fam3a, a cytokine-like protein, as a major Stat3 downstream effector in muscle stem cells. We demonstrate that Fam3a is required for muscle stem cell commitment and skeletal muscle development. We show that myogenic cells secrete Fam3a, and exposure of Stat3-ablated muscle stem cells to recombinant Fam3a in vitro and in vivo rescues their defects in mitochondrial respiration and myogenic commitment. Together, these findings indicate that Fam3a is a Stat3-regulated secreted factor that promotes muscle stem cell oxidative metabolism and differentiation, and suggests that Fam3a is a potential tool to modulate cell fate choices

    INFLUENCE OF NUTRITION AND GENETICS ON PERFORMANCE: A PILOT STUDY IN A GROUP OF GYMNASTS

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    Purpose. Energy requirements in sports performance are affected by numerous factors: physical characteristics, age, genetic basis, sports discipline. The Food and Nutrition Board recommended nutrition based on age, height, and body weight gain in relation to physical activity. Some genetic factors, such as the PPAR-encoding gene, play a key role in metabolism. The aim of the study was to investigate the effect of specific snacks on performance. Methods. Seventeen girls aged 10–14 years practising artistic gymnastics were enrolled. A carb or protein/carb snack was provided before the training, and a questionnaire was administered at the end. In addition, saliva samples were collected for genetic analyses. Results. Most girls represented the CC genotype (65%), while a small part had the GC (23%) and GG (12%). The average BMI equalled 20.05 ± 2.8 kg/m2 in the group with the CC genotype, 19.6 ± 2.8 kg/m2 with the GC genotype, and 20.2 ± 2.8 kg/m2 with the GG genotype. The questionnaire showed that 59% of girls experienced a performance improvement after eating a carb snack; slightly different results were observed after the intake of a protein/carb snack: 47% felt more energy and 12% more fatigue. Conclusions. This is a preliminary study that should be deepened by increasing the number of subjects, as well as diversifying the type of snacks administered and increasing the time of the study. It is important to be mindful of eating habits and lifestyle in order to prevent the onset of overweight

    UN ESTUDIO SOBRE LAS MOTIVACIONES PARA DEJAR LA PROFESIÓN DOCENTE EN CHILE

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    RESUMEN La investigación examina las decisiones de abandono de la docencia tomadas por maestros principiantes de enseñanza secundaria chilena. Se utilizaron, en una muestra de 145 docentes, técnicas cuantitativas y cualitativas para examinar los motivos que fundamentan estas decisiones. Los resultados establecen que las condiciones estructurales de la profesión docente, incluyendo la remuneración, y la perspectiva de otras oportunidades profesionales más atractivas son claves para entender este fenómeno. Además, surge un grupo de docentes decepcionados con los fines, funcionamiento y organización del sistema escolar. Finalmente, es necesario establecer nuevos incentivos para motivar a los profesores que se plantean dejar la profesión, y contemplar distintas trayectorias dentro del ámbito educativo

    Clinical characteristics and outcome of ceftazidime/avibactam-resistant Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae infections. A retrospective, observational, 2-center clinical study

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    Background Recently, Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) with resistance to ceftazidime/avibactam (CZA-R) has been described, including KPC variants that restore carbapenem susceptibility. The aim of the study was to analyze the clinical characteristics and outcomes of infections caused by CZA-R KPC-Kp. Methods From 2019 to 2021, a retrospective 2-center study including patients with infections due to CZA-R KPC-Kp hospitalized at 2 academic hospitals in Rome was conducted. Demographic and clinical characteristics were collected. Principal outcome was 30-day all-cause mortality. Statistical analyses were performed with Stata-IC17 software. Results Overall, 59 patients were included (mean age, 64.4 & PLUSMN; 14.6 years; mean Charlson comorbidity index score, 4.5 & PLUSMN; 2.7). Thirty-four patients (57.6%) had infections caused by CZA-R and meropenem (MEM)-susceptible strains. A previous CZA therapy was observed in 40 patients (67.8%), mostly in patients with MEM-susceptible KPC variant (79.4% vs 52%, P = .026). Primary bacteremia was observed in 28.8%, followed by urinary tract infections and pneumonia. At infection onset, septic shock was present in 15 subjects (25.4%). After adjustment for confounders, only the presence of septic shock was independently associated with mortality (P = .006). Conclusions Infections due to CZA-R KPC-Kp often occur in patients who had previously received CZA, especially in the presence of strains susceptible to MEM. Nevertheless, one-third of patients had never received CZA before KPC-Kp CZA-R. Since the major driver for mortality was infection severity, understanding the optimal therapy in patients with KPC-Kp CZA-R infections is of crucial importance.Clinical characteristics and outcomes of infections caused by ceftazidime/avibactam-resistant (CZA-R) Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae were analyzed. Ceftazidime/avibactam-resistant and meropenem-susceptible KPC variants accounted for more than half of patients. Infections due to CZA-R KPC-Kp often occur in patients who had previously received CZA, especially in the presence of strains susceptible to meropenem. Nevertheless, one-third of patients had never received CZA before isolation of CZA strains. Infection severity was the only independent predictor of 30-day mortality

    Genome-based retrospective analysis of a Providencia stuartii outbreak in Rome, Italy. Broad spectrum IncC plasmids spread the NDM carbapenemase within the hospital

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    Providencia stuartii is a member of the Morganellaceae family, notorious for its intrinsic resistance to several antibiotics, including last-resort drugs such as colistin and tigecycline. Between February and March 2022, a four-patient outbreak sustained by P. stuartii occurred in a hospital in Rome. Phenotypic analyses defined these strains as eXtensively Drug-Resistant (XDR). Wholegenome sequencing was performed on the representative P. stuartii strains and resulted in fully closed genomes and plasmids. The genomes were highly related phylogenetically and encoded various virulence factors, including fimbrial clusters. The XDR phenotype was primarily driven by the presence of the (NDM)-N-bla- 1 metallo- beta-lactamase alongside the rmtC 16S rRNA methyltransferase, conferring resistance to most beta-lactams and every aminoglycoside, respectively. These genes were found on an IncC plasmid that was highly related to an NDM-IncC plasmid retrieved from a ST15 Klebsiella pneumoniae strain circulating in the same hospital two years earlier. Given its ability to acquire resistance plasmids and its intrinsic resistance mechanisms, P. stuartii is a formidable pathogen. The emergence of XDR P. stuartii strains poses a significant public health threat. It is essential to monitor the spread of these strains and develop new strategies for their control and treatment

    Ceftazidime-avibactam resistance in Klebsiella pneumoniae sequence type 37: a decade of persistence and concealed evolution

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    The first reports of carbapenem-resistant Enterobacterales in our hospital date back to 2006. In that period, few ertapenem-resistant but meropenem-susceptible Klebsiella pneumoniae isolates belonging to sequence type (ST) 37 were retrieved from clinical samples. These strains produced the CTX-M-15 extended spectrum β-lactamase, OmpK35 was depleted due to a nonsense mutation, and a novel OmpK36 variant was identified. Yet, starting from 2010, Klebsiella pneumoniae carbapenemase (KPC)-producing ST512 isolates started prevailing and ST37 vanished from sight. Since 2018 the clinical use of the combination of ceftazidime-avibactam (CZA) has been introduced in clinical practice for the treatment of bacteria producing serine-β-lactamases, but KPC-producing, CZA-resistant K. pneumoniae are emerging. In 2021, four CZA-resistant ST37 isolates producing KPC variants were isolated from the same number of patients. blaKPC gene cloning in Escherichia coli was used to define the role of those KPC variants on CZA resistance, and whole genome sequencing was performed on these isolates and on three ST37 historical isolates from 2011. CZA resistance was due to mutations in the blaKPC genes carried on related pKpQIL-type plasmids, and three variants of the KPC enzyme have been identified in the four ST37 strains. The four ST37 isolates were closely related to each other and to the historical isolates, suggesting that ST37 survived without notice in our hospital for 10 years, waiting to re-emerge as a CZA-resistant K. pneumoniae clone. The ancestor of these contemporary isolates derives from ST37 wild-type porin strains, with no other mutations in chromosomal genes involved in conferring antibiotic resistance (parC, gyrA, ramR, mgrB, pmrB)

    Repeatability of skin-markers based kinematic measures from a multi-segment foot model in walking and running.

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    Skin-markers based multi-segment models are growing in popularity to assess foot joint kinematics in different motor tasks. However, scarce is the current knowledge of the effect of high-energy motor tasks, such as running, on the repeatability of these measurements. This study aimed at assessing and comparing the inter-trial, inter-session, and inter-examiner repeatability of skin-markers based foot kinematic measures in walking and running in healthy adults. The repeatability of 24 kinematic measures from an established multi-segment foot model were assessed in two volunteers during multiple barefoot walking and running trials by four examiners in three sessions. Statistical Parametric Mapping (1D-SPM) analysis was performed to assess the degree of shape-similarity between patterns of kinematic measurements. The average inter-trial variability across measurements (deg) was 1.0 ± 0.3 and 0.8 ± 0.3, the inter-session was 3.9 ± 1.4 and 4.4 ± 1.5, and the inter-examiner was 5.4 ± 2.3 and 5.7 ± 2.2, respectively in walking and running. Inter-session variability was generally similar between the two motor tasks, but significantly larger in running for two kinematic measures (p 0.01). Inter-examiner variability was generally larger than inter-trial and inter-session variability. While no significant differences in frame-by-frame offset variability was detected in foot kinematics between walking and running, 1D-SPM revealed that the shape of kinematic measurements was significantly affected by the motor task, with running being less repeatable than walking. Although confirmation on a larger population and with different kinematic protocols should be sought, attention should be paid in the interpretation of skin-markers based kinematics in running across sessions or involving multiple examiners

    Trend of Drug Abuse in 2011– 2014 in Italy

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    Doping, although was born as a medication and not with the purpose of enhancing performance, is a widespread practice in all sports, between amateur and gym-goers. The Italian sports federations were in second place worldwide for positive doping-test, after Russia. This review focuses on the analysis of data collected by Italian National Olympic Committee (CONI) in the 2012–2014 period, showing that the most commonly used substances were anabolic androgenic agents, glucocorticoids, diuretics and stimulants. Prevention in doping could be a key to limit the damage caused by this harmful practice both, for the physical health and the athlete’s moral integrity and anti-doping campaigns should be direct as much as possible to young people, since about two-thirds of adolescents appear to be dissatisfied with their body. Even coordination between the various professionals that surround athletes could help fight doping by planning specific training and adapted to the individual athlete, taking into account the actual physical limitations and physical features of each

    Age-Related Changes to Human Tear Composition.

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    Purpose We characterize age-associated alterations in the expression of inflammatory mediators and tissue remodeling factors in human tears. Methods A total of 75 consecutive volunteers (32 male/44 female; 19-93 years) underwent clinical assessment of ocular surface status, ocular surface disease index (OSDI) grading and tear sampling. The volunteers were categorized into three groups: young (18-40 years), middle-aged (41-60 years), and old (>60 years). Total protein profiles and chip-based protein array evaluations were conducted to investigate the expression of 60 potential candidates, including pro-/anti-inflammatory mediators and tissue remodeling factors. Appropriate validations were performed using conventional assays. Multiple comparisons for regression between potential candidates and age were performed, as well as statistical analyses among the three age groups. Nonpooled samples were used for quantifications. Results Pearson analysis of chip-arrays identified 9 of 60 potential candidates. Specifically, IL-8, IL-6, and regulated on activation, normal T cell expressed and secreted (RANTES; P < 0.0083) protein as well as matrix metalloproteinase (MMP)-1, IL-3, and TNF-α (P < 0.05) correlated positively with aging. MIP-3β showed an opposite tendency. Western blot and ELISA analysis corroborated the array data. OSDI grading did not correlate with aging. Conclusions Dynamic changes to tear protein profiles occur with aging. Our study identifies the expression of IL-8, IL-6, RANTES, MMP-1, and MIP-3β as increasing with age. These select inflammatory and matrix remodeling factors may be relevant to the development of novel diagnostic tools and therapeutics in the context of age-related ocular surface disease
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