745 research outputs found

    Urodynamic effects of oxybutynin and tolterodine in conscious and anesthetized rats under different cystometrographic conditions

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    BACKGROUND: Antimuscarinic agents are the most popular treatment for overactive bladder and their efficacy in man is well documented, producing decreased urinary frequency and an increase in bladder capacity. During cystometry in rats, however, the main effect reported after acute treatment with antimuscarinics is a decrease in peak micturition pressure together with little or no effect on bladder capacity. In the present experiments we studied the effects, in rats, of the two most widely used antimuscarinic drugs, namely oxybutynin and tolterodine, utilising several different cystometrographic conditions. The aim was to determine the experimental conditions required to reproduce the clinical pharmacological effects of antimuscarinic agents, as seen in humans, in particular their ability to increase bladder capacity. RESULTS: Intravenous or oral administration of tolterodine or oxybutynin in conscious rats utilized 1 day after catheter implantation and with saline infusion at constant rate of 0.1 ml/min, gave a dose-dependent decrease of micturition pressure (MP) with no significant change in bladder volume capacity (BVC). When the saline infusion rate into the bladder was decreased to 0.025 ml/min, the effect of oral oxybutynin was similar to that obtained with the higher infusion rate. Also, experiments were performed in rats in which bladders were infused with suramin (3 and 10 μM) in order to block the non-adrenergic, non-cholinergic component of bladder contraction. Under these conditions, oral administration of oxybutynin significantly reduced MP (as observed previously), but again BVC was not significantly changed. In conscious rats with bladders infused with diluted acetic acid, both tolterodine and oxybutynin administered at the same doses as in animals infused with saline, reduced MP, although the reduction appeared less marked, with no effect on BVC. In conscious rats utilized 5 days after catheter implantation, a situation where inflammation due to surgery is reduced, the effect of tolterodine (i.v.) and oxybutynin (p.o.) on MP was smaller and similar, respectively, to that observed in rats utilized 1 day after catheter implantation, but the increase of BVC was not statistically significant. In anesthetized rats, i.v. administration of oxybutynin again induced a significant decrease in MP, although it was of questionable relevance. Both BVC and threshold pressure were not significantly reduced. The number and amplitude of high frequency oscillations in MP were unmodified by treatment. Finally, in conscious obstructed rats, intravenous oxybutynin did not modify frequency and amplitude of non-voiding contractions or bladder capacity and micturition volume. CONCLUSION: Despite the different experimental conditions used, the only effect on cystometrographic parameters of oxybutynin and tolterodine in anesthetized and conscious rats was a decrease in MP, whereas BVC was hardly and non-significantly affected. Therefore, it is difficult to reproduce in rats the cystometrographic increase in BVC as observed in humans after chronic administration of antimuscarinic agents, whereas the acute effects seem more similar

    Does early specialization provide an advantage in physical fitness development in youth basketball?

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    The present study examined the influence of the specialization onset on the magnitude and patterns of changes in basketball-specific physical fitness within a competitive season and developmental fitness trends between 11 and 17 years in young basketball players. Repeated measures of 181 young basketball players (female, n = 40; male, n = 141) were examined. Anthropometry, age, estimated maturity status, and basketball-specific physical fitness (assessed with the countermovement jump, line drill, and yo-yo intermittent recovery level-1 and fitness score) were considered. Players were grouped by the onset of specialization as related to biological maturation milestones (pre-puberty, mid-puberty, and late-puberty specialization). The within-season and developmental changes in physical fitness were fitted using multilevel modeling in a fully Bayesian framework. The fitness outcomes were similar between-player and within-player changes when grouped by specialization across a season. Fitness improvements across a season were apparent for female players, while male players maintained their performance levels. There was no variation in the patterns of physical fitness development between 11 and 17 years associated with the onset of specialization. Conditional on our data and models, the assumption that early sport specialization provides a physical fitness advantage for future athletic success does not hold

    Biopolímeros y Nanotecnología: Desde el Laboratorio a la Planta Piloto

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    El desarrollo de nuevas formulaciones basadas en nano-biocompuestosbiodegradables es una temática de actualidad en función del cuidado del medio ambiente. El trabajo comenzó con la solicitud de una empresa Pyme transformadora de plástico que produce envases para el agro y consistió en la fabricación de películas para bolsas biodegradables en tierra. A nivel laboratorio, se obtuvieron películas por medio de casting usando diferentes formulaciones a base de almidón mezclándolo con otro biopolímero y agregando a la mezcla diferentes porcentajes de nanocelulosa bacteriana (NCB) y de nanoarcilla (NA). Para la fabricación de prototipos de bolsas se elegían las que formaran película y se biodegradaran en tierra. En la etapa de Planta Piloto, se usó una extrusora de simple tornillo y un equipo de extrusión-soplado. Se estudiaron las condiciones óptimas de procesamiento para obtener una burbuja estable. Luego de lo cual, estas películas en forma de tubos fueron caracterizadas mecánicamente y por biodegradación en suelo. En cuanto a la fabricación de nanocelulosa bacteriana, que fue uno de los aditivos usados, también se trabajó con otra empresa Pyme Primero estudiando el proceso en el laboratorio: la materia prima de partida, tipos de fermentadores y las condiciones óptimas del proceso. Para luego pasar a la etapa de planta piloto y su transferencia a una empresa.En estos dos trabajos de transferencia de tecnología se utilizaron los conocimientos adquiridos luego de muchos años de investigación junto con los conocimientosfundamentales adquiridos en las carreras de Ingeniería.Fil: Vazquez, Analia. Universidad de Buenos Aires; ArgentinaFil: Foresti, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnología en Polímeros y Nanotecnología. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Tecnología en Polímeros y Nanotecnología; ArgentinaFil: Cerrutti, Patricia. Universidad de Buenos Aires; ArgentinaFil: Melaj, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnología en Polímeros y Nanotecnología. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Tecnología en Polímeros y Nanotecnología; ArgentinaFil: Leonardi, Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnología en Polímeros y Nanotecnología. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Tecnología en Polímeros y Nanotecnología; ArgentinaFil: Giménez, Rocío Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnología en Polímeros y Nanotecnología. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Tecnología en Polímeros y Nanotecnología; ArgentinaFil: Principe Lopez, Nazareno. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnología en Polímeros y Nanotecnología. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Tecnología en Polímeros y Nanotecnología; ArgentinaFil: Rodriguez Batller, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnología en Polímeros y Nanotecnología. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Tecnología en Polímeros y Nanotecnología; ArgentinaFil: Fernandez Corujo, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnología en Polímeros y Nanotecnología. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Tecnología en Polímeros y Nanotecnología; ArgentinaFil: Bernal, Celina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnología en Polímeros y Nanotecnología. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Tecnología en Polímeros y Nanotecnología; Argentina5° Congreso Argentino de Ingeniería; 11° Congreso Argentino de Enseñanza de la Ingeniería y 3° Congreso Latinoamericano de IngenieríaCiudad Autónoma de Buenos AiresArgentinaUniversidad de Buenos Aires. Facultad de IngenieríaConsejo Federal de Decanos de Ingeniería de la República Argentin

    CERT1 mutations perturb human development by disrupting sphingolipid homeostasis

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    Neural differentiation, synaptic transmission, and action potential propagation depend on membrane sphingolipids, whose metabolism is tightly regulated. Mutations in the ceramide transporter CERT (CERT1), which is involved in sphingolipid biosynthesis, are associated with intellectual disability, but the pathogenic mechanism remains obscure. Here, we characterize 31 individuals with de novo missense variants in CERT1. Several variants fall into a previously uncharacterized dimeric helical domain that enables CERT homeostatic inactivation, without which sphingolipid production goes unchecked. The clinical severity reflects the degree to which CERT autoregulation is disrupted, and inhibiting CERT pharmacologically corrects morphological and motor abnormalities in a Drosophila model of the disease, which we call ceramide transporter (CerTra) syndrome. These findings uncover a central role for CERT autoregulation in the control of sphingolipid biosynthetic flux, provide unexpected insight into the structural organization of CERT, and suggest a possible therapeutic approach for patients with CerTra syndrome.This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS), NIH (R01NS109858, to VAG); the Paul A. Marks Scholar Program at the Columbia University Vagelos College of Physicians and Surgeons (to VAG); a TIGER grant from the TAUB Institute at the Columbia Vagelos College of Physicians and Scientists (to VAG); the Swiss National Science Foundation (SNF 31003A-179371, to TH); the European Joint Program on Rare Diseases (EJP RD+SNF 32ER30-187505, to TH); the Swiss Cancer League (KFS-4999-02-2020, to GD); the EPFL institutional fund (to GD); the Kristian Gerhard Jebsen Foundation (to GD); the Swiss National Science Foundation (SNSF) (310030_184926, to GD); the Swiss Foundation for Research on Muscle Disease (FSRMM, to MAL); the Natural Science and Engineering Research Council of Canada (Discovery Grant 2020-04241, to JEB); the Italian Ministry of Health Young Investigator Grant (GR-2011-02347754, to EL); the Fondazione Istituto di Ricerca Pediatrica – Città della Speranza (18-04, to EL); the Wroclaw Medical University (SUB.E160.21.004, to RS); the National Science Centre, Poland (2017/27/B/NZ5/0222, to RS); Telethon Undiagnosed Diseases Program (TUDP) (GSP15001); the Temple Street Foundation/Children’s Health Foundation Ireland (RPAC 19-02, to IK); the Deutsche Forschungsgemeinschaft (DFG) (PO2366/2–1, to BP); the Instituto de Salud Carlos III, Spain (to ELM, EBS, and BMD); the National Natural Science Foundation of China (81871079 and 81730036, to HG and KX); and the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH (R01 DK115574, to SSC).The DEFIDIAG study is funded by grants from the French Ministry of Health in the framewok of the national French initiative for genomic medicine. The funders were not involved in the study design, data acquisition, analysis, or writing of the manuscript. Funding for the DECIPHER project was provided by Wellcome. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between Wellcome and the Department of Health, and the Wellcome Sanger Institute (grant number WT098051). The views expressed in this publication are those of the author(s) and not necessarily those of Wellcome or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12, granted by the Republic of Ireland REC). The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network.S

    Caratterizzazione della dinamica produttiva di pascoli naturali italiani

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    This work studies herbage production and its seasonal distribution in indigenous pastures, and analyses the relationship between the environmental factors (soil, clima, vegetation) and the productivity of these resources. The investigations have been carried on during the period 1983-90 by the joint activity of 10 different University Istitutions in 23 different environments distributed along the Italian peninsula and the main islands. For each environment, pasture production has been measured with the Corrall and Fenlon method, analysing the more important vegetational and ecological conditions; altogether the total yearly production and the seasonal pattern of herbage production have been detected on 104 pastures. The total herbage yield is not significantly influenced by the latitudinal gradient, and the overall regional (alps, central Appenine, south Apennine and islands) production is about 2.3 t ha-1 year-1 The wide range (0.5-6.3 t ha-1 year-1) of herbage production, on small or medium scale, seems to be due to evident changeof environmental or management factors. Five types of seasonal distribution of herbage growth are evidenced with multivariate analysis methods, based on the growing season and the amplitude of the growth. With mean temperature above 12°C and total rainfall below 800 mm, herbage distribution shows a standstill during summer period and an evident regrowth in autumn. On the contrary, for the 4 other distribution types, the winter standstill become important, and the types are distinct by summer growth amplitude and by the growing season lenght. With cluster analysis method, for each type of herbage distribution, have been pointed out under-types characterized by interannual herbage production variation. Among the environmental factors, vegetation characheristics, expressed as Pasture Value following Daget and Poissonet seems to be strictly correlated with total production. The comparative poor role played by the soil and climatic factor, may be due to the strong past and present antropic influence, related with management and utilization techniques. Il presente lavoro ha come scopo l'approfondimento delle conoscenze sulla produzione e sulla distribuzione stagionale della crescita dell'erba dei pascoli naturali, nonché l'analisi delle interazioni tra i fattori ambientali, pedo-climatici e vegetazionali, e la risposta produttiva di queste risorse. La ricerca è stata condotta nel periodo 1983-90 da 10 diverse Istituzioni Universitarie, in 23 ambienti differenti, distribuiti lungo tutta la penisola e le isole maggiori. Per ogni ambiente, con il metodo di rilievo di Corrall e Fenlon, è stata saggiata la risposta produttiva di pascoli rappresentativi delle principali situazioni vegetazionali e di giacitura; complessivamente sono state rilevate la produzione totale annua e la curva di produttività media pluriennale di 104 pascoli. Riguardo la produzione annua complessiva si è osservato che essa non presenta variazioni significative lungo il gradiente latitudinale, collocandosi tra le diverse regioni (alpina, centro appenninica, suq, appenninica e insulare) attorno a 2.3 t ha-1 anno-1. La fitomassa raccolta è soggetta invece a variazioni sensibili (0.5-6.3 t ha-1 anno-1) riconducibili a fattori ambientali e gestionali che si esprimono su piccola e media scala. Con metodi di analisi multivariata si sono individuate 5 tipologie distributive della crescita dell'erba, in rapporto alla stagione vegetativa e alle variazioni dell'intensità di crescita nel corso della stagione stessa. Con temperature medie e precipitazioni annue rispettivamente maggiori di 12°C e minori di 800 mm, risulta evidente la stasi vegetativa nel trimestre estivo e la ripresa vegetativa autunnale. Nel caso opposto la stasi è invernale e le 4 tipologie afferenti a questo modello, sono distinguibili dall'entità della crescita nei mesi estivi e dalla durata della stagione vegetativa. Per ogni tipologia produttiva, sono state evidenziate, tramite l'analisi cluster, sotto-tipologie distinte per la variabilità produttiva interannuale. Tra i fattori ambientali, la vegetazione, espressa attraverso l'indice del valore pastorale di Daget e Poissonet, presenta una buona capacità predittiva nei confronti del livello produttivo dei pascoli. Il contributo comparativamente modesto offerto dai fattori pedoclimatici sembra attribuibile alla forte influenza antropica, pregressa e attuale, attraverso le cure colturali e l'utilizzazione

    Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

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    Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations

    Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

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    Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p < 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription

    The “Diabetes Comorbidome”: A Different Way for Health Professionals to Approach the Comorbidity Burden of Diabetes

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    (1) Background: The disease burden related to diabetes is increasing greatly, particularly in older subjects. A more comprehensive approach towards the assessment and management of diabetes’ comorbidities is necessary. The aim of this study was to implement our previous data identifying and representing the prevalence of the comorbidities, their association with mortality, and the strength of their relationship in hospitalized elderly patients with diabetes, developing, at the same time, a new graphic representation model of the comorbidome called “Diabetes Comorbidome”. (2) Methods: Data were collected from the RePoSi register. Comorbidities, socio-demographic data, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), and functional status (Barthel Index), were recorded. Mortality rates were assessed in hospital and 3 and 12 months after discharge. (3) Results: Of the 4714 hospitalized elderly patients, 1378 had diabetes. The comorbidities distribution showed that arterial hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and COPD (22.7%), were the more frequent in subjects with diabetes. The graphic comorbidome showed that the strongest predictors of death at in hospital and at the 3-month follow-up were dementia and cancer. At the 1-year follow-up, cancer was the first comorbidity independently associated with mortality. (4) Conclusions: The “Diabetes Comorbidome” represents the perfect instrument for determining the prevalence of comorbidities and the strength of their relationship with risk of death, as well as the need for an effective treatment for improving clinical outcomes

    Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

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    Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population
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