Ergogenic effect of bcaas and l-alanine supplementation: Proof-of-concept study in a murine model of physiological exercise

Background: Branched-chain amino acids (BCAAs: leucine, isoleucine, valine) account for 35% of skeletal muscle essential amino acids (AAs). As such, they must be provided in the diet to support peptide synthesis and inhibit protein breakdown. Although substantial evidence has been collected about the potential usefulness of BCAAs in supporting muscle function and structure, dietary supplements containing BCAAs alone may not be effective in controlling muscle protein turnover, due to the rate-limiting bioavailability of other AAs involved in BCAAs metabolism. Methods: We aimed to evaluate the in vivo/ex vivo effects of a 4-week treatment with an oral formulation containing BCAAs alone (2:1:1) on muscle function, structure, and metabolism in a murine model of physiological exercise, which was compared to three modified formulations combining BCAAs with increasing concentrations of L-Alanine (ALA), an AA controlling BCAAs catabolism. Results: A preliminary pharmacokinetic study confirmed the ability of ALA to boost up BCAAs bioavailability. After 4 weeks, mix 2 (BCAAs + 2ALA) had the best protective effect on mice force and fatigability, as well as on muscle morphology and metabolic indices. Conclusion: Our study corroborates the use of BCAAs + ALA to support muscle health during physiological exercise, underlining how the relative BCAAs/ALA ratio is important to control BCAAs distribution

The ergometry in the vigilance of the health in firemen

Artículos originales[ES] La indicación de la ergometría en determinados colectivos de personas trabajadoras está recogida con la categoría IIa (opinión a favor de su utilidad) de la American Hearth Association. Los protocolos de vigilancia en salud laboral (Ministerio de Sanidad y Consumo) no recogen la realización de ergometrías. Objetivo: analizar los datos de ergometrías realizadas a 31 bomberos mayores de 44 años. Método: Se aplico protocolo BRUCE sobre tapiz rodante. Se analizaron los siguientes datos: edad, consumo de tabaco, frecuencia cardiaca basal, PR, eje QRS, frecuencia cardiaca submáxima, TAS/TAD basal, TAS/TAD máxima, capacidad funcional, tiempo de duración de la prueba, colesterol total, HDL, LDL y glucemia. Se analizó el riesgo cardiovascular Resultados: La media de edad fue de 48,82 años. El 29,03% eran fumadores. Los datos analítico fueron: glucemia 85,37 mg/100 cc, colesterol total 205 mg/100 cc, HDL 53,03 mg/100 cc, LDL 151,07 mg/100 cc. Buena respuesta al ejercicio físico. La capacidad funcional fue de 12,87 Mets, y la duración de 11,46 minutos. [EN] The indication of the ergometry in certain groups of hard–working persons is gathered by the category IIa (opinion in favour of its utility) of the American Hearth Association. The protocols of alertness in labour health (Ministry of Health and Consumption) do not gather the accomplishment of ergometry. Objective: to analyze the information of ergometry realized to 31 44–year–old major firemen. Method: Applied protocol BRUCE on rolling tapestry. The following information was analyzed: age, consumption of tobacco, cardiac frequency basal, PR, axis(axle) QRS, cardiac submaximum frequency, TAS/ TAD basal, maximum TAS/TAD, functional capacity, time of duration of the test(proof), total cholesterol, HDL, LDL and glucose. The cardiovascular risk was analyzed Results: The average of age was 48,82 years. 29,03 % was smoking. The information analytical was: glycemia 85,37 mg/100 cc, total cholesterol 205 mg/100 cc, HDL 53,03 mg/100 cc, LDL 151,07 mg/100 cc. Good response to the physical exercise(fiscal year). The functional capacity was 12,87 Mets, and the duration of 11,46 minutes.N

The structure–activity relationships of L3MBTL3 inhibitors: flexibility of the dimer interface

We recently reported the discovery of UNC1215, a potent and selective chemical probe for the L3MBTL3 methyllysine reader domain. In this article, we describe the development of structure-activity relationships (SAR) of a second series of potent L3MBTL3 antagonists which evolved from the structure of the chemical probe UNC1215. These compounds are selective for L3MBTL3 against a panel of methyllysine reader proteins, particularly the related MBT family proteins, L3MBTL1 and MBTD1. A co-crystal structure of L3MBTL3 and one of the most potent compounds suggests that the L3MBTL3 dimer rotates about the dimer interface to accommodate ligand binding

Adaptation of Mouse Skeletal Muscle to Long-Term Microgravity in the MDS Mission

The effect of microgravity on skeletal muscles has so far been examined in rat and mice only after short-term (5–20 day) spaceflights. The mice drawer system (MDS) program, sponsored by Italian Space Agency, for the first time aimed to investigate the consequences of long-term (91 days) exposure to microgravity in mice within the International Space Station. Muscle atrophy was present indistinctly in all fiber types of the slow-twitch soleus muscle, but was only slightly greater than that observed after 20 days of spaceflight. Myosin heavy chain analysis indicated a concomitant slow-to-fast transition of soleus. In addition, spaceflight induced translocation of sarcolemmal nitric oxide synthase-1 (NOS1) into the cytosol in soleus but not in the fast-twitch extensor digitorum longus (EDL) muscle. Most of the sarcolemmal ion channel subunits were up-regulated, more in soleus than EDL, whereas Ca2+-activated K+ channels were down-regulated, consistent with the phenotype transition. Gene expression of the atrophy-related ubiquitin-ligases was up-regulated in both spaceflown soleus and EDL muscles, whereas autophagy genes were in the control range. Muscle-specific IGF-1 and interleukin-6 were down-regulated in soleus but up-regulated in EDL. Also, various stress-related genes were up-regulated in spaceflown EDL, not in soleus. Altogether, these results suggest that EDL muscle may resist to microgravity-induced atrophy by activating compensatory and protective pathways. Our study shows the extended sensitivity of antigravity soleus muscle after prolonged exposition to microgravity, suggests possible mechanisms accounting for the resistance of EDL, and individuates some molecular targets for the development of countermeasures

Temporal changes in the epidemiology, management, and outcome from acute respiratory distress syndrome in European intensive care units: a comparison of two large cohorts

Background: Mortality rates for patients with ARDS remain high. We assessed temporal changes in the epidemiology and management of ARDS patients requiring invasive mechanical ventilation in European ICUs. We also investigated the association between ventilatory settings and outcome in these patients. Methods: This was a post hoc analysis of two cohorts of adult ICU patients admitted between May 1–15, 2002 (SOAP study, n = 3147), and May 8–18, 2012 (ICON audit, n = 4601 admitted to ICUs in the same 24 countries as the SOAP study). ARDS was defined retrospectively using the Berlin definitions. Values of tidal volume, PEEP, plateau pressure, and FiO2 corresponding to the most abnormal value of arterial PO2 were recorded prospectively every 24 h. In both studies, patients were followed for outcome until death, hospital discharge or for 60 days. Results: The frequency of ARDS requiring mechanical ventilation during the ICU stay was similar in SOAP and ICON (327[10.4%] vs. 494[10.7%], p = 0.793). The diagnosis of ARDS was established at a median of 3 (IQ: 1–7) days after admission in SOAP and 2 (1–6) days in ICON. Within 24 h of diagnosis, ARDS was mild in 244 (29.7%), moderate in 388 (47.3%), and severe in 189 (23.0%) patients. In patients with ARDS, tidal volumes were lower in the later (ICON) than in the earlier (SOAP) cohort. Plateau and driving pressures were also lower in ICON than in SOAP. ICU (134[41.1%] vs 179[36.9%]) and hospital (151[46.2%] vs 212[44.4%]) mortality rates in patients with ARDS were similar in SOAP and ICON. High plateau pressure (> 29 cmH2O) and driving pressure (> 14 cmH2O) on the first day of mechanical ventilation but not tidal volume (> 8 ml/kg predicted body weight [PBW]) were independently associated with a higher risk of in-hospital death. Conclusion: The frequency of and outcome from ARDS remained relatively stable between 2002 and 2012. Plateau pressure > 29 cmH2O and driving pressure > 14 cmH2O on the first day of mechanical ventilation but not tidal volume > 8 ml/kg PBW were independently associated with a higher risk of death. These data highlight the continued burden of ARDS and provide hypothesis-generating data for the design of future studies

Organizational configuration of hospitals succeeding in attracting and retaining nurses

Organizational configuration of hospitals succeeding in attracting and retaining nurses. This paper contrasts structural and managerial characteristics of low- and high-turnover hospitals, and describes the organizational configuration of attractive hospitals. In countries facing nurse shortages and turnover, some hospitals succeed in recruiting and retaining nurses. In Magnet Hospitals, managerial practices and environmental characteristics increase nurses\u2019 job satisfaction and their commitment to the organization, which in turn decreases nurse turnover. Such an approach suggests that organizations are best understood as clusters of interconnected structures and practices, i.e. organizational configurations rather than entities whose components can be understood in isolation. From a sample of 12 hospitals whose nurse turnover was studied for 1 year, structural and organizational features of hospitals in the first and fourth quartiles, i.e. attractive (turnover11\uc68%) were contrasted. A questionnaire, including perceptions of health-related factors, job demands, stressors, work schedules, organizational climate, and work adjustments antecedent to turnover, was received from 401 nurses working in attractive hospitals (response rate - 53\uc68%) and 774 nurses in conventional hospitals (response rate \ubc 54\uc65%). Structural characteristics did not differentiate attractive and conventional hospitals, but employee perceptions towards the organization differed strikingly. Differences were observed for risk exposure, emotional demands, role ambiguity and conflicts, work-family conflicts, effort-reward imbalance and the meaning of work, all in favour of attractive hospitals (P < 0.01). Relationships with nursing management, work ability and satisfaction with working time, handover shifts and schedules were also better in attractive hospitals (P < 0.001). Job satisfaction and commitment were higher in attractive hospitals, whereas burnout and intention to leave were lower (P < 0.001). Organizational characteristics are key factors in nurse attraction and retention. Nurses face difficulties in their work situations, but some hospitals are perceived as healthy organizations. The concept of attractive institutions could serve as a catalyst for improvement in nurses\u2019 work environments in Europe