Chronic melatonin treatment improves obesity by inducing uncoupling of skeletal muscle SERCA-SLN mediated by CaMKII/AMPK/PGC1α pathway and mitochondrial biogenesis in female and male Zücker diabetic fatty rats.

Melatonin acute treatment limits obesity of young Zücker diabetic fatty (ZDF) rats by non-shivering thermogenesis (NST). We recently showed melatonin chronically increases the oxidative status of vastus lateralis (VL) in both obese and lean adult male animals. The identification of VL skeletal muscle-based NST by uncoupling of sarcoendoplasmic reticulum Ca2+-ATPase (SERCA)- sarcolipin (SLN) prompted us to investigate whether melatonin is a SERCA-SLN calcium futile cycle uncoupling and mitochondrial biogenesis enhancer. Obese ZDF rats and lean littermates (ZL) of both sexes were subdivided into two subgroups: control (C) and 12 weeks orally melatonin treated (M) (10 mg/kg/day). Compared to the control groups, melatonin decreased the body weight gain and visceral fat in ZDF rats of both sexes. Melatonin treatment in both sex obese rats restored the VL muscle skin temperature and sensitized the thermogenic effect of acute cold exposure. Moreover, melatonin not only raised SLN protein levels in the VL of obese and lean rats of both sexes; also, the SERCA activity. Melatonin treatment increased the SERCA2 expression in obese and lean rats (both sexes), with no effects on SERCA1 expression. Melatonin increased the expression of thermogenic genes and proteins (PGC1-α, PPARγ, and NRF1). Furthermore, melatonin treatment enhanced the expression ratio of P-CaMKII/CaMKII and P-AMPK/AMPK. In addition, it rose mitochondrial biogenesis. These results provided the initial evidence that chronic oral melatonin treatment triggers the CaMKII/AMPK/PGC1α axis by upregulating SERCA2-SLN-mediated NST in ZDF diabetic rats of both sexes. This may further contribute to the body weight control and metabolic benefits of melatonin.

Estrategia para optimizar la seguridad del paciente en el servicio de dispensación en farmacia comunitaria. Propuesta de listados de verificación / Strategy to optimize patient safety in community pharmacy dispensing service. Checklists Proposed

La dispensación es el servicio más demandado e importante dentro de las labores que realiza el farmacéutico, en su día a día, en la farmacia comunitaria. El objetivo de la dispensación es garantizar el acceso del paciente al medicamento de manera adecuada y controlada. En dicho proceso, el farmacéutico comunitario tiene la obligación, como profesional de la salud, de participar de forma activa y comprometida en la detección de posibles errores de medicación o relacionados con la misma. El Grupo de Trabajo de Seguridad del Paciente de SEFAC ha elaborado, como comienzo de una serie de futuros proyectos, unos listados de verificación y decálogos de buenas prácticas sobre medicamentos formulados en forma de parches transdérmicos, comprimidos bucodispersables o formas de liberación modificada. Con esta iniciativa se pretende, mediante una entrevista previa con el paciente y el uso de estas herramientas, minimizar en la medida de lo posible, los errores o problemas que puedan surgir con dichos medicamentos velando finalmente por la seguridad del paciente. A lo largo del 2023 se espera comenzar un pilotaje en farmacias comunitarias colaboradoras con el Grupo de Trabajo de Seguridad del paciente de SEFAC y así poder recoger y notificar los resultados que se obtengan (AU)

Result of the implementation of a quality management system based on the ISO 9001:2015 standard in a surgical intensive care unit.

INTRODUCTION: The implementation of Quality Management Systems (QMS) is one of the fundamental and future-oriented elements for the improvement of modern health systems. The objective of implementing a QMS in accordance with the requirements of the ISO 9001: 2015 Standard is to effectively carry out its activities, covering both technical and management aspects, guaranteeing the satisfaction of the needs and expectations of all its stakeholders, as well as compliance with legal and regulatory requirements. It must contemplate all those aspects that have an impact on the final quality of the product or service provided by the organization. OBJECTIVE: The main objective is to describe the process of implementing a QMS under the ISO 9001: 2015 Standard in the Surgical Intensive Care Unit of the General University Hospital of Elche and evaluate its results. METHODOLOGY: Carrying out and implementing a QMS in the Surgical Intensive Care Unit of the General University Hospital of Elche applying the points of the ISO 9001: 2015 Standard. The SGC has followed the benchmark of management by processes, identifying from its strategic core of mission, vision and values, the different processes involved and their interrelation reflected in the process map. Based on it, the necessary documents have been developed to describe the operation of the Unit both at an operational level through the key processes (admission and initial assessment of the patient, stabilization, follow-up, complementary tests, interconsultations, transfers and discharge) as well as which refers to procedures of a strategic or support type. RESULTS: The strategic lines that marked the beginning of the deployment of our QMS were defined with the drafting of 7 objectives, achieving 100% compliance. The key processes (7) that described the functioning of our organization were elaborated, as well as those of a strategic type (14) and support or support (5), complemented with 55 medical and nursing protocols. 20 monitoring indicators were analyzed: 6 organizational and planning type, and 14 clinical. 46 incidents were detected in the first year of implementation of the QMS that were analyzed by the Quality Commission, emerging 7 corrective actions. 14 improvement actions were developed after the application of the AMFE methodology for key processes, achieving an average of greater than 70% effectiveness after reassessment. From the analysis of patient and family satisfaction through SAIP case management, 41 of a total of 52 cases were acknowledgments in writing. CONCLUSIONS: Implementing a QMS in our Surgical Intensive Care Unit has made it possible to define the strategic lines of our organization, develop objectives, establish monitoring indicators, standardize the work of the Unit through procedures and protocols, increase safety at work through the use of lists of verification, initiate improvement actions to strengthen the weak points of the QMS itself, as well as know the degree of satisfaction and needs of our patients and the personnel who work in it.

Resultado de la implementación de un sistema de gestión de la calidad en base a la Norma ISO 9001: 2015 en una unidad de cuidados intensivos quirúrgica / Result of the implementation of a quality management system based on the ISO 9001: 2015 standard in a surgical intensive care unit

IntroducciónLa implantación de los sistemas de gestión de la calidad (SGC) es uno de los elementos fundamentales y de futuro para la mejora de los sistemas sanitarios modernos. El objetivo de la implementación de un SGC de acuerdo con los requisitos de la Norma ISO 9001:2015 es llevar a cabo de manera eficaz sus actividades, abarcando tanto los aspectos técnicos como los aspectos de gestión, garantizando la satisfacción de las necesidades y expectativas de todas las partes interesadas, así como el cumplimiento de los requisitos legales y reglamentarios. Debe contemplar todos aquellos aspectos que tengan incidencia en la calidad final del producto o servicio que presta la organización.ObjetivoEl objetivo principal es describir el proceso de implementación de un SGC bajo la Norma ISO 9001:2015 en la Unidad de Cuidados Intensivos Quirúrgica del Hospital General Universitario de Elche y evaluar sus resultados.MetodologíaRealización e implementación de un SGC en la Unidad de Cuidados Intensivos Quirúrgica del Hospital General Universitario de Elche aplicando los puntos de la Norma ISO 9001:2015. El SGC ha seguido el referente de la gestión por procesos, identificando desde su núcleo estratégico de misión, visión y valores, los diferentes procesos implicados y su interrelación plasmados en el mapa de procesos. A partir del mismo, se han desarrollado los documentos necesarios para describir el funcionamiento de la Unidad tanto a nivel operativo mediante los procesos clave (ingreso y valoración inicial del paciente, estabilización, seguimiento, pruebas complementarias, interconsultas, traslados y alta) como en lo que se refiere a procedimientos de tipo estratégico o de soporte.ResultadosSe definieron las líneas estratégicas que marcaron el inicio del despliegue de nuestro SGC con la redacción de 7 objetivos, alcanzándose su cumplimiento en el 100%...(AU)

Introduction: The implementation of Quality Management Systems (QMS) is one of the fundamental and future-oriented elements for the improvement of modern health systems. The objective of implementing a QMS in accordance with the requirements of the ISO 9001:2015 Standard is to effectively carry out its activities, covering both technical and management aspects, guaranteeing the satisfaction of the needs and expectations of all its stakeholders, as well as compliance with legal and regulatory requirements. It must contemplate all those aspects that have an impact on the final quality of the product or service provided by the organization. Objective: The main objective is to describe the process of implementing a QMS under the ISO 9001:2015 Standard in the Surgical Intensive Care Unit of the General University Hospital of Elche and evaluate its results. Methodology: Carrying out and implementing a QMS in the Surgical Intensive Care Unit of the General University Hospital of Elche applying the points of the ISO 9001:2015 Standard. The SGC has followed the benchmark of management by processes, identifying from its strategic core of mission, vision and values, the different processes involved and their interrelation reflected in the process map. Based on it, the necessary documents have been developed to describe the operation of the Unit both at an operational level through the key processes (admission and initial assessment of the patient, stabilization, follow-up, complementary tests, interconsultations, transfers and discharge) as well as which refers to procedures of a strategic or support type. Results: The strategic lines that marked the beginning of the deployment of our QMS were defined with the drafting of 7 objectives, achieving 100% compliance. The key processes (7) that described the functioning of our organization were elaborated, as well as those of a strategic type (14) and support or support (5)...(AU)

Transcriptomic and hormonal analysis of the roots of maize seedlings grown hydroponically at low temperature.

Prolonged cold stress has a strong effect on plant growth and development, especially in subtropical crops such as maize. Soil temperature limits primary root elongation, mainly during early seedling establishment. However, little is known about how moderate temperature fluctuations affect root growth at the molecular and physiological levels. We have studied root tips of young maize seedlings grown hydroponically at 30 ºC and after a short period (up to 24 h) of moderate cooling (20 ºC). We found that both cell division and cell elongation in the root apical meristem are affected by temperature. Time-course analyses of hormonal and transcriptomic profiles were achieved after temperature reduction from 30 ºC to 20 ºC. Our results highlighted a complex regulation of endogenous pathways leading to adaptive root responses to moderate cooling conditions.

Regulation of cardiac ion channels by transcription factors: Looking for new opportunities of druggable targets for the treatment of arrhythmias.

Cardiac electrical activity is governed by different ion channels that generate action potentials. Acquired or inherited abnormalities in the expression and/or function of ion channels usually result in electrophysiological changes that can cause cardiac arrhythmias. Transcription factors (TFs) control gene transcription by binding to specific DNA sequences adjacent to target genes. Linkage analysis, candidate-gene screening within families, and genome-wide association studies have linked rare and common genetic variants in the genes encoding TFs with genetically-determined cardiac arrhythmias. Besides its critical role in cardiac development, recent data demonstrated that they control cardiac electrical activity through the direct regulation of the expression and function of cardiac ion channels in adult hearts. This narrative review summarizes some studies showing functional data on regulation of the main human atrial and ventricular Na+, Ca2+, and K+ channels by cardiac TFs such as Pitx2c, Tbx20, Tbx5, Zfhx3, among others. The results have improved our understanding of the mechanisms regulating cardiac electrical activity and may open new avenues for therapeutic interventions in cardiac acquired or inherited arrhythmias through the identification of TFs as potential drug targets. Even though TFs have for a long time been considered as 'undruggable' targets, advances in structural biology have led to the identification of unique pockets in TFs amenable to be targeted with small-molecule drugs or peptides that are emerging as novel therapeutic drugs.

MicroRNA expression in male infertility.

Male infertility is a multifactorial disorder that involves different physiopathological mechanisms and multiple genes. In this sense, we analyse the role of miRNAs in this pathology. Gene expression analysis can provide relevant information to detect biomarkers, signalling pathways, pathologic mechanisms, and potential therapeutic targets for the disease. In this review, we describe four miRNA microarrays related to patients who present infertility diseases, including azoospermia, asthenozoospermia, and oligoasthenozoospermic. We selected 13 miRNAs with altered expressions in testis tissue (hsa-miR-122-5p, hsa-miR-145-5p, hsa-miR-16-5p, hsa-miR-193a-3p, hsa-miR-19a-3p, hsa-miR-23a-3p, hsa-miR-30b-5p, hsa-miR-34b-5p, hsa-miR-34c-5p, hsa-miR-374b-5p, hsa-miR-449a, hsa-miR-574-3p and hsa-miR-92a-3p), and systematically examine the mechanisms of four relevant miRNAs (hsa-miR-16-5p, hsa-miR-19a-3p, hsa-miR-92a-3p and hsa-miR-30b-5p) which we found that regulated a large number of proteins. An interaction network was generated, and its connections allowed us to identify signalling pathways and interactions between proteins associated with male infertility. In this way, we confirm that the most affected and relevant pathway is the PI3K-Akt signalling.

Auxin-Cytokinin Balance Shapes Maize Root Architecture by Controlling Primary Root Elongation and Lateral Root Development.

The root system is responsible for water and nutrients uptake from the soil, and therefore, its extension is basic for an efficient acquisition. The maize root system is formed by different types of roots, and the lateral root branching substantially increases the surface for nutrient uptake. Therefore, the regulation of lateral root formation is fundamental in the development of root functions. Root architecture is basically controlled by auxin and cytokinins, which antagonize in the formation of lateral roots (LR) along the primary root axis, with auxin, a stimulator, and cytokinins inhibitors of LR development. This interaction has been analyzed in several zones along the primary root where LRs in different developmental stages were located. The root has been divided into several zones, such as meristem, elongation zone, and mature zone, according to the developmental processes occurring in each one. As Arabidopsis root elongated more slowly than maize root, these zones are shorter, and its delimitation is more difficult. However, these zones have previously been delimitated clearly in maize, and therefore, they analyze the effect of exogenous hormones in several LR developmental stages. The inhibitory effect of cytokinin on lateral root formation was observed in already elongated primary root zones in which initial events to form new lateral roots are taking place. Contrarily, auxin increased LR formation in the primary root segments elongated in the presence of the hormone. The inhibitory effect of cytokinin was reversed by auxin in a concentration-dependent manner when both hormones were combined. However, auxin is unable to recover LR development in primary root zones that have been previously elongated only in the presence of cytokinin. This antagonistic auxin-cytokinin effect on LR development depended on the balance between both hormones, which controls the root system architecture and determines the formation of LR during the process of initiation.

A study on correlations between precipitation ETCCDI and airborne pollen/fungal spore parameters in the NE Iberian Peninsula.

Precipitation is one of the meteorological variables usually involved in the aerobiological studies, which presents a complex relationship with atmospheric levels of pollen and fungal spores and the temporal characteristics of their seasons. This complexity is due in a large part to rainfall's twofold impact of having, prior to pollination, a positive influence on subsequent pollen production and of contributing, during pollination, to pollen removal from the air through a wash-out effect. To better explore this impact, we place particular emphasis on extreme rainfall by calculating the correlation between airborne pollen and fungal spore parameters and the precipitation indices that the Expert Team on Climate Change Detection and Indices (ETCCDI) proposed for characterising climate extremes. Parameters for twenty-seven pollen and fungal spore taxa measured in six aerobiological stations in the NE Iberian Peninsula have been considered. We have distinguished between annual and winter ETCCDI in order to compare the correlations between extreme rainfall and airborne pollen concentrations and to avoid the wash-out effect as far as possible. Results show a positive influence from an increase in moderately extreme winter rainfall, specifically on subsequent pollen/fungal spore production: the percentage of all possible significant correlations is higher for winter than for annual rainfall. Furthermore, while annual rainfall in this region has nearly the same number of positive as negative correlations, the positive correlations for winter rainfall are more than twice that of the negative ones. The seasonal consideration on rainfall ETCCDI made with the aim to avoid the confounding overlapping of different rainfall impacts has led to more sharpened observations of its positive and negative effects on airborne pollen and fungal spore concentrations.

Raman Interferometry between Autoionizing States to Probe Ultrafast Wave-Packet Dynamics with High Spectral Resolution.

Photoelectron interferometry with femtosecond and attosecond light pulses is a powerful probe of the fast electron wave-packet dynamics, albeit it has practical limitations on the energy resolution. We show that one can simultaneously obtain both high temporal and spectral resolution by stimulating Raman interferences with one light pulse and monitoring the modification of the electron yield in a separate step. Applying this spectroscopic approach to the autoionizing states of argon, we experimentally resolved its electronic composition and time evolution in exquisite detail. Theoretical calculations show remarkable agreement with the observations and shed light on the light-matter interaction parameters. Using appropriate Raman probing and delayed detection steps, this technique enables highly sensitive probing and control of electron dynamics in complex systems.

A randomised controlled trial to evaluate a medication monitoring system for TB treatment.

BACKGROUND: Adherence to TB treatment and therefore treatment success could be improved using digital adherence technology.OBJECTIVE: To evaluate the effectiveness of a medication event reminder monitor system (MERM) on treatment success and treatment adherence in patients with drug-susceptible pulmonary TB in Perú.METHODS: This was an experimental, randomised, open-label, controlled study conducted among patients in the second phase of TB treatment. The intervention group received their medications through MERM with the support of a treatment monitor, whereas the control group used the usual strategy. Participants were followed until they completed the 54 doses of the second phase of treatment.RESULTS: The study included 53 patients in each group; four in the intervention group withdrew from the study. Treatment success was significantly more frequent in the MERM group (RR 1.15, 95% CI 1.02-1.30; P = 0.0322). There was no significant difference in the adherence outcomes; however, the percentage of patients who missed at least one dose and patients with more than 10% of total doses missed were lower in the intervention group.CONCLUSION: The use of MERM in the second phase of treatment showed a significant improvement in the treatment success rate in patients with drug-susceptible pulmonary TB.

LUCAS (lung ultrasonography in cardiac surgery) score to monitor pulmonary edema after congenital cardiac surgery in children.

AIM: Cardiopulmonary bypass (CPB) generates a systemic capillary leak syndrome with pulmonary edema. Lung ultrasound (LUS) could be useful to monitor it. Primary objective was to compare sensitivity, specificity, positive and negative predictive values of chest X-ray and LUS to detect pulmonary edema using a new score (LUCAS). Secondary objectives were to evaluate correlation between LUCAS score and respiratory and inotropic support. METHODS: Prospective intervention study including patients <2 months admitted to the Pediatric Intensive Care Unit after CPB. LUS was performed with a lineal probe, screening 3 points in each lung (parasternal, anterolateral and posterior area), pre and post-CPB. Pulmonary edema was evaluated clinically, through LUCAS score and with X-ray. RESULTS: 17 patients were included. LUS achieved higher sensitivity than X-ray to detect pulmonary edema (91.7 versus 44.0%) and greater predictive negative value (88.2 versus 53.3%). There was correlation between higher LUCAS score prior to surgery and longer mechanical ventilation. High values of LUCAS score after surgery correlated with longer CPB time, inotropic support, and FiO2 need. CONCLUSION: LUS detected pulmonary edema better than chest X-ray, with greater sensitivity and negative predictive value. LUCAS score was useful to predict more inotropic support and longer mechanical ventilation.Key notesCardiopulmonary bypass during cardiac surgery, generates a systemic capillary leak syndrome with pulmonary edema.In this prospective study performed in the Pediatric Intensive Care Unit, lung ultrasound detected pulmonary edema better than X-ray, with greater sensitivity and negative predictive value.LUCAS score was useful to predict more inotropic support and longer mechanical ventilation.

Practical recommendations for the management of the patient with chronic pain during the pandemic of COVID-19.

SARS-CoV-2 infection has evolved into a pandemic and a Public Health Emergency of International Importance that has forced health organizations at the global, regional and local levels to adopt a series of measures to address to COVID-19 and try to reduce its impact, not only in the social sphere but also in the health sphere, modifying the guidelines for action in the health services. Within these recommendations that include the Pain Treatment Units, patients with suspected or confirmed SARS-CoV-2 infection may be waiting for medical consult or interventional procedures for the management of chronic pain refractory to other therapies. A series of guidelines aimed at reducing the risk of infection of health personnel, other patients and the community are included in this manuscript.

Effects of the age/rage axis in the platelet activation.

Platelet activity is essential in cardiovascular diseases. Therefore our objective was to evaluate the main effects of activating RAGE in platelets which are still unknown. A search for RAGE expression in different databases showed poor or a nonexistent presence in platelets. We confirmed the expression in platelets and secreted variable of RAGE (sRAGE). Platelets from elderly adults expressed in resting showed 3.2 fold more RAGE from young individuals (p < 0.01) and 3.3 fold with TRAP-6 (p < 0.001). These results could indicate that the expression of RAGE is more inducible in older adults. Then we found that activating RAGE with AGE-BSA-derived from methylglyoxal and subthreshold TRAP-6, showed a considerable increase with respect to the control in platelet aggregation and expression of P-selectin (respectively, p < 0.01). This effect was almost completely blocked by using a specific RAGE inhibitor (FSP-ZM1), confirming that RAGE is important for the function and activation platelet. Finally, we predict the region stimulated by AGE-BSA is located in region V of RAGE and 13 amino acids are critical for its binding. In conclusion, the activation of RAGE affects platelet activation and 13 amino acids are critical for its stimulation, this information is crucial for future possible treatments for CVD.

Practical recommendations for the management of the patient with chronic pain during the pandemic of COVID-19. / Recomendaciones prácticas para el manejo del paciente con dolor crónico durante la pandemia de COVID-19.

SARS-CoV-2 infection has evolved into a pandemic and a Public Health Emergency of International Importance that has forced health organizations at the global, regional and local levels to adopt a series of measures to address to COVID-19 and try to reduce its impact, not only in the social sphere but also in the health sphere, modifying the guidelines for action in the health services. Within these recommendations that include the Pain Treatment Units, patients with suspected or confirmed SARS-CoV-2 infection may be waiting for medical consult or interventional procedures for the management of chronic pain refractory to other therapies. A series of guidelines aimed at reducing the risk of infection of health personnel, other patients and the community are included in this manuscript.

Multimorbidity and intention to retire: a cross-sectional study on 14 European countries.

OBJECTIVES: To describe the association between multimorbidity and intention of retirement in Europe and to understand whether this relationship is modified by the working environment and disability integration policies. METHODS: Participants were 11,790 employees aged 50-65 years old who responded to the sixth wave of SHARE project (2015). We modelled intention of retirement as a function of multimorbidity, adjusting for age, gender, education level, and household income by means of logistic models with country fixed effects. We then included the working conditions and an integration policy indicator as potential effect modifiers. RESULTS: Overall, 36.6% of participants reported multimorbidity and 56.1% were willing to retire earlier. Multimorbidity was significantly associated with intention of retirement (OR = 1.58, 95% CI 1.37-1.84). Unfavourable working conditions were positively related to the intention to retire (OR = 1.99, 95% CI 1.53-2.58), while the integration policy was unrelated (OR = 1.84, 95% CI 0.80-4.23). Both did not modify the studied association (interaction terms: OR = 1.14, 95% CI 0.77-1.67, and OR = 0.85, 95% CI 0.58-1.24, respectively). CONCLUSIONS: Multimorbidity is associated with intention of retirement in Europe. This association was unaltered by working conditions and integration policies.