[Medical nutrition therapy in amyotrophic lateral sclerosis - Do we act or react? A case report and multidisciplinary review]. / Tratamiento médico nutricional en la esclerosis lateral amiotrófica: ¿Actuamos o reaccionamos? Un caso clínico y revisión multidisciplinar.

BACKGROUND: amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a progressive course. The current prevalence is between 3 and 6 cases/100,000. Malnutrition is closely related to patient prognosis in ALS. The implications of this conditions have been that we should recommend patient care in a multidisciplinary unit. CASE REPORT: the case presented shows the evolution of a patient with ALS. The patient was referred to different clinical departments after neurological evaluation and her nutritional, functional and respiratory status were assessed. There was no nutritional deterioration at diagnosis; however, intake was below energy-protein requirements. The clinical evolution of the patient showed a decrease in muscle mass with preservation of weight and fat mass. "Aggressive" measures to control nutritional status such as gastrostomy were rejected in the initial stages of the disease, but had to be carried out after development of dysphagia and associated malnutrition. This situation of progressive morphofunctional deterioration and the development of disease-related complications made essential the participation of different health services and professionals in its control. DICUSSION: the management of ALS in a multidisciplinary manner allows to improve the course of the disease and the quality of life of both the patients and their families. Patient follow-up is based on the adjustment and management of complications. The basis of the relationship with these patients includes maintaining an adequate communication with them and their families, and ensuring joint decision-making about their condition.

Estudio retrospectivo del efecto de la vacunación frente al SARS-CoV-2 en enfermos graves que ingresan en una unidad de cuidados intensivos / Retrospective study of the effect of vaccination against SARS-CoV-2 in seriously ill patients admitted to an intensive care unit

Antecedentes y objetivo Planteamos nuestro trabajo con el objetivo de comparar las características clínico-epidemiológicas, la estancia en la UCI y la mortalidad de pacientes con COVID-19 que ingresaron en la UCI con vacunación completa, incompleta o sin vacunar. Pacientes y métodos Estudio retrospectivo de cohortes (marzo 2020-marzo 2022). Los pacientes fueron clasificados en pacientes no vacunados, pauta de vacunación completa y pauta de vacunación incompleta. Se realizó inicialmente un análisis descriptivo de la muestra, un análisis multivariable de la supervivencia ajustando un modelo de regresión de Cox y un análisis de supervivencia a 90 días con el método de Kaplan-Meier para la variable de tiempo de muerte. Resultados Fueron analizados los 894 pacientes: 179 con una pauta de vacunación completa, 32 con una pauta incompleta y 683 no estaban vacunados. Los enfermos vacunados presentaron con menor frecuencia (10 vs. 21% y 18%) un SDRA grave. La curva de supervivencia no presentó diferencias en la probabilidad de sobrevivir a los 90 días entre los grupos estudiados (p = 0,898). En el análisis de regresión de COX, únicamente la necesidad de VM durante el ingreso y el valor de LDH (por unidad de medida) en las primeras 24 h de ingreso se asociaron de forma significativa con la mortalidad a los 90 días (HR: 5,78; IC 95%: 1,36-24,48); p = 0,01 y HR: 1,01; IC 95%: 1,00-1,02; p = 0,03, respectivamente. Conclusiones Los pacientes vacunados frente a la COVID-19 con enfermedad grave por SARS-CoV-2 presentan unas tasas de SDRA grave y de VM menores que las de aquellos pacientes no vacunados (AU)

Background and objective Our study aims to compare the clinical and epidemiological characteristics, length of stay in the ICU, and mortality rates of COVID-19 patients admitted to the ICU who are fully vaccinated, partially vaccinated, or unvaccinated. Patients and methods Retrospective cohort study (March 2020-March 2022). Patients were classified into unvaccinated, fully vaccinated, and partially vaccinated groups. We initially performed a descriptive analysis of the sample, a multivariable survival analysis adjusting for a Cox regression model, and a 90-day survival analysis using the Kaplan-Meier method for the death time variable. Results A total of 894 patients were analyzed: 179 with full vaccination, 32 with incomplete vaccination, and 683 were unvaccinated. Vaccinated patients had a lower incidence (10% vs. 21% and 18%) of severe ARDS. The survival curve did not show any differences in the probability of surviving for 90 days among the studied groups (p = 0.898). In the Cox regression analysis, only the need for mechanical ventilation during admission and the value of LDH (per unit of measurement) in the first 24 hours of admission were significantly associated with mortality at 90 days (HR: 5.78; 95% CI: 1.36-24.48); p = 0.01 and HR: 1.01; 95% CI: 1.00-1.02; p = 0.03, respectively. Conclusions Patients with severe SARS-CoV-2 disease who are vaccinated against COVID-19 have a lower incidence of severe ARDS and mechanical ventilation than unvaccinated patients (AU)

Performance evaluation and users' perception of courtyards role in indoor areas of mediterranean social housing.

Cities confront two critical challenges: general overheating and inefficient use of energy resources within their housing buildings, both adversely affecting urban citizens' daily lives. To mitigate these issues, passive techniques offer promising solutions on enhancing building comfort levels from a sustainable approach. Although this energy efficiency of air-conditioning systems in buildings in warm climates has been extensively analysed, the influence of the microclimate of transitional spaces attached to them on this performance has not yet been properly assessed. Investigating the potential benefits of the implementation of courtyards within Seville's social housing infrastructure for passive conditioning purposes is one way of reducing this research gap. Furthermore, the study also includes the subjective perception of users' thermal well-being around these spaces and their own social relationship related to their use. The work relies on detailed data analyses carried out using DesignBuilder software to quantify the benefit effectively accrued from courtyard utilization. Concurrently, user surveys conducted help determine perceived thermal comfort aiding better configuration management and passive design strategies of urban social housing. Findings from monitoring and simulation reveal that courtyards work faultlessly as a highly effective and efficient passive cooling system whilst promoting energy efficiency up to 20,5%. Surveys confirmed these findings with data revealing significant improvements in thermal comforts perception inside courtyards and within indoor spaces adjacent to the courtyards. This research provides novel insights into how architects and urban managers might integrate passive strategies into future designs for optimizing comfort levels in social housing using courtyards as one possible environmental measure for achieving sustainability targets.

Análisis de las características de los pacientes mayores que ingresaron en una unidad de cuidados intensivos durante las 6 olas de la pandemia por SARS-CoV-2: implicaciones para la atención médica / Analysis of characteristics of elderly patients admitted to an intensive care unit during six waves of the SARS-CoV-2 pandemic: Implications for medical care

Objetivo Analizar las características de los enfermos adultos graves de mayor edad, durante las 6 olas de la pandemia COVID-19. Método Estudio retrospectivo, observacional y analítico sobre pacientes mayores de 70 años con ingreso en la UCI (marzo-2020/marzo-2022). Los pacientes se categorizaron en 3 grupos en función de la edad: 70-74 años, 75-79 años y >80 años. Se realizó inicialmente un análisis descriptivo y comparativo de la muestra, y un análisis de supervivencia a los 28, 60 y 90 días con el método de Kaplan-Meier. El análisis multivariable de la supervivencia se realizó ajustando un modelo de Cox. Resultados De 301 enfermos, el menor número de ingresos se produjo durante la primera ola (20 [6%]), frente a la que fue la ola con mayor número de ingresos: la sexta ola (76 [25%]). Las curvas de supervivencia a los 28, a los 60 días y a los 90 días evidenciaron una mayor probabilidad de sobrevivir en los grupos de menor edad (p<0,01 y p=0,01, respectivamente). La troponina al ingreso (por unidad, ng/l), evidenció un asociación significativa con la mortalidad a 28 y 60 días (HR: 1,00; IC 95%: 1,00-1,01; p<0,05). Tomando como referencia la 1.ª oleada de la pandemia, el ingreso en 3.ª oleada se comportó como un factor de protección frente a la mortalidad a los 28 y 60 días de seguimiento (HR: 0,18; IC 95%: 0,02-0,64; p<0,05; HR: 0,13; IC 95%: 0,02-0,64; p<0,05, respectivamente). Conclusiones El momento de ingreso y biomarcadores, como la troponina, se constituyen en marcadores pronósticos independientes de la edad en la población añosa (AU)

Objective To analyze the characteristics of seriously ill elderly patients during the six waves of the COVID-19 pandemic. Method Retrospective, observational and analytical study of patients over 70 years of age admitted to the ICU (March-2020 to March-2022). Patients were categorized into three groups based on age: 70-74 years; 75-79 years; and >80 years. A descriptive and comparative analysis of the sample was initially performed; and a 28-, 60- and 90-day survival analysis using the Kaplan–Meier method. Multivariate survival analysis was performed by fitting a Cox model. Results Of 301 patients, the lowest number of admissions occurred during the first wave (20 (6%)), compared to the wave with the highest number of admissions: the sixth wave (76 (25%)). The survival curves at 28 days, 60 days and 90 days showed a higher probability of survival in the younger age groups (P<.01 and P=.01, respectively). Troponin at admission (per unit, ng/l) showed a significant association with 28- and 60-day mortality (HR: 1.00; 95% CI: 1.00-1.01; P<.05). Taking the 1st wave of the pandemic as a reference, admission in the 3rd wave behaved as a protective factor against mortality at 28 and 60 days of follow-up (HR: 0.18; 95% CI: 0.02-0.64; P<.05; HR: 0.13; 95% CI: 0.02–0.64; P<.05, respectively). Conclusions The time of admission and biomarkers, such as troponin, constitute prognostic markers independent of age in the elderly population (AU)

[Analysis of characteristics of elderly patients admitted to an intensive care unit during six waves of the SARS-CoV-2 pandemic: Implications for medical care]. / Análisis de las características de los pacientes mayores que ingresaron en una unidad de cuidados intensivos durante las 6 olas de la pandemia por SARS-CoV-2: implicaciones para la atención médica.

OBJECTIVE: To analyze the characteristics of seriously ill elderly patients during the six waves of the COVID-19 pandemic. METHOD: Retrospective, observational and analytical study of patients over 70 years of age admitted to the ICU (March-2020 to March-2022). Patients were categorized into three groups based on age: 70-74 years; 75-79 years; and >80 years. A descriptive and comparative analysis of the sample was initially performed; and a 28-, 60- and 90-day survival analysis using the Kaplan-Meier method. Multivariate survival analysis was performed by fitting a Cox model. RESULTS: Of 301 patients, the lowest number of admissions occurred during the first wave (20 (6%)), compared to the wave with the highest number of admissions: the sixth wave (76 (25%)). The survival curves at 28 days, 60 days and 90 days showed a higher probability of survival in the younger age groups (P<.01 and P=.01, respectively). Troponin at admission (per unit, ng/l) showed a significant association with 28- and 60-day mortality (HR: 1.00; 95% CI: 1.00-1.01; P<.05). Taking the 1st wave of the pandemic as a reference, admission in the 3rd wave behaved as a protective factor against mortality at 28 and 60 days of follow-up (HR: 0.18; 95% CI: 0.02-0.64; P<.05; HR: 0.13; 95% CI: 0.02-0.64; P<.05, respectively). CONCLUSIONS: The time of admission and biomarkers, such as troponin, constitute prognostic markers independent of age in the elderly population.

Dolor y edema posquirúrgico en la regeneración cutánea nasal con fibrina rica en plaquetas y leucocitos

Introducción: La reconstrucción de defectos cutáneos nasales requiere del uso de procedimientos orientados a obtener la menor probabilidad de complicaciones posoperatorias en el menor período de tiempo posible. Novedosas técnicas utilizan los concentrados plaquetarios por sus propiedades moduladoras del dolor y el edema posoperatorio. Objetivo: Determinar el comportamiento del dolor y el edema posquirúrgico en la regeneración de defectos cutáneos nasales con el uso de la membrana de fibrina autóloga, rica en plaquetas y leucocitos. Método: Se realizó una investigación cuasiexperimental, con diseño antes-después, sin grupo control en el Servicio de Cirugía Maxilofacial del Hospital Universitario "Arnaldo Milián Castro" de la ciudad de Santa Clara, Villa Clara, Cuba, desde septiembre de 2015 a junio de 2019. La muestra seleccionada aleatoriamente fue de 46 pacientes. A partir de una autodonación de sangre del paciente se obtuvo una membrana de fibrina rica en plaquetas y leucocitos, la cual fue suturada en el defecto quirúrgico nasal. Resultados: La edad media fue 62,71 años y el 60,87 por ciento de la muestra correspondió al sexo masculino. Se presentaron el dolor en el 23,91 por ciento y el edema en el 28,26 por ciento de la muestra estudiada. Conclusiones: Se encontraron escasas complicaciones posoperatorias como el dolor y el edema, las que se manifestaron predominantemente de intensidad leve. Existió asociación entre estas complicaciones y la edad, la cantidad de subunidades anatómicas afectadas, la diabetes mellitus y el tabaquismo(AU)

Introduction: The reconstruction of nasal skin defects requires the use of procedures aimed at obtaining the lowest probability of postoperative complications in the shortest period of time possible. Novel techniques use platelet concentrates for their modulating properties of pain and postoperative edema. Objective: To determine the behavior of pain and post-surgical edema in the regeneration of nasal skin defects with the use of autologous platelet- and leukocyte-rich fibrin membrane. Method: A quasi-experimental research was carried out, with a before-after design, without a control group, in the Maxillofacial Surgery Service at Arnaldo Milián Castro University Hospital in Santa Clara, Villa Clara, Cuba, from September 2015 to June 2015. 2019. The randomly selected sample was 46 patients. A fibrin membrane rich in platelets and leukocytes was obtained from a patient's blood self-donation, which was sutured in the nasal surgical defect. Results: The mean age was 62.71 years and 60.87 por ciento f the sample was male. Pain was present in 23.91 por ciento and edema in 28.26 por ciento of the studied sample. Conclusions: Few postoperative complications such as pain and edema were found, showing to be mild predominantly. There was association between these complications and age, the number of affected anatomical subunits, diabetes mellitus and smoking habit(AU)

[Retrospective study of the effect of vaccination against SARS-CoV-2 in seriously ill patients admitted to an intensive care unit]. / Estudio retrospectivo del efecto de la vacunación frente al SARS-CoV-2 en enfermos graves que ingresan en una unidad de cuidados intensivos.

BACKGROUND AND OBJECTIVE: Our study aims to compare the clinical and epidemiological characteristics, length of stay in the ICU, and mortality rates of COVID-19 patients admitted to the ICU who are fully vaccinated, partially vaccinated, or unvaccinated. PATIENTS AND METHODS: Retrospective cohort study (March 2020-March 2022). Patients were classified into unvaccinated, fully vaccinated, and partially vaccinated groups. We initially performed a descriptive analysis of the sample, a multivariable survival analysis adjusting for a Cox regression model, and a 90-day survival analysis using the Kaplan-Meier method for the death time variable. RESULTS: A total of 894 patients were analyzed: 179 with full vaccination, 32 with incomplete vaccination, and 683 were unvaccinated. Vaccinated patients had a lower incidence (10% vs. 21% and 18%) of severe ARDS. The survival curve did not show any differences in the probability of surviving for 90 days among the studied groups (p = 0.898). In the Cox regression analysis, only the need for mechanical ventilation during admission and the value of LDH (per unit of measurement) in the first 24 hours of admission were significantly associated with mortality at 90 days (HR: 5.78; 95% CI: 1.36-24.48); p = 0.01 and HR: 1.01; 95% CI: 1.00-1.02; p = 0.03, respectively. CONCLUSIONS: Patients with severe SARS-CoV-2 disease who are vaccinated against COVID-19 have a lower incidence of severe ARDS and mechanical ventilation than unvaccinated patients.

Methods to Identify Cognitive Alterations from Animals to Humans: A Translational Approach.

The increasing prevalence of cognitive dysfunction and dementia in developed countries, associated with population aging, has generated great interest in characterizing and quantifying cognitive deficits in these patients. An essential tool for accurate diagnosis is cognitive assessment, a lengthy process that depends on the cognitive domains analyzed. Cognitive tests, functional capacity scales, and advanced neuroimaging studies explore the different mental functions in clinical practice. On the other hand, animal models of human diseases with cognitive impairment are essential for understanding disease pathophysiology. The study of cognitive function using animal models encompasses multiple dimensions, and deciding which ones to investigate is necessary to select the most appropriate and specific tests. Therefore, this review studies the main cognitive tests for assessing cognitive deficits in patients with neurodegenerative diseases. Cognitive tests, the most commonly used functional capacity scales, and those resulting from previous evidence are considered. In addition, the leading behavioral tests that assess cognitive functions in animal models of disorders with cognitive impairment are highlighted.

Resultados estéticos en defectos nasales posquirúrgicos regenerados con fibrina autóloga rica en plaquetas y leucocitos / Aesthetic results in post-surgical nasal defects regenerated with autologous platelet- and leukocyte-rich fibrin

Introducción: En la reconstrucción de los defectos cutáneos nasales se han utilizado varias técnicas a nivel mundial. Novedosas prácticas utilizan los concentrados plaquetarios por sus propiedades moduladoras y favorecedoras de la regeneración tisular. Objetivo: Determinar los resultados estéticos asociados al uso de la membrana de fibrina autóloga rica en plaquetas y leucocitos, para la regeneración de defectos cutáneos nasales posquirúrgicos. Métodos: Se realizó un estudio cuasiexperimental, longitudinal y prospectivo en el Servicio de Cirugía Maxilofacial del Hospital Universitario "Arnaldo Milián Castro" de la ciudad de Santa Clara, Villa Clara, Cuba, desde septiembre de 2015 hasta junio de 2019. Se efectuó un muestreo intencional, no probabilístico, de 31 pacientes. A partir de una donación de sangre del paciente, se obtuvo una membrana de fibrina rica en plaquetas y leucocitos, la que fue suturada en el defecto nasal posquirúrgico. Se estudiaron variables como el resultado estético, evaluado sobre la base de parámetros como la elasticidad, el color, el volumen y la superficie. Resultados: La edad media fue 62,71 ± 11,09 años y el 61,29 por ciento de la muestra correspondió al sexo masculino. Mostraron un buen resultado estético el 90,32 por ciento de los pacientes, lo que se asoció de forma significativa al grado de epitelización. Conclusiones: Se obtuvo un buen resultado estético en los pacientes donde se utilizó la membrana de fibrina autóloga rica en plaquetas y leucocitos, con independencia de la presencia de diabetes mellitus y hábitos tóxicos. El resultado estético estuvo asociado significativamente al grado de epitelización y a la edad(AU)

Introduction: In the reconstruction of nasal skin defects, several techniques have been used worldwide. Innovative practices use platelet concentrates for their modulating properties and favoring tissue regeneration. Objective: Determine the aesthetic results associated with the use of autologous fibrin rich in platelets and leukocytes, for the regeneration of post-surgical nasal skin defects. Methods: A quasi-experimental, longitudinal and prospective study was conducted in the Maxillofacial Surgery Service of "Arnaldo Milián Castro" University Hospital in the city of Santa Clara, Villa Clara province, Cuba, from September 2015 to June 2019. An intentional, non-probabilistic sampling of 31 patients was carried out. From a blood donation from the patient, a fibrin membrane rich in platelets and leukocytes was obtained, which was sutured in the post-surgical nasal defect. Variables such as the aesthetic result were studied, evaluated on the basis of parameters such as elasticity, color, volume and surface. Results: The mean age was 62.71 ± 11.09 years and 61.29 percent of the sample corresponded to the male sex. A good aesthetic result was shown by 90.32 percent of the patients, which was significantly associated with the degree of epithelialization. Conclusions: A good aesthetic result was obtained in patients where the fibrin membrane rich in leukocytes and autologous platelets was used, regardless of the presence of diabetes mellitus and toxic habits. The aesthetic result was significantly associated with the degree of epithelialization and age(AU)

Systematic evaluation of plasma signaling cascades by functional proteomics approaches: SARS-CoV-2 infection as model.

PURPOSE: Acute phase reactants (APRs) play a critical role in inflammation. The difference in their physiological functions or the different dynamic ranges of these proteins in plasma makes it difficult to detect them simultaneously and to use several of these proteins as a tool in clinical practice. EXPERIMENTAL DESIGN: A novel multiplex assay has been designed and optimized to carry out a high-throughput and simultaneous screening of APRs, allowing the detection of each of them at the same time and in their corresponding dynamic range. RESULTS: Using Sars-CoV-2 infection as a model, it has been possible to profile different patterns of acute phase proteins that vary significantly between healthy and infected patients. In addition, severity profiles (acute respiratory distress syndrome and sepsis) have been established. CONCLUSIONS AND CLINICAL RELEVANCE: Differential profiles in acute phase proteins can serve as a diagnostic and prognostic tool, among patient stratification. The design of this new platform for their simultaneous detection paves the way for them to be more extensive use in clinical practice.

Marital Adjustment in Patients with Cancer: Association with Psychological Distress, Quality of Life, and Sleep Problems.

Marital adjustment plays a key role in the physical and psychosocial wellbeing. We conducted a cross-sectional study to evaluate marital adjustment and its association with psychological distress, suicidal ideation, sleep problems, and quality of life in patients with cancer. We collected demographic and clinical information using a structured survey. We assessed marital adjustment, quality of life, psychological distress profile, and sleep problems of participants using validated instruments: the Locke and Wallace Marital Adjustment Test (LWMAT), the Short-Form Health Survey-12, the Beck's Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), and the Insomnia Severity Index (ISI). Suicidal ideation was assessed with item nine of the BDI. Of the 130 patients (52.3% females, mean age 57.9 ± 12.4 years) enrolled, 20 (15%) were classified as experiencing poor marital adjustment. Moderate to severe depression, anxiety, and insomnia were found in 25.4%, 34.6%, and 24.7% of participants, respectively. Positive suicidal ideation was documented in 13.8% of participants. We found a significant association between poor marital adjustment and depression, anxiety, suicidal ideation, and poor sleep. Our study confirms the relevance of marital adjustment in relation to the psychological wellbeing of patients with cancer. Depression, anxiety, and poor sleep were found to be significantly associated with poor marital adjustment.

Selenium and Vitamin E Concentrations in Miranda Jennies and Foals (Equus asinus) in Northeast Portugal.

The increase in donkeys treated by practitioners in recent years has led to an increased interest in finding more information on basic biochemical preliminary reference values. The aims of this study were to measure Se and Vit E levels in plasma from Miranda jennies peripartum and postpartum and in their foals to compare blood profiles of the jenny and foal related to the overall foal's health. Twenty-two healthy peripartum and postpartum Miranda donkeys were sampled (12 jennies and 10 foals) in the northeast of Portugal (Atenor and Paradela) from May to November, 2018. Amounts of selenium in soil were significantly correlated (0.97) to concentrations of selenium in jennies (42.412 µg/L in Atenor and 9.612 µg/L in Paradela) and foals (19.378 µg/L in Atenor and 6.430 µg/L in Paradela). Selenium levels were lower in foals than adults and in males than females. Vitamin E was associated with overall foal health. Foals with a mean vitamin E of 3.585-5.307 mg/L showed signs of weakness, but carpal flexural deformities were observed when the average vitamin E was 11.520 mg/L. Low vitamin E levels (5.307 mg/L) in jennies were related to foal mortality. Diets, location, parity, and age affect blood profiles of jennies and, ultimately, foal health.

Insights into the Use of Peripherally Acting µ-Opioid Receptor Antagonists (PAMORAs) in Oncologic Patients: from Scientific Evidence to Real Clinical Practice.

OPINION STATEMENT: Management of chronic pain is crucial to improve the quality of life of cancer and palliative care patients. Opioid-based treatments used to control pain can be prolonged over time. Unfortunately, constipation is one of the most disturbing adverse effects of long-term use of opioids. Opioid-induced constipation (OIC) occurs when opioids bind to the specific receptors present in the gastrointestinal (GI) tract, and can affect any patients receiving chronic opioid therapy, including cancer patients. The limited efficacy of laxatives to treat OIC symptoms prompted the search for new therapeutic strategies. Peripherally acting µ-opioid receptor antagonists (PAMORAs) have recently emerged as new effective drugs for OIC management due to their specific binding to enteric µ-receptors. Little information is available on the use of PAMORAs in real-life practice for OIC treatment in cancer patients. In this paper, a panel of experts specializing in cancer and palliative care pools their clinical experience with PAMORAs in cancer patients presenting OIC and highlights the importance of timing and choice of therapy in achieving prompt OIC management and benefitting patients.

Encefalitis multifocal como manifestación neurológica de la infección por COVID-19 / Multifocal encephalitis as a neurological manifestation of COVID-19 infection

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Mediterranean diet and endothelial function in patients with coronary heart disease: An analysis of the CORDIOPREV randomized controlled trial.

BACKGROUND: Endothelial dysfunction is a crucial step in atherosclerosis development, and its severity is determinant for the risk of cardiovascular recurrence. Diet may be an effective strategy to protect the endothelium, although there is no consensus about the best dietary model. The CORonary Diet Intervention with Olive oil and cardiovascular PREVention (CORDIOPREV) study is an ongoing prospective, randomized, single-blind, controlled trial in 1,002 coronary heart disease (CHD) patients, whose primary objective is to compare the effect of 2 healthy dietary patterns (low-fat versus Mediterranean diet) on the incidence of cardiovascular events. Here, we report the results of one secondary outcome of the CORDIOPREV study: to evaluate the effect of these diets on endothelial function, assessed by flow-mediated dilation (FMD) of the brachial artery. METHODS AND FINDINGS: From the total participants taking part in the CORDIOPREV study, 805 completed endothelial function study at baseline and were randomized to follow a Mediterranean diet (35% fat, 22% monounsaturated fatty acids [MUFAs], and <50% carbohydrates) or a low-fat diet (28% fat, 12% MUFAs, and >55% carbohydrates), with endothelial function measurement repeated after 1 year. As secondary objectives and to explore different underlying mechanisms in the modulation of endothelial function, we quantified endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) and evaluated, in 24 preselected patients, in vitro cellular processes related to endothelial damage (reactive oxygen species, apoptosis, and senescence) and endothelial repair (cell proliferation and angiogenesis), as well as other modulators (micro-RNAs [miRNAs] and proteins). Patients who followed the Mediterranean diet had higher FMD (3.83%; 95% confidence interval [CI]: 2.91-4.23) compared with those in the low-fat diet (1.16%; 95% CI: 0.80 to 1.98) with a difference between diets of 2.63% (95% CI: 1.89-3.40, p = 0.011), even in those patients with severe endothelial dysfunction. We observed higher EPC levels (group difference: 1.64%; 95% CI: 0.79-2.13, p = 0.028) and lower EMPs (group difference: -755 EMPs/µl; 95% CI: -1,010 to -567, p = 0.015) after the Mediterranean diet compared with the low-fat diet in all patients. We also observed lower intracellular reactive oxygen species (ROS) production (group difference: 11.1; 95% CI: 2.5 to 19.6, p = 0.010), cellular apoptosis (group difference: -20.2; 95% CI: -26.7 to -5.11, p = 0.013) and senescence (18.0; 95% CI: 3.57 to 25.1, p = 0.031), and higher cellular proliferation (group difference: 11.3; 95% CI: 4.51 to 13.5, p = 0.011) and angiogenesis (total master segments length, group difference: 549; 95% CI: 110 to 670, p = 0.022) after the Mediterranean diet than the low-fat diet. Each dietary intervention was associated with distinct changes in the epigenetic and proteomic factors that modulate biological process associated with endothelial dysfunction. The evaluation of endothelial function is a substudy of the CORDIOPREV study. As in any substudy, these results should be treated with caution, such as the potential for false positives because of the exploratory nature of the analyses. CONCLUSIONS: Our results suggest that the Mediterranean diet better modulates endothelial function compared with a low-fat diet and is associated with a better balance of vascular homeostasis in CHD patients, even in those with severe endothelial dysfunction. CLINICAL TRIAL REGISTRATION: URL, http://www.cordioprev.es/index.php/en. clinicaltrials.gov number NCT00924937.

Exposición a fármacos asociados a agravamiento de síntomas en pacientes con miastenia grave / Drug exposure associated with exacerbation of symptoms in patients with myasthenia gravis

INTRODUCCIÓN: Numerosos fármacos se han relacionado con el agravamiento de síntomas en pacientes con miastenia grave, pero hasta la fecha no existen estudios sobre la exposición a fármacos en estos pacientes. OBJETIVOS: Describir el consumo de fármacos y calcular la tasa anual de episodios de exacerbación en una cohorte de pacientes con miastenia grave, y explorar posibles factores de riesgo de exacerbaciones graves. PACIENTES Y MÉTODOS: Estudio observacional longitudinal retrospectivo que incluye a pacientes adultos con miastenia grave seguidos en consulta. Cálculo de frecuencias, tasas y construcción de modelo de eventos repetidos. RESULTADOS: De 91 pacientes incluidos, el 94,51% estuvo expuesto al menos a un fármaco durante el período de estudio (siete años y un mes). De ellos, 51 tuvieron al menos una prescripción de un fármaco contraindicado en la ficha técnica (56,04%). Se contabilizaron 145 exacerbaciones en 50 pacientes. La tasa anual de incidencia fue de 0,35 exacerbaciones por paciente y año. De estas exacerbaciones, 48 fueron graves (en 18 pacientes), con una tasa anual de incidencia de 0,12. Se halló una posible asociación entre diagnóstico de miastenia grave generalizada y timectomía, con un aumento del riesgo de episodios de exacerbación graves. CONCLUSIONES: En esta cohorte se encontró una amplia exposición a fármacos, pero no asociación con el riesgo de episodios de exacerbación graves. Algo más de la mitad de pacientes tuvo al menos un episodio de exacerbación durante el período de estudio, la mayoría leves. Son necesarios estudios que corroboren estas conclusiones y puedan estudiar posibles correlaciones entre fármacos y el riesgo de episodios de exacerbación

INTRODUCTION: Numerous drugs have been related to exacerbation of myasthenia gravis. So far there are no studies examining the extent of use of drugs related to exacerbation of myasthenia gravis. AIMS: We sought to assess the extent of use of drugs related to exacerbations and the annual incidence rate of exacerbations in a cohort of myasthenia gravis patients. We explored possible risk factors of severe exacerbations. PATIENTS AND METHODS: We performed a retrospective cohort study. We included adult patients followed in neurology department. We estimated frequencies, rates and built a recurrent events model. RESULTS: We included 91 patients. 94.51% of patients had at least one prescription of a drug. 51 patients had at least one prescription of a drug contraindicated according to its drug label. 145 exacerbation episodes were reported in 50 patients. The annual incidence rate of exacerbation episodes was 0.35. 48 exacerbations were severe (in 18 patients). The annual incidence rate of severe exacerbation episodes was 0.12. Generalized myasthenia gravis and thymectomy were associated with a higher risk of severe exacerbation episodes. CONCLUSIONS: Our patients were extensive and widespread exposed to drugs during the follow-up period but we did not find and association with severe exacerbation episodes. Just over half of the patients had at least one exacerbation episode during the study period, most of them were mild. Further studies with larger sample sizes are necessary to corroborate these conclusions and to study possible correlations between the use of drugs and the risk of exacerbation episodes

Satisfacción general laboral de los estomatólogos con el servicio de Estomatología General Integral. Sancti Spíritus. 2019 / Stomatologists´ general work satisfaction with the Comprehensive General Stomatology service. Sancti Spíritus. 2019

RESUMEN Fundamento: La satisfacción de los profesionales es importante para evaluar la calidad de la atención estomatológica. Objetivo: Evaluar la satisfacción general laboral de estomatólogos de Sancti Spíritus con el servicio de Estomatología General Integral según las dimensiones técnico-humano, entorno físico y resultados de tratamiento. Metodología: Se realizó una investigación en sistemas y servicios de salud del 2014 al 2019. Las 21 unidades de la provincia Sancti Spíritus; se dividieron en los estratos: Clínicas y Policlínicos. Se seleccionaron aleatoriamente 4 clínicas y 4 policlínicos. La muestra estuvo constituida por 179 estomatólogos generales integrales (98 en clínicas y 81 en policlínicos). Se midieron las variables: satisfacción con la dimensión técnico-humana, entorno físico y resultados de tratamiento. Se utilizaron métodos del nivel teórico, empírico y de la estadística descriptiva. Resultados: El 40.2 % y 49.2 % de los especialistas estuvieron medianamente satisfechos con las dimensiones técnico-humana y resultados de tratamiento respectivamente e insatisfechos el 41.3 % con la dimensión entorno físico. Conclusiones: La satisfacción general laboral de los estomatólogos fue calificada como medianamente satisfechos.

ABSTRACT Background: The satisfaction of professionals is important to evaluate the quality of dental care. Objective: To evaluate the stomatologists´ general work satisfaction from Sancti Spíritus with the Comprehensive General Stomatology service according to the technical-human dimensions, physical environment and treatment results. Methodology: A study about health system and services from 2014 to 2019 was made. The 21 units from the Sancti Spíritus province were divided into some stratus: clinical centers and polyclinics. It was aleatory selected the clinical centers and 4 polyclinics. The sample consisted of 179 general comprehensive stomatologists (98 from clinical centers and 81 from the polyclinics). Valued variables: satisfaction of technical-human dimension, physical environment and treatment results. Theoretical and empirical levels, also from statistical description were used. Results: 40.2 % and 49.2 % of the specialists were moderately satisfied with the technical-human dimensions and treatment results, respectively, and 41.3 % were dissatisfied with the physical environment dimension. Conclusions: The stomatologists´ general work satisfaction was rated as moderately satisfied.

Satisfacción general laboral de los estomatólogos con el servicio de Estomatología General Integral. Sancti Spíritus. 2019 / Stomatologists´ general work satisfaction with the Comprehensive General Stomatology service. Sancti Spíritus. 2019

RESUMEN Fundamento: La satisfacción de los profesionales es importante para evaluar la calidad de la atención estomatológica. Objetivo: Evaluar la satisfacción general laboral de estomatólogos de Sancti Spíritus con el servicio de Estomatología General Integral según las dimensiones técnico-humano, entorno físico y resultados de tratamiento. Metodología: Se realizó una investigación en sistemas y servicios de salud del 2014 al 2019. Las 21 unidades de la provincia Sancti Spíritus; se dividieron en los estratos: Clínicas y Policlínicos. Se seleccionaron aleatoriamente 4 clínicas y 4 policlínicos. La muestra estuvo constituida por 179 estomatólogos generales integrales (98 en clínicas y 81 en policlínicos). Se midieron las variables: satisfacción con la dimensión técnico-humana, entorno físico y resultados de tratamiento. Se utilizaron métodos del nivel teórico, empírico y de la estadística descriptiva. Resultados: El 40.2 % y 49.2 % de los especialistas estuvieron medianamente satisfechos con las dimensiones técnico-humana y resultados de tratamiento respectivamente e insatisfechos el 41.3 % con la dimensión entorno físico. Conclusiones: La satisfacción general laboral de los estomatólogos fue calificada como medianamente satisfechos.

ABSTRACT Background: The satisfaction of professionals is important to evaluate the quality of dental care. Objective: To evaluate the stomatologists´ general work satisfaction from Sancti Spíritus with the Comprehensive General Stomatology service according to the technical-human dimensions, physical environment and treatment results. Methodology: A study about health system and services from 2014 to 2019 was made. The 21 units from the Sancti Spíritus province were divided into some stratus: clinical centers and polyclinics. It was aleatory selected the clinical centers and 4 polyclinics. The sample consisted of 179 general comprehensive stomatologists (98 from clinical centers and 81 from the polyclinics). Valued variables: satisfaction of technical-human dimension, physical environment and treatment results. Theoretical and empirical levels, also from statistical description were used. Results: 40.2 % and 49.2 % of the specialists were moderately satisfied with the technical-human dimensions and treatment results, respectively, and 41.3 % were dissatisfied with the physical environment dimension. Conclusions: The stomatologists´ general work satisfaction was rated as moderately satisfied.

Novel EGR2 variant that associates with Charcot-Marie-Tooth disease when combined with lipopolysaccharide-induced TNF-α factor T49M polymorphism.

OBJECTIVE: To identify novel genetic mechanisms causing Charcot-Marie-Tooth (CMT) disease. METHODS: We performed a next-generation sequencing study of 34 genes associated with CMT in a patient with peripheral neuropathy. RESULTS: We found a non-previously described mutation in EGR2 (p.P397H). P397H mutation is located within the loop that connects zinc fingers 2 and 3, a pivotal domain for the activity of this transcription factor. Using promoter activity luciferase assays, we found that this mutation promotes decreased transcriptional activity of EGR2. In this patient, we also found a previously described nonpathogenic polymorphism in lipopolysaccharide-induced TNF-α factor (LITAF) (p.T49M). We show that the p.T49M mutation decreases the steady-state levels of the LITAF protein in Schwann cells. Loss of function of LITAF has been shown to produce deregulation in the NRG1-erbB signaling, a pivotal pathway for EGR2 expression by Schwann cells. Surprisingly, our segregation study demonstrates that p.P397H mutation in EGR2 is not sufficient to produce CMT disease. Most notably, only those patients expressing simultaneously the LITAF T49M polymorphism develop peripheral neuropathy. CONCLUSIONS: Our data support that the LITAF loss-of-function interferes with the expression of the transcriptional-deficient EGR2 P397H mutant hampering Schwann cell differentiation and suggest that in vivo both genes act in tandem to allow the proper development of myelin.

Hypothermia Plus Melatonin in Asphyctic Newborns: A Randomized-Controlled Pilot Study.

OBJECTIVES: To investigate the effect of adding melatonin to hypothermia treatment on neurodevelopmental outcomes in asphyctic newborns. DESIGN: Pilot multicenter, randomized, controlled, double-blind clinical trial. Statistical comparison of results obtained in two intervention arms: hypothermia plus placebo and hypothermia plus melatonin. SETTING: Level 3 neonatal ICU. PATIENTS: Twenty-five newborns were recruited. INTERVENTIONS: The hypothermia plus melatonin patients received a daily dose of IV melatonin, 5 mg per kg body weight, for 3 days. General laboratory variables were measured both at neonatal ICU admission and after intervention. All infants were studied with amplitude-integrated electroencephalography and brain MRI within the first week of life. The neurodevelopmental Bayley III test, the Gross Motor Function Classification System, and the Tardieu scale were applied at the ages of 6 and 18 months. MEASUREMENTS AND MAIN RESULTS: Clinical characteristics, laboratory evaluations, MRI findings, and amplitude-integrated electroencephalography background did not differ between the treatment groups. The newborns in the hypothermia plus melatonin group achieved a significantly higher composite score for the cognitive section of the Bayley III test at 18 months old, with respect to the hypothermia plus placebo group (p = 0.05). There were no differences between the groups according to the Gross Motor Function Classification System and Tardieu motor assessment scales. CONCLUSIONS: The early addition of IV melatonin to asphyctic neonates is feasible and may improve long-term neurodevelopment. To our knowledge, this is the first clinical trial to analyze the administration of IV melatonin as an adjuvant therapy to therapeutic hypothermia.