Evidence on the benefits of probiotics for preterm infants.

Introduction: This article reviews the evidence for the use of different strains of probiotics in the prevention of prevalent pathologies in premature neonates. A systematic review was conducted of the use of probiotics in neonates with less than 37 weeks of gestational age, based on a search for systematic reviews and observational and experimental studies performed during the period from January 2014 to February 2021. For this purpose, the PubMed, MEDLINE and Cochrane Library databases were consulted. The aim of this article was to review the existing data on the relationship between the administration of probiotics (with different strains and doses) and the risk of necrotising enterocolitis, mortality, late sepsis and other disease parameters in premature infants. The literature search obtained 240 articles, of which we selected 16, representing a total sample of over 200,000 premature infants. Analysis of the data obtained reveals statistical evidence that the combined administration of probiotics (especially of Lactobacillus and Bifidobacterium strains) reduces the incidence of grade II or higher necrotising enterocolitis, all-cause mortality, late sepsis, length of hospital stay and time until complete enteral nutrition is achieved. However, no benefits were apparent with respect to alleviating bronchopulmonary dysplasia, retinopathy of prematurity or intraventricular haemorrhage. Further research is needed to determine the most appropriate strains, doses and treatment duration for preterm infants to achieve the health benefits identified.

Introducción: En este artículo se revisa la evidencia del uso de las diferentes cepas de probióticos en la prevención de diversas patologías prevalentes en recién nacidos prematuros. Se ha realizado una revisión sistemática sobre el uso de probióticos en recién nacidos de menos de 37 semanas de edad gestacional, realizando una búsqueda de revisiones sistemáticas, estudios observacionales y experimentales desde enero de 2014 hasta febrero de 2021. Para ello se han utlizado motores de búsqueda como PubMed, MEDLINE y la biblioteca Cochrane. El objetivo de este artículo fue revisar los datos existentes sobre la relación entre la administración de probióticos (con diferentes cepas y dosis) y el riesgo de enterocolitis necrotizante, mortalidad, sepsis tardía, y otros parámetros de enfermedad en prematuros. En la búsqueda se obtuvieron 240 artículos, de los que seleccionamos 16, obteniendo más de 200.000 recién nacidos prematuros como muestra. En esta revisión se muestra con evidencia estadística, que la administración combinada de probióticos (espcialmente cepas de Lactobacillus y Bifidobacterium) reducen la incidencia de NEC en grado II o mayor, mortalidad por todas las causas, sepsis tardía, días de estancia hospitalaria y tiempo en lograr nutrición enteral completa. No se han podido evidenciar beneficios en cuanto a la displasia broncopulmonar, retinopatía de la prematuridad y hemorragia intraventricular. Se precisan nuevos estudios para conocer las cepas, dosis y tiempo de tratamiento más adecuados en neonatos prematuros para lograr beneficios en salud.

A Clustering Study of Sociodemographic Data, Dietary Patterns, and Gut Microbiota in Healthy and Breast Cancer Women Participating in the MICROMA Study.

SCOPE: This work is part of the clinical study NCT03885648 registered in ClinicalTrials.gov, aimed at studying the relationship among breast cancer, microbiota, and exposure to environmental pollutants. As a first step, we characterized and evaluated risk factors of the participants. METHODS AND RESULTS: A case-control study was designed with breast cancer (cases, n = 122) and healthy women (controls, n = 56) recruited in two hospitals of Andalusia (Southern Spain). Participants answered questionnaires of Mediterranean diet adherence and food frequency. Data were collected from medical histories and microbiota was analyzed on stool samples. Most cases (78.2%) were diagnosed as stages I and II. Cases had higher age, body mass index (BMI), glucose, cholesterol, and potassium values than controls. Cases exhibited higher adherence to the Mediterranean diet and their food consumption was closer to that dietary pattern. A hierarchical cluster analysis revealed that the Bacillota/Bacteroidota ratio was the most relevant variable in women with breast cancer, which was higher in this group compared with controls. CONCLUSION: Although cases exhibited higher adherence to the Mediterranean diet compared with controls, they presented features and microbiota alterations typical of the metabolic syndrome, probably due to their higher BMI and reflecting changes in their lifestyle around the time of diagnosis.

[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.

Introduction: 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.

Introducción: Introducción: la esclerosis lateral amiotrófica (ELA) es una enfermedad neurodegenerativa cuya prevalencia en la actualidad está entre 3 y 6 casos/100.000. La desnutrición está íntimamente relacionada con el pronóstico en el paciente con ELA. Las implicaciones de esta enfermedad hacen que se deba recomendar al paciente la asistencia en una unidad multidisciplinar. Caso clínico: el caso presentado muestra la evolución de una paciente con esclerosis lateral amiotrófica desde el diagnóstico. Tras la valoración por parte de Neurología, se remitió a la paciente a los distintos servicios de seguimiento (Endocrinología, Rehabilitación, Neumología). No se observó deterioro nutricional al diagnóstico; no obstante, la ingesta se encontraba por debajo de los requerimientos. En la progresión de la enfermedad se observó un deterioro de la masa muscular con estabilidad ponderal y de la masa grasa, pero la paciente desarrolló disfagia, síntoma típico de la enfermedad. El planteamiento de medidas "agresivas" para controlar el estado nutricional, como la gastrostomía, fue rechazado al inicio, pero hubo que realizarlas tras la progresión de la disfagia y la desnutrición asociada. Esta situación de deterioro morfofuncional y el desarrollo de complicaciones plantearon la participación de distintos profesionales sanitarios en su control. Discusión: el manejo de la ELA de manera multidisciplinar permite mejorar la evolución de la enfermedad y la calidad de vida del paciente y sus familiares. El seguimiento se basa en el ajuste y el manejo de las complicaciones, en mantener una adecuada comunicación con el paciente y sus familiares, y en tomar de manera conjunta las decisiones sobre su patología.

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.

[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 / Post-surgical pain and edema in nasal skin regeneration with fibrin rich in platelets and leukocytes

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.

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.

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.

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.

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.

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.

Cyclization of interlocked fumaramides into ß-lactams: experimental and computational mechanistic assessment of the key intercomponent proton transfer and the stereocontrolling active pocket.

A detailed mechanistic study of the diastereoselective CsOH-promoted cyclization of interlocked fumaramides to give ß-lactams is described. The mechanistic analysis comprises the experimental evaluation of the structure-reactivity relationship for a wide range of fumaramides [2]rotaxanes (Hammet-plots), KIE studies with deuterium-labelled interlocked fumaramides and computational analysis of two alternative mechanistic pathways for the cyclization process. The obtained results confirm that: (a) the rate-determining step is the deprotonation of the N-benzyl group of the thread by the amidate group of the macrocycle generated by the external base, (b) the polyamide macrocycle plays an important role not only as activating element but also as the stereodifferenciating factor responsible for the observed diastereoselection and (c) the higher flexibility of the adamantyl core speeds up the cyclization process in diadamantyl-derived rotaxanes.

Colgajo de reposición coronal asociado a fibrina rica en plaquetas y leucocitos en recesiones periodontales / Coronally repositioned flap with platelet-rich fibrin and leukocytes in periodontal recessions

RESUMEN El tratamiento de la recesión periodontal (cobertura de las raíces expuestas) constituye un reto para el periodontólogo y se considera una parte integral pero compleja de su práctica quirúrgica. La membrana de fibrina, rica en plaquetas y leucocitos, es un biomaterial autólogo que puede ser colocado debajo de los injertos de encía pediculados de reposición coronal, lo que propiciaría la regeneración de los tejidos perdidos. Se presentó una paciente de 40 años de edad, tratada con este biomaterial, que fue aplicado en recesiones múltiples de dientes con restauraciones cervicales de ionómero de vidrio. Se obtuvo un aumento de la encía insertada, la cobertura radicular y la eliminación de la hiperestesia dentinaria concomitante.

ABSTRACT The treatment of periodontal recession (coverage of exposed roots) constitutes a challenge for periodontists and is considered an integral but complex part of their surgical practice. Platelet-rich fibrin and leukocytes, is an autologous biomaterial that can be placed under coronally repositioned pedicle graft, which would promote the regeneration of lost tissues. We present a 40-year-old patient, treated with this biomaterial, which was applied in multiple gingival recessions with cervical glass-ionomer restorations. An increase of the attached gingiva, root coverage and elimination of concomitant dentin hyperesthesia was obtained.

Association of breast and gut microbiota dysbiosis and the risk of breast cancer: a case-control clinical study.

BACKGROUND: Breast cancer ranks first in women, and is the second cause of death in this gender. In addition to genetics, the environment contributes to the development of the disease, although the factors involved are not well known. Among the latter is the influence of microorganisms and, therefore, attention is recently being paid to the mammary microbiota. We hypothesize that the risk of breast cancer could be associated with the composition and functionality of the mammary/gut microbiota, and that exposure to environmental contaminants (endocrine disruptors, EDCs) might contribute to alter these microbiota. METHODS: We describe a case-control clinical study that will be performed in women between 25 and 70 years of age. Cases will be women diagnosed and surgically intervened of breast cancer (stages I and II). Women with antecedents of cancer or advanced tumor stage (metastasis), or who have received antibiotic treatment within a period of 3 months prior to recruitment, or any neoadjuvant therapy, will be excluded. Controls will be women surgically intervened of breast augmentation or reduction. Women with oncological, gynecological or endocrine history, and those who have received antibiotic treatment within a period of 3 months prior to recruitment will also be excluded. Blood, urine, breast tissue and stool samples will be collected. Data regarding anthropometric, sociodemographic, reproductive history, tumor features and dietary habits will be gathered. Metabolomic studies will be carried out in stool and breast tissue samples. Metagenomic studies will also be performed in stool and breast tissue samples to ascertain the viral, fungal, bacterial and archaea populations of the microbiota. Quantitation of estrogens, estrogen metabolites and EDCs in samples of serum, urine and breast tissue will also be performed. DISCUSSION: This is the first time that the contribution of bacteria, archaea, viruses and fungi together with their alteration by environmental contaminants to the risk of breast cancer will be evaluated in the same study. Results obtained could contribute to elucidate risk factors, improve the prognosis, as well as to propose novel intervention studies in this disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT03885648 , 03/25/2019. Retrospectively registered.