Abstract: Seasonal influenza is an infectious disease of multi-causal etiology and a major cause of mortality worldwide that has been associated with environmental factors. In the attempt to model and predict future outbreaks of seasonal influenza with multiple environmental factors, we face the challenge of increased dimensionality that makes the models more complex and unstable. In this paper, we propose a nowcasting and forecasting framework that compares the theoretical approaches of Single Environmental Factor and Multiple Environmental Factors. We introduce seven solutions to minimize the weaknesses associated with the increased dimensionality when predicting seasonal influenza activity levels using multiple environmental factors as external proxies. Our work provides evidence that using dimensionality reduction techniques as a strategy to combine multiple datasets improves seasonal influenza forecasting without the penalization of increased dimensionality.

Abstract: Cornelia de Lange Syndrome (CdLS) is a congenital autosomal dominant (NIPBL, SMC3 and RAD21) or Xlinked (SMC1A and HDAC8) disorder characterized by facial dysmorphism, pre and postnatal growth retardation, developmental delay and/or intellectual disability, and multiorgan involvement. Musculoskeletal malformations are usually bilateral and affect mainly the upper limbs; the range goes from brachyclinodactyly to severe reduction defects. Instead lower extremities are usually less and mildly involved. Here, we report on a 3-year-old Senegalese boy with typical craniofacial CdLS features, pre and postnatal growth retardation, atrial septal defect, developmental delay and right ipsilateral limb malformations, consistent with oligodactyly of the 3rd and 4th fingers, tibial agenesis and fibula hypoplasia. Exome sequencing and Sanger sequencing showed a novel missense mutation in NIPBL gene (c.6647A>G; p.(Tyr2216Cys)), which affects a conserved residue located within NIPBL HEAT repeat elements. Pyrosequencing analysis of NIPBL gene, disclosed similar levels of wild-type and mutated alleles in DNA and RNA samples from all tissues analyzed (oral mucosa epithelial cells, peripheral blood leukocytes and fibroblasts). These findings indicated the absence of somatic mosaicism, despite of the segmental asymmetry of the limbs, and confirmed biallelic expression for NIPBL transcripts, respectively. Additionally, conditions like Split-hand/foot malformation with long-bone deficiency secondary to duplication of BHLHA9 gene have been ruled out by the array-CGH and MLPA analysis. To our knowledge, this is the first CdLS patient described with major ipsilateral malformations of both the upper and lower extremities, that even though this finding could be due to a random event, expands the spectrum of limb reduction defects in CdLS.

Abstract: The disorders caused by mutations in genes encoding subunits and accessory proteins of cohesin complex are collectively termed as cohesinopathies. The best known cohesinopathy is Cornelia de Lange Syndrome (CdLS), which is a multisystem developmental disorder characterized by facial dysmorphism, limb malformations, growth and cognitive impairment. Mutations in five genes, encoding subunits of the cohesin complex (SMC1A, SMC3, RAD21) and its regulators (NIPBL, HDAC8), are responsible for ∼70% of CdLS cases. We describe a 16-year-old boy with facial dysmorphism, growth retardation, intellectual disability, hirsutism and small hands, who has a small Supernumerary Marker Chromosome (sSMC) present in mosaic form. sSMC is composed of two duplicated segments encompassing 17 genes including SMC1A gene, at the regions Xp11.22 and Xp11.21q11.1. Clinical comparison between our patient with a previously reported individual with a SMC1A duplication and four male carriers of similar sSMC reported in databases, suggest that they all share clinical features related to cohesinopathies. Although our patient does not have the classical CdLS craniofacial phenotype, he has pre and postnatal growth retardation, intellectual disability and mild musculoskeletal anomalies, features commonly seen in patients with cohesinopathies.

Abstract: Botulism is caused by a potent neurotoxin that blocks neuromuscular transmission, resulting in death by asphyxiation. Currently, the therapeutic options are limited and there is no antidote. Here, we harness the structural and trafficking properties of an atoxic derivative of botulinum neurotoxin (BoNT) to transport a function-blocking single-domain antibody into the neuronal cytosol where it can inhibit BoNT serotype A (BoNT/A1) molecular toxicity. Post-symptomatic treatment relieved toxic signs of botulism and rescued mice, guinea pigs, and nonhuman primates after lethal BoNT/A1 challenge. This platform might enable delivery of antibodies and other protein-based therapeutics to previously inaccessible intraneuronal targets. Resumen: El botulismo es causado por una potente neurotoxina que bloquea la transmisión neuromuscular, provocando la muerte por asfixiamiento. Actualmente, las opciones de tratamiento son limitadas y no existe un antídoto. En este artículo aprovechamos las propiedades estructurales y de tráfico neuronal de un derivado atóxico de la neurotoxina botulínica (BoNT) para transportar un anticuerpo que bloquea la función al citosol neuronal, donde puede inhibir la toxicidad molecular del serotipo A de la BoNT (BoNT /A1). El tratamiento post-sintomático alivió los signos tóxicos del botulismo y rescató de la muerte a ratones, conejillos de indias y primates no humanos después de la exposición letal a BoNT / A1. Esta plataforma podría permitir la administración de anticuerpos y otros terapéuticos basados en proteínas a blancos intraneuronales que previamente eran inaccesibles.

Abstract: Mixed microbial cultures have become a preferred choice of biocatalyst for chain elongation systems due to their ability to convert complex substrates into medium chain carboxylates. However, the complexity of the effects of process parameters on the microbial metabolic networks is a drawback that makes the task of optimizing product selectivity challenging. Here, we studied the effects of small air contaminations on the microbial community dynamics and the product formation in anaerobic bioreactors fed with lactate, acetate and H2/CO2. Two stirred tank reactors and two bubble column reactors were operated with H2/CO2 gas recirculation for 139 and 116 days, respectively, at pH 6.0 and 32°C with a hydraulic retention time of 14 days. One reactor of each type had periods with air contamination (between 97 ± 28 and 474 ± 33 mL O2 L−1 d−1, lasting from 4 to 32 days), while the control reactors were kept anoxic. During air contamination, production of n-caproate and CH4 was strongly inhibited, whereas no clear effect on nbutyrate production was observed. In a period with detectable O2 concentrations that went up to 18%, facultative anaerobes of the genus Rummeliibacillus became predominant and only n-butyrate was produced. However, at low air contamination rates and with O2 below the detection level, Coriobacteriia and Actinobacteria gained a competitive advantage over Clostridia and Methanobacteria, and propionate production rates increased to 0.8–1.8 mmol L−1 d−1 depending on the reactor (control reactors 0.1–0.8 mmol L−1 d−1). Moreover, i-butyrate production was observed, but only when Methanobacteria abundances were low and, consequently, H2 availability was high. After air contamination stopped completely, production of n-caproate and CH4 recovered, with n-caproate production rates of 1.4–1.8 mmol L−1 d−1 (control 0.7–2.1 mmol L−1 d−1). The results underline the importance of keeping strictly anaerobic conditions in fermenters when consistent n-caproate production is the goal. Beyond that, micro-aeration should be further tested as a controllable process parameter to shape the reactor microbiome. When odd-chain carboxylates are desired, further studies can develop strategies for their targeted production by applying micro-aerobic conditions.

El ambiente escolar es uno de los entornos más relevantes y significativos de nuestra vida, pues allí se tejen comportamientos, relaciones y hábitos que suelen modelar patrones de alimentación que impactan en nuestras preferencias de consumo. En este sentido, si bien es cierto que existe una combinación de factores individuales, como cuestiones psicológicas y culturales, que impactan en nuestros hábitos alimentarios, diversos estudios han demostrado el carácter determinante de los existen factores ambientales, entre ellos la disponibilidad, la accesibilidad y la invasiva publicidad de alimentos en los entornos donde nos relacionamos. Según UNICEF, en Colombia 3 de cada 10 niños y niñas entre 6 y 12 años padecen de sobrepeso. Esto lo confirman los datos recolectados por la ENSIN, reflejando que en 2005. El 4,3% de la población escolar (niños y niñas entre 5 y 12 años) tenía exceso de peso. Ya para el 2010 esta cifra habría aumentado a 18,8% y para el 2015 este porcentaje alcanzó el 24,4%. Este panorama es altamente preocupante, pues según la Organización Mundial de la Salud, la obesidad infantil se asocia con una mayor probabilidad de muerte prematura y discapacidad en la edad adulta. Esta cartilla resume los argumentos legales y de salud pública, por los cuales la regulación de venta y publicidad de ultraprocesados en entornos escolares es una política necesaria para favorecer la salud y la alimentación de los niños y niñas en Colombia. Descripción tomada de: https://www.dejusticia.org/publication/promoviendo-ambientes-escolares-libres-de-comida-chatarra-en-colombia/

El objetivo de este estudio es analizar la relación de las variables de rendimiento físico con los grupos de equipos ganadores, empatados y perdedores de los partidos de la Copa Mundial de la FIFA Rusia 2018. La muestra seleccionada para realizar el presente análisis fue de 32 selecciones nacionales participantes, examinadas por medio de 57 partidos en total. Los equipos fueron divididos en tres diferentes grupos, dependiendo del resultado obtenido: (0) equipos ganadores (N=48), (1) equipos que empataron (N=18) y (2) equipos perdedores (N=48). Los datos recogidos del presente trabajo de investigación han sido analizados a través de la página web https://www.fifa.com. Las variables utilizadas para el análisis de los datos fueron: distancia total recorrida, distancia recorrida con el balón en posesión, distancia recorrida sin el balón en posesión, sprints, posesión del balón lanzamientos a favor, diferencia de lanzamientos, tiempo empleado en la mitad del equipo oponente (OH), tiempo empleado en el tercio ofensivo (A3); Tiempo empleado en el área de penalti (PA), zona 1 de velocidad: 0-7 km/h, zona 2 de velocidad: 7-15 km/h, zona 3 de velocidad: 15-20 km/h, zona 4 de velocidad: 20-25 km/h, zona 5 de velocidad: > 25 km/h. Se realizó la prueba de Kolmogorov-Smirnov, para establecer la normalidad de los datos y posteriormente la prueba ANOVA de un factor para analizar los datos de distribución normal y la prueba de Kruskal-Wallis para muestras independientes, para datos de distribución no normal. Los datos observados no arrojaron diferencias significativas entre los grupos. La conclusión de la presente investigación es que ni las variables de rendimiento físico, ni las variables técnico-tácticas utilizadas, fueron determinantes para ganar, empatar o perder partidos en la Copa Mundial de la FIFA Rusia 2018.

Colombia is an upper middle-income country with an estimated population of 49.2 million people, and road traffic collisions (RTCs) are the second most common cause of traumatic death. The government established the National Road Safety Plan (PNSV) for the period 2011-2021, to reduce RTC-related deaths by 26%. Study aim was to evaluate whether Road Safety Laws have had a long-term effect on road safety in the country. Data on RTC from January 1, 2001 through December 31, 2017 were collated from official Colombian governmental publications. Three periods were considered for analysis: 2001-2010 evaluating the Transit Code; 2011-2017 evaluating the PNSV; and 2001-2017 evaluating the full study period. A total of 102,723 deaths (12.7%) and 707,778 injuries (87.3%) were reported from 2001 through 2017. Transit Code period showed a 10.1% decline in deaths, 16.6% decline in injuries, and rates per 100,000 inhabitants and per 10,000 registered vehicles also declined. During the PNSV period, there was an increase in deaths by 16.6%, injuries decreased by 1.7%, and death rates per 100,000 inhabitants also increased. During the total study period, a 12.4% reduction in the total number of casualties was achieved, and death and injury rates per 100,000 inhabitants decreased by 12.4% and 27.5%, respectively. Overall, the absolute number of RTCs and deaths has increased. RTCs rates per 10,000 registered vehicles has decreased. Although the goals of the PNSV may not be realized, some laws may be having a beneficial effect. Further study is required to determine the longer-term impact of these initiatives.

Background: The effect of early surgery in elderly patients with hip fractures has been controversial during the last five decades due to equivocal evidence both in favour and against it. The objective of this thesis is to systematically assess all the available evidence on the effect(s) of early surgery compared with delayed surgery in elderly patients with hip fractures. Methods: Searches for randomised controlled trials (RCTs) or prospective observational studies were conducted from inception to July 2017 in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), EMBASE (OVID), and they were complemented with list of references searching, review of both clinical trials registers and archives of orthopaedic meetings. Two reviewers independently selected studies for inclusion, extracted data and evaluated risk of bias; and a third reviewer resolved discrepancies. Risk ratios (RR) were calculated for dichotomous data, and mean difference (MD) or standardised mean difference (SMD) was calculated for continuous data. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: 39 studies were included with 51,857 participants (range of mean age: 74 to 93 years) comparing early versus delayed surgery. Three studies were RCTs and 36 were observational studies. The evidence from RCTs and observational studies showed that early surgery reduces risk of all-cause 3 mortality in elderly patients with a hip fracture (RR 0.73, 95% confidence interval (CI) 0.65 to 0.83; I2 = 67%; number needed to treat for benefit (NNTB) 20; low quality of evidence). Observational studies showed reduced risk of all-cause mortality by early surgery at 6 (RR 0.77, 95% CI 0.66 to 0.91; I2 = 56%; very low quality of evidence) and 12 months postoperative (RR 0.69, 95% CI 0.55 to 0.87; I2 = 76%; very low quality of evidence), and when surgery is performed within the first 48 hours upon hospital admission (RR 0.72, 95% CI 0.62 to 0.84; I2 = 65%; very low quality of evidence). Observational studies also showed a reduction of complications (RR 0.61, 95% CI 0.51 to 0.73; I2 = 64%; very low quality of evidence) and length of hospital stay (MD -5.06, 95% CI -6.52 to -3.60; I2 = 87%; very low quality of evidence) by early surgery, but the evidence was uncertain for functionality (SMD 0.05, 95% CI -0.04 to 0.14; I2 = 0%; low quality of evidence) and pain (RR 0.89, 95% CI 0.67 to 1.17; I2 = 0%; very low quality of evidence). RCTs showed that early surgery reduces length of stay (MD -6.73, 95% CI -12.92 to -0.54; I2 = 54%; very low quality of evidence) and improves functionality (SMD 0.32, 95% CI 0.04 to 0.59; I2 = 5%; low quality of evidence). Conclusions: Low-quality evidence showed that early surgery reduces all-cause mortality at 6 and 12 months post-surgery, especially when it is performed during the first 48 hours after hospital admission. There was very low-quality evidence of a reduction in complications including pneumonia and pressure sores, and low-quality evidence for a reduced risk of urinary tract infection for early compared with delayed surgery. Reductions in length of hospital stay and improvement of postoperative functionality with early surgery were also observed but with very low- and low-quality of evidence respectively. There was very low-quality evidence for no effect of early surgery on postoperative pain.

El desgaste por empatía es un concepto relativamente reciente y en evolución que ha captado el interés de los profesionales sanitarios debido a que el trabajo en el ámbito de la salud implica un coste emocional que repercute en la misma salud del trabajador y en su labor profesional. Según la literatura revisada, los programas en prevención en todos los niveles de este tipo de estrés son escasos, por lo tanto, el objetivo de este trabajo es proponer un programa de prevención del desgaste por empatía en profesionales sanitarios de una unidad de diálisis de hospital. La idea surgió de la necesidad manifiesta por la Unidad de Diálisis del Hospital Universitario Infanta Sofía (HUIS), hacia la Unidad de Salud Mental del mismo Hospital y de la confianza depositada en la investigación académica, relacionada con la dificultad en el afrontamiento a la muerte de pacientes de la Unidad, por parte del personal asistencial. El propósito es entonces entrenar a los profesionales en estrategias de regulación emocional del desgaste por empatía, con el fin de disminuir los niveles de este tipo de estrés y prevenir su futura aparición, por medio del desarrollo de 6 módulos, que se llevarán a cabo a través de diferentes ciclos y que puede tener continuidad a través de una modalidad de Formación Continuada. Se ha diseñado una evaluación estandarizada con el fin de medir la presunta efectividad del programa para prevenir el desgaste por empatía. Se realiza una valoración sobre los resultados esperados, las conclusiones del diseño de la propuesta del programa, así como de sus limitaciones y sobre futuras líneas de investigación. Abstract: The compassion fatigue is a relatively recent and evolving concept that has captured the interest of health professionals because working in health implies an emotional cost that affects the health and the worker performance. According to the revised literature, prevention programs at all levels of this kind of stress are scarce, therefore, the objective of this work is to propose a program of prevention of compassion fatigue in healthcare professionals of a dialysis unit of a hospital. The idea came up from the necessity exposed by the Dialysis Unit of the Hospital Universitario Infanta Sofia (HUIS), towards the Mental Health Unit of the same Hospital and from the confidence placed in the academic research, related to the difficulty of facing death of patients of the unit, by the assistance personnel. The purpose is then to train professionals in strategies of emotional regulation of compassion fatigue, in order to reduce the levels of this type of stress and prevent its future emergence, through the development of 6 modules, which will be carried out through different cycles and that can have continuity through a continuous training modality. A standardized assessment has been designed to measure the presumed effectiveness of the program to prevent the compassion fatigue. An assessment is made of the expected results, the conclusions of the design of the program proposal, as well as its limitations and future lines of research.