Gene expression imputation provides clinical and biological insights into treatment-resistant schizophrenia polygenic risk.

Genome-wide association studies (GWAS) have revealed the polygenic nature of treatment-resistant schizophrenia TRS. Gene expression imputation allowed the translation of GWAS results into regulatory mechanisms and the construction of gene expression (GReX) risk scores (GReX-RS).  In the present study we computed GReX-RS from the largest GWAS of TRS to assess its association with clinical features. We perform transcriptome imputation in the largest GWAS of TRS to find GReX associated with TRS using brain tissues. Then, for each tissue, we constructed a GReX-RS of the identified genes in a sample of 254 genotyped first episode of psychosis (FEP) patients to test its association with clinical phenotypes, including clinical symptomatology, global functioning and cognitive performance. Our analysis provides evidence that the polygenic basis of TRS includes genetic variants that modulate the expression of certain genes in certain brain areas (substantia nigra, hippocampus, amygdala and frontal cortex), which at the same time are related to clinical features in FEP patients, mainly persistence of negative symptoms and cognitive alterations in sustained attention, which have also been suggested as clinical predictors of TRS. Our results provide a clinical explanation of the polygenic architecture of TRS and give more insight into the biological mechanisms underlying TRS.

Predictores del estado de salud funcional posingreso en cuidados intensivos en pacientes sépticos / Predictors of Post-Admission Functional Health Status in Intensive Care in Septic Patients

Introducción: Los pacientes críticos pediátricos son susceptibles de presentar alteraciones del flujo sanguíneo cerebral que impliquen un deterioro de su estado de salud funcional. Objetivo: Identificar factores predictores de mayor riesgo de mala evolución funcional en pacientes pediátricos críticos con sepsis. Métodos: Se realizó un estudio de cohortes retrospectivo con menores de 18 años de edad con sepsis, ingresados en la unidad de cuidados intensivos pediátricos. Se recogieron variables epidemiológicas, clínicas y del estado de salud funcional previas al ingreso, al alta y a los 6 meses. El estado de salud funcional se evaluó mediante la escala de categorías de estado global y cerebral pediátrico. Se evaluó el cambio del estado funcional entre el ingreso y a los 6 meses del alta. Se realizó un análisis univariante para comparar grupos considerando el mal pronóstico y el cambio del estado funcional y su relación con las variables. Resultados: Se incluyeron 46 pacientes. A los 6 meses del alta, cuatro (8,7 por ciento) presentaron mal pronóstico funcional y ocho (17,4 por ciento) empeoramiento funcional respecto al ingreso. No se encontraron asociaciones entre las variables predictoras y la morbilidad, aunque se observó cierta tendencia en algunas como mayor soporte inotrópico (VIS > 20: 12,5 por ciento vs. 50 por ciento, p= 0,075), extracorpóreo y de reemplazo renal (25 por ciento vs. 2,6 por ciento, p= 0,074) y estancia hospitalaria más prolongada (50 por ciento vs. 15,8 por ciento , p= 0,055). Conclusiones: El soporte en la unidad de cuidados intensivos pediátricos no fue un predictor de morbilidad funcional en la muestra(AU)

Introduction: Critically ill pediatric patients are susceptible to cerebral blood flow alterations that imply a deterioration of their functional health status. Objective: To identify predictors of a higher risk of poor functional outcome in critically ill pediatric patients with sepsis. Methods: A retrospective cohort study was conducted with children under 18 years of age with sepsis, who were admitted to the pediatric intensive care unit. Epidemiological, clinical, and functional health status variables were collected prior to admission, discharge, and after 6 months. Functional health status was assessed using the Pediatric Global State and Brain Status Category Scale. The change in performance status between admission and 6 months after discharge was assessed. A univariate analysis was performed to compare groups considering poor prognosis and change in functional status and their relationship with the variables. Results: A total of 46 patients were included. At 6 months after discharge, four (8.7 percent) had a poor functional prognosis and eight (17.4 percent) had functional worsening at admission. No associations were found between the predictor variables and morbidity, although some trends were observed in some variables, such as greater inotropic support (SIV > 20: 12.5 percent vs. 50 percent, p = 0.075), extracorporeal and renal replacement (25 percent vs. 2.6 , percent p = 0.074), and longer hospital stay (50 percent vs. 15.8 percent , p = 0.055). Conclusions: Support in the pediatric intensive care unit was not a predictor of functional morbidity in the sample(AU)

Neonatal CD4+ T cells have a characteristic transcriptome and epigenome and respond to TCR stimulation with proliferation and yet a limited immune response.

The adaptive immune response is coordinated by CD4+ T cells, which determine the type and strength of the immune response and the effector cells involved. It has been reported that CD4+ T cells are less responsive in neonates, leading to low activation of the cellular response and poor antibody production by B cells. This low response is essential for the tolerant window that favors birth transition from the sterile environment in the womb to the outside world but leaves neonates vulnerable to infection, which is still an important health issue. Neonates have a high morbidity and mortality rate due to infections, and the molecular reasons are still understudied. We asked whether the neonatal naive CD4+ T cells have a genomic program that predisposes them to a low response. Therefore, we evaluated the transcriptome and epigenome of human neonatal and adult naive CD4+ T cells. Our results point to a gene expression profile forming a distinct regulatory network in neonatal cells, which favors proliferation and a low T-cell response. Such expression profile is supported by a characteristic epigenetic landscape of neonatal CD4+ T cells, which correlates with the characteristic transcriptome of the neonatal cells. These results were confirmed by experiments showing a low response to activation signals, higher proliferation, and lower expression of cytokines of neonatal CD4+ T cells as compared to adult cells. Understanding this network could lead to novel vaccine formulations and better deal with life-threatening diseases during this highly vulnerable period of our lives.

Clinical Genetics Assessment Triangle (CGAT): A simple tool to identify patients with genetic conditions.

OBJECTIVE: The objective of this study was to develop a simple tool for general physicians to promptly identify and refer pediatric patients with a higher probability of having a genetic condition. STUDY DESIGN: This retrospective, descriptive study was conducted at a tertiary pediatric hospital's Clinical Genetics Unit from June 2019 to January 2020. We included patients under 18 years of age who visited the unit, excluding those without genetic testing. Epidemiological, clinical, and genetic variables were collected from electronic medical records. The primary outcome was the diagnosis of a genetic condition based on genetic testing. RESULTS: Among 445 patients, 304 were included; 163 (53.6%) were male, and mean age was 7.4 years (SD 5.1 years). A genetic condition was diagnosed in 139 patients (45.7%). Using a multiple logistic regression model, five variables significantly contributed to reaching a diagnosis: suspected diagnosis at referral (OR 3.45, P < 0.001), short stature (OR 3.11, P < 0.001), global developmental delay/intellectual disability (OR 2.65, P < 0.001), dysmorphic craniofacial features (OR 1.99, P = 0.035), and multiple congenital anomalies (OR 2.54, P = 0.033). The association strength (OR) increased when these variables were paired with each other. The study's findings are presented in the form of a triangle, known as the Clinical Genetics Assessment Triangle (CGAT), which summarizes the results. A decision tree model is applied to guide clinical department referrals based on the affected sides of the triangle. CONCLUSIONS: The CGAT has the potential to enable general physicians to promptly identify pediatric patients with an increased probability of having a genetic condition.

VTAM: A robust pipeline for validating metabarcoding data using controls.

To obtain accurate estimates for biodiversity and ecological studies, metabarcoding studies should be carefully designed to minimize both false positive (FP) and false negative (FN) occurrences. Internal controls (mock samples and negative controls), replicates, and overlapping markers allow controlling metabarcoding errors but current metabarcoding software packages do not explicitly integrate these additional experimental data to optimize filtering. We have developed the metabarcoding analysis software VTAM, which uses explicitly these elements of the experimental design to find optimal parameter settings that minimize FP and FN occurrences. VTAM showed similar sensitivity, but a higher precision compared to two other pipelines using three datasets and two different markers (COI, 16S). The stringent filtering procedure implemented in VTAM aims to produce robust metabarcoding data to obtain accurate ecological estimates and represents an important step towards a non-arbitrary and standardized validation of metabarcoding data for conducting ecological studies. VTAM is implemented in Python and available from: https://github.com/aitgon/vtam. The VTAM benchmark code is available from: https://github.com/aitgon/vtam_benchmark.

Organic amendment treatments for antimicrobial resistance and mobile element genes risk reduction in soil-crop systems.

Agricultural fertilization with organic amendments of animal origin often leads to antibiotic resistance dissemination. In this study, we evaluated the effect of different treatments (anaerobic digestion, biochar application, ozonation, zerovalent iron nanoparticle application, and spent mushroom substrate addition) on the resistome in dairy cow manure-derived amendments (slurry, manure, and compost). Anaerobic digestion and biochar application resulted in the highest reduction in antibiotic resistance gene (ARG) and mobile genetic element (MGE) gene abundance. These two treatments were applied to cow manure compost, which was then used to fertilize the soil for lettuce growth. After crop harvest, ARG and MGE gene absolute and relative abundances in the soil and lettuce samples were determined by droplet digital PCR and high-throughput qPCR, respectively. Prokaryotic diversity in cow manure-amended soils was determined using 16S rRNA metabarcoding. Compared to untreated compost, anaerobic digestion led to a 38% and 83% reduction in sul2 and intl1 absolute abundances in the soil, respectively, while biochar led to a 60% reduction in intl1 absolute abundance. No differences in lettuce gene abundances were observed among treatments. We conclude that amendment treatments can minimize the risk of antibiotic resistance in agroecosystems.

VA-ECMO rescue therapy in propofol infusion syndrome after cardiac surgery.

INTRODUCTION: Propofol infusion syndrome (PRIS) is a rare entity that could lead to profound cardiogenic shock (CS). Mitochondrial toxicity and sympathetic blockade are the mechanisms leading to CS in PRIS. CASE REPORT: We present a 22-year-old woman who developed refractory CS due to PRIS after aortic valve replacement surgery secondary to Coxiella infective endocarditis. She was rescued with VA-ECMO (veno-arterial extracorporeal membrane oxygenation) and was discharged 2 months later with no cardiac dysfunction. DISCUSSION: PRIS diagnosis is difficult even though propofol is frequently used in critical care units. Abrupt refractory CS in patients with recent use of high doses of propofol (> 4 mg/Kg/h) together with rhabdomyolysis should raise the suspicion. Diagnostic confirmation is based on muscle biopsy and fat enzyme analysis. CONCLUSION: Propofol withdrawal and support therapies-including VA-ECMO-are the treatment of choice in severe PRIS. VA-ECMO could increase survival as a bridge to recovery due to reversibility of PRIS.

Clinical description, molecular delineation and genotype-phenotype correlation in 340 patients with KBG syndrome: addition of 67 new patients.

BACKGROUND: KBG syndrome is a highly variable neurodevelopmental disorder and clinical diagnostic criteria have changed as new patients have been reported. Both loss-of-function sequence variants and large deletions (copy number variations, CNVs) involving ANKRD11 cause KBG syndrome, but no genotype-phenotype correlation has been reported. METHODS: 67 patients with KBG syndrome were assessed using a custom phenotypical questionnaire. Manifestations present in >50% of the patients and a 'phenotypical score' were used to perform a genotype-phenotype correlation in 340 patients from our cohort and the literature. RESULTS: Neurodevelopmental delay, macrodontia, triangular face, characteristic ears, nose and eyebrows were the most prevalentf (eatures. 82.8% of the patients had at least one of seven main comorbidities: hearing loss and/or otitis media, visual problems, cryptorchidism, cardiopathy, feeding difficulties and/or seizures. Associations found included a higher phenotypical score in patients with sequence variants compared with CNVs and a higher frequency of triangular face (71.1% vs 42.5% in CNVs). Short stature was more frequent in patients with exon 9 variants (62.5% inside vs 27.8% outside exon 9), and the prevalence of intellectual disability/attention deficit hyperactivity disorder/autism spectrum disorder was lower in patients with the c.1903_1907del variant (70.4% vs 89.4% other variants). Presence of macrodontia and comorbidities were associated with larger deletion sizes and hand anomalies with smaller deletions. CONCLUSION: We present a detailed phenotypical description of KBG syndrome in the largest series reported to date of 67 patients, provide evidence of a genotype-phenotype correlation between some KBG features and specific ANKRD11 variants in 340 patients, and propose updated clinical diagnostic criteria based on our findings.

Durable ventricular assist device in Spain (2007-2020). First report of the REGALAD registry.

INTRODUCTION AND OBJECTIVES: This report presents the clinical characteristics, outcomes and complications of all consecutive patients implanted with a long-term mechanical circulatory support device in Spain between 2007 and 2020. METHODS: Analysis of the Spanish Registry of durable ventricular assist devices (REGALAD) including data form Spanish centers with a mechanical circulatory support program. RESULTS: During the study period, 263 ventricular assist devices were implanted in 22 hospitals. The implanted device was an isolated continuous-flow left ventricular assist device in 182 patients (69%), a pulsatile-flow device (58 isolated left ventricular and 21 biventricular) in 79 (30%), and a total artificial heart in 2 patients (1%). The strategy of the implant was as bridge to heart transplant in 78 patients (30%), bridge to candidacy in 110 (42%), bridge to recovery in 3 (1%) and destination therapy in 72 patients (27%). Overall survival at 6, 12 and 24 months was 79%, 74% and 69%, respectively, and was better in continuous-flow left ventricular assist devices (84%, 80%, and 75%). The main adverse events related to this therapy were infections (37% of patients), bleeding (35%), neurological (29%), and device malfunction (17%). CONCLUSIONS: Durable ventricular assist devices have emerged in Spain in the last few years as a useful therapy for patients with advanced heart failure. As in other international registries, the current trend is to use continuous-flow intracorporeal left ventricular devices, which are associated with better results. Adverse events continue to be frequent and severe.

Evaluation of a droplet digital PCR assay for quantification of Mycobacterium avium subsp. paratuberculosis DNA in whole-blood and fecal samples from MAP-infected Holstein cattle.

Bovine paratuberculosis (PTB) is an infectious disease that affects ruminants worldwide and is a burden on the dairy industry. PTB control measures include culling of Mycobacterium avium subsp. paratuberculosis (MAP)-infected animals from the herd and the enhancement of farm-biosecurity measures. Diagnostics tools for the direct detection of MAP are fecal real-time qPCR and bacteriological culture, the last one being considered the gold standard. However, both show limitations for detecting subclinical MAP-infected cattle with low bacterial load in feces and gut tissues. Droplet digital polymerase chain reaction (ddPCR) is a third-generation PCR method that shows high reproducibility for the quantification of low DNA copy numbers. The objective of this study was to design a ddPCR assay to detect and quantify a fragment of the F57 MAP-specific sequence in samples of naturally MAP-infected Holstein cattle. DNA was isolated from whole-blood and fecal samples from control cows with a negative ELISA and qPCR result (N = 75) and from cows with PTB-associated focal (N = 32), multifocal (N = 21), and diffuse lesions (N = 17) in gut tissues. After ddPCR, the DNA extracted from fecal samples of cows with diffuse lesions showed higher mean copies per microliter (13,791.2 copies/µl) than samples from cows with multifocal lesions (78.8 copies/µl), focal lesions (177.1 copies/µl) or control cows (4.8 copies/µl) (P ≤ 0.05). Significant differences in mean DNA copies/µl were also observed in the blood samples from cows with focal lesions (47.7 copies/µl) when compared with cows with multifocal and diffuse lesions; 18.1 and 12.4 copies/µl, respectively. Using a principal component analysis, the results of the fecal ddPCR clustered together with the results of a commercial ELISA for the specific detection of MAP antibodies, fecal and tissue qPCR, and bacteriological culture results. In contrast, blood ddPCR results clustered together with the results of an ELISA for the detection of a biomarker of subclinical PTB, the ABCA13 transporter. Blood ddPCR was the most sensitive tool (sensitivity 71%, specificity 100%) of all the quantitative methods used in the study for the detection of subclinical cows with focal lesions.

Un estudio de las necesidades de formación del profesorado en las prácticas basadas en evidencias científicas en el ámbito del alumnado con trastorno del espectro del autismo / A Study of Teacher Training Needson Evidence-Based Practice in the Field of Autism Spectrum Disorder Students

La presencia de alumnado con Trastorno del Espectro del Autismo (TEA) ha aumentado considerablemente en las aulas. El propósito del estudio fue investigar la familiaridad, el uso y las necesidades formativas del profesorado de Audición y Lenguaje (AL) y Pedagogía Terapéutica (PT), a partir de sus percepciones sobre las prácticasbasadas en la evidencia (PBE) dirigidas a este alumnado. Se realizó un estudio de encuesta, mediante un cuestionario en línea del que se seleccionaron 116 respuestas. El análisis de datos se realizó desde un enfoque cuantitativo mediante estadística descriptiva, análisis inferencial y correlacional. Los resultados muestran la necesidad de formación percibida con respecto a estas prácticas; una familiaridad y uso inferior a lo indicado en estudios internacionales similares; y la identificación de las variables para el diseño de futuros planes formativos. Como conclusiones cabe señalar la necesidad de mejora de la formación inicial y permanente en estas prácticas, así como de ampliar su familiaridad para promover el posterior uso. Los planes formativos deberían dirigirse al profesorado que ha trabajado con menor número de alumnado con TEA, no ha recibido formación específica, con una percepción baja de competencia en la intervención y de que su práctica no se basa en la evidencia. (AU)

The presence of students with Autism Spectrum Disorder (ASD) has in-creased considerably in classrooms. The purpose of the study was to investigate the familiarity, use and training needs of Hearing and Language (AL) and Therapeutic Pedagogy (PT) teachers, based on their perceptions, on evidence-based practices (EBP) aimed at these students. A survey study was conducted using an online questionnaire from which 116 responses were selected. The data analysis was performed from a quan-titative approach using descriptive statistics, inferential and correlational analysis. The results indicate a perceived need for teacher training regarding these practices, lower familiarity and use than those obtained in similar studies carried out in other countries, and the identification of the target variables in the design of future training plans. Con-clusions include the need to improve initial and in-service training in these practices, as well as to expand their familiarity to promote later use. Training plans should be ad-dressed to teachers who have worked with a smaller number of students with ASD, who have not received specific training on the subject, with a low perception of competence in the intervention with these students, and with a perception that their teaching practice is not based on evidence. (AU)

Impact of a Disaster Drill on Waiting Times in a Pediatric Emergency Department.

OBJECTIVE: Emergency departments should improve their preparedness for mass casualty incidents (MCIs) through periodic drills. These exercises are conducted while maintaining regular care. The aim of this study was to determine the impact of a disaster drill in a pediatric emergency department (PED) on real patients' waiting times. METHODS: On September 10, 2019, a 4-h disaster drill was conducted in the PED of a tertiary pediatric hospital, with minimal staff reinforcement (2 nurses). Cases were real patients that came to the PED during the drill. The patients that visited the PED the day before were the control group. Variables analyzed were: age, sex, destination, triage level, time-to-triage, time-to-physician, length of PED stay, and percentage of patients visited within the optimal time according to triage level. RESULTS: Sixty-eight patients (case group) and 63 patients (control group) were analyzed; both groups were comparable except for the median age. There were no differences in time-to-triage, time-to-physician, and length of PED stay between the 2 groups. The percentage of patients visited within optimal time according to triage level was higher in the case group. CONCLUSIONS: Conducting an MCI drill in the PED, with minimal staff reinforcement, was not detrimental to real patients' waiting times.

Uso del índice de esfuerzo percibido en contextos competitivos de baloncesto femenino y masculino / Uso do índice de esforço percebido em contextos competitivos do basquete feminino e masculino / Use of the rate of perceived exertion in competitive contexts of men's and women's basketball

Objetivo: Valorar la aplicabilidad del índice de esfuerzo percibido como herramienta para el control de la carga interna en baloncesto femenino y masculino.Método: Se llevó a cabo un estudio descriptivo, observacional y prospectivo durante una temporada completa. En cada sesión de entrenamiento se registraron tiempo de exposición, índice de esfuerzo percibido, carga de trabajo, lesionabilidad y el rendimiento durante la competición.Resultados: El equipo femenino mostró una media de esfuerzo percibido de 4.8 ± 1.52 y 9 lesiones “time-loss” y el masculino un esfuerzo percibido de 4.24 ± 2.23 y 7 lesiones “time-loss”. Las variables analizadas se comportaron de manera independiente entre los equipos (p<0.01). Se observaron correlaciones significativas en ambos equipos: grandes y moderadas para esfuerzo percibido y tiempo de exposición (p<0.01); bajas para esfuerzo percibido y valoración (p<0.01); moderadas y triviales para esfuerzo percibido y victoria (p<0.023) y bajas para carga de trabajo y valoración (p<0.01). Además, fueron triviales para esfuerzo percibido y lesión “physio attention” en el equipo femenino (p<0.01) y para esfuerzo percibido y lesiones “time-loss” en el masculino (p<0.002).Conclusiones: Los resultados sugieren que el índice de esfuerzo percibido es una herramienta útil para el control de carga interna en baloncesto, asociada al rendimiento y la lesionabilidad. (AU)

Objective: To assess the applicability of the Rating of Perceived Exertion as a tool to control internal loads in female and male basketball.Method: a descriptive, observational and prospective study was carried out during a full season. Exposure time, rating of perceived exertion, workload, lesionability and performance during the competition were registered in each training session.Results: The women's team showed an average of perceived exertion of 4.8 ± 1.52 and 9 injuries time-loss and the men's team an average of 4.24 ± 2.23 and 7 injuries time-loss. The variables analyzed behaved independently between the teams (p<0.01). Significant correlations were observed in both teams: Between perceived exertion and exposure time (p<0.01) were large and moderate; between perceived exertion and performance in game (p<0.01) were low, between perceived exertion and victory (p<0.01) were moderate and trivial and between workload and performance in game (p<0.01) were small. Plus they were trivial between perceived exertion and injuries physiotherapist attention in the female team (p<0.01) and between perceived exertion and injuries time-loss in the male team (p <0.002).Conclusions: The results suggest that rate of perceived exertion is a tool that can be used to obtain useful information about internal load in basketball, associated with performance and the incidence of injuries. (AU)

Objectivo: Avaliar a aplicabilidade do índice de esforço percebido como uma ferramenta para controlar a carga interna no basquete feminino e masculino.Método: Foi realizado um estudo descritivo, observacional e prospectivo durante toda a época. Em cada sessão de treinamento foram registrados o tempo de exposição, índice de esforço percebido, carga de trabalho, lesionabilidade e desempenho durante a competição.Resultados: A equipe feminina apresentou uma média de esforço percebido de 4.8 ± 1.52 e 9 lesões por perda de tempo e a equipe masculina um esforço percebido de 4.24 ± 2.23 e 7 lesões por perda de tempo. As variáveis analisadas se comportaram de forma independente entre as equipes (p<0.01). Correlações significativas foram observadas em ambas as equipes: grandes e moderadas para percepção de esforço e tempo de exposição (p<0.01); baixas por esforço percebido e avaliação (p<0.01); moderado e trivial para percepção de esforço e vitória (p<0.023) e baixo para carga de trabalho e avaliação (p<0.01). Além disso, foram triviais para a percepção de esforço e lesão da atenção do fisioterapeuta na equipe feminina (p<0.01) e para a percepção de lesão por esforço e perda de tempo na equipe masculina (p<0.002).Conclusioes: Os resultados sugerem que o índice de esforço percebido é uma ferramenta útil para controlar a carga interna no basquete, associada ao desempenho e lesões. (AU)

Reduction of the resistome risk from cow slurry and manure microbiomes to soil and vegetable microbiomes.

In cow farms, the interaction between animal and environmental microbiomes creates hotspots for antibiotic resistance dissemination. A shotgun metagenomic approach was used to survey the resistome risk in five dairy cow farms. To this purpose, 10 environmental compartments were sampled: 3 of them linked to productive cows (fresh slurry, stored slurry, slurry-amended pasture soil); 6 of them to non-productive heifers and dry cows (faeces, fresh manure, aged manure, aged manure-amended orchard soil, vegetables-lettuces and grazed soil); and, finally, unamended control soil. The resistome risk was assessed using MetaCompare, a computational pipeline which scores the resistome risk according to possible links between antibiotic resistance genes (ARGs), mobile genetic elements (MGEs) and human pathogens. The resistome risk decreased from slurry and manure microbiomes to soil and vegetable microbiomes. In total (sum of all the compartments), 18,157 ARGs were detected: 24% related to ansamycins, 21% to multidrugs, 14% to aminoglycosides, 12% to tetracyclines, 9% to ß-lactams, and 9% to macrolide-lincosamide-streptogramin B. All but two of the MGE-associated ARGs were only found in the animal dejections (not in soil or vegetable samples). Several ARGs with potential as resistome risk markers (based on their presence in hubs of co-occurrence networks and high dissemination potential) were identified. As a precautionary principle, improved management of livestock dejections is necessary to minimize the risk of antibiotic resistance.

Coneixements sobre sedació pal·liativa en pediatria / Conocimientos sobre sedación paliativa en pediatría / Current knowledge on palliative sedation in pediatrics

FONAMENT: Donat l'augment en la prevalença de malalties que amenacen o limiten la vida, resulta cada vegada més necessari tenir coneixements d'atenció pal·liativa, incloent-hi també la sedació pal·liativa (SP), per al tractament dels símptomes refractaris. OBJECTIU: Saber quin és el coneixement, la formació I les necessitats que tenen els pediatres hospitalaris sobre l'SP. MÈTODE: Estudi transversal dut a terme a partir de les respostes d'un qüestionari en línia (Google Forms) distribuït a pediatres de nou hospitals de Catalunya. RESULTATS: S'han obtingut 176 respostes. Pel que fa a la legalitat dels procediments, el 88,6% creia que l'SP era legal a Espanya I el 98,3% que l'eutanàsia no ho era. Respecte al consentiment informat, el 57,4% afirmava que per a l'SP se'n requereix un que pot ser verbal I ha de constar en la història clínica. L'SP havia estat pautada alguna vegada pel 66,5% dels enquestats. El midazolam era el fàrmac més utilitzat (65,9%), tot I que el 56,1% creia que el sedant d'elecció era la morfina. En cas de refractarietat, els símptomes no físics no eren considerats tributaris d'SP per al 30,7% I el 66,5% creia que hauria de ser possible l'objecció de consciència. Quant a la formació, el 83% creia que en tenia insuficient o molt poca en l'àmbit de l'SP I el 91,5% estava interessat a rebre'n més. CONCLUSIONS: L'estudi suggereix que els pediatres hospitalaris necessiten més coneixements I experiència en l'àmbit de l'SP. Calen programes de formació específics I una reflexió profunda sobre quins coneixements han de tenir els pediatres dels hospitals, independentment de la seva especialitat

FUNDAMENTO: Dado el aumento en la prevalencia de enfermedades que amenazan o limitan la vida, resulta cada vez más necesario tener conocimientos en atención paliativa, incluyendo también la sedación paliativa (SP), para el tratamiento de los síntomas refractarios. OBJETIVO: Saber cuál es el conocimiento, la formación y las necesidades que tienen los pediatras hospitalarios sobre la SP. MÉTODO: Estudio transversal realizado a partir de las respuestas de un cuestionario online (Google Forms) distribuido a pediatras de nueve hospitales de Cataluña. RESULTADOS: Se han obtenido 176 respuestas. En cuanto a la legalidad de los procedimientos, el 88,6% creía que la SP era legal en España y el 98,3% que la eutanasia no lo era. Respecto al consentimiento informado, el 57,4% afirmaba que para la SP se requiere de él, y que puede ser verbal y debe constar en la historia clínica. La SP había sido pautada alguna vez por el 66,5% de los encuestados. El midazolam era el fármaco más utilizado (65,9%), aunque el 56,1% creía que el sedante de elección era la morfina. En caso de refractariedad, los síntomas no físicos no eran considerados tributarios de SP por el 30,7% y el 66,5% creía que debería ser posible la objeción de conciencia. En cuanto a la formación, el 83% creía que tenía insuficiente o muy poca en el ámbito de la SP y el 91,5% estaba interesado en recibir más. CONCLUSIONES: El estudio sugiere que los pediatras hospitalarios necesitan más conocimientos y experiencia en el ámbito de la SP. Hacen falta programas de formación específicos y una profunda reflexión sobre qué conocimientos deben tener los pediatras de los hospitales, independientemente de su especialidad

BACKGROUND: Given the increasing prevalence of life-threatening or life-limiting diseases, palliative care is increasingly needed, including palliative sedation (PS), for the treatment of refractory symptoms. OBJECTIVE: To assess the knowledge, training and needs of hospital pediatricians about PS. METHOD: Cross-sectional study based on the answers of an online questionnaire (Google Forms) distributed to pediatricians in 9 hospitals in Catalonia. RESULTS: 176 responses were obtained. Regarding the legality of the procedures, 88.6% believed that the PS was legal in Spain and 98.3% that euthanasia was not. Regarding informed consent (IC), 57.4% stated that for PS, IC is required and that it can be verbal and must be recorded in the medical record. PS had been prescribed by 66.5% of the respondents. Midazolam was the most widely used drug (65.9%), although 56.1% believed that the sedative of choice was morphine. In the case of refractoriness, the non-physical symptoms were not considered tributary of PS by 30.7% of respondents, and 66.5% believed that conscientious objection should be possible. In terms of training, 83% believed that they had insufficient or very little training in the area of PS and 91.5% were interested in receiving more. CONCLUSIONS: The study suggests that hospital pediatricians need more knowledge and experience in the field of PS. A thorough reflection is needed on what knowledge pediatricians in hospitals need to have and the specific training programs that are needed, regardless of their specialty

[Consultations for digestive foreign bodies ingestion in a pediatric emergency department.] / Consultas por ingestión de cuerpos extraños digestivos en unas urgencias pediátricas.

OBJECTIVE: Foreign body (FB) ingestion distresses many families who consult the emergency department promptly. The objective of the study is to determine the epidemiological characteristics of children who consult due to suspected FB intake and its consequences. METHODS: Descriptive-observational study, carried out in a third-level maternal and child center. Emergency reports were selected from patients under 18 years of age with a diagnosis of discharge "Ingesta CE" (code 938 CIM-9-MC until May 2018; code T18.9XXA CIM-10-MC later) from 1/1/2017 until 12/31/2018. Miscoded and reconsultations within the same episode were excluded. Data was analysed with the statistics program SPSS 25.0. RESULTS: 458 cases were included; median age 3.8 years (p25-75: 1.9-6.6 years); 267 (58.3%) males. 78.9% consulted in the first 6 hours after intake. Accidental cause was reported in 98.9% of cases. In 96.7% a single FB was ingested. The most frequent types of object were metallic (46.7%), plastics (16.4%) and food bones/shells (12.9%). The 23.6% of FB involved were sharp/pointed. 49.1% of the patients presented symptoms. A complementary test was performed in 69.4%, especially radiographs (63.5%). Metal detector was used in 10%. 9.6% required endoscopy. 90.4% were discharged from the emergency department, with 12.1% of reconsultations. CONCLUSIONS: Consultations for FB ingestion are relatively frequent in the emergency department and, although most of them are discharged, many patients require complementary tests and a non-negligible number, endoscopy. The patient's profile is that of a preschooler who spontaneously goes to the emergency room due to an accidental ingestion of a blunt metallic object.

OBJETIVO: La ingestión de un cuerpo extraño (CE) angustia a muchas familias que consultan con premura a Urgencias. El objetivo del estudio fue determinar las características epidemiológicas de los niños que consultaban por sospecha de ingesta de CE y sus consecuencias. METODOS: Se realizó un estudio descriptivo-observacional, realizado en un centro materno-infantil de tercer nivel. Se seleccionaron los informes de Urgencias de pacientes menores de 18 años con diagnóstico de alta por "Ingesta CE" (código 938 CIM-9-MC hasta mayo 2018; código T18.9XXA CIM-10-MC posteriormente) del 1/1/2017 al 31/12/2018. Los datos fueron analizados con el programa estadístico SPSS 25.0. RESULTADOS: Se incluyeron 458 casos. La edad mediana fue de 3,8 años (p25-75: 1,9-6,6 años); 267 personas (58,3%) fueron varones. El 78,9% consultaron durante las 6 horas posteriores a la ingesta. Refirieron causa accidental el 98,9% los casos. En el 96,7%, la ingesta fue de un único CE. Los objetos más frecuentes fueron metálicos (46,7%), plásticos (16,4%) y huesos/cáscaras de alimentos (12,9%). El 23,6% de CE implicados fueron afilados/puntiagudos. El 49,1% de los pacientes presentaron algún síntoma. Se realizó alguna prueba complementaria en un 69,4% de los casos, sobre todo radiografías (63,5%). Se usó el detector de metales en el 10%. El 9,6% precisó endoscopia. El 90,4% fue dado de alta desde Urgencias, con un 12,1% de reconsultas. CONCLUSIONES: Las consultas por ingestión de CE son relativamente frecuentes en Urgencias y, aunque la mayoría son dados de alta, muchos pacientes requieren pruebas complementarias, y un número no despreciable, necesita endoscopia. El perfil del paciente es el de un varón en edad preescolar que acude espontáneamente a Urgencias por ingesta accidental de un objeto romo metálico.

Consultas por ingestión de cuerpos extraños digestivos en unas urgencias pediátricas / Consultations for digestive foreign bodies ingestion in a pediatric emergency department

OBJETIVO: La ingestión de un cuerpo extraño (CE) angustia a muchas familias que consultan con premura a Urgencias. El objetivo del estudio fue determinar las características epidemiológicas de los niños que consultaban por sospecha de ingesta de CE y sus consecuencias. MÉTODOS: Se realizó un estudio descriptivo-observacional, realizado en un centro materno-infantil de tercer nivel. Se seleccionaron los informes de Urgencias de pacientes menores de 18 años con diagnóstico de alta por "Ingesta CE" (código 938 CIM-9-MC hasta mayo 2018; código T18.9XXA CIM-10-MC posteriormente) del 1/1/2017 al 31/12/2018. Los datos fueron analizados con el programa estadístico SPSS 25.0. RESULTADOS: Se incluyeron 458 casos. La edad mediana fue de 3,8 años (p25-75: 1,9-6,6 años); 267 personas (58,3%) fueron varones. El 78,9% consultaron durante las 6 horas posteriores a la ingesta. Refirieron causa accidental el 98,9% los casos. En el 96,7%, la ingesta fue de un único CE. Los objetos más frecuentes fueron metálicos (46,7%), plásticos (16,4%) y huesos/cáscaras de alimentos (12,9%). El 23,6% de CE implicados fueron afilados/puntiagudos. El 49,1% de los pacientes presentaron algún síntoma. Se realizó alguna prueba complementaria en un 69,4% de los casos, sobre todo radiografías (63,5%). Se usó el detector de metales en el 10%. El 9,6% precisó endoscopia. El 90,4% fue dado de alta desde Urgencias, con un 12,1% de reconsultas. CONCLUSIONES: Las consultas por ingestión de CE son relativamente frecuentes en Urgencias y, aunque la mayoría son dados de alta, muchos pacientes requieren pruebas complementarias, y un número no despreciable, necesita endoscopia. El perfil del paciente es el de un varón en edad preescolar que acude espontáneamente a Urgencias por ingesta accidental de un objeto romo metálico

OBJECTIVE: Foreign body (FB) ingestion distresses many families who consult the emergency department promptly. The objective of the study is to determine the epidemiological characteristics of children who consult due to suspected FB intake and its consequences. METHODS: Descriptive-observational study, carried out in a third-level maternal and child center. Emergency reports were selected from patients under 18 years of age with a diagnosis of discharge "Ingesta CE" (code 938 CIM-9-MC until May 2018; code T18.9XXA CIM-10-MC later) from 1/1/2017 until 12/31/2018. Miscoded and reconsultations within the same episode were excluded. Data was analysed with the statistics program SPSS 25.0. RESULTS: 458 cases were included; median age 3.8 years (p25-75: 1.9-6.6 years); 267 (58.3%) males. 78.9% consulted in the first 6 hours after intake. Accidental cause was reported in 98.9% of cases. In 96.7% a single FB was ingested. The most frequent types of object were metallic (46.7%), plastics (16.4%) and food bones/shells (12.9%). The 23.6% of FB involved were sharp/pointed. 49.1% of the patients presented symptoms. A complementary test was performed in 69.4%, especially radiographs (63.5%). Metal detector was used in 10%. 9.6% required endoscopy. 90.4% were discharged from the emergency department, with 12.1% of reconsultations. CONCLUSIONS: Consultations for FB ingestion are relatively frequent in the emergency department and, although most of them are discharged, many patients require complementary tests and a non-negligible number, endoscopy. The patient's profile is that of a preschooler who spontaneously goes to the emergency room due to an accidental ingestion of a blunt metallic object

TAGOOS: genome-wide supervised learning of non-coding loci associated to complex phenotypes.

Genome-wide association studies (GWAS) associate single nucleotide polymorphisms (SNPs) to complex phenotypes. Most human SNPs fall in non-coding regions and are likely regulatory SNPs, but linkage disequilibrium (LD) blocks make it difficult to distinguish functional SNPs. Therefore, putative functional SNPs are usually annotated with molecular markers of gene regulatory regions and prioritized with dedicated prediction tools. We integrated associated SNPs, LD blocks and regulatory features into a supervised model called TAGOOS (TAG SNP bOOSting) and computed scores genome-wide. The TAGOOS scores enriched and prioritized unseen associated SNPs with an odds ratio of 4.3 and 3.5 and an area under the curve (AUC) of 0.65 and 0.6 for intronic and intergenic regions, respectively. The TAGOOS score was correlated with the maximal significance of associated SNPs and expression quantitative trait loci (eQTLs) and with the number of biological samples annotated for key regulatory features. Analysis of loci and regions associated to cleft lip and human adult height phenotypes recovered known functional loci and predicted new functional loci enriched in transcriptions factors related to the phenotypes. In conclusion, we trained a supervised model based on associated SNPs to prioritize putative functional regions. The TAGOOS scores, annotations and UCSC genome tracks are available here: https://tagoos.readthedocs.io.

Qualitative Dynamical Modelling Can Formally Explain Mesoderm Specification and Predict Novel Developmental Phenotypes.

Given the complexity of developmental networks, it is often difficult to predict the effect of genetic perturbations, even within coding genes. Regulatory factors generally have pleiotropic effects, exhibit partially redundant roles, and regulate highly interconnected pathways with ample cross-talk. Here, we delineate a logical model encompassing 48 components and 82 regulatory interactions involved in mesoderm specification during Drosophila development, thereby providing a formal integration of all available genetic information from the literature. The four main tissues derived from mesoderm correspond to alternative stable states. We demonstrate that the model can predict known mutant phenotypes and use it to systematically predict the effects of over 300 new, often non-intuitive, loss- and gain-of-function mutations, and combinations thereof. We further validated several novel predictions experimentally, thereby demonstrating the robustness of model. Logical modelling can thus contribute to formally explain and predict regulatory outcomes underlying cell fate decisions.

LedPred: an R/bioconductor package to predict regulatory sequences using support vector machines.

UNLABELLED: Supervised classification based on support vector machines (SVMs) has successfully been used for the prediction of cis-regulatory modules (CRMs). However, no integrated tool using such heterogeneous data as position-specific scoring matrices, ChIP-seq data or conservation scores is currently available. Here, we present LedPred, a flexible SVM workflow that predicts new regulatory sequences based on the annotation of known CRMs, which are associated to a large variety of feature types. LedPred is provided as an R/Bioconductor package connected to an online server to avoid installation of non-R software. Due to the heterogeneous CRM feature integration, LedPred excels at the prediction of regulatory sequences in Drosophila and mouse datasets compared with similar SVM-based software. AVAILABILITY AND IMPLEMENTATION: LedPred is available on GitHub: https://github.com/aitgon/LedPred and Bioconductor: http://bioconductor.org/packages/release/bioc/html/LedPred.html under the MIT license. CONTACT: aitor.gonzalez@univ-amu.fr SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.