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Resumen Introduccion El uso de anestesia general en ninos pequenos conlleva riesgos, a corto y largo plazo. El objetivo de este estudio fue evaluar la eficacia de la tecnica de resonancia magnetica (RM) cerebral sin anestesia mediante fijacion con colchon en ninos menores de 3 meses. Pacientes y metodos Estudio prospectivo de casos y controles realizado en el ano 2019. Los casos fueron pacientes menores de 3 meses con indicacion de RM craneal, estables y sin soporte ventilatorio; las resonancias se realizaron usando la tecnica de dar de comer y dormir y un colchon inmovilizador. Los controles fueron pacientes de la misma edad y sexo, inestables clinicamente, derivados para realizar RM craneal con anestesia general. Tres radiologos pediatricos evaluaron el exito de la RM (si respondia a la pregunta clinica), si era necesario repetirla y calificaron la presencia de artefactos de movimiento en una escala del 1 al 4. Resultados 47 casos fueron incluidos en este estudio (28 ninos, 19 ninas; media: 31 dias de vida), de los cuales (89%) 42 RM fueron llevadas a cabo de manera exitosa. Los estudios realizados de manera ambulatoria se asociaron a mayor posibilidad de fallo de la tecnica que los realizados a ingresados (valor de p 0,02). El 60% de las RM de los casos realizados tuvieron calidad optima y el 30%, suboptima (artefacto de movimiento en una o dos secuencias). No se detectaron problemas de seguridad con esta tecnica. La media de duracion de los estudios fue de 16,6 minutos (rango 6-30 minutos). El 100% de las RM de los controles bajo anestesia general se llevaron a cabo con exito, con una calidad optima en el 89% y suboptima en el 11% restante. En el primer ano de experiencia con esta tecnica, de 47 RM realizadas, se evito el uso de anestesia general a 42 recien nacidos. Conclusion La tecnica de dar de comer y dormir y fijacion con colchon neumatico para realizar RM sin anestesia puede realizarse de forma eficaz y segura en ninos menores de 3 meses.

OBJECTIVE To evaluate survival outcomes of fetuses with right sided congenital diaphragmatic hernia (CDH) treated in Latin American centres and to assess the utility of left lung area to predict neonatal survival. METHODS A retrospective cohort including isolated right sided CDH cases managed expectantly during pregnancy in six tertiary centers from five Latin American countries. The utility of the observed/expected lung-to-head ratio (O/E-LHR) in predicting neonatal survival was assessed, and the best cut-off to predict prognosis was automatically selected by decision tree analysis. RESULTS A total of 99 right sided CDH cases were recruited, 58 isolated fetuses were selected at a median gestational age of 26.2 weeks, showing an overall survival rate of 26.2%. A linear trend was observed between survival and the O/E-LHR, showing that at higher O/E-LHR, the greater probability of survival (r = 0.56, p

Background and objectives Atrial fibrillation (AF) detection in patients with embolic stroke of underdetermined source (ESUS), entails a change of medical treatment and a significant decrease in the incidence of new strokes. It is necessary to determine which patients would benefit more from prolonged electrocardiographic monitoring. Our aim was to find electrocardiographic and echocardiographic AF predictors in patients with ESUS. Methods We performed a cohort study that included 95 consecutive patients admitted to the hospital because of an ESUS. An electrocardiogram, each subject in the study underwent a 24-h Holter-electrocardiogram (Holter-ECG) and an echocardiogram. A 2-year follow up was also conducted, with a 24-h Holter-ECG every three months for the first year, and every 6 months during the second one. Results During the follow-up, AF was detected in 11 patients (11.6%), with a detection rate of 3.2% at 6 months, 7.4% at 12 months, and 11.6% at 18 months as well as at 24 months. The variables that were independently related to AF detection included moderate or severe left atrium dilation (p = .02), interatrial advanced block (p = .04) and more than 1000 premature atrial beats on 24 h Holter-ECG (p = .01). Conclusions Moderate or severe atrial dilation, interatrial advanced block, and the presence of more than 1000 premature atrial beats on 24 h Holter-ECG behave as AF predictors in patients with ESUS.

Gender significantly influences sociodemographic, medical, psychiatric and addiction variables in cocaine outpatients. Educational level may be a protective factor showing less severe addictive disorders, longer abstinence periods, and better cognitive performance. The aim was to estimate gender-based differences and the influence of educational level on the clinical variables associated with cocaine use disorder (CUD). A total of 300 cocaine-consuming patients undergoing treatments were recruited and assessed using the Psychiatric Research Interview for Substance and Mental Diseases according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Women developed CUD later but exhibited more consumption of anxiolytics, prevalence of anxiety disorders, eating disorders, and major depressive disorders. Alcohol and cannabis use disorders were more frequent in men. A predictive model was created and identified three psychiatric variables with good prognosis for distinguishing between women and men. Principal component analysis helped to describe the different profile types of men and women who had sought treatment. Low educational levels seemed to be a risk factor for the onset, development, and duration of CUD in both genders. Women and men exhibited different clinical characteristics that should be taken into account when designing therapeutic policies. The educational level plays a protective/risk role in the onset, development and progression of CUD, thus prolonging the years of compulsory education and implementing cognitive rehabilitation programmes could be useful.

1. Understanding species habitat use and factors affecting changes in their distribu-tions are necessary to promote the conservation of any biological community. We evaluated the changes in wetland use of the non- breeding waterbird community. Based on long-term citizen-science data (1988–2020), we tested the hypotheses that wetland use is associated with species diet and potential range-shift drivers (the tendency to occupy the same sites in consecutive years—site affinity—and the species' average temperature across its wintering range—species temperature index).2. We analysed species-specific wetland use of 25 species of waterbirds wintering in Czechia over a period of 33 years. The analyses explained variability in trends in numbers of the studied waterbird species across four inland wetland types: reser-voirs; fishponds; industrial waters created by flooding of former mining sites; and running waters.3. Trends in waterbird abundance positively correlated with species’ diet on fish-ponds, industrial and running waters. Among the diet groups, invertivores showed the largest increase in abundances on industrial waters, closely followed by her-bivores. Herbivores showed the largest increase in abundances in fishponds, and piscivores did so in running waters. Regarding range-shift drivers, species with higher site affinity showed higher abundances on running waters, while species with low species temperature index (i.e. wintering on average in sites with lower temperature) were more abundant on reservoirs. The abundance of both warm- dwelling and species with low site affinity increased on fishponds and industrial waters.4. Our findings suggest that the increased importance of the wetland types consid-ered here for wintering waterbirds is likely to be linked to diet related changes in habitat use and changes in species distributions; and highlight that wintering waterbirds are expected to select sites with higher availability of food, higher en-ergy content, and lower foraging cost.5. Recent and rapid changes in species distributions may lead to a decrease in the effectiveness of national and international conservation efforts. When planning conservation measures, it should be kept in mind that climate change does not only imply large-scale north/north- eastwards shifts of entire waterbird distribu-tions, but can also modify the use of the habitats by waterbird species inside their traditional wintering range. artificial wetlands, long-term monitoring, range-shift drivers, waterbirds, wetland type

The access to COVID vaccines by millions of human beings and their high level of protection against the disease, both in its mild and severe forms, together with a plausible decrease in the transmission of the infection from vaccinated patients, has prompted a series of questions from the members of the College of Physicians of Madrid (ICOMEM) and the society. The ICOMEM Scientific Committee on this subject has tried to answer these questions after discussion and consensus among its members. The main answers can be summarized as follows: The occurrence of new SARS-CoV-2 infections in both vaccinated and previously infected patients is very low, in the observation time we already have. When breakthrough infections do occur, they are usually asymptomatic or mild and, purportedly, should have a lower capacity for transmission to other persons. Vaccinated subjects who have contact with a SARS-CoV-2 infected patient can avoid quarantine as long as they are asymptomatic, although this decision depends on variables such as age, occupation, circulating variants, degree of contact and time since vaccination. In countries with a high proportion of the population vaccinated, it is already suggested that fully vaccinated persons could avoid the use of masks and social distancing in most circumstances. Systematic use of diagnostic tests to assess the immune response or the degree of protection against reinfection after natural infection or vaccination is discouraged, since their practical consequences are not known at this time. The existing information precludes any precision regarding a possible need for future revaccination. This Committee considers that when mass vaccination of health care workers and the general population is achieved, SARS-CoV-2 screening tests could be avoided at least in outpatient care and in the case of exploratory procedures that do not require hospitalization. post-print 156 KB

Since the beginning of the SARS-CoV-2 epidemic, virus isolation in the infected patient was only possible for a short period of time and it was striking that this occurred constantly and did not provide guidance on the clinical course. This fact led to confusion about the efficacy of some of the drugs initially used, which seemed to have a high efficiency in viral clearance and proved ineffective in modifying the course of the disease. The immune response also did not prove to be definitive in terms of evolution, although most of the patients with very mild disease had a weak or no antibody response, and the opposite was true for the most severe patients. With whatever the antibody response, few cases have been re-infected after a first infection and generally, those that have, have not reproduced a spectrum of disease similar to the first infection. Among those re-infected, a large number have been asymptomatic or with very few symptoms, others have had a moderate picture and very few have had a poor evolution. Despite this dynamic of rapid viral clearance, laboratory tests were still able to generate positive results in the recovery of genomic sequences and this occurred in patients who were already symptom-free, in others who were still ill and in those who were very seriously ill. There was also no good correlate. For this reason and with the perspective of this year and the half of pandemic, we compiled what the literature leaves us in these aspects and anticipating that, as always in biology, there are cases that jump the limits of the general behavior of the dynamics of infection in general. post-print 116 KB

Introducción: El papel de la Enfermería Nefrológica en el cuidado y atención humanizada de los pacientes en hemodiálisis es fundamental. Objetivos: Analizar la satisfacción percibida por pacientes y profesionales sanitarios de unidades de hemodiálisis tras la implementación de un programa para potenciar la humanización de la asistencia. Material y Método: Estudio analítico longitudinal prospectivo cuasiexperimental con grupo control histórico. La recogida de datos se realizó en un periodo de 13 meses en 16 centros de la Fundación Renal Íñigo Álvarez de Toledo, a un total de 667 pacientes y 180 trabajadores. Se emplearon dos cuestionarios autoadministrados, uno para pacientes y otro para profesionales. Resultados: Tras la implantación del programa, el número de pacientes que considera que el personal siempre les informa sobre los procedimientos aumentó de forma significativa (p=0,043) y un 62,4% de los pacientes valoró como importante que pueda entrar algún familiar o persona cercana durante la sesión. Tras la implantación del proyecto, el 49,2% de los profesionales sanitarios consideraron siempre necesaria la formación en el ámbito de la humanización y opinaban que sería conveniente mejorarla (p>0,005). Conclusiones: Se ha advertido un incremento significativo en la satisfacción de los pacientes respecto a la información proporcionada por los profesionales y la cercanía de éstos. Se han verificado valores muy positivos respecto al trato humanizado que reciben los pacientes y su comodidad durante las sesiones de hemodiálisis. Por otra parte, los profesionales consideran necesaria la formación en el ámbito de la humanización y creen que sería conveniente mejorarla en las unidades.

To analyze the effects of a program composed of resistance training and nutritional interventions on functional capacity, maximal strength, and power output after 2 years of follow-up, including 2 periods of 16 weeks of intervention followed by several weeks of intervention cessation in frail patients with type 2 diabetes.MIDPOW is a substudy of a multicenter, multimodal intervention composed of resistance training combined with a structured diabetes and nutritional education program in frail and prefrail older people with type 2 diabetes (MID-Frail).This study recruited 52 participants (mean age: 79 ± 5.6, 63% women), with type 2 diabetes mellitus, frail or prefrail using Fried's frailty phenotype.Primary outcomes of this substudy were Short Physical Performance Battery (SPPB) and maximal power output at 30% and 80% of 1RM.Each set of 16 weeks of intervention resulted in significant improvements in SPPB performance by a mean of 36.1% at week 18 (P.001) and 10.2% at week 68 (P.05). Maximal power output improvements at 30% and 80% of the 1RM ranged from 45.2% to 57.2% at week 18 (P.01-.001); and no significant changes were observed after the second period of intervention. After 2 years of follow-up, the SPPB and maximal power values observed remained significantly higher than the baseline.Resistance training combined with nutritional program improved SPPB, maximal strength, and power output in older frail patients with diabetes. These improvements were maintained above the basal levels after several weeks of intervention cessation during a 2-year follow-up.

Cognitive reserve (CR) is the capability of an individual to cope with a brain pathology through compensatory mechanisms developed through cognitive stimulation by mental and physical activity. Recently, it has been suggested that CR has a protective role against the initiation of substance use, substance consumption patterns and cognitive decline and can improve responses to treatment. However, CR has never been linked to cognitive function and neurotrophic factors in the context of alcohol consumption. The present cross-sectional study aims to evaluate the association between CR (evaluated by educational level), cognitive impairment (assessed using a frontal and memory loss assessment battery) and circulating levels of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in patients with alcohol use disorder (AUD). Our results indicated that lower educational levels were accompanied by earlier onset of alcohol consumption and earlier development of alcohol dependence, as well as impaired frontal cognitive function. They also suggest that CR, NT-3 and BDNF may act as compensatory mechanisms for cognitive decline in the early stages of AUD, but not in later phases. These parameters allow the identification of patients with AUD who are at risk of cognitive deterioration and the implementation of personalized interventions to preserve cognitive function.

The present work aimed to examine the association between physical activity (PA) and sedentary behaviour with maximal fat oxidation (MFO) in young individuals. A total of 77 active adults (30 women; 22.8 ± 4.5 years) were included in this cross-sectional study in which PA and sedentary behaviour were measured using accelerometers for 7 consecutive days. PA was classified into different intensities (i.e. light, moderate, vigorous, and moderate-to-vigorous) and sedentary behaviour into sedentary time (i.e. time, and the number of bouts) and sedentary breaks (i.e. time, and the number of bouts). MFO was determined using a graded cycloergometer test through indirect calorimetry and relativized to lean mass (MFOLM) and lean leg mass (MFOLL). Positive associations were found for light and vigorous PA in relation with MFO, MFOLM and MFOLL, independently of cofounders (P≤0.01). Moreover, a negative association was found between MFO and MFOLM and the length of sedentary behaviour which was accentuated after adjusting by cardiorespiratory fitness (P≤0.05). No associations were found between sedentary time and MFOLM or MFOLL (P>0.05). These results suggest that light and vigorous PA and sedentary behaviour are related to MFO during exercise. Despite this, further interventional studies are needed to clarify if increments of light and vigorous PA could enhance MFO in different populations.

Liposuction remains one of the most frequently performed cosmetic surgical procedures and its popularity is increasing every year. However, since its inception, justified concerns regarding patient safety have placed limits on the volume of fat that can be aspirated, influenced by hemodynamic fluctuations and blood loss during liposuction. Tranexamic acid (TXA) is an antifibrinolytic agent that competitively inhibits the conversion of plasminogen to plasmin, thus preventing the binding and degradation of fibrin. Despite the existence of evidence of the effectiveness of TXA in orthopedic and cardiac surgeries, there is little evidence of its use in liposuction. The objective of this study was to evaluate the efficacy and safety of tranexamic acid in the control of surgical bleeding in patients undergoing liposuction, through a prospective, open, randomized and controlled clinical trial. Two groups of 25 participants each were formed to whom the application of TXA in a tumescent solution prior to liposuction or liposuction with the traditional technique was randomly assigned. The results showed a decrease in blood loss reflected by the differences in the final hematocrit values, as well as decrease in the same per aspirated volume (p = 0.003). No adverse events were found related with the TXA application and no blood transfusions were required in this group, in contrast to the control group where the need for blood transfusion was present in 20% of the intervened participants. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Resumen El objetivo del desarrollo de una PET dedicada al cerebro (CareMiBrain) ha evolucionado desde su enfoque inicial de diagnostico y monitorizacion de demencias hasta el mas ambicioso de crear una via clinica revolucionaria para el conocimiento y tratamiento personalizado de multiples enfermedades neurologicas. La principal caracteristica innovadora de CareMiBrain es el uso de detectores con cristales continuos que permiten una determinacion de alta resolucion de la profundidad de interaccion de los fotones de aniquilacion dentro del espesor del cristal de centelleo. La fase de validacion tecnica del equipo consistio en un estudio piloto, prospectivo y observacional cuyo objetivo era obtener las primeras imagenes (40 pacientes), analizarlas y realizar ajustes en parametros de adquisicion, reconstruccion y correccion, comparando la calidad de la imagen del equipo CareMiBrain con la del equipo PET-TC de cuerpo completo. Gracias a las reuniones del equipo y al analisis conjunto de las imagenes fue posible detectar sus puntos debiles y algunas de sus causas. Se optimizaron los procesos de calibracion, de adquisicion y procesado, asi como la reconstruccion, se fijo el numero de iteraciones para conseguir la mejor relacion senal-ruido, se optimizo la correccion aleatoria y se incluyo un algoritmo de posprocesamiento en el algoritmo de reconstruccion. Se expondran las principales mejoras tecnicas implementadas en esta fase de validacion tecnica realizada mediante colaboracion de los Servicios de Medicina Nuclear y Neurologia del Hospital Clinico San Carlos con la empresa espanola Oncovision en un proyecto financiado con fondos de la Union Europea (programa de innovacion Horizonte 2020, 713323).

Objective To establish the prevalence of potentially inappropriate prescription (PIP) in older people with advanced dementia, monitored by a Geriatric Home Care Unit (GHC), as well as the associated risk factors and costs. Methods Community-dwelling patients ≥65 years with an advanced dementia diagnosis (GDS-FAST ≥ 7a) and poor 1-year vital prognosis (Frail-VIG ≥ 0.6) were included. Pharmacotherapy history was reviewed retrospectively, collecting functional and cognitive status, on the first GHC visit, of patients assessed January 2016–January 2019. Potentially inappropriate medication was defined following STOPP-Frail criteria. Results 100 patients included (76% women, 89.15 ± 5.8 years). Total medications prescribed 760 (7.63 ± 3.4 drugs per patient). 85% patients were given at least one drug considered to be PIP. 26% (196) of the total drugs registered were PIPs. Patients who were prescribed an inappropriate drug showed a higher number of total prescribed drugs (7.92 ± 3.42 vs 6.00 ± 2.24; p 0.04) and a higher frequency of polypharmacy (84.7% vs 60%; p 0.025). Risk of receiving inappropriate medication increased by 24% for each additional drug prescribed (OR 1.24; 95% CI 1.01–1.52; p 0.04). The costs associated with PIP were 113.99 euros per 100 patients/day; 41,606.35 euros per 100 patients/year. Conclusions Prescription of PIP to community-dwelling patients with severe dementia and poor vital prognosis is common and is associated with high economic impact in this population group.

Key summary points Aim The objective of this study is to describe the baseline characteristics of oldest-old patients admitted with COVID-19 to an acute geriatric unit and to determine the factors associated with in-hospital mortality. Findings Dementia, incident delirium, and the CURB-65 score ≥ 3 are independent mortality risk factors. The concurrent use of angiotensin-converting enzyme inhibitors is a protective factor. Message Recognition of geriatric syndromes may be useful to help clinicians establish the prognosis of oldest-old patients admitted to hospital with COVID-19., Purpose To determine predictors of in-hospital mortality related to COVID-19 in oldest-old patients. Design Single-center observational study. Setting and participants Patients ≥ 75 years admitted to an Acute Geriatric Unit with COVID-19. Methods Data from hospital admission were retrieved from the electronic medical records: demographics, geriatric syndromes (delirium, falls, polypharmacy, functional and cognitive status) co-morbidities, previous treatments, clinical, laboratory, and radiographic characteristics. Cox proportional hazard models were used to evaluate in-hospital mortality. Results Three hundred patients were consecutively included (62.7% females, mean age of 86.3 ± 6.6 years). Barthel Index (BI) was

• Several cardiovascular/hemostatic disturbances haves been reported in patients with COVID-19, but the real frequency and their potential association with the pathogenic mechanisms of SARS-CoV-19 still remain to be defined. • We investigated the relative frequency of acute coronary syndrome, deep venous thrombosis, pulmonary embolism, stroke and upper gastrointestinal bleeding in COVID patents attending emergency departments (EDs), before hospitalization and compared them with frequencies in the general ED population attending 50 Spanish EDs. • We found that the risk of pulmonary embolism is clearly increased in COVID patients, with an OR of 4.53 with respect to non-COVID patients (95% confidence interval 4.03- 5.10). Additionally, the diagnosis of pulmonary embolism was 2 fold more frequent among ED comers in 2020 compared to 2019, suggesting a SARS-CoV-2 role in such increment of cases.. The remaining entities studied were not found to be unequivocally increased in the present study and need further investigation.

Aspirin-exacerbated respiratory disease (AERD) consists of asthma, chronic rhinosinusitis with polyps, and hypersensitivity to aspirin and/or nonsteroidal anti-inflammatory drugs (NSAIDs). Nasal Lysine Aspirin Challenge is an effective tool for the diagnosis of hypersensitivity to aspirin and/or NSAIDs in patients with AERD. However, there is no unified international consensus version to perform nasal provocation tests (NPTs).To investigate the effect of a leukotriene receptor antagonist (LTRA), montelukast, on the lysine-acetylsalicylate (L-ASA) nasal challenge.We included 86 patients divided into 3 samples: group A (AERD without LTRA), group B (AERD with LTRA), and the control group (NSAID-tolerant asthmatics). NPT with L-ASA was performed with 25 mg of L-ASA every 30 minutes 4 times followed by rhinomanometry and spirometric measurements and evaluation of symptoms using a novel clinical scale.In group A, 94.5% of patients (35 of 37) developed a positive response to NPT (drop40% in total nasal flow), whereas only 46% of group B subjects (13 of 28) showed a positive response to the nasal challenge (P.001). Control subjects did not show any response to the L-ASA challenge. A novel clinical score demonstrated accuracy in classifying the hypersensitivity to aspirin and/or NSAIDs when patients avoid LTRA (33 of 37).Patients with AERD without LTRA showed a greater positive response to the L-ASA challenge than those taking this drug; therefore, LTRA treatment should be discontinued before the challenge for optimal diagnostic accuracy.

Objective: Experts recommended that direct discharge without hospitalization (DDWH) for emergency departments (EDs) able to observe acute heart failure (AHF) patients should be 40%, and these discharged patients should fulfil the following outcome standards: 30-day all-cause mortality 40%. Considering DDWH patients altogether, outcomes A/C were above the recommended standards (4.3%/29.4%), while outcome B was nearly met (B = 10.1%). When analyzing individual EDs, 58.1% of them achieved the outcome B standard, while outcomes A/C standards were barely achieved (19.3%/9.7%). We observed clinically relevant linear/quadratic relationships between higher DDWH and worse outcomes B (weighted R-2 = 0.184/0.322) and C (weighted R-2 = 0.430/0.624), but not with outcome A (weighted R-2 = 0.002/0.022). Conclusions: The EDs of this nationwide cohort do not fulfil the standards for AHF patients with DDWH. High DDWH rates negatively impact ED revisit or hospitalization but not mortality. This may represent an opportunity for improvement in better selecting patients for early ED discharge and in ensuring early follow-up after ED discharge. (c) 2020 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.

Lysophosphatidic acid (LPA) species are bioactive lipids participating in neurodevelopmental processes. The aim was to investigate whether the relevant species of LPA were associated with clinical features of alcohol addiction. A total of 55 abstinent alcohol use disorder (AUD) patients were compared with 34 age/sex/body mass index-matched controls. Concentrations of total LPA and 16:0-LPA, 18:0-LPA, 18:1-LPA, 18:2-LPA and 20:4-LPA species were quantified and correlated with neuroplasticity-associated growth factors including brain derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1) and IGF-2, and neurotrophin-3 (NT-3). AUD patients showed dysexecutive syndrome (22.4%) and memory impairment (32.6%). Total LPA, 16:0-LPA, 18:0-LPA and 18:1-LPA concentrations, were decreased in the AUD group compared to control group. Total LPA, 16:0-LPA, 18:2-LPA and 20:4-LPA concentrations were decreased in men compared to women. Frontal lobe functions correlated with plasma LPA species. Alcohol-cognitive impairments could be related with the deregulation of the LPA species, especially in 16:0-LPA, 18:1-LPA and 20:4-LPA. Concentrations of BDNF correlated with total LPA, 18:2-LPA and 20:4-LPA species. The relation between LPA species and BDNF is interesting in plasticity and neurogenesis functions, their involvement in AUD might serve as a biomarker of cognitive impairment. The present study has been supported by the following programs and research projects: Subprograma Redes Temáticas RETICS (Red de Trastornos Adictivos RD16/0017/001 and RD12/0028/0021) funded by Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad (MINECO) and the European Regional and European Regional Development Funds/European Social Fund (ERDF/ESF); Proyectos de Investigación en Salud (PI16/01953, PI16/01698 and PI17/02026) funded by ISCIII and ERDF/ESF; Proyectos de Investigación en Drogodependencias (PND2017/043, PND2018/033, PND2018/044 and PND2019/040) funded by Delegación del Gobierno para el Plan Nacional sobre Drogas, Ministerio de Sanidad, Secretaría de Estado de Sanidad and ERDF/ESF; Proyecto de Investigación en Salud (PI-0140-2018) funded by Consejería de Salud y Bienestar Social, Junta de Andalucía and ERDF/ESF. NGM holds a “Sara Borrell” research contract (CD19/00019) funded by ISCIII and ERDF/ESF. FJP, AS and JS hold a “Miguel Servet II” research contract (CPII19/00022, CPII19/00031 and CPII17/00024, respectively) funded by ISCIII and ERDF/ESF. RTF holds a Grant (2017 SGR 138) funded by Departament d’Economia i Coneixement de la Generalitat de Catalunya (CIBEROBN), ISCIII and ERDF/ESF. Yes

Resumen Introduccion y objetivos El pronostico de la estenosis aortica (EAo) grave asintomatica en la poblacion anciana, que a menudo asocia fragilidad y comorbilidades no ha sido estudiado. Se propuso analizar que factores podrian influir en la mortalidad precoz esta poblacion. Metodos Estudio ambispectivo de cohortes en 104 pacientes con edad ≥ 70 anos y EAo grave asintomatica. Se recogieron variables epidemiologicas, geriatricas, clinicas y ecocardiograficas y se compararon entre pacientes fragiles y no fragiles. Durante el seguimiento se recogio el tiempo desde el diagnostico hasta la mortalidad. Resultados El 59,6% de los pacientes eran fragiles. El 69,4% de los pacientes fragiles fallecieron, con una mediana de supervivencia de 2,52 anos (IC95%, 1,36-3,69). La tasa de supervivencia global al ano en estos sujetos fue del 76%. En el analisis multivariante la edad (HR = 2,47; IC95%, 1,00-6,12), el indice de Charlson ≥ 5 (HR = 3,75; IC95%, 1,47-9,52) y la fragilidad (HR = 6,67; IC95%, 1,43-9,52) se asociaron independientemente a la mortalidad. Un 8,7% de los pacientes presentaron un indice de Charlson ≥ 5 y tuvieron una mediana de supervivencia de 1,01 anos (IC95%, 0,36-1,67). El area bajo la curva receiver operating characteristic del indice de Charlson fue 0,739 (IC95%, 0,646-0,832). Los valores ≥ 5 mostraron una elevada especificidad (100%) pero baja sensibilidad. Conclusiones Existe una elevada prevalencia de fragilidad en pacientes ancianos con EAo grave asintomaticos. La edad, un indice de Charlson ≥ 5 y la fragilidad son marcadores independientes de mortalidad, asociando un pronostico desfavorable a corto plazo.

Rationale: The emergence of the consumption of highly potent synthetic cannabinoid receptor agonists (spice drugs) that produce important neurological symptoms has prompted the research on the consequences of acute and chronic use of these new psychoactive substances. Most studies on cannabinoid dependence have been performed in male animals, and there is a need of studies using female subjects. Objectives: In the present study, we evaluated only in female animals the role of dopamine D1 receptors in the behavioral responses induced by acute and repeated stimulation of cannabinoid CB1 receptors, including the development of physical dependence, since cannabinoid CB1 receptors are co-localized with dopamine D1 receptors on GABAergic neurons projecting to the substantia nigra. Methods: To this end, female dopamine D1 receptor-deficient mice and wild-type littermates were treated with HU-210, a potent synthetic cannabinoid agonist. Results: Mutant mice displayed an enhanced response to acute motor and hypothermic effects to HU-210 when compared with wild-type females. The administration of SR141716A precipitated behavioral signs of withdrawal in mice treated subchronically with HU-210. Severity of cannabinoid withdrawal syndrome was potentiated in dopamine D1-deficient female mice. Indeed, 4 of 6 abstinence signs were increased in mutant mice. Conclusions: These results support for a role of dopamine D1 receptors in the acute, chronic, and withdrawal actions of spice drugs., This work was supported by Red de Trastornos Adictivos, Instituto de Salud Carlos III and European Regional Development Funds-European Union (RD16/0017/001 to F.R.F); Ministerio de Economía y Competitividad, Instituto de Salud Carlos III and European Regional Development Funds-European Union (PI19/01755 to F.R.F and PI17/02026 to A.S); and Plan Nacional sobre Drogas and Ministerio de Sanidad, Servicios Sociales e Igualdad (PND2019/040, PND2018/044, PND2018/033, PND2017/043). AS, FJP and JS hold Miguel Servet research contracts funded by Instituto de Salud Carlos III and European Regional Development Funds-European Union (CP14/00173 to A.S, CP14/00212 to F.J.P and CPII17/00024 to J.S.).

En diciembre del 2019, en la provincia de Wuhan, China, se describió una nueva enfermedad respiratoria, aguda y potencialmente letal, causada por un coronavirus. A esta enfermedad se le denominó Covid-19. En México, la mortalidad por esta enfermedad es elevada y un porcentaje importante de los enfemos muere en los hospitales. Por ahora no existe en México un protocolo específico en el sistema de salud tanto público como privado, para que las familias puedan decirle adiós a los enfermos con Covid-19. Un panel de expertos en cuidados paliativos y bioética proponen uno, para que pueda servir como referencia en cada unidad de salud de nuestro país

No large-scale genome-wide association studies (GWASs) of psychosis have been conducted in Mexico or Latin America to date. Schizophrenia and bipolar disorder in particular have been found to be highly heritable and genetically influenced. However, understanding of the biological basis of psychosis in Latin American populations is limited as previous genomic studies have almost exclusively relied on participants of Northern European ancestry. With the goal of expanding knowledge on the genomic basis of psychotic disorders within the Mexican population, the National Institute of Psychiatry Ramón de la Fuente Muñiz (INPRFM), the Harvard T.H. Chan School of Public Health, and the Broad Institute’s Stanley Center for Psychiatric Research launched the Neuropsychiatric Genetics Research of Psychosis in Mexican Populations (NeuroMex) project to collect and analyze case-control psychosis samples from 5 states across Mexico. This article describes the planned sample collection and GWAS protocol for the NeuroMex study. The 4-year study will span from April 2018 to 2022 and aims to recruit 9,208 participants: 4,604 cases and 4,604 controls. Study sites across Mexico were selected to ensure collected samples capture the genomic diversity within the Mexican population. Blood samples and phenotypic data will be collected during the participant interview process and will contribute to the development of a local biobank in Mexico. DNA extraction will be done locally and genetic analysis will take place at the Broad Institute in Cambridge, MA. We will collect extensive phenotypic information using several clinical scales. All study materials including phenotypic instruments utilized are openly available in Spanish and English. The described study represents a long-term collaboration of a number of institutions from across Mexico and the Boston area, including clinical psychiatrists, clinical researchers, computational biologists, and managers at the 3 collaborating institutions. The development of relevant data management, quality assurance, and analysis plans are the primary considerations in this protocol article. Extensive management and analysis processes were developed for both the phenotypic and genetic data collected. Capacity building, partnerships, and training between and among the collaborating institutions are intrinsic components to this study and its long-term success.

Introduction: Subcutaneous allergen-specific immunotherapy (SCIT) is one of the main cornerstones in the treatment of allergic rhinitis in pediatric patients. It has demonstrated symptoms and quality of life improvement, but it is not exempt from adverse reactions (ADVrs). Nevertheless, there are a few reports that have evaluated their safety. Our objective was to evaluate the ADVr to SCIT in pediatric patients. Methods: We reviewed 786 clinical records with SCIT from 2005 to 2018, comparing the clinical characteristics of patients with ADVrs with SCIT versus a group of a similar number of patients who completed SCIT (control group, CG). The analysis of ADVrs was according to the World Allergy Organization (WAO) 2010 grading system by frequency analysis, survival curve, and log rank. Results: Of 786 patients, 106 (13.4%) presented ADVrs, and the patients with ADVr had sensitivity and immunotherapy with at least 2 allergens versus CG p < 0.001, containing a combination of standardized and nonstandardized allergens (p = 0.003). The ADVrs were in the buildup phase (p < 0.001). The survival curve showed that 50% had some reaction at 12 weeks of SCIT. The most frequent ADVr was grade 1 in 73/106 patients (68.8%) and grade 2 in 33/106 (31.1%). The log-rank analysis between the grades of the WAO grading system showed a statistically significant difference (p = 0.02). Conclusions: The SCIT is safe in pediatric patients. The ADVrs are infrequent, grade 1 being the most reported; however, at >12 weeks, the risk of ADVrs that involve 2 organs systems increases.

Guayaquil is proposed as a tourist and business destination, aiming to stand out as a digital city, with a suitable airport, a convention centre and high-level accommodation capacity. The city receives many domestic and international tourists, although not always as the main destination of their visit. One of the tourist markets offered by the city is that of business, due to the important economic activity that takes place here, being the venue of congresses and international events. This has allowed the city to gain significant value in the business tourism sector, providing constant and profitable growth. However, the lack of study of the international market, specifically the millennial business sector, is affecting Guayaquil's competitiveness compared to other destinations that have already recognized the differentiated profile of visitors from this age group, and that consequently offer a fusion of business and leisure tourism. This research was carried out during the second semester of 2018, evaluating the market of the new bleisure trend in Guayaquil. The results evidence the limited supply directed to this market segment, the lack of exploitation of business tourism and the continued lack of capacity of the tourism sector to satisfy the bleisure market. The conclusions focus on how tourism competitiveness can be achieved in business cities that also encompass places or activities where visitors can have a relaxing time.

Objective: The authors investigated the incidence, risk factors, clinical characteristics, and outcomes of upper gastrointestinal bleeding (UGB) in patients with coronavirus disease 2019 (COVID-19), who were attending the emergency department (ED), before hospitalization. Methods: We retrospectively reviewed all COVID-19 patients diagnosed with UGB in 62 Spanish EDs (20% of Spanish EDs, case group) during the first 2 months of the COVID-19 outbreak. We formed 2 control groups: COVID-19 patients without UGB (control group A) and non-COVID-19 patients with UGB (control group B). Fifty-three independent variables and 4 outcomes were compared between cases and controls. Results: We identified 83 UGB in 74,814 patients with COVID-19 who were attending EDs (1.11%, 95% CI=0.88-1.38). This incidence was lower compared with non-COVID-19 patients [2474/1,388,879, 1.78%, 95% confidence interval (CI)=1.71-1.85; odds ratio (OR)=0.62; 95% CI=0.50-0.77]. Clinical characteristics associated with a higher risk of COVID-19 patients presenting with UGB were abdominal pain, vomiting, hematemesis, dyspnea, expectoration, melena, fever, cough, chest pain, and dysgeusia. Compared with non-COVID-19 patients with UGB, COVID-19 patients with UGB more frequently had fever, cough, expectoration, dyspnea, abdominal pain, diarrhea, interstitial lung infiltrates, and ground-glass lung opacities. They underwent fewer endoscopies in the ED (although diagnoses did not differ between cases and control group B) and less endoscopic treatment. After adjustment for age and sex, cases showed a higher in-hospital all-cause mortality than control group B (OR=2.05, 95% CI=1.09-3.86) but not control group A (OR=1.14, 95% CI=0.59-2.19) patients. Conclusions: The incidence of UGB in COVID-19 patients attending EDs was lower compared with non-COVID-19 patients. Digestive symptoms predominated over respiratory symptoms, and COVID-19 patients with UGB underwent fewer gastroscopies and endoscopic treatments than the general population with UGB. Inhospital mortality in COVID-19 patients with UGB was increased compared with non-COVID patients with UGB, but not compared with the remaining COVID-19 patients.

ObjectiveMyofascial pain syndrome is one of the primary causes of health care visits. In recent years, physical exercise programs have been developed for the treatment of myofascial trigger points, but their effect on different outcomes has not been clarified. Thus, this study aimed to assess the effect of physical exercise programs on myofascial trigger points.MethodsA systematic search was conducted in Pubmed, Web of Science, and Scopus. Articles analyzing the effect of physical exercise programs on pain intensity, pressure pain threshold, range of motion, and disability were included. Risk of bias was assessed using the Cochrane RoB2 tool. The DerSimonian-Laird method was used to compute the pooled effect sizes (ES) and their 95% confidence interval (95% CI) for pain intensity, pressure pain threshold, range of motion, and disability.ResultsA total of 24 randomized controlled trials were included in this systematic review and meta-analysis. The pooled ES were –0.47 (95% CI = –0.61 to –0.33) for pain intensity, 0.63 (95% CI = 0.31 to 0.95) for pressure pain threshold, 0.43 (95% CI = 0.24 to 0.62) for range of motion, and –0.18 (95% CI = –0.45 to 0.10) for disability.ConclusionsPhysical exercise programs may be an effective approach in the treatment of pain intensity, pressure pain threshold, and range of motion among patients with myofascial trigger points.

[Background] The “Ex-Utero Intrapartum Treatment” (EXIT) procedure allows to ensure fetal airway before completion of delivery and umbilical cord clamping while keeping uteroplacental circulation. Airway obstruction in fetal oropharyngeal and cervical masses can be life-threatening at birth. In those situations, controlled access to fetal airway performed by a trained multidisciplinary team allows safe airway management, while feto-maternal circulation is preserved. We aim to review the indications and outcome of the EXIT procedure in a case series of fetal cervical and oropharyngeal masses., [Methods] We have carried out a retrospective review of all patients with fetal cervical and oropharyngeal masses who underwent an EXIT procedure between 2008 and 2019. Variables evaluated included indication for EXIT, ultrasound and MRI findings, the need of amnioreduction, gestational age at EXIT, birth weight, complications, operative time, survival rate, pathological findings, and postnatal evolution. Five patients are included in this series. One additional case has already been published., [Results] The diagnosis were cervical teratoma (n = 1), epulis (n = 1) and lymphangioma (n = 3). Polyhydramnios was present in 2 patients, requiring amnioreduction in one of them. Mean gestational age at EXIT was 36–37 weeks (range, 34–38 weeks). Median EXIT time in placental support was 9 min (range, 3–22 min). Access to airway was successfully established in EXIT in all cases. All children born by EXIT are currently healthy and without complications., [Conclusion] The localization and characteristics of the mass, its relationship to the airway, and the presence of polyhydramnios seem to be major factors determining indications for EXIT and clinical outcome.

BACKGROUND Major depressive disorder (MDD) is a global health issue that affects 350 million people of all ages. Although between 2% and 5.6% of affected individuals are adolescents, research on young patients is limited. The inflammatory response contributes to the onset of depression, and in adult MDD patients, symptom severity has been linked to chemokine levels. AIM To determine the differences in circulatory levels of chemokines in healthy volunteers (HVs) and adolescents with MDD, and assess the changes induced by fluoxetine consume. METHODS The 22 adolescents with MDD were monitored during the first 8 wk of clinical follow-up and clinical psychiatric evaluation was done using the Hamilton depresión rating scale (HDRS). The serum levels of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1α, MIP-1β, interleukin (IL)-8, interferon gamma-induced protein (IP)-10, and eotaxin were measured in patients and HVs. RESULTS In all cases, significant differences were detected in circulating chemokine levels between patients before treatment and HVs (P < 0.0001). All chemokines decreased at 4 wk, but only MCP-1 and IL-8 significantly differed (P < 0.05) between 0 wk and 4 wk. In the patients, all chemokines rose to their initial concentrations by 8 wk vs 0 wk, but only IP-10 did so significantly (P < 0.05). All patients experienced a significant decrease in HDRS scores at 4 wk (P < 0.0001) and 8 wk (P < 0.0001) compared with 0 wk. CONCLUSION Despite the consumption of fluoxetine, patients had significantly higher chemokine levels, even after considering the improvement in HDRS score. The high levels of eotaxin, IP-10, and IL-8 partially explain certain aspects that are affected in MDD such as cognition, memory, and learning.

Dentro de los Sistemas de Distribución Eléctrica (SDE), los consumidores generan la demanda energética, lo que es tema principal de discusión, puesto que es necesario satisfacer la misma. A partir de este punto, es importante considerar que el hecho de entregar energía desde los puntos de generación centralizada hasta las cargas supone una gran inversión y gasto, si se pone sobre la mesa las siguientes consideraciones: pérdidas de energía, costos de operación, niveles de voltaje, etc. La Generación Distribuida (GD), usando energías renovables no convencionales (ERNC), abre un espacio como posible solución a los problemas mencionados, dado que la GD se ubica en puntos estratégicos y cercanos a las cargas y cuentan con la capacidad de satisfacer la demanda requerida en dicho nodo, como también entregar energía al SDE, de ser necesario; por lo que se logra minimizar los problemas técnicos, económicos y operativos que puedan existir. En este documento se expone la óptima ubicación y dimensionamiento de las unidades de GD con tecnología fotovoltaica que serán introducidas al SDE por medio de un algoritmo, que permita minimizar los costos de operación, basado en el método de generación de columnas que será implementado; además de generar una micro red sin enrutamiento, que represente un escenario, lo más real posible, a partir de la georreferenciación con ayuda de la teoría de grafos que se implementará en MATLAB.

La tungiasis es una ectoparasitosis causada por la pulga hematófaga Tunga penetrans. Se considera una de las enfermedades dermatológicas más comunes de los viajeros que visitan áreas tropicales. El ser humano es un hospedero accidental. Afecta exclusivamente la piel. Las lesiones suelen localizarse en los pies y sus manifestaciones clínicas son polimorfas. El diagnóstico es clínico y el tratamiento consiste en la extracción del parásito. En algunos casos es necesario agregar tratamiento con antibióticos, antiparasitarios sistémicos y profilaxis antitetánica.

Background Scientific journals play a critical role in research validation and dissemination and are increasingly vocal about the identification of research priorities and the targeting of research results to key audiences. No new journals specialising in health policy and systems research (HPSR) and focusing in the developing world or in a specific developing world region have been established since the early 1980s. This paper compares the growth of publications on HPSR across Latin America and the world and explores the potential, feasibility and challenges of innovative publication strategies. Methods A bibliometric analysis was undertaken using HPSR MeSH terms with journals indexed in Medline. A survey was undertaken among 2500 authors publishing on HPSR in Latin America (LA) through an online survey, with a 13.1% response rate. Aggregate indicators were constructed and validated, and two-way ANOVA tests were performed on key variables. Results HPSR publications on LA observed an average annual growth of 27.5% from the years 2000 to 2018, as against 11.4% worldwide and yet a lag on papers published per capita. A total of 48 journals with an Impact Factor publish HPSR on LA, of which 5 non-specialised journals are published in the region and are ranked in the bottom quintile of Impact Factor. While the majority of HPSR papers worldwide is published in specialised HPSR journals, in LA this is the minority. Very few researchers from LA sit in the Editorial Board of international journals. Researchers highly support strengthening quality HPSR publications through publishing in open access, on-line journals with a focus on the LA region and with peer reviewers specialized on the region. Researchers would support a new open access journal specializing in the LA region and in HPSR, publishing in English. Open access up-front costs and disincentives while waiting for an Impact Factor can be overcome. Conclusion Researchers publishing on HPSR in LA widely support the launching of a new specialised journal for the region with a vigorous editorial policy focusing on regional and country priorities. Strategies should be in place to support English-language publishing and to develop a community of practice around the publication process. In the first years, special issues should be promoted through a priority-setting process to attract prominent authors, develop the audience and attain an Impact Factor.

Introduction: There is not much information about the care of infants with hypoxic-ischaemic encephalopathy (HIE) treated with therapeutic hypothermia (TH) in Spain. This includes whether protocols are routinely used, the type of neuro-monitoring performed, and how information on the neurological prognosis is presented to families. The answers to these would allow to detect and implement areas of improvement. Method: A cross-sectional analysis was performed on the responses to structured questionnaires sent to all the Spanish neonatal units that were performing TH in June 2015. Questions were divided into 5 sections: (1) the availability of protocols and technological resources, (2) the use of neuro-monitoring tools, (3) the knowledge and training of the professionals; (4) the prognostic information given to the parents; and (5) the discharge report and the follow-up plan. Results: Most centres (95%) use servo controlled whole-body cooling methods and have specific management protocols. Sedation is used in 70% of centres, and in 68% of them the onset of enteral feeding is delayed until the end of the cooling period. Amplitude-integrated electroencephalography monitoring is used in more than 80% of the centres, although only in 50% are nurses able to interpret it. Cerebral oxygen saturation is not often monitored (16%). As regards diagnostic-prognostic studies, neuroimaging is universal, but brain damage biomarkers are hardly used (29%). Prognostic information is offered within the first 72 posnatal hours in 21% of the centres, and is given without the presence of the nurse in 70% of the centres. Follow-up is performed by a neuro-paediatrician (84%), with an uneven duration between centres. Conclusions: The care of infants with HIE treated with TH in Spain is generally adequate, although there are areas for improvement in neuromonitoring, sedation, prognostic information, teamwork, and duration of follow-up. Resumen: Introducción: Apenas conocemos cómo es la asistencia de los recién nacidos (RN) con encefalopatía hipóxico-isquémica (EHI) en hipotermia terapéutica (HT), especialmente si existen protocolos asistenciales, la neuromonitorización que se realiza o cómo es la aproximación al pronóstico neurológico. Este conocimiento permite detectar e implementar áreas de mejora asistencial. Método: Estudio transversal de los 57 hospitales españoles que realizaban HT en 2015, mediante cuestionario sobre: 1) la disponibilidad de protocolos y de recursos tecnológicos; 2) el uso de herramientas de neuromonitorización; 3) los conocimientos de los profesionales; 4) la información pronóstica que se da los padres, y 5) el informe al alta y del plan de seguimiento. Resultados: El 95% utiliza enfriamiento corporal-total servocontrolado y dispone de protocolos específicos de actuación. El 70% utiliza sedación y el 68% deja al paciente a dieta absoluta. La monitorización con electroencefalografía integrada por amplitud se utiliza en más del 80% de los centros, aunque solo en el 50% la enfermera es capaz de interpretarlo. La saturación de oxígeno cerebral es escasamente monitorizada (16%). Entre los estudios diagnóstico-pronósticos, la neuroimagen es universal, pero los neurobiomarcadores apenas se utilizan (29%). Solo el 21% ofrece información pronóstica antes de las 72 h de vida; sin presencia de la enfermera en el 70%. El seguimiento lo realiza el neuropediatra (84%), con una duración desigual entre centros. Conclusiones: La asistencia del RN con EHI en España es adecuada, con áreas de mejora en: neuromonitorización, sedación, marco temporal de la información pronóstica, trabajo en equipo y estandarización de la duración del seguimiento.

Purpose Bipolar disorder (BD) is a condition associated with structural alterations in the prefrontal cortex (PFC); some genetic variants and mood stabilizer medications like lithium or valproate are associated with these changes. CACNA1C is a gene involved in BD pathology and brain function; carriers of the A allele of rs1006737 are reported to have increased risk for BD and increased cortical thickness (CT) in the PFC compared to non-carriers. Lithium is also associated with increased CT in the PFC of BD subjects compared to the ones on valproate. The influence of these treatments and gene variants over the PFC structure of Mexican subjects has not been explored. Therefore, we evaluate the effects of mood stabilizers and risk A allele of CACNA1C rs1006737 on the prefrontal cortical thickness of Mexican BD patients treated with lithium or valproate. Patients and methods A cross-sectional study of 40 BD type I euthymic adult outpatients (20 treated with lithium and 20 with valproate) who underwent a 3T T1-weighted 3D brain scan and genotyping for CACNA1C risk allele rs1006737 was conducted. We performed a cortical thickness analysis of the dorsolateral and orbitofrontal regions of the prefrontal cortex with Brain Voyager 20.6. The effects of treatment and gene variants were analyzed with a two-way multivariate analysis of covariance. Results There was no association of CACNA1C risk allele rs1006737 with CT measures of both PFCs nor significant interaction between the genetic variant and treatment. Mood stabilizers reported the main effect on the CT measures of the right PFC of our sample. Patients on treatment with lithium showed higher mean CT on the right orbitofrontal cortex. Conclusion We did not find any association between the prefrontal CT and CACNA1C risk A allele rs1006737 in BD Mexican patients treated with lithium or valproate. Our results suggest that mood stabilizers had the main effect in the CT of the right PFC.

BACKGROUND AND PURPOSE Protective mechanisms of the endogenous cannabinoid system against drug-induced liver injury (DILI) are actively being investigated regarding the differential regulatory role of the cannabinoid CB1 and CB2 receptors in liver fibrogenesis and inflammation. EXPERIMENTAL APPROACH The 2-arachidonoylglycerol (2-AG)-related signalling receptors and enzymatic machinery, and inflammatory/fibrogenic factors were investigated in the liver of a mouse model of hepatotoxicity induced by acute and repeated overdoses (750 mg·kg-1 ·day-1 ) of paracetamol (acetaminophen), previously treated with selective CB1 (ACEA) and CB2 (JWH015) agonists (10 mg·kg-1 ), or lacking CB1 and CB2 receptors. KEY RESULTS Acute paracetamol increased the expression of CB2 , ABHD6 and COX-2, while repeated paracetamol increased that of CB1 and COX-2 and decreased that of DAGLβ. Both acute paracetamol and repeated paracetamol decreased the liver content of acylglycerols (2-AG, 2-LG and 2-OG). Human liver samples from a patient suffering APAP hepatotoxicity confirmed CB1 and CB2 increments. Acute paracetamol-exposed CB2 KO mice had higher expression of the fibrogenic αSMA and the cytokine IL-6 and lower apoptotic cleaved caspase 3. CB1 deficiency enhanced the repeated APAP-induced increases in αSMA and cleaved caspase 3 and blocked those of CYP2E1, TNF-α, the chemokine CCL2 and the circulating γ-glutamyltransferase (γGT). Although JWH015 reduced the expression of αSMA and TNF-α in acute paracetamol, ACEA increased the expression of cleaved caspase 3 and CCL2 in repeated paracetamol. CONCLUSION AND IMPLICATIONS The differential role of CB1 versus CB2 receptors on inflammatory/fibrogenic factors related to paracetamol-induced hepatotoxicity should be considered for designing alternative therapies against DILI.

Resumen La estimacion preoperatoria del riesgo de mortalidad tras una fractura de cadera es de gran utilidad para planificar el momento de la cirugia y los cuidados perioperatorios, informar al paciente y familiares acerca del pronostico, y establecer comparaciones entre distintas unidades. Se han desarrollado varios modelos para estratificar el riesgo de mortalidad, pero muestran heterogeneidad en cuanto a tipo de poblacion, variables incluidas, tiempo de seguimiento y metodos estadisticos empleados, lo que hace dificil establecer comparaciones entre ellos. La gran mayoria esta pendiente de validacion externa en poblaciones diferentes de aquellas en las que se propusieron originalmente. El Nottingham Hip Fracture Score (NHFS) y el Orthopaedic Physiologic and Operative Severity Score for the enUmeration of Mortality and Morbidity (O-POSSUM) son los modelos mas utilizados hasta el momento. El NHFS es mas sencillo y rapido de aplicar, y al no incluir variables intraoperatorias se puede emplear en el momento del ingreso.

This study addresses the usage of different features to complement synset-based and bag-of-words representations of texts in the context of using classical ML approaches for spam filtering (Ferrara, 2019). Despite the existence of a large number of complementary features, in order to improve the applicability of this study, we have selected only those that can be computed regardless of the communication channel used to distribute content. Feature evaluation has been performed using content distributed through different channels (social networks and email) and classifiers (Adaboost, Flexible Bayes, Naïve Bayes, Random Forests, and SVMs). The results have revealed the usefulness of detecting some non-textual entities (such as URLs, Uniform Resource Locators) in the addressed distribution channels. Moreover, we also found that compression properties and/or information regarding the probability of correctly guessing the language of target texts could be successfully used to improve the classification in a wide range of situations. Finally, we have also detected features that are influenced by specific fashions and habits of users of certain Internet services (e.g. the existence of words written in capital letters) that are not useful for spam filtering. Financiado para publicación en acceso aberto: Universidade de Vigo/CISUG Xunta de Galicia | Ref. ED481D-2021/024 Agencia Estatal de Investigación | Ref. TIN2017-84658-C2-1-R

BACKGROUND: Tracheostomy is a frequent surgical procedure in subjects with chronic disorders of consciousness (DOC). There is no consensus about safety of tracheostomy decannulation in this population.The aim of our study was to estimate if DOC improvement is a predictor for tracheostomy decannulation. Secondary outcomes include mortality rate and discharge destination. METHODS: We conducted an observational, retrospective, case-control study at a weaning and rehabilitation center (WRC). We included tracheostomized subjects with DOC admitted between August 2015 and December 2017. We matched groups based on the consciousness level at admission assessed withthe coma recovery scale revised (CRS-R). Subjects who were later decannulated formed the cases, while those that remained tracheostomized at the end of follow-up formed the controls. Improvement of DOC was defined as a progress in the categories of the CRS-R. RESULTS: 22 subjects were included in each group. No significant differences were found in clinical and demographic variables, except that controls had longer neurologic injury evolution (65.5 vs 51 days, P = .047), more tracheostomy days at admission to ourinstitution (53 vs 33.5, P = .02), and higher prevalence of neurological comorbidities (12 vs 4, P = .03). Subjects who improved their DOC had more chances of being decannulated (OR 11.28, 95% CI 1.96–123.08). Tracheostomy decannulation could not be achieved in most subjects who did not improve from vegetative state (VS) (OR 0.13, 95% CI 0.02–0.60). 8 subjects, however, could be decannulated in VS, with only one decannulation failure and no deaths. Mortality was higher in controls (0 vs 6, P = .02), especially among VS (0 vs 5, P = .049). No significant differences were found in discharge destination between groups. CONCLUSIONS: Subjects who improve their DOC are more likely to achieve tracheostomy decannulation. Some subjects in VS were decannulated, with lower mortality than those who remained tracheostomized.

Several health organizations, mainly in Western countries, have recently authorized the use of a booster dose of the COVID-19 vaccine for patients previously vaccinated with mRNA vaccines, with criteria that do not always coincide. The COVID Scientific Committee of the Illustrious College of Physicians of Madrid (ICOMEM) has received and asked several questions about this situation, to which the group has tried to give answers, after deliberation and consensus. The efficacy of the vaccines administered so far is beyond doubt and they have managed to reduce, fundamentally, the severe forms of the disease. The duration of this protection is not well known, is different in different individuals and for different variants of the virus and is not easily predictable with laboratory tests. Data on the real impact of a supplementary or “booster” dose in the scientific literature are scarce for the moment and its application in large populations such as those in the state of Israel may be associated with a decrease in the risk of new and severe episodes in the short observation period available. We also lack sufficient data on the safety and potential adverse effects of these supplementary doses and we do not know the ideal time to administer them in different situations. In this state of affairs, it seems prudent to administer supplemental doses to those exposed to a higher risk, such as immunocompromised individuals and the elderly. On the other hand, we consider that this is not the time to accelerate, on the spur of the moment, a massive administration of a third dose to other population groups that are less exposed and at lower risk, without waiting for adequate scientific information, which will undoubtedly arrive gradually. We do not believe that this position is incompatible with the practical and ethical warnings made by the World Health Organization in this respect. post-print 162 KB

The H2020 METRO-HAUL European project has architected a latency-aware, cost-effective, agile, and programmable optical metro network. This includes the design of semidisaggregated metro nodes with compute and storage capabilities, which interface effectively with both 5G access and multi-Tbit/s elastic optical networks in the core. In this paper, we report the automated deployment of 5G services, in particular, a public safety video surveillance use case employing low-latency object detection and tracking using on-camera and on-the-edge analytics. The demonstration features flexible deployment of network slice instances, implemented in terms of European Telecommunications Standards Institute (ETSI) network function virtualization network services. We summarize the key findings in a detailed analysis of end-to-end quality of service, service setup time, and soft-failure detection time. The results show that the round-trip time over an 80 km link is under 800s and the service deployment time is under 180s., Comment: 10 pages

The revised European consensus defined sarcopenia as a progressive and generalized skeletal muscle disorder that is associated with an increased likelihood of adverse outcomes including falls, fractures, physical disability and mortality. The aim of this study was to determine the prevalence of sarcopenia and analyse the influence of diet, physical activity (PA) and obesity index as risk factors of each criteria of sarcopenia. A total of 629 European middle-aged and older adults were enrolled in this cross-sectional study. Anthropometrics were assessed. Self-reported PA and adherence to the Mediterranean diet were evaluated with the Global Physical Activity Questionnaire (GPAQ) and Prevention with Mediterranean Diet questionnaire (PREDIMED), respectively. The functional assessment included handgrip strength, lower body muscle strength, gait speed and agility/dynamic balance. Of the participants, 4.84% to 7.33% showed probable sarcopenia. Sarcopenia was confirmed in 1.16% to 2.93% of participants. Severe sarcopenia was shown by 0.86% to 1.49% of participants. Male; age group ≤65 years; lower body mass index (BMI); high levels of vigorous PA; and the consumption of more than one portion per day of red meat, hamburgers, sausages or cold cuts and/or preferential consumption of rabbit, chicken or turkey instead of beef, pork, hamburgers or sausages (OR = 0.126–0.454; all p < 0.013) resulted as protective factors, and more time of sedentary time (OR = 1.608–2.368; p = 0.032–0.041) resulted as a risk factor for some criteria of sarcopenia. In conclusion, age, diet, PA, and obesity can affect the risk of having low muscle strength, low muscle mass or low functional performance, factors connected with sarcopenia.

Background: Elderly COVID-19 patients have a high risk of pulmonary embolism (PE), but factors that predict PE are unknown in this population. This study assessed the Wells and revised Geneva scoring systems as predictors of PE and their relationships with D-dimer (DD) in this population. Methods: This was a longitudinal, observational study that included patients ≥75 years old with COVID-19 and suspected PE. The performances of the Wells score, revised Geneva score and DD levels were assessed. The combinations of the DD level and the clinical scales were evaluated using positive rules for higher specificity. Results: Among 305 patients included in the OCTA-COVID study cohort, 50 had suspected PE based on computed tomography pulmonary arteriography (CTPA), and the prevalence was 5.6%. The frequencies of PE in the low-, intermediate- and high-probability categories were 5.9%, 88.2% and 5.9% for the Geneva model and 35.3%, 58.8% and 5.9% for the Wells model, respectively. The DD median was higher in the PE group (4.33 mg/L, interquartile range (IQR) 2.40–7.17) than in the no PE group (1.39 mg/L, IQR 1.01–2.75) (p &lt, 0.001). The area under the curve (AUC) for DD was 0.789 (0.652–0.927). After changing the cutoff point for DD to 4.33 mg/L, the specificity increased from 42.5% to 93.9%. Conclusions: The cutoff point DD &gt, 4.33 mg/L has an increased specificity, which can discriminate false positives. The addition of the DD and the clinical probability scales increases the specificity and negative predictive value, which helps to avoid unnecessary invasive tests in this population.

Canine parvovirus type II (CPV-2) infection induces canine parvoviral enteritis (CPE), which in turn promotes sepsis and systemic inflammatory response syndrome (SIRS). Mortality in this disease is usually registered within 48–72 h post-hospitalization, the critical period of the illness. It has been recently described that the use of an immunomodulator, whose major component is monomeric ubiquitin (mUb) without the last two glycine residues (Ub∆GG), in pediatric human patients with sepsis augments survival. It is known that CXCR4 is the cell receptor of extracellular ubiquitin in humans. This work aimed to explore the effect of one immunomodulator (human Dialyzable Leukocyte Extract-hDLE) as a therapeutic auxiliary in puppies with sepsis and SIRS induced by CPE. We studied two groups of puppies with CPV-2 infection confirmed by polymerase chain reaction. The first group received conventional treatment (CT) and vehicle (V), while the second group received CT plus the immunomodulator (I). We assessed both groups' survival, clinical condition, number of erythrocytes, neutrophils, and lymphocytes during the hospitalization period. In addition, hematocrit, hemoglobin, plasma proteins and cortisol values, as well as norepinephrine/epinephrine and serotonin concentration were determined. Puppies treated with CT + I showed 81% survival, mild clinical signs, and a significant decrease in circulating neutrophils and lymphocytes in the critical period of the treatment. In contrast, the CT + V group presented a survival of 42%, severe clinical status, and no improvement of the parameters evaluated in the critical period of the disease. We determined in silico that human Ub∆GG can bind to dog CXCR4. In conclusion, the administration of a human immunomodulator (0.5 mg/day × 5 days) to puppies with CPE under six months of age reduces the severity of clinical signs, increases survival, and modulates inflammatory cell parameters. Further studies are necessary to take full advantage of these clinical findings, which might be mediated by the human Ub∆GG to canine CXCR4 interaction.

The movements and efforts of a circular economy, aiming to tap into the resource potential of ash, require an intimate knowledge of the material, often, target elements within this material are part of complex ash phases. This work shows how automated SEM investigations measure up to other laboratory techniques for the analysis of elemental composition and particle size. Three sewage sludge ash (SSA) samples have been studied in this comparison, showing material variation for SSA and highlighting the strengths and shortcomings of the methods chosen. Inductively coupled plasma optical emission spectroscopy (ICP-OES), X-ray fluorescence (XRF) and scanning electron microscopy with energy dispersive X-ray analysis (SEM-EDX) show relevant phosphate phases, but also a number of other elements. The extent of the accompanying elements, most likely hindering efficient phosphorus (P) recovery, varies. Propensities for detection in fine-grained and largely amorphous material such as ash vary, as is explored in this thorough comparison. ICP-OES data suffers from incomplete sample mobilization, and XRF-derived values suffer from matrix effects. Both are the only techniques studied which show trace elements, such as potentially toxic elements. SEM-EDX automated mineralogy delivers more reliable data for main elements while not reporting traces. By showing SEM-EDX automated mineralogy particle size distributions, alongside laser diffraction derived particle size distributions, the extent of the strain ash puts on traditional techniques is visible. Ashes tend to agglomerate, and the porous nature of particles hinders accurate detection. This work highlights where SSA recycling needs to be careful and hints at the extent of discrepancies between different methods. When understanding ash as a potential resource and designing efficient extraction strategies, this knowledge is crucial.

The current state of the web, which is dominated by centralized cloud services, raises several concerns regarding different aspects such as governance, privacy, surveillance, and security. A way to address these issues is to decentralize the platforms by adopting new distributed technologies, such as IPFS and Blockchain, which follow a full peer-to-peer model. This work proposes a set of guidelines to design decentralized systems, taking the different trade-offs these technologies face with regard to their consistency requirements into consideration. These guidelines are then illustrated with the design of a decentralized questions and answers system. This system serves to illustrate a framework to create decentralized services and applications that uses IPFS and Blockchain technologies and incorporates the discussion and guidelines of the paper, providing solutions for data access, data provenance, and data discovery. Thus, this work proposes a framework to assist in the design of new decentralized systems, proposing a set of guidelines to choose the appropriate technologies depending on the relevant requirements, e.g., considering if Blockchain technology may be required or IPFS might be sufficient.

Simple Summary Clinical management of sarcomas is complex because they are rare and heterogeneous tumors. Management requires a coordinated multidisciplinary approach, especially in children. Genomic characterization of this complex group of tumors contributes to the identification of prognostic biomarkers and to the continued expansion of therapeutic options. In this article, we present the positive experience of two Spanish hospitals in the use of genomic analysis in the overall clinical management of sarcomas in children and young adults. We describe on a case-by-case basis how genomic analysis has contributed to both diagnosis and treatment. Abstract Genomic techniques enable diagnosis and management of children and young adults with sarcomas by identifying high-risk patients and those who may benefit from targeted therapy or participation in clinical trials. Objective: to analyze the performance of an NGS gene panel for the clinical management of pediatric sarcoma patients. We studied 53 pediatric and young adult patients diagnosed with sarcoma, from two Spanish centers. Genomic data were obtained using the Oncomine Childhood Cancer Research Assay, and categorized according to their diagnostic, predictive, or prognostic value. In 44 (83%) of the 53 patients, at least one genetic alteration was identified. In 80% of these patients, the diagnosis was obtained (n = 11) or changed (n = 9), and thus genomic data affected therapy. The most frequent initial misdiagnosis was Ewing’s sarcoma, instead of myxoid liposarcoma (FUS-DDDIT3), rhabdoid soft tissue tumor (SMARCB1), or angiomatoid fibrous histiocytoma (EWSR1-CREB1). In our series, two patients had a genetic alteration with an FDA-approved targeted therapy, and 30% had at least one potentially actionable alteration. NGS-based genomic studies are useful and feasible in diagnosis and clinical management of pediatric sarcomas. Genomic characterization of these rare and heterogeneous tumors also helps in the search for prognostic biomarkers and therapeutic opportunities.

The use of Machine Learning-based systems within ICUs is an effective enhancement of traditional scoring systems. Those systems provide an automated diagnosis for faster and accurate decision making by medical proffesionals. Thus, it permits a shorter patient stays and increased ICU capacity. Several parameters exists on which and automated diagnostic system can be performed. However, this paper focuses on the automated detection of cardiac pathologies related to the 12-lead electrocardiogram (ECG) for early action. First of all, Wavelet Transform is employed to remove any possible noise in order to extract relevant features of the QRS complex. This data will be the input of the subsequent Machine Learning system, where two unsupervised classification methods are tried. Previously, an estimated number of clusters is set from an internal validation, which measures the performance of classifiers. Results show that classifiers are limited with a performance of less than 0.5, even thought they are able to achieve some reasonable subgroups inside the clusters.