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MET inhibitors have shown activity in non‐small‐cell lung cancer patients (NSCLC) with MET amplification and exon 14 skipping (METΔex14). However, patient stratification is imperfect, and thus, response rates have varied widely. Here, we studied MET alterations in 474 advanced NSCLC patients by nCounter, an RNA‐based technique, together with next‐generation sequencing (NGS), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and reverse transcriptase polymerase chain reaction (RT–PCR), exploring correlation with clinical benefit. Of the 474 samples analyzed, 422 (89%) yielded valid results by nCounter, which identified 13 patients (3%) with METΔex14 and 15 patients (3.5%) with very‐high MET mRNA expression. These two subgroups were mutually exclusive, displayed distinct phenotypes and did not generally coexist with other drivers. For METΔex14, 3/8 (37.5%) samples positive by nCounter tested negative by NGS. Regarding patients with very‐high MET mRNA, 92% had MET amplification by FISH and/or NGS. However, FISH failed to identify three patients (30%) with very‐high MET RNA expression, among which one received MET tyrosine kinase inhibitor treatment deriving clinical benefit. Our results indicate that quantitative mRNA‐based techniques can improve the selection of patients for MET‐targeted therapies.

Fundamento: un tipo de violencia particular, que en los últimos años se ha convertido en un problema social y de salud de primer orden, es la violencia en el noviazgo.Objetivo: estimar la violencia en el noviazgo percibida por estudiantes de medicina de la Universidad Médica de Cienfuegos. Métodos: estudio exploratorio que incluyó 240 estudiantes de segundo año de medicina del curso escolar 2018-2019, seleccionados por muestreo intencional de una población de 370 estudiantes. Se empleó un cuestionario autoadministrado para obtener los datos. Se analizaron las variables: sexo, edad, violencia en el noviazgo percibida, tipos de violencia en el noviazgo (en función de su naturaleza, física, psicológica y sexual).Resultados: el 63,8 % tiene 19 años y el 67,9 % son del sexo femenino. El 24 % percibe que hay violencia en los noviazgos, el 16 % no sabe y el 60 % dice que no. El conocimiento sobre los tres tipos de violencia es bajo, solo el 0,8 % reconoce los tres tipos de violencia; el 22,1% la física y psicológica; el 8,8 % solo la psicológica y el 1,3 % la física.Conclusiones: la investigación evidencia que los estudiantes de medicina en sus primeros años tienen baja percepción de la presencia de violencia en los noviazgos existentes en la institución y en la tipología de las expresiones, siendo la psicológica la más visible. Resulta imprescindible continuar estudios que profundicen en el estado del arte de este fenómeno.

Background: Point of care ultrasound study (POCUS) is a relatively new technique in Spanish Emergency Departments (EDs). Nonetheless, its use is increasing, and the number of emergency doctors and the number of papers published in our country has skyrocketed in last decade. Despite this fact, there is still no evidence of how POCUS is taught in our medical schools. Objective: To ascertain the level of knowledge about POCUS in first year resident doctors of three hospitals in Madrid, and one year after having worked in ED with POCUS practice. Methods and study design: The study looked at demographic aspects, POCUS knowledge, and opinions about its usefulness in the ED, prior to and after working in ED with routine use of POCUS. Results: Of the 265 questionnaires, 197 were first-year residents (Group 1) and 68 second-year residents (Group 2). Another 55 senior medical students completed the questionnaire (Group 3). The majority of Groups 1 and 3 stated to have a very low POCUS level. Almost three-quarters (73%) of Group 2 stated having an intermediate or high level, and 26% even declared having full knowledge. More than half of the students agreed that POCUS was a useful tool in ED. Conclusions: There is a low level of knowledge about POCUS among first-year residents. After working in POCUS qualified EDs, these resident doctors state both the importance and their higher level of knowledge of POCUS. Resumen: Introducción: La ecografía a pie de cama (EPC) es una técnica diagnóstica cada día más utilizada por los médicos urgenciólogos en los servicios de urgencias hospitalarios españoles. No obstante, desconocemos el nivel de la EPC de nuestros médicos residentes de primer año (R1). Objetivo: Determinar el nivel de conocimientos sobre la EPC de los R1, en 3 hospitales universitarios de Madrid, y el conocimiento un año después de haber trabajado en servicios de urgencias con utilización habitual de la EPC. Métodos: Nuestra encuesta investigaba datos demográficos, nivel previo de conocimiento de la EPC y opinión acerca de su utilidad en el servicio de urgencias. También se aplicó la encuesta a 55 estudiantes de medicina del último curso (EM6). Resultados: De 265 encuestas: 197 fueron de R1 y 68 de R2. También se pasó la encuesta a otros 55 estudiantes de medicina del último curso (EM6). La mayoría de los R1 y EM6, revelaron un nivel previo muy bajo de conocimientos de la EPC. En cambio, el 73% de los R2, manifestaron un nivel intermedio o alto, e incluso un 26% declararon un conocimiento amplio. Más de la mitad de los encuestados manifestó estar de acuerdo en que la EPC era una herramienta muy útil en el servicio de urgencias. Conclusiones: Existe un bajo nivel de conocimientos sobre la EPC entre los R1. Después de haber trabajado en servicios de urgencias con práctica habitual de EPC, estos mismos médicos residentes, reconocieron tanto la importancia de la EPC como su alto nivel de conocimientos de la EPC.

This study aimed to analyse and compare the storytelling of 25 children with Autism Spectrum Disorder (ASD) with a comparison group of 25 children with typical development. Children’s narratives were transcribed verbatim, and their forms and contents were analysed. The two groups were matched according to the narrative cohesion of the story using the Bears Family Projective Test, equivalent verbal age, sex, and socioeconomic level. No differences in the forms of the stories emerged, but compared with the narratives of the typical development group, the narrative contents of the ASD group showed more adaptive and maladaptive behaviours of the characters, more problems, and less use of the atmosphere outside the home. These contents are related to the intensity of the anxious symptomatology indicated by the ASD group, their family members and teachers.

Los estudios seroepidemiológicos permiten conocer la distribución indirecta de las enfermedades, detectando marcadores séricos de inmunidad y demostrando infecciones no diagnosticadas en la población general. El objetivo fue estimar la seroprevalencia de anticuerpos contra el SARS-CoV-2, en Córdoba, Argentina, entre diciembre de 2020 y enero de 2021, e identificar factores asociados a la contagiosidad del virus. Se realizó un estudio observacional transversal, de base poblacional, con 3.225 individuos mayores de 2 años, residentes en Córdoba Capital, que fueron seleccionados mediante un diseño de muestreo aleatorio en múltiples etapas, proporcional a la distribución por género, franja etaria y nivel socioeconómico de la población de Córdoba. Las características clínicas, antropometría y comorbilidades se recogieron mediante entrevistas. Se realizó un test serológico cualitativo para la detección de anticuerpos IgG antinucleocápside para SARS-CoV-2 (ARCHITECT, Abbott). La seroprevalencia del SARS-CoV-2 se estimó en la población y por franja de edad, sexo, nivel socioeconómico y presencia de las patologías estudiadas. Las razones de prevalencia (RP) se estimaron usando un modelo de regresión log-binomial. La seropositividad para SARS-CoV-2 fue de 16,68% (IC95%: 15,41-18,01). Tener entre 2 y 18 años, residir en barrios con nivel socioeconómico bajo y la presencia de obesidad, aumentaron la oportunidad de seropositividad (RP = 1,50; IC95%: 1,10-2,04, RP = 1,91; IC95%: 1,34-2,67 y RP = 1,39; IC95%: 1,04-1,85). Los resultados indican que en Córdoba Capital existen atributos diferenciales que aumentan la posibilidad de ser seropositivo para SARS-CoV-2. Esto permite dirigir estrategias de vigilancia epidemiológica para reducir la propagación del virus.

On January 30, 2020, the World Health Organization (WHO) declared SARS-CoV-2 infection an international public health emergency. The autopsy, considered the best method of studying the patient and the disease, corroborates that patients can die from the direct action of the virus (who died from COVID-19), while others positive for SARS-CoV-2 did not show morphological lung changes attributed to the action of the virus. It is proposed to establish the morphological diagnostic criteria in the context of the SARS-CoV-2 and COVID-19 epidemic in the deceased in Cuba based on the systematic study of autopsies. The morphological patterns that are established in the lungs of patients who died under the effect of COVID-19 have been identified. The pulmonary edema of permeability with the widening of the pulmonary septum, the deposit of the disorganized hyaline membrane inside the alveoli, the detachment of epithelial cells (pneumocytes and bronchial and bronchiolar cells), followed by epithelial hyperplasia with sometimes the presence of metaplastic changes and atypia, and finally, fibrosis. When autopsies are performed, it is possible to locate each disease in its place, in chronopathogram, which allows death certificates repair to be carried out to assess the place that COVID-19 has occupied as a cause of death in the population studied. In the opinion of the group, identifying morphological alterations is essential to prepare the chronopathogram of the deceased and the adequate clinical-pathological evaluation of the patient.

Introducción: Se presenta un caso de paciente fallecido por la COVID-19, que los autores consideran prototipo de la mayor parte de los fallecidos por esta afección, que se le realizó a autopsia. Objetivo: Divulgar las experiencias en el estudio de la autopsia de este tipo de pacientes y contribuir a su aplicación en la práctica asistencial y científica. Caso clínico: Se presenta un paciente masculino de 78 años, con hipertensión arterial, diabetes mellitus y obesidad, que comenzó con tos, fiebre, secreción nasal, que ingresa con diagnóstico de la COVID-19, evoluciona hacia la gravedad y fallece 10 días después de su ingreso. Se presentan los elementos fundamentales de la historia clínica, los diagnósticos de causas de muerte pre mortem y post mortem. Se precisan los diagnósticos en la autopsia y los resultados de la evaluación de la calidad de los diagnósticos de causas de muerte clínicos. Conclusiones: Las experiencias del estudio de esta autopsia como prototipo, reafirman los daños ocasionados por el SARS-CoV-2 y aporta a los conocimientos de este campo.

Finalizada la Segunda Guerra Mundial, el gobierno de Giral puso en marcha una campaña de propaganda cinematográfica con el objetivo de obtener apoyos contra Franco y conseguir recursos para el socorro de los refugiados. La película de Guillermo Fernández Zuñiga, Spain in exile, permite analizar tanto el mensaje político como la necesidad humanitaria de los republicanos españoles exiliados en Francia.

The piriform cortex is a paleocortical area, located in the ventrolateral surface of the rodent forebrain, receiving direct input from the olfactory bulb. The three layers of the PC are defined by the diversity of glial and neuronal cells, marker expression, connections, and functions. However, the glial layering, ontogeny, and sibling cell relationship along the PC is an unresolved question in the field. Here, using multi-color genetic lineage tracing approaches with different StarTrack strategies, we performed a rigorous analysis of the derived cell progenies from progenitors located at the subpallium ventricular surface. First, we specifically targeted E12-progenitors with UbC-StarTrack to analyze their adult derived-cell progeny and their location within the piriform cortex layers. The vast majority of the cell progeny derived from targeted progenitors were identified as neurons, but also astrocytes and NG2 cells. Further, to specifically target single Gsx-2 subpallial progenitors and their derived cell-progeny in the piriform cortex, we used the UbC-(Gsx-2-hyPB)-StarTrack to perform an accurate analysis of their clonal relationships. Our results quantitatively delineate the adult clonal cell pattern from single subpallial E12-progenitors, focusing on glial cells. In summary, there is a temporal pattern in the assembly of the glial cell diversity in the piriform cortex, which also reveals spatio-temporal progenitor heterogeneity.

Reencontrando a Gaia <> Carlos de Castro Carranza Ediciones del Genal, Málaga, 2019. 269 pp. 13,30€Pags: 196

Abstract Aims Residual pulmonary congestion at hospital discharge can worsen the outcomes in patients with heart failure (HF) and can be detected by lung ultrasound (LUS). The aim of this study was to analyse the prevalence of subclinical pulmonary congestion at discharge and its impact on prognosis in patients admitted for acute HF. Methods and results This is a post‐hoc analysis of the LUS‐HF trial. LUS was performed by the investigators in eight chest zones with a pocket device. Physical exam was subsequently performed by the treating physicians. Primary outcome was a combined endpoint of rehospitalization, unexpected visit for HF worsening or death at 6‐ month follow‐up. Subclinical pulmonary congestion at discharge was defined as the presence of ≥5 B‐lines in LUS in absence of rales in the auscultation employing the area under the ROC curve. At discharge, 100 patients (81%) did not show clinical signs of pulmonary congestion. Of these, 41 had ≥5 B‐lines. Independent factors related with the presence of subclinical pulmonary congestion were anaemia, higher New York Heart Association (NYHA) class, and N terminal pro brain natriuretic peptide (NT‐proBNP). After adjusting by propensity score analysis including age, renal insufficiency, atrial fibrillation, NYHA class, NT‐proBNP levels, clinical congestion, and the trial intervention, the presence of subclinical pulmonary congestion at discharge was a risk factor for the occurrence of the primary outcome (hazard ratio 2.63; 95% confidence interval: 1.08–6.41; P = 0.033). Conclusions Up to 40% of patients considered ‘dry’ according to pulmonary auscultation presents subclinical congestion at hospital discharge that can be detected by LUS and implies a worse prognosis at 6‐ month follow‐up. Comorbidities, high values of natriuretic peptides, and higher NYHA class are the factors related with its presence.

Child emotion regulation (ER) skills and specific parenting practices during the COVID-19 pandemic are likely to influence children adjustment in these unprecedented times. On this assumption, we first aimed to examine the predictive value of ER skills in relation to diverse indicators of behavioral and socioemotional adjustment. Then, we tested whether some of these associations could be partially explained through the mediator role of the specific parenting practices displayed within the pandemic context. These hypotheses were tested considering the previous levels of child reactivity as a potential moderator of the examined relations. Using parent-reported data from a sample of 874 Galician children (49.6% girls) aged 5 to 9 (Mage = 7.09; SD = 1.04), multiple regression and mediation analyses were conducted. Robust associations between ER skills and diverse indicators of child adjusment were found. Moreover, it was found that specific parenting practices mediate the relation between child ER skills and specific behavioral outcomes (i.e., child routine maintenance). Thus, our findings highlight the importance of ER skills for child adjustment during the COVID-19 crisis, not only through direct, but also indirect effects, suggesting that the kind of parenting style that children receive during the pandemic conditions might be partially elicited by their individual characteristics.

En este artículo se presentan claves contextuales para entender quiénes son los nuevos actores del ámbito educativo en la enseñanza superior y, a su vez, se exponen algunas de las crisis sistémicas a las que se enfrentan los programas de humanidades. Para esto se citan fuentes críticas en temas de globalización y política educativa, así como acuerdos internacionales firmados entre gobiernos e instituciones de distintos países. En el contexto de comercialización de la educación y de las posibles estrategias de enseñanza y los modos artísticos no canónicos, se examina la relevancia de la poesía experimental como objeto de estudio en las humanidades. Se pretende ofrecer aquí un espacio de reflexión ante los rumbos actuales de las políticas educativas supranacionales que fomentan la comercialización de la enseñanza y se alejan del concepto tradicional de cultura. Las líneas argumentales parten del marco de los estudios culturales para enfocarse en los, cada vez más populares, estudios globales, eje paradigmático que condiciona en la actualidad el devenir de los estudios de las humanidades y cambia el concepto tradicional de las artes liberales. La ubicación de las humanidades dentro del marco de los estudios globales genera un distanciamiento ideológico y múltiples crisis en la educación con respecto a los referentes y los valores tradicionales. El artículo destaca el caso de artes marginales, la escritura experimental, en cuanto objeto de estudio de este nuevo modus operandi. Además, se proponen algunas estrategias educativas y se profundiza en el estado actual de la educación de las humanidades.

Abstract Background Since enzyme replacement therapy for Gaucher disease (MIM#230800) has become available, both awareness of and the natural history of the disease have changed. However, there remain unmet needs such as the identification of patients at risk of developing bone crisis during therapy and late complications such as cancer or parkinsonism. The Spanish Gaucher Disease Registry has worked since 1993 to compile demographic, clinical, genetic, analytical, imaging and follow-up data from more than 400 patients. The aims of this study were to discover correlations between patients’ characteristics at diagnosis and to identify risk features for the development of late complications; for this a machine learning approach involving correlation networks and decision trees analyses was applied. Results A total of 358 patients, 340 type 1 Gaucher disease and 18 type 3 cases were selected. 18% were splenectomyzed and 39% had advanced bone disease. 81% of cases carried heterozygous genotype. 47% of them were diagnosed before the year 2000. Mean age at diagnosis and therapy were 28 and 31.5 years old (y.o.) respectively. 4% developed monoclonal gammopathy undetermined significance or Parkinson Disease, 6% cancer, and 10% died before this study. Previous splenectomy correlates with the development of skeletal complications and severe bone disease (p = 0.005); serum levels of IgA, delayed age at start therapy (> 9.5 y.o. since diagnosis) also correlates with severe bone disease at diagnosis and with the incidence of bone crisis during therapy. High IgG (> 1750 mg/dL) levels and age over 60 y.o. at diagnosis were found to be related with the development of cancer. When modelling the decision tree, patients with a delayed diagnosis and therapy were the most severe and with higher risk of complications. Conclusions Our work confirms previous observations, highlights the importance of early diagnosis and therapy and identifies new risk features such as high IgA and IgG levels for long-term complications.

The Big Crested Mastiff Bat, Promops centralis (Thomas, 1915), is widely distributed from Mexico to South America but has yet to be reported in the state of Sinaloa, Mexico. We collected 122 acoustic recordings of P. centralis from tropical dry forest and agroecosystems in Sinaloa and Sonora for two years (2015 and 2016). We documented a new record for P. centralis outside the known distribution area in northwestern Mexico. Our results reveal that the current P. centralis distribution needs to be reevaluated.

Tras el golpe de estado del 18 de julio de 1936, el panorama mediático en España sufre una gran transformación, con la consecuente erradicación de cabeceras y emisoras de radio, al mismo tiempo que la aparición de nuevos medios de comunicación en apoyo a la defensa de uno u otro bando. En esta coyuntura, los directivos, periodistas, fotógrafos y demás trabajadores, implicados en el negocio periodístico, serán los primeros afectados. Este artículo ubica su geografía de estudio en Málaga y tiene como finalidad reconstruir los acontecimientos sucedidos durante el verano de 1936 hasta la entrada de las tropas franquistas, el 8 de febrero de 1937, y se enmarca en el contexto de la represión en el sector periodístico. El foco está centrado en la primera oleada represora que afectará a la prensa malagueña conservadora, en particular, el caso del diario La Unión Mercantil y en la figura del que fue su último director, Manuel García Santos. La metodología de trabajo se ha basado en el análisis cualitativo de fondos documentales jurídicos, hemerográficos y fuentes personales de familiares de los investigados. Los resultados obtenidos pretenden contribuir a paliar la gran escasez de investigaciones en este campo, especialmente en Andalucía. Gracias a las fuentes consultadas, este trabajo ofrece una radiografía de los acontecimientos, rescatando del olvido a numerosas figuras del periodismo malagueño que, habiendo ejercido su profesión libremente, sufrieron la censura, persecución, cárcel, exilio y muerte durante el periodo de guerra y la inmediata posguerra.

Este número de Oñati Socio-Legal Series, titulado El género de los sistemas penales juveniles: Debates necesarios, es el resultado de las ponencias e intercambios mantenidos en un taller interdisciplinario que tuvo lugar en 2018. Se encuentra integrado por once artículos que discurren sobre las experiencias en justicia penal juvenil dirigidas hacia adolescentes mujeres y otras temáticas vinculadas, a partir de la exposición de resultados de investigaciones e intervenciones realizadas en América Latina (Argentina, Brasil, Chile, México y Uruguay) y el Estado Español (Cataluña, Madrid, País Vasco, Zaragoza). Las discusiones mantenidas en este espacio y los artículos publicados son una muestra más del auge punitivo global que viven las sociedades capitalistas contemporáneas y que podemos observar en los diferentes contextos a través de la extensión de las formas de control y alcance de los sistemas penales que se produce sobre la población tanto adulta como joven y adolescente. En este marco, es interesante contextualizar cómo son los tránsitos de las mujeres más jóvenes por los sistemas penales, haciendo énfasis en la necesaria inclusión de una perspectiva de género que pueda comprender las singularidades que forman parte del tratamiento de las mismas en estos sistemas. This issue of Oñati Socio-Legal Series, entitled The Gender of Juvenile Criminal Systems: Necessary Debates, is the result of the communications and exchanges held at a interdisciplinary workshop that took place in 2018. It is composed of eleven articles that discuss experiences in juvenile criminal justice aimed at adolescent women and other related issues, based on the presentation of the results of research and interventions carried out in Latin America (Argentina, Brazil, Chile, Mexico and Uruguay) and the Spanish State (Catalonia, Madrid, Basque Country, Zaragoza). The discussions held in this space and the articles published are one more example of the global punitive expansion that contemporary capitalist societies are experiencing and that we can observe in the different contexts through the extension of the forms of control and scope of the penal systems that are produced on the adult, young and adolescent population. In this framework, it is interesting to contextualize how the transits of younger women through the penal systems are, emphasizing the necessary inclusion of a gender perspective that can understand the singularities that are part of the treatment of women in these systems. Available from: https://doi.org/10.35295/osls.iisl/0000-0000-0000-1116

Foundation: intrauterine growth restriction constitutes a complication of pregnancy. Newborns with this condition are exposed to an increased risk of perinatal and postnatal morbidity and mortality. Objective: to evaluate morphological markers of hypoxia in fetal and kidney development, using a model of placental insufficiency treated with human erythropoietin with low sialic acid content (neuro-Epo) in rats. Methods: three groups of gestated rats from the Wistar line were used. A control group (group I) and two experimental groups (groups II and III) with six rats each. Rats of groups II and III had uterine artery ligation on day 16 of pregnancy (E 16). Group III from E16 to E19 was administered a dose of 0.5 mg / kg / day of neuro-Epo subcutaneously and group II was administered placebo. On the 20th day of gestation the fetuses and their placentas were weighed. The fetuses’ size and cephalic diameters were measured. Morphometric and histological features in the fetal kidney were studied with hematoxylin-eosin staining and PAS. A qualitative histopathological analysis of their cell types was performed. Results: fetuses with intrauterine growth restriction did not improve growth markers. Hypoxia lesions were found in the fetal kidney of the untreated RCIU group that improved by administering neuro-Epo. Conclusions: the administration of neuro-Epo only showed reparative and protective effects on histological alterations caused by hypoxia in the fetal kidney.

Introduction Exercise intolerance and fatigue are the most common symptoms in patients with chronic COVID-19 after hospital discharge. Supervised exercise training programmes improve symptoms, but scarce research has been done on home-based exercise programmes on the maximal functional capacity for discharged symptomatic COVID-19 patients. This study evaluates whether a home-based inspiratory muscle training (IMT) programme improves maximal functional capacity in chronic COVID-19 after hospital admission.Methods and analysis This single-centre, assessor-blinded randomised controlled trial, powered for superiority, seeks to evaluate maximal functional capacity as the primary endpoint. A total of 26 eligible patients with a previous admission for acute respiratory syndrome coronavirus 2 pneumonia (>3 months after hospital discharge) will be randomised (1:1) to receive a 12-week programme of IMT versus usual care alone. A blinded assessor will measure outcomes at baseline and after the intervention (12 weeks). An analysis of variance will be used to compare continuous outcomes among the two-intervention groups. As of 21 March 2022, eight patients have been enrolled.Ethics and dissemination The research ethics committee (Comité Ético de Investigación con Medicamentos de l'Hospital Clínic Universitari de València) approved the protocol following the principles of the Declaration of Helsinki and national regulations (Approval Number: 021/226). Findings will be published in peer-reviewed journals and conference publications.Trial registration number NCT05279430.

Glycogen synthase kinase 3β (GSK3β) is a core protein, with a relevant role in many neurodegenerative disorders including Alzheimer’s disease. The enzyme has been largely studied as a potential therapeutic target for several neurological diseases. Unfortunately, preclinical and clinical studies with several GSK3β inhibitors have failed due to many reasons such as excessive toxicity or lack of effects in human subjects. We previously reported that meridianins are potent GSK3β inhibitors without altering neuronal viability. In the present work, we examine whether meridianins are capable to inhibit neural GSK3β in vivo and if such inhibition induces improvements in the 5xFAD mouse model of Alzheimer’s Disease. Direct administration of meridianins in the third ventricle of 5xFAD mice induced robust improvements of recognition memory and cognitive flexibility as well as a rescue of the synaptic loss and an amelioration of neuroinflammatory processes. In summary, our study points out meridianins as a potential compound to treat neurodegenerative disorders associated with an hyperactivation of GSK3β such as Alzheimer’s disease.

BackgroundThe current COVID-19 pandemic has overloaded the diagnostic capacity of laboratories by the gold standard method rRT-PCR. This disease has a high spread rate and almost a quarter of infected individuals never develop symptoms. In this scenario, active surveillance is crucial to stop the virus propagation.MethodsBetween July 2020 and April 2021, 11,580 oropharyngeal swab samples collected in closed and semi-closed institutions were processed for SARS-CoV-2 detection in pools, implementing this strategy for the first time in Córdoba, Argentina. Five-sample pools were constituted before nucleic acid extraction and amplification by rRT-PCR. Comparative analysis of cycle threshold (Ct) values from positive pools and individual samples along with a cost-benefit report of the whole performance of the results was performed.ResultsFrom 2,314 5-sample pools tested, 158 were classified as positive (6.8%), 2,024 as negative (87.5%), and 132 were categorized as indeterminate (5.7%). The Ct value shift due to sample dilution showed an increase in Ct of 2.6±1.53 cycles for N gene and 2.6±1.78 for ORF1ab gene. Overall, 290 pools were disassembled and 1,450 swabs were analyzed individually. This strategy allowed correctly identifying 99.8% of the samples as positive (7.6%) or negative (92.2%), avoiding the execution of 7,806 rRT-PCR reactions which represents a cost saving of 67.5%.ConclusionThis study demonstrates the feasibility of pooling samples to increase the number of tests performed, helping to maximize molecular diagnostic resources and reducing the work overload of specialized personnel during active surveillance of the COVID-19 pandemic.

Although the nasopharyngeal swab (NPS) is considered the gold standard for the diagnosis of the SARS-CoV-2 infection, the Nasal Mid-Turbinate swab (NMTS) is often used due to its higher tolerance among patients. We compared the diagnostic performance of the NPS and the NMTS for the Panbio™ COVID-19 antigen-detecting rapid diagnostic test (Ag-RDT). Two hundred and forty-three individuals were swabbed three times by healthcare professionals: a NMTS and a NPS specimen for the Ag-RDT and an oropharyngeal swab for real time RT-PCR. Forty-nine participants were RNA-SARS-CoV-2 positive by real time RT-PCR: 45 and 40 were positive by the Ag-RDT with NPS and NMTS, respectively. The overall sensitivity and specificity were 91.8% (95% CI: 83.2-100.0) and 99.5% (95% CI: 98.2-100.0) for Ag-RDT with NPS, and 81.6% (95% CI: 69.8-93.5) and 100.0% (95% CI: 99.7-100.0) for the Ag-RDT with NMTS. The Cohen's kappa index was 0.92 (95% CI: 0.85-0.98). Among asymptomatic individuals, the Ag-RDT with both sampling techniques showed a high sensitivity [100.0% (95% CI: 95.5-100.0) with NPS; 90.9% (95% CI: 69.4-100.0) with NMTS], while the performance of the test decreased in samples with Ct≥ 30 and in patients tested after the first 7 days from symptom onset. Although the NMTS yielded a lower sensitivity compared to NPS, it might be considered a reliable alternative, as it presents greater adherence among patients, enabling scaling of antigen testing strategies, particularly in countries with under-resourced health systems.

Climate change is triggering regional-scale alterations in vegetation including land cover change such as forest die-off. At sufficient magnitudes, land cover change from forest die-off in one region can change not only local climate but also vegetation including agriculture elsewhere via changes in larger scale climate patterns, termed an ‘ecoclimate teleconnection’. Ecoclimate teleconnections can therefore have impacts on vegetative growth in distant regions, but the degrees to which the impact decays with distance or directionally diffuses relative to the initial perturbation are general properties that have not been evaluated. We used the Community Earth system model to study this, examining the implications of tree die-off in 14 major US forested regions. For each case we evaluated the ecological impact across North America as a function of distance and direction from the location of regional tree die-off. We found that the effects on gross primary productivity (GPP) generally decayed linearly with distance, with notable exceptions. Distance from the region of tree die-off alone explained up to ∼30% of the variance in many regions. We also found that the GPP impact was not uniform across directions and that including an additional term to account for direction to regional land cover change from tree die-off was statistically significant for nearly all regions and explained up to ∼40% of the variance in many regions, comparable in magnitude to the influence of El Nino on GPP in the Western US. Our results provide novel insights into the generality of distance decay and directional diffusion of ecoclimate teleconnections, and suggest that it may be hard to identify expected impacts of tree die-off without case-specific simulations. Such patterns of distance decay, directional diffusion, and their exceptions are relevant for cross-regional policy that links forests and other agriculture (e.g. US Department of Agriculture).

El objetivo del trabajo fue describir las acciones de educación ambiental realizadas entre los años 2017 y 2019 por especialistas del Parque Nacional Caguanes, con el apoyo de otras instituciones, para sensibilizar a un grupo de pescadores residentes en el municipio Yaguajay, sobre la importancia de proteger los recursos naturales. El plan de acciones se diseñó con un enfoque de Manejo Integrado de Zonas Costeras. Para ello, se empleó la metodología cualitativa. Se basó, fundamentalmente, en la capacitación a través de talleres de intercambio de experiencias, conferencias, cursos y charlas sobre diversos temas, con el uso de técnicas participativas. También tuvo lugar el saneamiento de playa Vitoria. Se trabajó con el grupo meta de los pescadores, los que han adquirido conocimientos sobre la problemática ambiental de la zona costera con un enfoque holístico, y la importancia de la conservación de la diversidad biológica. Como impacto positivo se destaca el inicio de un proceso de concientización, teniendo en cuenta como premisa el Manejo Integrado de la Zona Costera, en virtud de la transformación de los problemas ambientales del área, donde ellos contribuyen a su solución. Recibido: 7-10-2020 Aceptado: 25-3-2021 Publicado: 20-12-2021 Editor: Ana María Suárez

Las áreas protegidas cumplen un rol esencial en la conservación de los ecosistemas y a su vez contribuyen a la generación de ingresos para la economía nacional, por los bienes y servicios ecosistémicos que proveen. Cuba cuenta con escasos estudios de valoración económica de áreas protegidas. El presente trabajo tiene como objetivo estimar el Valor Económico Total (VET) de los bienes y servicios ecosistémicos (BSE) del Parque Nacional Caguanes (PNC). Para ello, se evaluó la composición de dicho valor, atendiendo a los BSE más relevantes, de acuerdo al criterio de los autores, y a la disponibilidad de datos paradesarrollar la valoración económica. Se utilizó el concepto del VET y se aplicaron las técnicas de valoración: precios de mercado, beneficio bruto, gastos defensivos y transferencia de beneficios. Del total (34 BSE) identificados fueron valorados 11 para estimar el VET. El presente estudio presenta como principal limitación la ausencia o difícil acceso a la información necesaria para su realización. No obstante, los resultados del VET/ha obtenidos en el rango de 3 296.00 USD/ha mínimo y 8 238.00 USD/ha máximo demuestran los valores significativos que posee el PNC. Se destaca la necesidad de contar con un equipo multidisciplinario, que integre criterios naturales y socioeconómicos, para continuar actualizando el VET del PNC y socializar los resultados con los actores necesarios para contribuir a la optimización de las acciones de manejo del área, así como al mejoramiento del bienestar humano de las comunidades cercanas. Recibido: 30-11-2020 Aceptado: 21-05-2021 Publicado: 20-12-2021 Editor: Ana María Suárez

Limosilactobacillus fermentum CECT5716, a probiotic strain isolated from human milk, has reported beneficial effects on different gastrointestinal disorders. Moreover, it has shown its ability to restore altered immune responses, in association with microbiome modulation in different pathological conditions. Therefore, our aim was to assess the effects of a Limosilacbacillus fermentum CECT5716 in a rat experimental model of irritable bowel syndrome (IBS) that resembles human IBS. The experimental IBS was induced by deoxycholic acid (DCA) in rats and then, Limosilactobacillus fermentum CECT5716 (109 CFU/day/rat) was administered. Behavioral studies, hyperalgesia and intestinal hypersensitivity determinations were performed and the impact of the probiotic on the inflammatory and intestinal barrier integrity was evaluated. Additionally, the gut microbiota composition was analyzed. Limosilactobacillus fermentum CECT5716 attenuated the anxiety-like behavior as well as the visceral hypersensitivity and referred pain. Moreover, this probiotic ameliorated the gut inflammatory status, re-establishing the altered intestinal permeability, reducing the mast cell degranulation and re-establishing the gut dysbiosis in experimental IBS. Therefore, our results suggest a potential use of Limosilactobacillus fermentum CECT5716 in clinical practice for the management of IBS patients.

Introduction: The COVID-19 pandemic has been the largest in the current century and the reason for numerous scientific works. In Cuba, the Temporary Group of Pathological Anatomy has been established to study the autopsies of those who died from COVID-19 (more than 400). The medical death certificates, documents of inestimable value, in Cuba are repaired according to the results of the autopsies, to raise their quality. Objectives: To evaluate the results of autopsies with COVID-19 diagnoses, compared to medical death certificates. Methods: The diagnoses of causes of death of 65 autopsies of the year 2020 were evaluated with their medical death certificates. The diagnoses were processed in the Automated System for the Registration and Control of Pathology. Direct causes of death, basic causes of death, intermediate causes of death, and contributing causes of death were analyzed. The total agreement of both diagnoses was defined, partial agreement, diagnostic mismatch or discrepancy, and insufficient data. Results: Diagnostic discrepancies of basic and direct cause of death are 46.2 % and 60.0 % of all cases and 19.4 % and 64.5 % when COVID-19 was basic cause of death. The high figures for diagnostic discrepancies correspond to those reported in previous studies, both in clinical diagnoses and in medical death certificates. Conclusions: There are high numbers of diagnostic discrepancies compared with the results of autopsies with COVID-19 diagnoses, compared to medical death certificates.

Systemic inflammatory response of COVID-19 and its morphological expression, multiple organ damage

Clonal cell analysis outlines the ontogenic potential of single progenitor cells, allowing the elucidation of the neural heterogeneity among different cell types and their lineages. In this work, we analyze the potency of retinal stem/progenitor cells through development using the chick embryo as a model. We implemented in ovo the clonal genetic tracing strategy UbC-StarTrack for tracking retinal cell lineages derived from individual progenitors of the ciliary margin at E3.5 (HH21-22). The clonal assignment of the derived-cell progeny was performed in the neural retina at E11.5-12 (HH38) through the identification of sibling cells as cells expressing the same combination of fluorophores. Moreover, cell types were assessed based on their cellular morphology and laminar location. Ciliary margin derived-cell progenies are organized in columnar associations distributed along the peripheral retina with a limited tangential dispersion. The analysis revealed that, at the early stages of development, this region harbors multipotent and committed progenitor cells.

The enteric nervous system (ENS) is a part of the autonomic nervous system that intrinsically innervates the gastrointestinal (GI) tract. Whereas enteric neurons have been deeply studied, the enteric glial cells (EGCs) have received less attention. However, these are immune-competent cells that contribute to the maintenance of the GI tract homeostasis through supporting epithelial integrity, providing neuroprotection, and influencing the GI motor function and sensation. The endogenous cannabinoid system (ECS) includes endogenous classical cannabinoids (anandamide, 2-arachidonoylglycerol), cannabinoid-like ligands (oleoylethanolamide (OEA) and palmitoylethanolamide (PEA)), enzymes involved in their metabolism (FAAH, MAGL, COX-2) and classical (CB1 and CB2) and non-classical (TRPV1, GPR55, PPAR) receptors. The ECS participates in many processes crucial for the proper functioning of the GI tract, in which the EGCs are involved. Thus, the modulation of the EGCs through the ECS might be beneficial to treat some dysfunctions of the GI tract. This review explores the role of EGCs and ECS on the GI tract functions and dysfunctions, and the current knowledge about how EGCs may be modulated by the ECS components, as possible new targets for cannabinoids and cannabinoid-like molecules, particularly those with potential nutraceutical use.

Alterations in the levels of serum sphingolipids and phospholipids have been reported in Gaucher disease and in Parkinson’s disease, suggesting a potential role of these lipids as biomarkers. This project’s objective is to detect novel associations and novel candidate biomarkers in the largest Spanish Gaucher and Parkinson diseases of the Iberian Peninsula. For that, 278 participants were included: 100 sporadic Parkinson’s patients, 70 Gaucher patients, 15 GBA1-mutation-carrier Parkinson’s patients and 93 controls. A serum lipidomics array including 10 phospholipid groups, 368 species, was performed using high-performance liquid chromatography–mass spectrometry. Lipid levels were compared between groups via multiple-regression analyses controlling for clinical and demographic parameters. Additionally, lipid levels were compared within the Gaucher and Parkinson’s groups controlling for medication and/or disease severity. Results were controlled for robustness by filtering of non-detectable lipid values. There was an increase in the levels of phosphatidylcholine, with a simultaneous decrease in lyso-phosphatidylcholine, in the Gaucher, Parkinson’s and GBA1-mutation-carrier Parkinson’s patients vs. controls. Phosphatidylethanolamine, lyso- and plasmalogen-phosphatidylethanolamine were also increased in Gaucher and Parkinson’s. Gaucher patients also showed an increase in lyso-phosphatidylserine and phosphatidylglycerol. While in the Gaucher and Parkinson’s groups, velaglucerase alpha and dopamine agonists, respectively, showed positive associations with the lipid changes, miglustat treatment in Gaucher patients normalized the altered phosphatidylcholine/lyso-phosphatidylcholine ratio. In conclusion, Gaucher and Parkinson’s patients showed changes in various serum phospholipid levels when compared with healthy controls, further supporting the role of such lipids in disease development and, possibly, as putative biomarkers. This hypothesis was reinforced by the normalizing effect of miglustat, and by controlling for data robustness, even though the limited number of participants, especially in the sub-distribution by treatment groups in GD requires validation in a larger number of patients.

Spatial navigation is a key aspect of human behavior and it is still not completely understood. A number of experimental approaches exist, although most of the published data in the last decades have relied on virtual maze on-screen simulation or not-completely freely moving 3D devices. Some interesting recent developments, such as circular mazes, have contributed to analyze critical aspects of freely moving human spatial navigation in real space, although dedicated protocols only allow for simple approaches. Here, we have developed both specifically designed and home-assembled hardware equipment, and a customized protocol for spatial navigation evaluation in freely moving humans in a real space circular arena. The spatial navigation protocol poses an imitation of a real-space multiple-choice path maze with cul-de-sac and instances of non-linear movement. We have compared the results of this system to those of a number of validated, both virtual and real, spatial navigation tests in a group of participants. The system composed by hardware, the test protocol, and dedicated measure analysis designed in our laboratory allows us to evaluate human spatial navigation in a complex maze with a small and portable structure, yielding a highly flexible, adaptable, and versatile access to information about the subjects’ spatial navigation abilities.

MicroRNAs have emerged as important regulators of the metastatic process. In addition, circulating miRNAs appear to be surprisingly stable in peripheral blood making them ideal noninvasive biomarkers for disease diagnosis. Here, we performed a proof-of-principle study to investigate the expression profile of circulating miRNAs and their association with the metastatic lymph node status in early breast cancer patients. Sentinel lymph node status was detected by one-step nucleic acid (OSNA) analysis. We performed RNA-sequencing in 16 plasma samples and validated the results by qPCR. Gene Ontology term enrichment and KEGG pathway analyses were carried out using DAVID tools. We found16 differentially expressed miRNAs (q < 0.01) in patients with positive SLNs. Fourteen miRNAs were down-regulated (miR-339-5p, miR-133a-3p, miR-326, miR-331-3p, miR-369-3p, miR-328-3p, miR-26a-3p, miR-139-3p, miR-493-3p, miR-664a-5p, miR-146a-5p, miR-323b-3p, miR-1307-3p and miR-423-3p) and 2 were up-regulated (miR-101-3pand miR-144-3p). Hierarchical clustering using differentially expressed miRNAs clearly distinguished patients according to their lymph node status. Gene ontology analysis showed a significant enrichment of biological processes associated with the regulation of the epithelial mesenchymal transition, cell proliferation and transcriptional regulation. Our results suggest the potential role of several circulating miRNAs as surrogate markers of lymph node metastases in early breast cancer patients. Further validation in a larger cohort of patients will be necessary to confirm our results.

Impaired behavioral activation and effort-related motivational dysfunctions like fatigue and anergia are debilitating treatment-resistant symptoms of depression. Depressed people show a bias towards the selection of low effort activities. To determine if the broadly used antidepressant fluoxetine can improve behavioral activation and reverse dopamine (DA) depletion-induced anergia, male CD1 mice were evaluated for vigorous escape behaviors in an aversive context (forced swim test, FST), and also with an exercise preference choice task [running wheel (RW)-T-maze choice task]. In the FST, fluoxetine increased active behaviors (swimming, climbing) while reducing passive ones (immobility). However, fluoxetine was not effective at reducing anergia induced by the DA-depleting agent tetrabenazine, further decreasing vigorous climbing and increasing immobility. In the T-maze, fluoxetine alone produced the same pattern of effects as tetrabenazine. Moreover, fluoxetine did not reverse tetrabenazine-induced suppression of RW time but it reduced sucrose intake duration. This pattern of effects produced by fluoxetine in DA-depleted mice was dissimilar from devaluing food reinforcement by pre-feeding or making the food bitter since in both cases sucrose intake time was reduced but animals compensated by increasing time in the RW. Thus, fluoxetine improved escape in an aversive context but decreased relative preference for active reinforcement. Moreover, fluoxetine did not reverse the anergic effects of DA depletion. These results have implications for the use of fluoxetine for treating motivational symptoms such as anergia in depressed patients.

Las acciones más importantes que enfrentamos en nuestras vidas son más fáciles cuando establecemos metas ya que son herramientas extraordinarias para conocer hacia dónde vamos, las razones por las cuales vamos hacia ya así como la manera como lo conseguiremos. La creación de un plan de clase debe comenzar con el establecimiento de un objetivo claro de aprendizaje que nos prevenga de perdernos en el camino, asimismo, provee de certeza a docentes y estudiantes. Los objetivos de aprendizaje hacen nuestras vidas como docentes tanto más fáciles como más complicadas. Más fáciles pues nos ayudan a determinar hasta qué punto nuestros estudiantes han realmente desarrollado las competencias en cuestión, también nos ayudan a, objetivamente, responder la pregunta ¿han aprendido? Más complicada, ya que, en sí, es un reto importante establecerlas.

Abstract Background Chronic fatigue (CFg) is a prevalent symptom in Gaucher disease (GD) at diagnosis (79%) and remains in a quarter of patients after years of therapy. Bone abnormalities are present in over 70% and peripheral neuropathy in about 11% of the patients, which contributes to the disabling and debilitating complications. Our hypothesis is that other factors such as muscle-tendinous weakness could have influence in the development of CFg. Methods We have evaluated the fiber structure and elasticity of muscle-tendinous unit by strain-elastography (S-ELA) and analyzed their influence in the CFg. S-ELA study was performed in Achilles tendon in 25 type 1 and two type 3 GD patients, all of them with fatigue and were on enzymatic replacement therapy for mean 13 years; simultaneously, bone marrow burden by MRI and calcaneus ultrasound densitometry were evaluated. Blood cell counts, plasma biomarkers, GBA1 genotyping, and SF36 quality of life scale (QoL) were also performed. Statistical analysis: descriptive and comparative test. Results All patients showed a normal Achilles tendinous structure. Abnormal stiff grade 2–3 was found in 17/27 (62.9%); in 11/27 (40.7%) of patients, the alteration was bilateral. There were no correlations between the S-ELA results to other variables; nevertheless, a significant correlation between the degree of tendon hardness and the low score on the QoL scales (p = 0.0035) was found. The S-ELA is a sensitive painless, fast, and low cost method to detect muscle-tendinous subclinical dysfunction that could contribute to CFg in GD. The identification of subclinical tendon alteration would be a sign of alarm, focused on the risk of development of bone complications. Conclusion Intratendinous alteration in strain-elastography is an independent variable in GD patients with persistent fatigue.

Abstract Background Penicillin G Benzathine (PGB) is the cornerstone of syphilis treatment. However, its intramuscular (IM) administration is associated with pain at the site of injection. The dilution of PGB with local anesthetics is recommended in some guidelines, but the evidence that supports it, particularly in adults and in HIV infection, is scarce. Preliminary clinical experience also suggests that the IM administration of PGB through increased needle gauges might improve its tolerability. The aim of the study to identify less painful ways of administering IM PGB in the treatment of syphilis in adults. Methods Multicenter, randomized, double-blinded clinical trial in patients diagnosed with primary syphilis that required a single IM injection of PGB 2400,00 IU. Patients were randomized to receive PGB diluted with 0.5 mL mepivacaine 1% (MV) or PGB alone, and both groups either with a long 19G or short 21G IM needle. The primary objective was the effect on local pain immediately after the administration through a visual scale questionnaire on pain (0 to 10). Results One hundred eight patients were included, 27 in each group. Ninety-four (94.4%) were male, and 41.7% were also HIV-infected. Mean age 36.6 years (SD 11). Significant differences in immediate pain intensity were observed when comparing the long 19G group with anesthesia (mean pain intensity, [MPI] 2.92 [CI 95% 1.08-4.07]) vs long 19G without anesthesia (MPI 5.56 [CI 95% 4.39-6.73), p

Abstract Background Cancer is a rapidly evolving, multifactorial disease that accumulates numerous genetic and epigenetic alterations. This results in molecular and phenotypic heterogeneity within the tumor, the complexity of which is further amplified through specific interactions between cancer cells. We aimed to dissect the molecular mechanisms underlying the cooperation between different clones. Methods We produced clonal cell lines derived from the MDA-MB-231 breast cancer cell line, using the UbC-StarTrack system, which allowed tracking of multiple clones by color: GFP C3, mKO E10 and Sapphire D7. Characterization of these clones was performed by growth rate, cell metabolic activity, wound healing, invasion assays and genetic and epigenetic arrays. Tumorigenicity was tested by orthotopic and intravenous injections. Clonal cooperation was evaluated by medium complementation, co-culture and co-injection assays. Results Characterization of these clones in vitro revealed clear genetic and epigenetic differences that affected growth rate, cell metabolic activity, morphology and cytokine expression among cell lines. In vivo, all clonal cell lines were able to form tumors; however, injection of an equal mix of the different clones led to tumors with very few mKO E10 cells. Additionally, the mKO E10 clonal cell line showed a significant inability to form lung metastases. These results confirm that even in stable cell lines heterogeneity is present. In vitro, the complementation of growth medium with medium or exosomes from parental or clonal cell lines increased the growth rate of the other clones. Complementation assays, co-growth and co-injection of mKO E10 and GFP C3 clonal cell lines increased the efficiency of invasion and migration. Conclusions These findings support a model where interplay between clones confers aggressiveness, and which may allow identification of the factors involved in cellular communication that could play a role in clonal cooperation and thus represent new targets for preventing tumor progression.

Introducción: La Enfermedad Renal Crónica es un problema de salud mundial.Objetivo: Determinar el comportamiento de la mortalidad en pacientes con enfermedad renal en el Instituto de Nefrología durante 2016 y 2017.Material y Métodos: Estudio observacional descriptivo transversal de pacientes fallecidos con necropsia realizada. Se registraron variables demográficas, de laboratorio, las relacionadas con la terapia de reemplazo de la función renal y con el diagnóstico anatomo-patológico. Para cada una de las variables se calcularon frecuencias absolutas y relativas. En el caso de la variable “presencia de sepsis” en las defunciones, fue empleada la prueba de chi-cuadrado para la bondad del ajuste, para probar la hipótesis nula H0: de igualdad de la distribución de las tres categorías de la variable.Resultados: Se estudiaron 48 fallecidos con necropsia, 48,9% del total de fallecidos en el periodo. La correspondencia clínico patológica fue 80,1%. Predominó el sexo masculino, el grupo de edad superior a 60 años y la hipertensión arterial como antecedente. El método de terapia de reemplazo renal más documentado fue la hemodiálisis, mediante catéter venoso central un 87,8%. El 61,8% de los fallecidos recibieron tratamiento hemodialítico por 3 meses o menos. La sepsis fue la segunda causa de muerte precedida por eventos cardio y cerebrovasculares; no obstante, en el análisis de la totalidad de necropsias, la infección asociada directa o indirecta a la muerte tuvo una frecuencia mayor.Conclusiones: La infección directa o indirectamente asociada a la muerte, la hipoalbuminemia y el acceso vascular mediante catéter se relacionan con la mortalidad en el periodo.Palabras clave: mortalidad, enfermedad renal crónica, hemodiálisis, acceso vascular, infección.

We conducted an observational study from January 2016 through January 2017 of patients admitted to a reference pediatric hospital in Madrid, Spain, for neurologic symptoms and enterovirus infection. Among the 30 patients, the most common signs and symptoms were fever, lethargy, myoclonic jerks, and ataxia. Real-time PCR detected enterovirus in the cerebrospinal fluid of 8 patients, nasopharyngeal aspirate in 17, and anal swab samples of 5. The enterovirus was genotyped for 25 of 30 patients; enterovirus A71 was the most common serotype (21/25) and the only serotype detected in patients with brainstem encephalitis or encephalomyelitis. Treatment was intravenous immunoglobulins for 21 patients and corticosteroids for 17. Admission to the pediatric intensive care unit was required for 14 patients. All patients survived. At admission, among patients with the most severe disease, leukocytes were elevated. For children with brainstem encephalitis or encephalomyelitis, clinicians should look for enterovirus and not limit testing to cerebrospinal fluid.

Co-creation is a process that directly involves different stakeholders in the idea generation phase of a new product development process. A pool of 112 new aquaculture fish product ideas was obtained by applying a combination of creative and projective techniques to the co-creation process with consumers in six focus groups conducted in three European countries (Germany, France, and Spain). The subjectivity of qualitative data analysis (e.g., focus groups) is one of its recognised disadvantages. To overcome this drawback, a combination of specialised software (i.e., Alceste), along with word frequency, co-occurrence, and context checking, was applied to provide a different approach to data analyses in qualitative studies. The method identified the most salient dimensions behind the participants’ discourse (naturalness, quality, ethics, price, and health) and inferred the importance those dimensions had for them, thus proving the existence of a correlation of 0.7 between what the participants said (frequency of mention) and what they liked the most (importance). Overall, the exploratory approach proposed is deemed useful for drawing key conclusions from qualitative research, thus offering an alternative to traditional content analysis. In future, the results obtained may be useful for selecting the co-created ideas with the greatest potential to be well received in the market.

Background: The early developmental interventions might be designed with a preventative approach to improving the development of at-risk preterm infants. The present study aimed to evaluate the effectiveness of an early physiotherapy intervention on preterm infants’ motor and global development, and on parents’ stress index. Methods: 48 infants were enrolled and randomized into two groups. Infants allocated to the intervention group received an early physiotherapy intervention, based on parental education sessions and tactile and kinesthetic stimulation during the NICU period, as well as a home-based activity program. The intervention commenced after 32 weeks post-menstrual age and ended at 2 months corrected age. Infants allocated to the control group received the usual care based on the NIDCAP-care. Results: No differences were found between groups on the Alberta Infant Motor Scale at 2- or 8-months corrected age. Infants in the intervention group showed more optimal fine motor, problem-solving, personal-social, and communication development at 1 month corrected age. Conclusions: The results showed no effect on the early physiotherapy intervention. Results might be related to the dose or intensity of the intervention, but also to the poor parental compliance. ClinicalTrials.gov NCT03313427.

IntroductionSacubitril/valsartan (SV) promotes cardiac remodeling and improves prognosis in patients with heart failure (HF). However, the response to the drug may vary between patients and its implementation in daily clinical practice has been slower than expected. Our objective was to develop a score predicting the super-response to SV in HF outpatients.MethodsThis is a retrospective analysis of 185 consecutive patients prescribed SV from two tertiary hospitals between September 2016 and February 2018. Super-responder was defined as a patient taking the drug and (i) without HF admissions, death, or heart transplant, and (ii) with a ≥50% reduction in NT-proBNP levels and/or an increase of ≥10 points in LVEF in a 12-month follow-up period after starting SV. Clinical, echocardiographic, ECG, and biochemical variables were used in a logistic regression analysis to construct a score for super-response to SV which was internally validated using bootstrap method.ResultsOut of 185 patients, 65 (35%) fulfilled the super-responder criteria. Predictors for super-response to SV were absence of both previous aldosterone antagonist and diuretic treatment, NYHA I-II class, female gender, previous 1-year HF admission, and sinus rhythm. An integrating score distinguished a low- (80%) for 1-year super-response to SV. The AUC for the model was 0.72 (95%CI: 0.64–0.80), remaining consistent after internal validation.ConclusionOne-third of our patients presented a super-response to SV. We propose an easy-to-calculate score to predict super-response to SV after 1-year initiation based on variables that are currently assessed in clinical practice.

BackgroundThis study was designed to evaluate the beneficial effects of a botanical extract combination containing soy isoflavone extract (100mg), Aframomum melegueta seed dry extract (50 mg), and Punica granatum skin dry extract (100mg) on health-related Quality of Life in healthy Spanish menopausal women with hot flashes, anxiety, and depressive symptoms using the validated Cervantes Scale.Methods and resultsFifty-seven outpatient women (45-65 years) with menstrual problems associated with climacteric syndrome were enrolled from April 2018 to April 2019 in the context of a prospective, placebo-controlled, double-blind study. Women were randomized to receive treatment with either the botanical combination (250 mg daily divided into two doses) or placebo for eight weeks. At the beginning and end of the study, health-related Quality of Life was assessed using the Cervantes Scale. Subjects treated with the botanical extract, compared to subjects in the placebo group, showed a significant improvement in the Global health-related Quality of Life score (38% [11.3-50.0]% vs. 18.8% [0-37.7]%; P = 0.04) on the Cervantes Scale and, specifically, in the menopause and health domain (13.6% [0-45.4]% vs. 40.7% [20.6-61.0]%; P = 0.05). By contrast, there were no significant changes in the psychic, sexuality, and couple relationship related domains of the Cervantes Scale. Patients who concluded the study did not report substantial side effects.ConclusionShort-term intake of the botanical combination improved the Global Quality of Life of climateric women, according to the Cervantes Scale. Since this is a pilot trial, results should be analysed with caution.Trial registrationNCT04381026; ClinicalTrial.gov (retrospectively registered).

Evidence that microRNAs (miRNAs) regulate the various steps of metastasis is increasing. Several studies have looked at the miRNA expression profile in primary breast tumors but few have compared primary tumor and sentinel lymph node (SLN) metastasis. We correlated the expression of miRNAs with the SLN status and the outcome of axillary lymph node dissection (ALND) in 60 patients with early breast cancer. We profiled the expression of miRNAs in paired breast tumor samples and SLNs using the NextSeq500 Illumina platform and key findings were validated by qPCR. MultiMiR Bioconductor and Reactome pathways analysis were performed to identify target genes and signaling pathways affected by altered expressed miRNAs. Our results show that nine miRNAs were differentially expressed in tumor tissues (q ≤ 0.05). In tumor samples, a 13.5-fold up-regulation of miR-7641-2 (q < 0.001) and a 2.9-fold down-regulation of miR-1291 (q < 0.001) were associated with tumors with positive SLNs. However, only down-regulation of miR-1291 (q = 0.048) remained significant in paired SLNs samples. Interestingly, a 10.5 up-regulation of miR-1291 in SLNs samples was associated with additional axillary lymph node involvement (q < 0.001). The enrichment analyses showed that canonical and non-canonical WNT pathways and negative regulation of various receptor tyrosine kinases signaling pathways were targets of miR-1291 and supports the role of miR-1291 as a tumor suppressor gene (TSG). Further studies are warranted to investigate the use of miR-1291 as a surrogate biomarker of SLN node metastasis in patients with early-stage breast cancer.

The COVID-19 pandemic has changed the lives of millions of people around the globe and some of the unprecedent emerged disruptions, are likely to have been particularly challenging for young children (e.g., school closures, social distancing measures, movement restrictions). Studying the impact of such extraordinary circumstances on their well-being is crucial to identify processes leading to risk and resilience. To better understand how Spanish children have adapted to the stressful disruptions resulting from the pandemic outbreak, we examined the effects of child coping and its interactions with contextual stressors (pandemic and family related) on child adjustment, incorporating in our analysis a developmental perspective. Data was collected in April 2020, through parent-reports, during the acute phase of the pandemic and, temporarily coinciding with the mandatory national quarantine period imposed by the Spanish Government. A sample of 1,123 Spanish children (50% girls) aged 3 to 12 (Mage = 7.26; SD = 2.39) participated in the study. Results showed differences in the use of specific strategies by children in different age groups (i.e., 3–6, 7–9 and 10–12-year-olds). Despite the uncontrollable nature of the pandemic-related stressors, child disengagement coping was distinctively associated to negative outcomes (i.e., higher levels of behavioral and emotional difficulties), whereas engagement coping predicted psychosocial adjustment across all age groups. Moreover, interactively with child coping, parent fear of the future and parent dispositional resilience appear as relevant contextual factors to predict both negative and positive outcomes, but their effects seem to be age dependent, suggesting a higher contextual vulnerability for younger children. These findings might have implications for identifying individual and contextual risk and informing potential preventive interventions aimed to reduce the impact of future pandemic outbreaks on children of different ages.

El reconocimiento de prácticas culturales en torno a los bienes arqueológicos documentados en el altiplano Cundiboyacense, Andes orientales de Colombia, permitió identificar narrativas que dan cuenta de posibles relaciones entre mitos, ritos y bienes arqueológicos registrados. A través de un estudio etnoarqueológico e iconográfico en 31 copas arqueológicas y 20 vasijas etnográficas del Museo Arqueológico de Tunja se pudo identificar relaciones de tipo discursivo, tipológico y morfológico entre el rito de sembrar agua que aún practican campesinos del altiplano y el mito de origen muisca Bachué.