Are circulating cytokines reliable biomarkers for amyotrophic lateral sclerosis?

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that has no effective treatment. The lack of any specific biomarker that can help in the diagnosis or prognosis of ALS has made the identification of biomarkers an urgent challenge. Multiple panels have shown alterations in levels of numerous cytokines in ALS, supporting the contribution of neuroinflammation to the progressive motor neuron loss. However, none of them is fully sensitive and specific enough to become a universal biomarker for ALS. This review gathers the numerous circulating cytokines that have been found dysregulated in both ALS animal models and patients. Particularly, it highlights the opposing results found in the literature to date, and points out another potential application of inflammatory cytokines as therapeutic targets

Sistema y método de medida de geometría de vías

Sistema y método de medida de geometría de vías (SMGV), para identificar y cuantificar irregularidades en una vía (1), donde el sistema comprende una estructura (2) rígida, para acoplarse a un medio de desplazamiento externo por la vía (1); un módulo de visión (3) para capturar imágenes de los carriles de la vía (1) durante un desplazamiento de la estructura (2); un módulo de proyección (4) para generar una línea de perfil del carril (5); un módulo de medida inercial (6), que comprende al menos un giróscopo para obtener la orientación de la estructura (2) y al menos un acelerómetro para obtener la aceleración y dirección de la vertical; un módulo de posicionamiento (7), para obtener información de posición; y un módulo de control (8) conectado a los módulos para calcular en tiempo real las irregularidades en las vías (1), ancho (D), peralte (A), alineamiento (C) y nivelación (B).Españ

Influence of immigration on tuberculosis transmission patterns in Castellón, Spain (2004–2007)

Objetivo Describir los patrones de transmisión de la tuberculosis en Castellón en un periodo de importantes cambios demográficos. Métodos Estudio prospectivo descriptivo de los pacientes con cultivo positivo en la provincia de Castellón entre 2004 y2007. Se describen los pacientes por año y nacionalidad, y se cotejan con los casos declarados a la Dirección General de Salud Pública (DGSP). Se estudia la población con patrón molecular disponible por RFLP (restriction fragment length polymorphism) y se analizan las variables de los pacientes agrupados (clusters) a partir de los datos de la DGSP y del Programa de Gestión del Laboratorio. Resultados Según la DGSP, la tasa global de tuberculosis por 100.000 habitantes en la provincia de Castellón fue de 15,7 en 2004, 19,9 en 2005, 18,2 en 2006 y 17,5 en 2007. En nuestro laboratorio se identificaron las cepas de 301 pacientes, que suponen el 77% (301/390) de los casos declarados y el 94% (301/321) aquellos con cultivo positivo. El porcentaje de tuberculosis en extranjeros aumentó hasta superar el 50% en 2007. Se disponía de estudio molecular en el 95% de los casos (286), con un 58% de españoles y un 42% de extranjeros. El porcentaje de agregación fue del 40%, con un 30% de clusters mixtos. Según el estudio convencional de contactos, el 85% de los pacientes en cluster habían sido considerados casos aislados. Conclusiones El aumento de la tasa de tuberculosis en Castellón se debe, principalmente, al creciente número de los casos en extranjeros. Disponer del estudio molecular de todos los pacientes con cultivo positivo nos ha permitido analizar cómo y dónde se transmite la tuberculosis. El 40% de los pacientes se agruparon en clusters, y eran mixtos un tercio de ellos, lo que indica una elevada integración de los inmigrantes.Background This study aimed to identify tuberculosis transmission patterns in Castellón in a period of major demographic changes. Methods A prospective study of patients with positive culture in the province of Castellon over a 4-year period (2004–2007) was carried out. Cases were described by year and nationality and were compared with those reported to the Department of Public Health. We studied the population with available molecular patterns, identified through restriction fragment length polymorphism (RFLP) and analyzed the variables from patient clusters, based on data collected in surveys of the Department of Health and the Laboratory Management Program. Results According to data from the Department of Public Health, the overall rate of tuberculosis per 100,000 inhabitants in the province of Castellón was 15.7 in 2004, 19.9 in 2005, 18.2 in 2006 and 17.5 in 2007. In our laboratory, strains were identified from 301 patients, representing 77% (301/390) of reported cases and 94% (301/321) of reported cases with a positive culture. The percentage of tuberculosis among foreigners increased with age, exceeding 50% in 2007. Molecular studies were available in 95% of patients (286); 58% were Spanish and 42% were foreigners, of whom 54% were Romanians. The cluster percentage was 40%, with 30% of mixed clusters. According to conventional contact studies, 85% of patients in clusters had been considered isolated cases. Conclusions The increased rate of tuberculosis in Castellón was mainly due to the increasing number of cases among foreigners, mostly Romanians. The availability of molecular studies in all patients with a positive culture allowed us to analyze how and where tuberculosis is transmitted in our province. Forty percent of the patients were grouped into clusters; of these, mixed clusters accounted for one third, indicating the high integration of immigrants in our area

Phosphorylation-dependent regulation of the NOTCH1 intracellular domain by dual-specificity tyrosine-regulated kinase 2

NOTCH proteins constitute a receptor family with a widely conserved role in cell cycle, growing and development regulation. NOTCH1, the best characterised member of this family, regulates the expression of key genes in cell growth and angiogenesis, playing an essential role in cancer development. These observations provide a relevant rationale to propose the inhibition of the intracellular domain of NOTCH1 (Notch1-IC) as a strategy for treating various types of cancer. Notch1-IC stability is mainly controlled by post-translational modifications. FBXW7 ubiquitin E3 ligase-mediated degradation is considered one of the most relevant, being the previous phosphorylation at Thr-2512 residue required. In the present study, we describe for the first time a new regulation mechanism of the NOTCH1 signalling pathway mediated by DYRK2. We demonstrate that DYRK2 phosphorylates Notch1-IC in response to chemotherapeutic agents and facilitates its proteasomal degradation by FBXW7 ubiquitin ligase through a Thr-2512 phosphorylation-dependent mechanism. We show that DYRK2 regulation by chemotherapeutic agents has a relevant effect on the viability, motility and invasion capacity of cancer cells expressing NOTCH1. In summary, we reveal a novel mechanism of regulation for NOTCH1 which might help us to better understand its role in cancer biology

Fatores biopsicossociais associados ao risco de preconceito CMF n° 9. Campechuela

Introducción: el riesgo reproductivo preconcepcional (RRPC) se aplica a mujeres en edad reproductiva no embarazadas, que según el riesgo tienen posibilidad de sufrir daños a su salud o la del futuro hijo si se involucraran en el proceso reproductivo. Se realizó un estudio descriptivo de corte transversal sobre los factores biopsicosociales asociados al riesgo reproductivo preconcepcional.Objetivo: determinar los factores biopsicosociales asociados al riesgo reproductivo preconcepcional en el CMF No 9 en el Policlínico Gustavo Aldereguía Lima, en el periodo octubre 2016-abril 2018.Método: se realizó un estudio descriptivo con pacientes dispensarizadas y evaluadas como riesgo preconcepcional en el Consultorio Médico de la Familia No 9 perteneciente al Policlínico Gustavo Aldereguía Lima. Campechuela. Octubre 2016- abril 2018. La muestra de estudio seleccionada de forma intencional estuvo constituida por 80 mujeres dispensarizadas de riego preconcepcional y que cumplieron con los criterios de inclusión y de exclusión. Se utilizaron variables como edad, nivel escolar, ocupación, estado civil, tipo de anticoncepción que utilizaban, afecciones biológicas y antecedentes obstétricos desfavorables. Para obtener la información se utilizó una encuesta la cual se procesó de forma computarizada, mostrando los resultados mediante tablas.Resultados: predominaron las pacientes con edades menores de 20 años, con un nivel de escolaridad de pre universitario sin concluir, amas de casa, solteras, siendo el preservativo el anticonceptivo más utilizado. El asma bronquial fue la afección más diagnosticada, la HTA gravídica el antecedente obstétrico desfavorable que predominó y desconocimiento general del Programa para el Control de Riesgo Preconcepcional. A partir del resultado obtenido se elaboró un sistema de actividades educativas sustentadas en la educación para la salud.Conclusiones: trabajar intencionadamente desde la promoción y la prevención en aspectos de riesgo preconcepcional en la adolescencia, intensificando la prevención del embarazo en esta edad vulnerable. Intensificar la prevención de las enfermedades crónicas desde edades tempranas.Introduction: the preconception reproductive risk (RRPC) applies to women of non-pregnant reproductive age, who according to the risk have the possibility of suffering damage to their health or that of the future child if they are involved in the reproductive process. A descriptive cross-sectional study was conducted on the biopsychosocial factors associated with preconception reproductive risk.Objective: to determine the biopsychosocial factors associated with preconception reproductive risk in CMF No 9 at the Gustavo Aldereguía Lima Polyclinic, in the period October 2016-April 2018.Method: a descriptive study was conducted with patients dispensed and evaluated as preconception risk in the Family Medical Office No. 9 belonging to the Gustavo Aldereguía Lima Polyclinic. Campechuela October 2016- April 2018. The intentionally selected study sample consisted of 80 women dispensed with preconception irrigation and who met the inclusion and exclusion criteria. Variables such as age, school level, occupation, marital status, type of contraception used, biological conditions and unfavorable obstetric history were used. To obtain the information, a survey was used which was processed in a computerized way, showing the results through tables.Results: patients under 20 years of age predominated, with an unfinished level of pre-university education, housewives, single women, the condom being the most commonly used contraceptive. Bronchial asthma was the most diagnosed condition, gravitational AHT, the predominant unfavorable obstetric history and general ignorance of the Preconception Risk Control Program. From the result obtained, a system of educational activities based on health education was developed.Conclusions: to work intentionally from the promotion and prevention in aspects of preconception risk in adolescence, intensifying the prevention of pregnancy in this vulnerable age. Intensify the prevention of chronic diseases from an early age.Introdução: o risco reprodutivo preconceito (RRPC) aplica-se a mulheres em idade reprodutiva não gestantes, que, de acordo com o risco, têm a possibilidade de sofrer danos à sua saúde ou à do futuro filho se estiverem envolvidas no processo reprodutivo. Foi realizado um estudo descritivo de corte transversal sobre os fatores biopsicossociais associados ao risco reprodutivo pré-concepção. Objetivo: determinar os fatores biopsicossociais associados ao risco reprodutivo pré-conceitual no CMF n.o 9 da Policlínica Gustavo Aldereguía Lima, no período de outubro de 2016 a abril de 2018. Método: foi realizado um estudo descritivo com pacientes dispensados e avaliados como risco de preconceito no Serviço Médico da Família nº 9 pertencente à Policlínica Gustavo Aldereguía Lima. Campechuela Outubro de 2016 a abril de 2018. A amostra selecionada intencionalmente foi composta por 80 mulheres dispensadas de irrigação por preconceito e que preencheram os critérios de inclusão e exclusão. Foram utilizadas variáveis como idade, escolaridade, ocupação, estado civil, tipo de contracepção utilizado, condições biológicas e história obstétrica desfavorável. Para obter as informações, utilizou-se uma pesquisa que foi processada de forma computadorizada, mostrando os resultados através de tabelas.Resultados: predominaram pacientes com menos de 20 anos de idade, com nível de educação pré-universitário inacabado, donas de casa, mulheres solteiras, sendo o preservativo o contraceptivo mais utilizado. A asma brônquica foi a condição mais diagnosticada, a AHT gravitacional, a história obstétrica desfavorável predominante e o desconhecimento geral do Programa de Controle de Risco de Preconceito. A partir do resultado obtido, foi desenvolvido um sistema de atividades educativas baseadas na educação em saúde.Conclusões: trabalhar intencionalmente a partir da promoção e prevenção em aspectos de risco de preconceito na adolescência, intensificando a prevenção da gravidez nessa idade vulnerável. Intensificar a prevenção de doenças crônicas desde tenra idade

Intravenous single dose of tranexamic acid safely reduces blood loss and the need for transfusion in elderly patients with hip fracture. A randomized double-blinded controlled trial at 1-year follow-up

Background: A hip fracture usually presents significant blood loss in the perioperative period, with a transfusion rate of 20-60%. In order to reduce the complications associated with this procedure, the administration of Tranexamic Acid (TXA) has been implemented in the treatment of perioperative anemia. The objectives were to evaluate the effectiveness and safety of a single dose of intravenous Tranexamic Acid (TXA) in reducing perioperative blood loss and the requirement for transfusion in elderly patients undergoing hip fracture surgery within one postoperative year. Methods: A double-blind randomized controlled trial was conducted on 129 patients with hip fractures. After randomization, at the start of the surgery, 65 patients received a single dose of 1 gram of intravenous TXA (TXA group), and 64 received a placebo (placebo group). The primary effectiveness outcomes were the total blood loss and transfusion rate. The primary safety outcome was the rate of thromboembolic events. Data on surgical or medical infection, readmission and death were also collected. Results: The TXA group had a significant decrease in blood loss (p = 0.006) and requirement for transfusion (p < 0.001) compared with the placebo group. Likewise, there were no thromboembolic events in the TXA group and seven in the placebo group (p = 0.006). Mortality within 1-year postoperatively was not significantly different (p = 0.115). Conclusion: Using a single dose of intravenous TXA at the start of the surgery significantly reduces blood loss and the requirement for transfusion without increasing the risk of thromboembolic events or mortality within 1-year postoperatively in patients with hip fracture undergoing surgery. Registration number: NCT03211286. https://clinicaltrials.gov/ct2/show/NCT03211286. Level of evidence: I

The Moderating Role of Surgency, Behavioral Inhibition, Negative Emotionality and Effortful Control in the Relationship between Parenting Style and Children’s Reactive and Proactive Aggression

The principal aim of this study is to explore the moderating role of temperament in the relationship between parenting style and the reactive and proactive aggressive behavior of 8-year-old children. The participants are 279 children (154 boys and 125 girls). To measure reactive and proactive aggression, children completed the reactive and proactive questionnaire (RPQ). Child temperament and parenting styles were evaluated by both parents using the temperament in middle childhood questionnaire (TMCQ) and the parenting styles and dimensions questionnaire (PSDQ). The results revealed that boys with high surgency levels and authoritarian fathers displayed more reactive aggression, whereas behaviorally inhibited boys with mothers who scored low for authoritarian parenting displayed less reactive aggression. Finally, girls with high levels of effortful control and mothers who scored low for authoritative parenting displayed more proactive aggression. The results highlight the value of studying the moderating role of temperament in the relationship between children’s aggressive behavior and both mothers’ and fathers’ parenting styles, and underscores the importance of doing so separately for boys and girls.This research was funded by the Spanish Ministry of Economy and Competitiveness [PSI2016-75462-P], the UPV/EHU GIU18/103 Project Grants and the Basque Country Government, grant number [PRE_2018_1_0111]

Lack of a synergistic effect of a non-viral ALS gene therapy based on BDNF and a TTC fusion molecule

Significant improvements in behavioral and electrophysiological results, motoneuron survival and anti-apoptotic/survival-activated pathways were observed with BDNF-TTC treatment. However, no synergistic effect was found for this fusion molecule. Although BDNF in the fusion molecule is capable of activating autocrine and neuroprotective pathways, TTC treatment alone yielded similar neuroprotection. Therefore, an accurate study of the neuroprotective effects of TTC fusion molecules should be performed to obtain a better understanding of its effect

Gut Microbiota Cannot Compensate the Impact of (quasi) Aposymbiosis in Blattella germanica

The German cockroach Blattella germanica is a good model to study complex symbiotic relationships because the following two symbiotic systems coexist in a single individual: the endosymbiont Blattabacterium (living inside specialized cells called bacteriocytes) and the gut microbiota. Although the role of the endosymbiont has been fully elucidated, the function of the gut microbiota remains unclear. The study of the gut microbiota will benefit from the availability of insects deprived of Blattabacterium. Our goal is to determine the effect of the removal (or, at least, the reduction) of the endosymbiont population on the cockroach's fitness, in a normal gut microbiota community. For this purpose, we treated our cockroach population with rifampicin to decrease the amount of endosymbiont in the following generation. As the treatment also affects rifampicin-sensitive gut bacteria, we allowed it to recover for at least 20 days before sampling. We found that after this antibiotic treatment, the endosymbiont population remained extremely reduced and only the microbiota were able to recover, although it could not compensate for the endosymbiont role, and the host's fitness was drastically affected. This accomplished reduction, however, is not homogenous and requires further study to develop stable quasi-aposymbiotic cockroaches

CHK1 expression in gastric cancer is modulated by p53 and RB1/E2F1: Implications in chemo/radiotherapy response

Radiation has a limited but relevant role in the adjuvant therapy of gastric cancer (GC) patients. Since Chk1 plays a critical function in cellular response to genotoxic agents, we aimed to analyze the role of Chk1 in GC as a biomarker for radiotherapy resistance. We analyzed Chk1 expression in AGS and MKN45 human GC cell lines by RT-QPCR and WB and in a small cohort of human patient’s samples. We demonstrated that Chk1 overexpression specifically increases resistance to radiation in GC cells. Accordingly, abrogation of Chk1 activity with UCN-01 and its expression with shChk1 increased sensitivity to bleomycin and radiation. Furthermore, when we assessed Chk1 expression in human samples, we found a correlation between nuclear Chk1 accumulation and a decrease in progression free survival. Moreover, using a luciferase assay we found that Chk1’s expression is controlled by p53 and RB/E2F1 at the transcriptional level. Additionally, we present preliminary data suggesting a posttranscriptional regulation mechanism, involving miR-195 and miR-503, which are inversely correlated with expression of Chk1 in radioresistant cells. In conclusion, Chk1/microRNA axis is involved in resistance to radiation in GC, and suggests Chk1 as a potential tool for optimal stratification of patients susceptible to receive adjuvant radiotherapy after surgeryThis work was supported by Instituto de Salud Carlos III–Fondo de Investigación Sanitaria (PS09/1988 to ISP; PI11-00949, pI014-1495 and Feder Funds to RP); Comunidad Autónoma de Madrid-Universidad Autónoma de Madrid (CCG10-UAM/BIO-5871 to ISP); Fundación Leticia Castillejo Castillo and Ministerio de Ciencia e Innovación (SAF2012-30862 to RSP), Spain