Nuclear Apaf-1 and cytochrome c redistribution following stress-induced apoptosis

AbstractApoptotic protease activating factor-1 (Apaf-1) and cytochrome c are cofactors critical for inducing caspase-9 activation following stress-induced apoptosis. One consequence of caspase-9 activation is nuclear–cytoplasmic barrier disassembly, which is required for nuclear caspase-3 translocation. In the nucleus, caspase-3 triggers proteolysis of the caspase-activated DNA nuclease (CAD) inhibitor, causing CAD induction and subsequent DNA degradation. Here we demonstrate that apoptotic cells show perinuclear cytochrome c aggregation, which may be critical for nuclear redistribution of cytochrome c and Apaf-1. We thus indicate that the nuclear redistribution of these cofactors concurs with the previously reported caspase-9-induced nuclear disassembly, and may represent an early apoptotic hallmark

Systematic review and meta-analysis on certolizumab pegol for rheumatoid arthritis in adults

Background The appearance of tumor necrosis factor-alpha (TNFalpha) inhibitors dramatically changed the prognosis of rheumatoid arthritis. Certolizumab pegol (CZP) is a human Fab fragment of anti-TNFalpha monoclonal antibody which is approved for the treatment of rheumatoid arthritis. We performed a systematic review and meta-analysis, with Cochrane methodology, of the effects of CZP in rheumatoid arthritis. Objectives To assess the clinical benefits and harms of CZP in patients with rheumatoid arthritis. Methods We performed a search of electronic database (Cochrane Database, MEDLINE, EMBASE, Web of Knowledge and clinicaltrials.gov) until 26th September 2016. We searched for randomized controlled trials of CZP in rheumatoid arthritis compared to any other agent including placebo. Results 14 trials were included for the meta-analysis, 12 (5422 patients) in the pooled analysis for benefits and 14 (5499 patients) in the pooled analysis for safety. The overall possibility of bias seemed to be low but the quality of the evidence was low due to the risk of attrition bias. With the approved dose - CZP 200 mg subcutaneous every other week with the first three doses of 400 mg - CZP showed statistically significant improvements at 24 weeks compared to placebo in: ACR50 absolute improvement 27% (95% CI 20% to 33%), RR 3.8 (95% CI 2.42 to 5.95) and NNT=4 (95% CI 3 to 8); DAS28 <2.6 - original definition of remission - with RR 3.79 (95% CI 1.90 to 7.56); HAQ with -12% absolute improvement (95% CI -9% to -14%); and erosion score with -0.29% (95% CI -0.42% to -0.17%). There are also data available at 12 weeks with RR of 1.99 (95% CI 1.44 to 2.76) of achieving DAS28<2.6 with CZP 200 mg dose. The proportion of patients achieving DAS28<2.6 was still higher with CZP at 52 weeks with RR of 1.83 (95% CI 1.53 to 2.18). Serious adverse events were more frequent for CZP 200 mg dose with a RR of 1.47 (95% CI 1.13 to 1.91) and NNH of 32. There have been eight adverse events leading to death in CZP 200 mg group versus two in the control group (not statistically significant) and 10 patients developing tuberculosis versus two in the control group (not statistically significant). Conclusions There is low level evidence from randomized controlled trials that CZP as monotherapy or combined with methotrexate improved ACR50, DAS28, HAQ and joint damaged on x-ray. Adverse events were more frequent with active treatment

Sleep quality and sleep deprivation: relationship with academic performance in university students during examination period

The beginning of the university brings together maturational, psychosocial and academic changes that make university students more prone to suffer from insufficient or poor quality sleep, which can negatively influence their academic performance. The period of taking exams is a key part of the academic year. However, there are few studies that analyze sleep during this period of time. Our aim is to study the association of sleep quality and sleep deprivation with academic performance during the examination period. A descriptive, cross-sectional and correlational study was carried out with the participation of 640 subjects in the first three years of five faculties belonging to the Universidad Autónoma de Madrid. The instrument used consisted of a questionnaire that included sociodemographic and academic data, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and information about the academic performance. During the examination period, a positive association was found between sleep quality and academic performance. University students slept less than desired, both on weekdays and weekends, and the sleep debt during the week was associated with a worse students’ perception of their academic performance. In total, 61.3% of the students believed that their performance would improve by getting more sleep. In addition, low drowsiness and napping were also found. In conclusion, during periods of greater academic demand, an insufficient sleep and poor quality is commonly observed, affecting negatively to their academic performance. Actually, about 2/3 of our subjects believed that their performance would improve by getting more slee

Características coligadas al estilo de vida en pacientes adultos mayores en un Centro de Salud de los Andes en el Perú: Characteristics related to lifestyle in elderly patients in a Health Center of the Andes in Peru

Introduction:&nbsp;A correct lifestyle is vital in older adults to reduce their risk of diseases and loss of functionality.&nbsp;Objective:&nbsp;To determine the lifestyles of elderly patients in a Health Center in the Peruvian Andes. Method: Observational, descriptive study with elderly patients from a health center. We worked with a previously collected database. Descriptive statistics were used. The study was approved by the institutional ethics committee.&nbsp;Results:&nbsp;Of the 74 patients evaluated, the mean age was 75.4 years and 52% were females. The mean BMI was 24.8 kg / m2 and that of the abdominal circumference was 86.8 cm. 32.7% had a visual acuity of 70 in the right eye and 36.4% of 50 in the left eye. Glucose (mg / dL), hemoglobin (g / dL) and uric acid (mg / dL) had a median of 97, 15.4 and 7; respectively. Triglycerides and cholesterol had a mean of 182.2 mg / dL and 189.9 mg / dL; respectively. 5.4% of men had reactive PSA. 4% had diabetes, 21.6% hypertension, and 22.2% anemia; while 70.3% consumed alcohol, 6.8% smoked and 89.2% consumed soda.&nbsp;Conclusions:&nbsp;Some indicators of poor lifestyle were found, such as the consumption of alcohol and soft drinks, as well as indicators of conditions related to a poor lifestyle such as an average BMI close to being overweight, high triglycerides and cholesterol.Introducción:&nbsp;Un correcto estilo de vida es vital en los adultos mayores para reducir su riesgo de enfermedades y de perder funcionalidad.&nbsp;Objetivo:&nbsp;Determinar las características coligadas al estilo de vida en pacientes adultos mayores en un Centro de Salud de los andes peruanos. Método: Estudio observacional, descriptivo con pacientes adultos mayores de un centro de salud. Se trabajó con una base de datos previamente recolectada. Se usó estadística descriptiva. El estudio fue aprobado por el comité de ética institucional.&nbsp;Resultados:&nbsp;De los 74 pacientes evaluados, la media de edad fue de 75,4 años y el 52% fue de sexo femenino. La media del IMC fue de 24,8 Kg/m2 y la del perímetro abdominal de 86,8 cm. 32,7% tuvieron una agudeza visual de 70 en el ojo derecho y 36,4% de 50 en el ojo izquierdo. La glucosa (mg/dL), hemoglobina (g/dL) y el ácido úrico (mg/dL) tuvieron una mediana de 97, 15,4 y 7; respectivamente. Los triglicéridos y el colesterol tuvieron una media de 182,2 mg/dL y 189,9 mg/dL; respectivamente. Un 5,4% de hombres tuvieron PSA reactivo. 4% tuvieron diabetes, 21,6% hipertensión arterial y 22,2% anemia; mientras que 70,3% consumía alcohol, 6,8% tenía tabaquismo y 89,2% consumía bebidas gaseosas.&nbsp;Conclusiones:&nbsp;Se encontraron algunos indicadores de mal estilo de vida, como el consumo de alcohol y bebidas gaseosas, así como indicadores de condiciones relacionadas a un mal estilo de vida como una media del IMC cercano al sobrepeso, de triglicéridos y colesterol elevados

High-intensity high-volume swimming induces more robust signaling through PGC-1α and AMPK activation than sprint interval swimming in <i>m. triceps brachii</i>

We aimed to test whether high-intensity high-volume training (HIHVT) swimming would induce more robust signaling than sprint interval training (SIT) swimming within the m. triceps brachii due to lower metabolic and oxidation. Nine well-trained swimmers performed the two training procedures on separate randomized days. Muscle biopsies from m. triceps brachii and blood samples were collected at three different time points: a) before the intervention (pre), b) immediately after the swimming procedures (post) and c) after 3 h of rest (3 h). Hydroperoxides, creatine kinase (CK), and lactate dehydrogenase (LDH) were quantified from blood samples, and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and the AMPKpTHR172/AMPK ratio were quantified by Western blot analysis. PGC-1α, sirtuin 3 (SIRT3), superoxide-dismutase 2 (SOD2), and vascular endothelial growth factor (VEGF) mRNA levels were also quantified. SIT induced a higher release of LDH (

Gamification Patterns: A Catalog to Enhance the Learning Motivation

Currently, the gamification has been a tool used in many contexts, in order to improve the user experiences, playability, among others. However, it just not has been focused in entertainment, but also this knowledge area has been applied from other perspectives like health, tourism and education. In fact, the traditional teaching methodology does not generate enough motivation in students to approach their learning and training objectives, that is why in this work we provide a patterns catalog of gamification that increase student motivation through its implementation in activities both inside and outside of classroom with the support of mobile devices and game applications. Besides, we show the outcomes of an experiment done with different student groups in an education institution in Colombia to evaluate its impact on the student motivation

Factores asociados al uso de métodos anticonceptivos en mujeres en edad fértil de 15 a 49 años según encuesta demográfica en Perú

Background: Contraceptive methods are an important tool to achieve the desired family planning. Objective: To determine the factors associated within the use of contraceptive methods in women of childbearing age between 15 to 49 years old according to the ENDES 2018. Material and methods: Descriptive, observational, analytical and retrospective study. The sample, of the National Demographic Survey of Family Health (ENDES) 2018, to Peruvian women between 15 to 49 years old who responded to the contraceptive methods module was analyzed. Results: There is a higher prevalence of women using contraceptive methods in the urban area (PR = 1,046, CI: 1,037 - 1,054), according the marital status there is a high use in married women of contraceptive use (PR = 1,080 CI: 1,071 - 1,090), in the educational level it's obtained that women with higher education have a higher prevalence of contraceptive use (PR = 1,021, CI: 1,016 - 1,026) and, finally, that the age in the first sex relationship before 17 years has a higher prevalence (PR = 1,017 CI: 1,016 - 1,026). Conclusion: There is a positive association between living in an urban area, age of first sexual intercourse less than 17 years, being married and having high educational level in the use of contraceptive methods.Introducción: Los métodos anticonceptivos son importantes herramientas para lograr una planificación familiar deseada. Objetivo: Determinar los factores asociados al uso de métodos anticonceptivos en mujeres en edad fértil de 15 a 49 años según ENDES 2018. Material y métodos: Estudio descriptivo, observacional, analítico y retrospectivo. Se analizó la muestra de la Encuesta Nacional Demográfica de Salud Familiar (ENDES), del año 2018 a mujeres peruanas entre 15 a 49 años que respondieron el módulo de métodos anticonceptivos. Resultados: Mayor prevalencia de usuarias de métodos anticonceptivos en el área urbana (RP=1,046, IC:1,037 – 1,054), según estado conyugal se evidencia un mayor uso en casadas o convivientes (RP=1,080 IC:1,071 – 1,090), en el nivel educativo se obtiene que mujeres con estudios superiores tiene mayor prevalencia de uso de anticonceptivos (RP= 1,021, IC:1,016 – 1,026) y, finalmente, la edad en la 1ª relación sexual menor a los 17 años tiene mayor prevalencia (RP = 1,017 IC:1,016 – 1,026). Conclusión: Existe asociación positiva entre residir en área urbana, edad de primera relación sexual menor a 17 años, ser casada o conviviente y tener grado de instrucción superior y el uso de métodos anticonceptivos

The BCL2A1 gene as a pre–T cell receptor–induced regulator of thymocyte survival

The pre–T cell receptor (TCR) is expressed early during T cell development and imposes a tight selection for differentiating T cell progenitors. Pre-TCR–expressing cells are selected to survive and differentiate further, whereas pre-TCR− cells are “negatively” selected to die. The mechanisms of pre-TCR–mediated survival are poorly understood. Here, we describe the induction of the antiapoptotic gene BCL2A1 (A1) as a potential mechanism regulating inhibition of pre–T cell death. We characterize in detail the signaling pathway involved in A1 induction and show that A1 expression can induce pre–T cell survival by inhibiting activation of caspase-3. Moreover, we show that in vitro “knockdown” of A1 expression can compromise survival even in the presence of a functional pre-TCR. Finally, we suggest that pre-TCR–induced A1 overexpression can contribute to T cell leukemia in both mice and humans

Las alteraciones metabólicas asociadas a la obesidad están ya presentes en los primeros años de vida: estudio colaborativo español

Los objetivos de este estudio son, realizar una descrip-ción de las características demográficas, antropométricas y de las alteraciones metabólicas de niños atendidos por obe-sidad resaltando las características aquellos casos de obesidad de inicio temprano (< 10 años) y los de inicio precoz (< 5 años), y evaluar la capacidad diagnóstica de la definición de síndrome metabólico (SM) según diferentes criterios. Métodos: Es un estudio retrospectivo, caso-control, trans-versal, multicéntrico. Han participado un total de 10 Uni-dades de Endocrinología Pediátrica de diferentes hospitales españoles con un grupo de 469 niños con obesidad de inicio temprano y otro grupo de 30 niños con obesidad de inicio precoz. El grupo control estuvo constituido por 224 niños sanos menores de 10 años. Se realizó una valoración antro-pométrica y determinación analítica de parámetros del me-tabolismo de los hidratos de carbono y lipidograma. Resultados: La presencia de alteraciones metabólicas asociadas a la obesidad en la etapa infanto-juvenil en Espa-ña es notable, de forma aislada, o englobada bajo la defini-ción de SM. La prevalencia de éste aumenta sustancialmen-te cuando se considera la resistencia periférica a la acción de la insulina como criterio diagnóstico. Se demuestra cómo en niños menores de 10 años, dichas alteraciones están presen-tes en un porcentaje reseñable, y se encuentran las primeras alteraciones metabólicas ya en niños obesos < 5 años. Conclusión: En los niños españoles existen alteracio-nes metabólicas asociadas a la obesidad en la etapa in-fanto-juvenil de forma aislada o englobada bajo la de-finición de SM, y ya están presentes a edades precoces. The objectives of this study are to provide a description of the demographic, anthropometric characteristics and metabolic abnormalities in children with early-onset (< 10 years) and of very-early-onset obesity (< 5 years). We also evaluate the diagnostic ability using the definition of meta-bolic syndrome (MS) according to different criteria. Methods: It is a retrospective, case-control, cross-sec-tional, multicenter study. A total of 10 Pediatric Endo-crinology Units in different Spanish hospitals were in-volved. A group of 469 children with early-onset obesity and another group of 30 children with very early-onset obesity were studied. The control group consisted of 224 healthy children younger than 10 years. Anthropometric and analytical determination of carbohydrates metabo-lism parameters and the lipid profile were performed. Results: The presence of metabolic alterations associa-ted with obesity in children and adolescents in Spain is remarkable, either on their own, or encompassed within the definition of MS. This prevalence increases substan-tially when considering the peripheral resistance to in-sulin action as a diagnostic criterion. It also shows how children who could not be diagnosed with MS according to the definition provided by the International Diabetes Federation (IDF) due to age below 10 years, these altera-tions are already present in a remarkable percentage. In fact, metabolic abnormalities are already present in the very-early-onset obese children (<5 years). Conclusion: In Spanish children there are metabolic alterations associated with obesity in the infant-juvenile stages alone or encompassed within the definition of MS, and are already present at earlier ages

Electrochemical impedance biosensor for Chagas Disease diagnosis in clinical samples

Chagas disease (CD) is one of the main neglected tropical diseases, diagnosed mainly by serological tests performed in centralized laboratories, which severely limits the clinical management of the disease in communities with scarce resources. Herein, an electrochemical impedance biosensor for the detection of CD was developed for the first time using a cruzipain-based sensor surface. The protein, highly immunogenic and isolated from Trypanosoma cruzi, was immobilized over the surface of gold disc electrodes modified with 11-mercaptoundecanoic (MUA) and 6-mercapto-1-hexanol (MCH) self-assembled monolayers (SAMs). Reproducible sensor surfaces, yielding 38 ± 3% coverage as measured by Surface Plasmon Resonance, were obtained by amide coupling of 120 μg/mL cruzipain onto 1/10 MUA/MCH SAMs for 30 min. Under optimized operational conditions, the impedimetric immunosensor recognized specific interactions for anti-T. cruzi antibodies in 1/800 diluted human serum patient samples. The charge transfer resistance of the biosensors increases by ~18% in the presence of the positive samples, whereas the negative samples give rise to a negligible increase of around 6%. An excellent selectivity to clinical samples from patients infected with T. cruzi was obtained. The clear signal difference obtained for positive and negative clinical samples highlights the applicability of the sensors for the point-of-care diagnosis of CD.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada