Prevalencia de la no adherencia farmacológica en adultos con enfermedades crónicas en un centro médico de baja complejidad / Prevalence of pharmacological non-adherence in adults with chronic diseases in a low complexity medical center

Introducción: la falta de adherencia farmacológica, siendo un problema de salud pública es una de las principales causas de incremento de la morbimortalidad, discapacidad y costos sanitarios en los pacientes con enfermedades crónicas no transmisibles. Objetivo: describir la prevalencia de la no adherencia al tratamiento farmacológico de los pacientes adultos con patología crónica que asistieron a un centro médico de la ciudad de Tunja, desde septiembre a noviembre del año 2022. Materiales y métodos: estudio observacional de corte transversal que incluyó adultos mayores de 18 años con enfermedad crónica no transmisible en el servicio de consulta externa de un centro de salud de baja complejidad, se recolectó los datos de las historias clínicas, se utilizó estadística descriptiva y Odds Ratio para análisis de asociación. Resultados: se analizaron 216 pacientes. La prevalencia de no adherencia al tratamiento farmacológico fue del 75%, el promedio de edad de pacientes con patología crónica fue 65,5 años, el sexo femenino representó el 56,9%, la mayoría de los casos tuvieron hipertensión arterial sistémica (94,4%), más de la mitad presentaron comorbilidades (73,1%) y el 45,3% estaban polimedicados. Los factores relacionados con la no adherencia farmacológica según el test de Morisky-Green fueron edad menor a 60 años (p=0,033), sexo masculino (p=0,045), consumo de alcohol (p=0,003) y tabaco (p=0,003), ausencia de comorbilidades (p=0,008) y no polifarmacia (p=0,004). Conclusión: la no adherencia farmacológica presentó una prevalencia, por encima a la reportada en la literatura y el principal factor asociado fue el consumo de tabaco. Los resultados obtenidos proporcionan conocimientos para nuevas investigaciones (AU)

Introduction: lack of pharmacological adherence, being a public health problem, is one of the main causes of increased morbidity and mortality, disability and health costs in patients with chronic non-communicable diseases. Objective: to describe the prevalence of non-adherence to pharmacological treatment in adult patients with chronic pathology who attended a medical center in the city of Tunja, from September to November 2022. M aterials and methods: cross-sectional observational study that included adults over 18 years of age with chronic non-communicable disease in the outpatient service of a low-complexity health center, data was collected from medical records, descriptive statistics were used and Odds Ratio for association analysis. Results: 216 patients were analyzed. The prevalence of non-adherence to pharmacological treatment was 75%, the average age of patients with chronic pathology was 65.5 years, the female sex represented 56.9%, the majority of cases had systemic arterial hypertension (94,4%), more than half had comorbidities (73.1%) and 45.3% were polypharmacy. The factors related to pharmacological non-adherence according to the Morisky-Green test were age under 60 years (p=0.033), male sex (p=0.045), alcohol consumption (p=0.003) and tobacco (p=0.003), absence of comorbidities (p=0.008) and no polypharmacy (p=0.004). Conclusion: pharmacological non-adherence had a high prevalence above that reported in the literature and the main associated factor was tobacco consumption. The results obtained provide knowledge for new research (AU)

Prevalencia de malnutrición por exceso en niños, niñas y adolescentes en pandemia, en centro médico de la Escuela de Medicina de la Universidad de Tarapaca / Prevalence of malnutrition due to excess in children, girls and adolescents during pandemic, in a medical center of the School of Medicine of the University of Tarapacá

INTRODUCCIÓN: La malnutrición por exceso afecta aproximadamente a 337 millones de niños, niñas y adolescentes en el mundo. Entre los aspectos multifactoriales asociados a la obesidad, destaca el contexto Pandemia por COVID-19, el cual ha aumentado las cifras de obesidad infantil. Por otro lado, la obesidad es considerada un factor de riesgo para desarrollar de forma grave la enfermedad por COVID-19. Este estudio busca analizar el efecto de la pandemia en los índices de malnutrición por exceso en los niños, niñas y adolescentes atendidos en el centro médico de la carrera de medicina de la Universidad de Tarapacá durante el año 2021 y compararlos con estudios previos realizados en Chile. METODOLOGÍA: La investigación tiene un enfoque analítico, transversal, retrospectivo y observacional. El estudio se basó en la revisión de fichas clínicas de 1094 pacientes entre 2 y 17 años atendidos en el Centro Médico de la Escuela de Medicina de la Universidad de Tarapacá en la ciudad de Arica. Los datos obtenidos fueron almacenados en plantilla Excel para ser ingresados en un programa estadístico. RESULTADOS: Del total de 1094 fichas analizadas, 611 pacientes (55,8%) se encontraron en un estado nutricional concordante con malnutrición por exceso, predominando en el sexo masculino (54,7%) y a mayor edad mayor malnutrición por exceso, encontrando mayor prevalencia de obesidad y obesidad severa en los(las) adolescentes. DISCUSIÓN: La malnutrición por exceso ha adquirido las características de epidemia y es un problema frecuente de los países en vías de desarrollo, convirtiéndose en un problema de salud pública. En este estudio se demuestra un aumento en los niveles de malnutrición por exceso durante el año 2021, comparando los resultados obtenidos en relación a la realidad nacional y regional en los años 2019 y 2020.

INTRODUCTION: Malnutrition due to excess affects approximately 337 million children and adolescents in the world. Among the multifactorial aspects associated with obesity, the COVID-19 Pandemic context stands out, which has warned the figures of childhood obesity. On the other hand, obesity is considered a risk factor for severely developing COVID-19 disease. This study seeks to analyze the effect of the pandemic on the rates of malnutrition due to excess in children and adolescents treated at the medical center of the University of Tarapacá during the year 2021 and compare them with previous studies carried out in Chile. METHODOLOGY: The research has an analytical, cross-sectional, retrospective and observational approach. The study was based on the review of clinical records of 1094 patients between 2 and 17 years of age treated at the Medical Center of the School of Medicine of the University of Tarapacá in the city of Arica. The data obtained was stored in an Excel template to be entered into a statistical program. RESULTS: Of the total of 1094 records analyzed, 611 patients (55.8%) were found to be in a nutritional state consistent with malnutrition due to excess, predominating in males (54.7%) and at older ages, finding a higher prevalence of obesity and severe obesity in adolescents. DISCUSSION: Malnutrition due to excess has acquired the characteristics of an epidemic and is a frequent problem in developing countries, becoming a public health problem. This study demonstrates an increase in the levels of malnutrition by excess during the year 2021, comparing the results obtained in relation to the national and regional reality in the years 2019 and 2020.

Sex and age-related changes in performance in the duathlon world championships / Sexo e mudanças relacionadas com a idade no desempenho em campeonatos mundiais de duatlo / Sexo y cambios relacionados con la edad en el desempeño en campeonatos mundiales de duatlón

ABSTRACT Objective Our study analyses differences in performance between sexes, and changes in performance between age groups at Olympic distance during the ITU Duathlon World Championships, held between 2005 and 2016. During this period, a total of 9,772 duathletes were analysed (6,739 men and 3,033 women). Methods Two-way analyses of variance (ANOVA) were used to examine sex- and age-related differences in performance (time, percentage of time and performance ratio) in the first running and cycling legs, the second running leg, and total race for the top 10 male and female athletes in each age group at the Duathlon World Championships. Results The age group with the highest participation, in both male and female categories, was 40-44 years, and it was found that the mean age of female finisher participants across all age groups was 23.5±12. With regards to performance, the best results for total race time and the cycling segment were achieved in the 30-34-year age group, for both male and female athletes. With regards to performance in the first and third segments (running legs), the best times were achieved in the 25-29 and 30-34 age groups, for men and women respectively. Conclusion According to the results of our study, the best results in the professional career of a duathlete are achieved at between 30 and 35 years, therefore the athlete should incorporate this factor into their training plan. Level of evidence III; Retrospective comparative study.

RESUMO Objetivo Nosso estudo analisa as diferenças de desempenho entre os sexos e as mudanças do desempenho entre as faixas etárias quanto à distância olímpica durante o Campeonato Mundial de Duatlo da ITU, realizado entre 2005 e 2016. Nesse período, foram analisados 9.772 duatletas (6.739 homens e 3.033 mulheres). Métodos As análises de variância bidirecional (ANOVA) foram usadas para examinar as diferenças de desempenho relacionadas com sexo e idade (tempo, porcentagem de tempo e coeficiente de desempenho) na primeira corrida, ciclismo, segunda corrida e competição total dos 10 melhores atletas do sexo masculino e feminino em cada faixa etária no Campeonato Mundial de Duatlo. Resultados A faixa etária com maior participação, tanto dos homens quanto das mulheres foi de 40 a 44 anos, e verificou-se que a média de idade das participantes do sexo feminino que concluíram a competição em todas as faixas etárias foi de 23,5 ± 12. Com relação ao desempenho, os melhores resultados para o tempo total de competição e o segmento de ciclismo foram na faixa etária de 30 a 34 anos, tanto em atletas masculinos quanto femininos. Com relação ao desempenho no primeiro e terceiro segmentos (corridas), o melhor desempenho foi alcançado nas faixas de 25 a 29 e 30 a 34 anos, em homens e mulheres, respectivamente. Conclusão De acordo com os resultados obtidos neste estudo, os melhores resultados na carreira profissional de um duatleta poderiam ser alcançados entre 30 e 35 anos, portanto o atleta deve incorporar esse fator em seu plano de treinamento. Nível de evidência III; Estudo retrospectivo comparativo.

RESUMEN Objetivo Nuestro estudio analiza las diferencias de desempeño entre los sexos y los cambios de desempeño entre los grupos de edad con respecto a la distancia olímpica durante el Campeonato Mundial de Duatlón de ITU, realizado entre 2005 y 2016. En ese período, fueron analizados 9.772 duatletas (6.739 hombres y 3.033 mujeres). Métodos Los análisis de variancia bidireccional (ANOVA) fueron usados para examinar las diferencias de desempeño relacionadas con sexo y edad (tiempo, porcentaje de tiempo y coeficiente de desempeño) en la primera carrera, ciclismo, segunda carrera y competición total de los 10 mejores atletas de sexo masculino y femenino en cada grupo de edad en el Campeonato Mundial de Duatlón. Resultados El grupo de edad con mayor participación, tanto de los hombres como de las mujeres, fue de 40 a 44 años y se verificó que la edad promedio de las participantes femeninas que concluyeron la competición en todos los grupos de edad fue de 23,5 ± 12,5. Con relación al desempeño, los mejores resultados para el tiempo total de competición y el segmento de ciclismo fueron en el grupo de edad de 30 a 34 años, tanto en atletas masculinos como femeninos. Con relación al desempeño en el primer y tercer segmentos (carreras), el mejor desempeño fue alcanzado en los grupos de 25 a 29 y 30 a 34 años, en hombres y mujeres, respectivamente. Conclusión De acuerdo con los resultados obtenidos en este estudio, los mejores resultados en la carrera profesional de un duatleta podrían ser alcanzados entre 30 y 35 años, por lo tanto el atleta debe incorporar ese factor en su plan de entrenamiento. Nivel de evidencia III; Estudio retrospectivo comparativo.

Percepción materna sobre el estado nutricional en escolares de 5 a 6 años pertenecientes a establecimientos de educación especial en la ciudad de Arica / Maternal perception of nutritional condition in students of 5 to 6 years old belonging to special education facilities from the city of Arica

La obesidad corresponde a la acumulación anormal de grasa en el organismo, además es un importante factor de riesgo para el desarrollo de enfermedades cardiovasculares, diabetes, cáncer, etc. En Chile, su prevalencia ha aumentado a lo largo de los años llegando a 24,4% en menores de primer año básico en el año 2018. Hay estudios que reportan que la distorsión de la percepción materna de la imagen corporal del niño podría ser un factor de riesgo para el desarrollo de obesidad infantil ya que de ella dependen principalmente los hábitos alimenticios que el niño adquiera. La sociedad y cultura en la que se desarrolle el individuo también juegan un rol fundamental. El objetivo del estudio fue analizar la percepción materna de la imagen corporal sobre el estado nutricional real del niño con necesidades educativas especiales. La investigación tuvo un diseño observacional de corte transversal. El estudio se realizó en 60 escolares, de 5 y 6 años de edad, pertenecientes a 5 establecimientos de educación especial en la ciudad de Arica. Se aplicó un cuestionario a las madres sobre su percepción del estado nutricional de sus hijos mediante siluetas y conceptos, luego se evaluó peso y estatura en los escolares. Se observó una prevalencia de 38,3% de malnutrición por exceso en la muestra de escolares con necesidades educativas especiales. Además, destaca que un 71,7% de las madres fueron capaces de reconocer el concepto que corresponde al estado nutricional real de su hijo, mientras que un 46,6% lo identificó por medio del uso de siluetas. Se concluyó que las madres con alteración de la percepción materna sobre el estado nutricional de los escolares muestran una tendencia a percibir a su hijo con sobrepeso u obesidad cuando se encuentra en la categoría normal.

Obesity corresponds to the abnormal accumulation of fat, negative situations for health. In childhood, it is an important risk factor for the development of cardiovascular diseases, diabetes, cancer, etc. In Chile, its prevalence has increased over the years reaching 24.4% in children of the first basic year in 2018. Studies indicate that the discrimination of the maternal perception of the child's body image could be a risk factor for the development of childhood obesity that depends on the eating habits that the child acquires. The society and culture in which the individual develops also plays a fundamental role. The objective of the study was to analyze the maternal perception of the body image on the real nutritional status of the child with special educational needs. The research has an observational and transversal design. The study was conducted in 60 students between 5 and 6 years old belonging to 5 special education establishments in the city of Arica. A questionnaire was applied to the mothers about their perception of the nutritional status of their children through silhouettes and concepts, then weight and height were evaluated in schoolchildren. A prevalence of 38.3% of excess malnutrition was observed in the sample of schoolchildren with special educational needs. In addition, it is highlighted that 71.7% of the mothers were able to recognize the concept that corresponds to the actual nutritional status of their child, while 46.6% identified it through the use of silhouettes. We concluded that mothers with an altered maternal perception of the nutritional status of schoolchildren show a tendency to perceive their child as overweight or obese when it is in the normal category.

La gestión del tiempo como competencia docente en la clase de Danza Clásica / A gestão do tempo como competência docente na classe de Dança Clássica / Time management as a teaching competence in classical Dance Lessons

Esta investigación se ha llevado a cabo para conocer las diferencias en las variables temporales que conforman la competencia docente "Tiempo de compromiso motor" en la clase de Danza Clásica, bien acompañada de música grabada o por profesor pianista acompañante de danza. Se ha procedido al análisis de 50 grabaciones con ambos soportes musicales en un Conservatorio Superior de Danza de 89 alumnas que realizaban sus clases en un aula de ballet. Los resultados obtenidos destacan que según el soporte musical utilizado hay diferencias en las categorías de "Tiempo de Tarea" y "Tiempo de Organización", mostrándose un mayor valor en el "Tiempo de Tarea" en las sesiones en las que se utilizó la música en vivo, así como un menor tiempo en la "Organización", por lo que emplear la música en vivo podría proporcionar sesiones más productivas y con menor pérdida de tiempo

Esta pesquisa foi realizada com o objetivo de conhecer as diferenças nas variáveis temporais que compõem a competência docente, "Tempo de compromisso motor" nas aulas de Dança Clássica, seja acompanhado por música gravada ou por professor pianista acompanhando a dança. A análise de 50 gravações com ambos os suportes musicais foi realizada em um Conservatório Superior de Dança de 89 alunos que realizaram suas aulas em uma sala de ballet. Os resultados obtidos destacam que, de acordo com o suporte musical utilizado, existem diferenças nas categorias de "Tempo de Tarefa" e "Tempo de Organização", mostrando um maior valor no "Tempo de Tarefa" nas sessões em que a música ao vivo foi utilizada, bem como um menor tempo na "Organização", de modo que o uso de música ao vivo poderia proporcionar sessões mais produtivas com menor perda de tempo

This study looked into time variable differences in the teaching competence "Time of motor commitment" in Classical Dance lessons accompanied by either recorded music or a pianist teacher. Fifty recordings of 89 students of a Higher Education Dance Conservatory were analyzed in their ballet lessons with both musical supports. The results show differences in the categories of "Task Time" and "Organization Time" according to the musical support used, showing longer "Task Time" and shorter "Organization time" in lessons with live music. Therefore, live music could provide more productive lessons with less loss of time

Conspicuousness, color resemblance, and toxicity in geographically diverging mimicry: The pan-Amazonian frog Allobates femoralis.

Predation risk is allegedly reduced in Batesian and Müllerian mimics, because their coloration resembles the conspicuous coloration of unpalatable prey. The efficacy of mimicry is thought to be affected by variation in the unpalatability of prey, the conspicuousness of the signals, and the visual system of predators that see them. Many frog species exhibit small colorful patches contrasting against an otherwise dark body. By measuring toxicity and color reflectance in a geographically variable frog species and the syntopic toxic species, we tested whether unpalatability was correlated with between-species color resemblance and whether resemblance was highest for the most conspicuous components of coloration pattern. Heterospecific resemblance in colorful patches was highest between species at the same locality, but unrelated to concomitant variation in toxicity. Surprisingly, resemblance was lower for the conspicuous femoral patches compared to the inconspicuous dorsum. By building visual models, we further tested whether resemblance was affected by the visual system of model predators. As predicted, mimic-model resemblance was higher under the visual system of simulated predators compared to no visual system at all. Our results indicate that femoral patches are aposematic signals and support a role of mimicry in driving phenotypic divergence or mimetic radiation between localities.

Solithromycin for the treatment of community-acquired bacterial pneumonia.

INTRODUCTION: Community-acquired pneumonia is a major public health problem worldwide. In recent years, there has been an increase in the frequency of resistance to the antimicrobials such as ß-lactams or macrolides which have habitually been used against the causative pathogens. Solithromycin, a next-generation macrolide, is the first fluoroketolide with activity against most of the frequently isolated bacteria in community-acquired pneumonia, including typical and atypical bacteria as well as macrolide-resistant Streptococcus pneumoniae. Areas covered: A detailed assessment of the literature relating to the antimicrobial activity, pharmacokinetic/pharmacodynamic properties, efficacy, tolerability and safety of solithromycin for the treatment of community-acquired bacterial pneumonia Expert commentary: Recent randomized controlled phase II/III trials have demonstrated the equivalent efficacy of oral and intravenous solithromycin compared with fluoroquinolones in patients with lower mild-to-moderate respiratory infections, and have shown that systemic adverse events are comparable between solithromycin and alternative treatments. However, studies of larger populations which are able to identify infrequent adverse events are now needed to confirm these findings. On balance, current data supports solithromycin as a promising therapy for empirical treatment in adults with community-acquired bacterial pneumonia.

FUNCIONALIDAD FAMILIAR DESDE LA PERSPECTIVA DE UN INTEGRANTE CON DIABETES MELLITUS TIPO 2 EN LA SIERRA NEGRA DE PUEBLA / FAMILY FUNCTION FROM THE VIEWPOINT OF A MEMBER WITH TYPE 2 DIABETES MELLITUS IN THE SIERRA NEGRA DE / PUEBLA FUNCIONALIDADE FAMILIAR SOB A ÓTICA DE UM MEMBRO COM DIABETES MELLITUS TIPO 2 EM SIERRA NEGRA DE PUEBLA

Objetivo: identificar y Describir la Funcionalidad Familiar de Adultos con DMT2 en la Sierra Negra de Puebla. Métodos: el diseño fue descriptivo, transversal, el muestreo probabilístico aleatorio simple. La muestra fue de 118 adultos con diagnóstico de DMT2. La recolección de la información fue mediante una cédula y la Escala de Efectividad en el Funcionamiento Familiar. Resultados: el rango de edad de los adultos fue de 41-59 años, predominó el sexo femenino con el 78%, el 80.6% cuenta con seguro popular, de ocupación ama de casa con el 48.4%. Con respecto a las características sociodemográficas de las familias de los adultos con DMT2, predomina la familia nuclear con el 63.5%, con 4 a 5 integrantes en la familia en el 50%. En el propósito planteado se encontró que el 61.9% tuvo una funcionalidad familiar moderada. Conclusión: la relación de la FF y FF moderada versus disfunción familiar es de casi 2.3:1 lo que indica que en la sierra negra de Puebla aún se encuentran familias integradas aun en estadios de enfermedad crónica como la DMT2.

Objective: identify and describe the Family Functionality of Adults with DMT2 in the Sierra Negra of Puebla. Method: the design was descriptive, cross-sectional, random simple probabilistic sampling. The sample consisted of 118 adults diagnosed with DMT2. The collection of the information was through a cedula and Scale of Effectiveness in the Familiar Functioning. Results: the age range of the adults was 41-59 years, predominantly the female sex with 78%, the 80.6% with the popular insurance, occupancy of the housewife with 48.4%. With regard to the sociodemographic characteristics of the families of adults with T2DM, the nuclear family predominates with 63.5%, with 4 to 5 members in the family in 50%. In the purpose presented, 61.9% had moderate family functionality. Conclusion: the relationship between FF and FF against moderate family dysfunction is about 2.3: 1, indicating that in Sierra Negra de Puebla still integrated families are found even in stages of the chronic disease like DM2.

Objetivo: identificar e descrever a funcionalidade familiar de adultos com DM2 em Sierra Negra de Puebla. Método: o desenho foi descritivo, transversal, amostragem probabilística aleatória simples. A amostra foi composta por 118 adultos diagnosticados com DM2. A coleta de informações foi através de uma cédula e da Escala de Efetividade do Funcionamento Familiar. Resultados: a faixa etária dos adultos foi de 41-59 anos, o sexo feminino predominou com 78%, 80,6% possuíam seguro popular e 48,4% eram donas de casa. Em relação às características sociodemográficas das famílias de adultos com diabetes mellitus tipo 2, a família nuclear predominou com 63,5%, com 4 a 5 membros da família em 50%. Na presente propósito verificou-se que 61,9% tiveram um funcionamento familiar moderado. Conclusão: a relação entre o FF e FF contra disfunção familiar moderada é de cerca de 2.3:1, indicando que em Sierra Negra de Puebla ainda se encontram famílias integradas mesmo em estágios da doença crônica como DM2.

Prescription patterns of antihypertensives in a community health centre in Mexico City: a drug utilization study.

Hypertension is highly prevalent; in Mexico, the 2012 National Health and Nutrition Survey reported a prevalence of hypertension of 31.5% in the adult population. Pharmacological treatment is the commonest intervention and has been shown to reduce cardiovascular mortality and morbidity, and total mortality. Accordingly, the type and number of antihypertensives used and the outcome - in terms of blood pressure (BP) control - are important. Therefore, our purpose is to learn the pattern of antihypertensive drug prescription and explore the determinants of BP control in an urban population in Mexico. A retrospective cross-sectional drug utilization study was conducted. Medical records from a community health centre were searched to identify those corresponding to patients diagnosed with hypertension; information upon antihypertensives used and control of the disease was carefully retrieved. A logistic regression model was built to know the main determinants of BP control. A sample of 345 clinical records of interest was identified. Most patients received antihypertensives (86.4%); the leading medications used were angiotensin-converting enzyme inhibitors, 63.8%; beta-blockers (26.5%), diuretics (19.8%), angiotensin-receptor blockers (15.8%) and calcium-channel blockers (6.4%). Only the age (≥55 years) and BMI (>30) of the patients, and the age of the doctors (≥55 years), had an important influence on BP control. Obesity is a particular and important determinant of uncontrolled hypertension; it is worth to act on body weight, on an individual basis. As lack of control has been also tied to elderly doctors, an education programme could be envisaged.

Whole-Exome Sequencing in a South American Cohort Links ALDH1A3, FOXN1 and Retinoic Acid Regulation Pathways to Autism Spectrum Disorders.

Autism spectrum disorders (ASDs) are a range of complex neurodevelopmental conditions principally characterized by dysfunctions linked to mental development. Previous studies have shown that there are more than 1000 genes likely involved in ASD, expressed mainly in brain and highly interconnected among them. We applied whole exome sequencing in Colombian-South American trios. Two missense novel SNVs were found in the same child: ALDH1A3 (RefSeq NM_000693: c.1514T>C (p.I505T)) and FOXN1 (RefSeq NM_003593: c.146C>T (p.S49L)). Gene expression studies reveal that Aldh1a3 and Foxn1 are expressed in ~E13.5 mouse embryonic brain, as well as in adult piriform cortex (PC; ~P30). Conserved Retinoic Acid Response Elements (RAREs) upstream of human ALDH1A3 and FOXN1 and in mouse Aldh1a3 and Foxn1 genes were revealed using bioinformatic approximation. Chromatin immunoprecipitation (ChIP) assay using Retinoid Acid Receptor B (Rarb) as the immunoprecipitation target suggests RA regulation of Aldh1a3 and Foxn1 in mice. Our results frame a possible link of RA regulation in brain to ASD etiology, and a feasible non-additive effect of two apparently unrelated variants in ALDH1A3 and FOXN1 recognizing that every result given by next generation sequencing should be cautiously analyzed, as it might be an incidental finding.

Single Chain Variable Fragments Produced in Escherichia coli against Heat-Labile and Heat-Stable Toxins from Enterotoxigenic E. coli.

BACKGROUND: Diarrhea is a prevalent pathological condition frequently associated to the colonization of the small intestine by enterotoxigenic Escherichia coli (ETEC) strains, known to be endemic in developing countries. These strains can produce two enterotoxins associated with the manifestation of clinical symptoms that can be used to detect these pathogens. Although several detection tests have been developed, minimally equipped laboratories are still in need of simple and cost-effective methods. With the aim to contribute to the development of such diagnostic approaches, we describe here two mouse hybridoma-derived single chain fragment variable (scFv) that were produced in E. coli against enterotoxins of ETEC strains. METHODS AND FINDINGS: Recombinant scFv were developed against ETEC heat-labile toxin (LT) and heat-stable toxin (ST), from previously isolated hybridoma clones. This work reports their design, construction, molecular and functional characterization against LT and ST toxins. Both antibody fragments were able to recognize the cell-interacting toxins by immunofluorescence, the purified toxins by ELISA and also LT-, ST- and LT/ST-producing ETEC strains. CONCLUSION: The developed recombinant scFvs against LT and ST constitute promising starting point for simple and cost-effective ETEC diagnosis.

Relative displacement method for track-structure interaction.

The track-structure interaction effects are usually analysed with conventional FEM programs, where it is difficult to implement the complex track-structure connection behaviour, which is nonlinear, elastic-plastic and depends on the vertical load. The authors developed an alternative analysis method, which they call the relative displacement method. It is based on the calculation of deformation states in single DOF element models that satisfy the boundary conditions. For its solution, an iterative optimisation algorithm is used. This method can be implemented in any programming language or analysis software. A comparison with ABAQUS calculations shows a very good result correlation and compliance with the standard's specifications.

Modeling of the hypothalamic-pituitary-adrenal axis-mediated interaction between the serotonin regulation pathway and the stress response using a Boolean approximation: a novel study of depression.

Major depressive disorder (MDD) is a multifactorial disorder known to be influenced by both genetic and environmental factors. MDD presents a heritability of 37%, and a genetic contribution has also been observed in studies of family members of individuals with MDD that imply that the probability of suffering the disorder is approximately three times higher if a first-degree family member is affected. Childhood maltreatment and stressful life events (SLEs) have been established as critical environmental factors that profoundly influence the onset of MDD. The serotonin pathway has been a strong candidate for genetic studies, but it only explains a small proportion of the heritability of the disorder, which implies the involvement of other pathways. The serotonin (5-HT) pathway interacts with the stress response pathway in a manner mediated by the hypothalamic-pituitary-adrenal (HPA) axis. To analyze the interaction between the pathways, we propose the use of a synchronous Boolean network (SBN) approximation. The principal aim of this work was to model the interaction between these pathways, taking into consideration the presence of selective serotonin reuptake inhibitors (SSRIs), in order to observe how the pathways interact and to examine if the system is stable. Additionally, we wanted to study which genes or metabolites have the greatest impact on model stability when knocked out in silico. We observed that the biological model generated predicts steady states (attractors) for each of the different runs performed, thereby proving that the system is stable. These attractors changed in shape, especially when anti-depressive drugs were also included in the simulation. This work also predicted that the genes with the greatest impact on model stability were those involved in the neurotrophin pathway, such as CREB, BDNF (which has been associated with major depressive disorder in a variety of studies) and TRkB, followed by genes and metabolites related to 5-HT synthesis.

[Protection against ionizing radiation by leaded glass googles during interventional cardiology]. / ¿Es suficiente la protección otorgada por gafas plomadas en cardiología intervencionista?

BACKGROUND: It is not known whether leaded glass goggles with 0.25 mm Pb equivalency, used in interventional cardiology procedures, attenuate radiation below the levels established by the latest recommendation of the International Commission on Radiological Protection (ICRP). AIM: To assess if the degree of attenuation of the secondary ionizing radiation achieved by the use of 0.25 mm Pb leaded glass goggles, in occupationally exposed workers in interventional cardiology procedures, meets the latest ICRP recommendations. MATERIAL AND METHODS: A prospective investigation was carried out to compare the eye exposure to secondary ionizing radiation received by occupationally exposed personnel in a 9 months period. A set of two thermo luminescent dosimeters was arranged in the front and back of leaded glass goggles in a cohort of seven members of an interventional cardiology service, exposed to 1057 consecutive procedures. RESULTS: The monthly dose equivalent measurement performed in front of the goggles ranged between 1.1 and 6.5 mSv, for paramedics and interventional cardiologists. The radiation measured in the back of the glass varied between 0.66 and 2.75 mSv, respectively. The degree of attenuation of the dose at eye level ranged from 40% to 57.7%, respectively. The projected annual exposure would reach 33 mSv for the interventional cardiologist. CONCLUSIONS: With a similar load of work and wearing 0.25 mm Pb equivalent glass goggles, interventional cardiologists will exceed the crystalline equivalent dose limit recommended by the ICRP (20 mSv/year averaged over the past 5 years).

¿Es suficiente la protección otorgada por gafas plomadas en cardiología intervencionista? / Protection against ionizing radiation by leaded glass googles during interventional cardiology

Background: It is not known whether leaded glass goggles with 0.25 mm Pb equivalency, used in interventional cardiology procedures, attenuate radiation below the levels established by the latest recommendation of the International Commission on Radiological Protection (ICRP). Aim: To assess ifthe degree of attenuation of the secondary ionizing radiation achieved by the use of 0.25 mm Pb leaded glass goggles, in occupationally exposed workers in interventional cardiology procedures, meets the latest ICRP recommendations. Material and Methods: A prospective investigation was carried out to compare the eye exposure to secondary ionizing radiation received by occupationally exposed personnel in a 9 months period. A set of two thermo luminescent dosimeters was arranged in the front and back of leaded glass goggles in a cohort ofseven members of an interventional cardiology service, exposed to 1057 consecutive procedures. Results: The monthly dose equivalent measurement performed in front ofthe goggles ranged between 1.1 and 6.5 mSv, for paramedics and interventional cardiologists. The radiation measured in the back of the glass varied between 0.66 and 2.75 mSv, respectively. The degree of attenuation of the dose at eye level ranged from 40% to 57.7%, respectively. The projected annual exposure would reach 33 mSvfor the interventional cardiologist. Conclusions: With a similar load ofwork and wearing 0.25 mm Pb equivalent glass goggles, interventional cardiologists will exceed the crystalline equivalent dose limit recommended by the ICRP (20 mSv/year averaged over the past 5 years).

Hypocretinergic neurons are activated in conjunction with goal-oriented survival-related motor behaviors.

Hypocretinergic neurons are located in the area of the lateral hypothalamus which is responsible for mediating goal-directed, survival-related behaviors. Consequently, we hypothesize that the hypocretinergic system functions to promote these behaviors including those patterns of somatomotor activation upon which they are based. Further, we hypothesize that the hypocretinergic system is not involved with repetitive motor activities unless they occur in conjunction with the goal-oriented behaviors that are governed by the lateral hypothalamus. In order to determine the veracity of these hypotheses, we examined Fos immunoreactivity (as a marker of neuronal activity) in hypocretinergic neurons in the cat during: a) Exploratory Motor Activity; b) Locomotion without Reward; c) Locomotion with Reward; and d) Wakefulness without Motor Activity. Significantly greater numbers of hypocretinergic neurons expressed c-fos when the animals were exploring an unknown environment during Exploratory Motor Activity compared with all other paradigms. In addition, a larger number of Hcrt+Fos+neurons were activated during Locomotion with Reward than during Wakefulness without Motor Activity. Finally, very few hypocretinergic neurons were activated during Locomotion without Reward and Wakefulness without Motor Activity, wherein there was an absence of goal-directed activities. We conclude that the hypocretinergic system does not promote wakefulness per se or motor activity per se but is responsible for mediating specific goal-oriented behaviors that take place during wakefulness. Accordingly, we suggest that the hypocretinergic system is responsible for controlling the somatomotor system and coordinating its activity with other systems in order to produce successful goal-oriented survival-related behaviors that are controlled by the lateral hypothalamus.

Cloning approach and functional analysis of anti-intimin single-chain variable fragment (scFv).

BACKGROUND: Intimin is an important virulence factor involved in the pathogenesis of enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic Escherichia coli (EHEC). Both pathogens are still important causes of diarrhea in children and adults in many developing and industrialized countries. Considering the fact that antibodies are important tools in the detection of various pathogens, an anti-intimin IgG2b monoclonal antibody was previously raised in immunized mice with the conserved sequence of the intimin molecule (int388-667). In immunoblotting assays, this monoclonal antibody showed excellent specificity. Despite good performance, the monoclonal antibody failed to detect some EPEC and EHEC isolates harboring variant amino acids within the 338-667 regions of intimin molecules. Consequently, motivated by its use for diagnosis purposes, in this study we aimed to the cloning and expression of the single-chain variable fragment from this monoclonal antibody (scFv). FINDINGS: Anti-intimin hybridoma mRNA was extracted and reversely transcripted to cDNA, and the light and heavy chains of the variable fragment of the antibody were amplified using commercial primers. The amplified chains were cloned into pGEM-T Easy vector. Specific primers were designed and used in an amplification and chain linkage strategy, obtaining the scFv, which in turn was cloned into pAE vector. E. coli BL21(DE3)pLys strain was transformed with pAE scFv-intimin plasmid and subjected to induction of protein expression. Anti-intimin scFv, expressed as inclusion bodies (insoluble fraction), was denatured, purified and submitted to refolding. The protein yield was 1 mg protein per 100 mL of bacterial culture. To test the functionality of the scFv, ELISA and immunofluorescence assays were performed, showing that 275 ng of scFv reacted with 2 mg of purified intimin, resulting in an absorbance of 0.75 at 492 nm. The immunofluorescence assay showed a strong reactivity with EPEC E2348/69. CONCLUSION: This study demonstrated that the recombinant anti-intimin antibody obtained is able to recognize the conserved region of intimin (Int388-667) in purified form and the EPEC isolate.

Losac, the first hemolin that exhibits procogulant activity through selective factor X proteolytic activation.

Envenoming by the contact of human skin with Lonomia obliqua caterpillars promotes a hemorrhagic syndrome characterized by a consumptive coagulopathy. Losac (Lonomia obliqua Stuart factor activator) is a component of the bristle of L. obliqua that is probably partially responsible for the observed syndrome because it activates factor X and is recognized by an effective antilonomic serum. Here we unveil the proteolytic activity of Losac and demonstrate the feasibility of its recombinant production. On the other hand, Losac has no homology to known proteases, but it can be inhibited by PMSF, a serine protease inhibitor. Instead, it shows closer homology to members of the hemolin family of proteins, a group of cell adhesion molecules. The recombinant protein (rLosac) shortened the coagulation time of normal and deficient plasmas, whereas it was ineffective in factor X-deficient plasma unless reconstituted with this protein. rLosac was able to activate factor X in a dose- and time-dependent manner but not γ-carboxyglutamic acid domainless factor X. Moreover, phospholipids and calcium ions increased rLosac activity. Also, rLosac had no effect on fibrin or fibrinogen, indicating its specificity for blood coagulation activation. Linear double reciprocal plots indicate that rLosac follows a Michaelis-Menten kinetics. Cleavage of factor X by rLosac resulted in fragments that are compatible with those generated by RVV-X (a well known factor X activator). Together, our results validate Losac as the first protein from the hemolin family exhibiting procoagulant activity through selective proteolysis on coagulation factor X.

Losac, the first hemolin that exhibits procogulant activity through selective factor X proteolytic activation

Envenoming by the contact of human skin with Lonomia obliqua caterpillars promotes a hemorrhagic syndrome characterized by a consumptive coagulopathy. Losac (Lonomia obliqua Stuart factor activator) is a component of the bristle of L. obliqua that is probably partially responsible for the observed syndrome because it activates factor X and is recognized by an effective antilonomic serum. Here we unveil the proteolytic activity of Losac and demonstrate the feasibility of its recombinant production. On the other hand, Losac has no homology to known proteases, but it can be inhibited by PMSF, a serine protease inhibitor. Instead, it shows closer homology to members of the hemolin family of proteins, a group of cell adhesion molecules. The recombinant protein (rLosac) shortened the coagulation time of normal and deficient plasmas, whereas it was ineffective in factor X-deficient plasma unless reconstituted with this protein. rLosac was able to activate factor X in a dose- and time-dependent manner but not ã-carboxyglutamic acid domainless factor X. Moreover, phospholipids and calcium ions increased rLosac activity. Also, rLosac had no effect on fibrin or fibrinogen, indicating its specificity for blood coagulation activation. Linear double reciprocal plots indicate that rLosac follows a Michaelis-Menten kinetics. Cleavage of factor X by rLosac resulted in fragments that are compatible with those generated by RVV-X (a well known factor X activator). Together, our results validate Losac as the first protein from the hemolin family exhibiting procoagulant activity through selective proteolysis on coagulation factor X.

Cloning approach and functional analysis of anti-intimin single-chain variable fragment (scFv)

Intimin is an important virulence factor involved in the pathogenesis of enteropathogenic Escherichiacoli (EPEC) and enterohemorrhagic Escherichia coli (EHEC). Both pathogens are still important causes of diarrhea inchildren and adults in many developing and industrialized countries. Considering the fact that antibodies areimportant tools in the detection of various pathogens, an anti-intimin IgG2b monoclonal antibody was previously raised in immunized mice with the conserved sequence of the intimin molecule (int388-667). In immunoblotting assays, this monoclonal antibody showed excellent specificity. Despite good performance, the monoclonal antibody failed to detect some EPEC and EHEC isolates harboring variant amino acids within the 338-667 regions of intimin molecules. Consequently, motivated by its use for diagnosis purposes, in this study we aimed to the cloning and expression of the single-chain variable fragment from this monoclonal antibody (scFv).Anti-intimin hybridoma mRNA was extracted and reversely transcripted to cDNA, and the light and heavy chains of the variable fragment of the antibody were amplified using commercial primers. The amplified chains were cloned into pGEM-T Easy vector. Specific primers were designed and used in an amplification and chain linkage strategy, obtaining the scFv, which in turn was cloned into pAE vector. E. coli BL21(DE3)pLys strainwas transformed with pAE scFv-intimin plasmid and subjected to induction of protein expression. Anti-intimin scFv,expressed as inclusion bodies (insoluble fraction), was denatured, purified and submitted to refolding. The proteinyield was 1 mg protein per 100 mL of bacterial culture. To test the functionality of the scFv, ELISA andimmunofluorescence assays were performed, showing that 275 ng of scFv reacted with 2 mg of purified intimin,resulting in an absorbance of 0.75 at 492 nm.