Design and methodology for a proof of mechanism study of individualized neuronavigated continuous Theta burst stimulation for auditory processing in adolescents with autism spectrum disorder.

It has been suggested that aberrant excitation/inhibition (E/I) balance and dysfunctional structure and function of relevant brain networks may underlie the symptoms of autism spectrum disorder (ASD). However, the nomological network linking these constructs to quantifiable measures and mechanistically relating these constructs to behavioral symptoms of ASD is lacking. Herein we describe a within-subject, controlled, proof-of-mechanism study investigating the pathophysiology of auditory/language processing in adolescents with ASD. We utilize neurophysiological and neuroimaging techniques including magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG) metrics of language network structure and function. Additionally, we apply a single, individually targeted session of continuous theta burst stimulation (cTBS) as an experimental probe of the impact of perturbation of the system on these neurophysiological and neuroimaging outcomes. MRS, fMRI, and MEG measures are evaluated at baseline and immediately prior to and following cTBS over the posterior superior temporal cortex (pSTC), a region involved in auditory and language processing deficits in ASD. Also, behavioral measures of ASD and language processing and DWI measures of auditory/language network structures are obtained at baseline to characterize the relationship between the neuroimaging and neurophysiological measures and baseline symptom presentation. We hypothesize that local gamma-aminobutyric acid (GABA) and glutamate concentrations (measured with MRS), and structural and functional activity and network connectivity (measured with DWI and fMRI), will significantly predict MEG indices of auditory/language processing and behavioral deficits in ASD. Furthermore, a single session of cTBS over left pSTC is hypothesized to lead to significant, acute changes in local glutamate and GABA concentration, functional activity and network connectivity, and MEG indices of auditory/language processing. We have completed the pilot phase of the study (n=20 Healthy Volunteer adults) and have begun enrollment for the main phase with adolescents with ASD (n=86; age 14-17). If successful, this study will establish a nomological network linking local E/I balance measures to functional and structural connectivity within relevant brain networks, ultimately connecting them to ASD symptoms. Furthermore, this study will inform future therapeutic trials using cTBS to treat the symptoms of ASD.

Association of APOE gene with longitudinal changes of CSF amyloid beta and tau levels in Alzheimer's disease: racial differences.

BACKGROUND: The Apolipoprotein E (APOE) ε4 allele is a risk factor for late-onset Alzheimer's disease (AD). However, no investigation has focused on racial differences in the longitudinal effect of APOE genotypes on CSF amyloid beta (Aß42) and tau levels in AD. METHODS: This study used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI): 222 participants with AD, 264 with cognitive normal (CN), and 692 with mild cognitive impairment (MCI) at baseline and two years follow-up. We used a linear mixed model to investigate the effect of APOE-ε4-genotypes on longitudinal changes in the amyloid beta and tau levels. RESULTS: Individuals with 1 or 2 APOE ε4 alleles revealed significantly higher t-Tau and p-Tau, but lower amyloid beta Aß42 compared with individuals without APOE ε4 alleles. Significantly higher levels of log-t-Tau, log-p-Tau, and low levels of log-Aß42 were observed in the subjects with older age, being female, and the two diagnostic groups (AD and MCI). The higher p-Tau and Aß42 values are associated with poor Mini-Mental State Examination (MMSE) performance. Non-Hispanic Africa American (AA) and Hispanic participants were associated with decreased log-t-Tau levels (ß = - 0.154, p = 0.0112; ß = - 0.207, and p = 0.0016, respectively) as compared to those observed in Whites. Furthermore, Hispanic participants were associated with a decreased log-p-Tau level (ß = - 0.224, p = 0.0023) compared to those observed in Whites. There were no differences in Aß42 level for non-Hispanic AA and Hispanic participants compared with White participants. CONCLUSION: Our study, for the first time, showed that the APOE ε4 allele was associated with these biomarkers, however with differing degrees among racial groups.

Anaplastic thyroid carcinoma: advances in molecular profiling and targeted therapy.

PURPOSE OF REVIEW: Anaplastic thyroid carcinomas (ATCs) are rare cancers with a globally very poor prognosis, because of their immensely aggressive behaviour, resulting in predominantly advanced stage of disease at diagnosis. Response to available therapies is still disappointing. Aim of the present review is to illustrate the diverse new strategies under investigation, to improve the poor outcome of these patients. RECENT FINDINGS: Applying molecular analysis in ATC is unravelling potentially actionable targets of therapy. If a mutation of BRAF V600E is found, a combination of Dabrafenib and Trametinib is the recommended treatment. In the presence of another druggable mutation, a specific targeted therapy may be proposed. In the absence of druggable mutations, immunotherapy is an alternative approach, especially in case of significant PD-L1 expression. SUMMARY: The molecular profiling of tumour samples is elucidating the genetic alterations involved in ATC development, and new preclinical models are under study to define innovative approaches for individualized treatment of such patients. Hopefully this approach could improve ATC prognosis.

Utilidad del triángulo de evaluación pediátrica en un servicio de emergencia pediátrica / Usefulness of the pediatric assessment triangle in an emergency pediatric service

En el servicio de emergencia pediátrica es fundamental reconocer de forma precoz los signos clínicos que indican amenaza para la vida del paciente. Con el objetivo de establecer la utilidad del Triángulo de Evaluación Pediátrica (TEP) en pacientes que asistieron al Servicio de Emergencia Pediátrica del Servicio Desconcentrado Hospital Pediátrico Dr. Agustín Zubillaga durante el lapso marzo-abril 2018, se realizó un estudio descriptivo, transversal, con una muestra de 216 pacientes, reportando un promedio de edad de 2,98 ± 3,06 años, de los cuales 36,11% eran lactantes menores de un año y 22,69% lactantes mayores, con ligero predominio del sexo masculino (53,7%). Al desglosar cada componente del TEP, se encontraron alterados la apariencia, lenguaje (61,54%), estado de conciencia (53,85%) y tono (50%); en la respiración predominó el tiraje subcostal (86,21%), tiraje intercostal (34,48%), quejido espiratorio (24,14%) y dificultad para hablar (17,24%). Para la circulación se registró palidez en membranas mucosas (91,89%) y piel (54,05%). El 68,98% de los pacientes tenían una situación estable, 9,26% dificultad respiratoria y 9,72% shock compensado. El 86,11% de los pacientes se manejaron de forma ambulatoria. Este estudio aporta información relevante sobre el TEP como herramienta útil para identificar y clasificar la gravedad de una emergencia pediátrica en nuestro hospital(AU)

In the pediatric emergency room it is essential to recognize the clinical signs that indicate the threat of the patient's condition on time. In order to establish the usefulness of the Pediatric Assessment Triangle (PET) in pediatric patients who attended the Emergency Service of the Servicio Desconcentrado Hospital Pediátrico Dr. Agustin Zubillaga during the period March-April 2018, a cross-sectional descriptive study was conducted with a total of 216 patients, with an average age of 2,98 ± 3,06 years, of which 36,11% were under one year old and 22,69% infants were one to two years old, with a slight predominance of males (53,70%). According to each component of the PET, 61,54% of patients had alterations in their appearance and general state, language (61,54%), state of consciousness (53,85%) and tone (50%). With respect to the work of breathing, subcostal retractions prevailed (86,21) as well as intercostal retractions (34,48%), expiratory moans (24,14%) and difficulty in speaking (17,24%). For the circulation part of the PET, pallor was register in mucous membranes (91,86%) and skin (54,05%). The physiopathological diagnoses were stability in 68,98% of cases, 9,26% had respiratory difficulty and 9,72% had compensated shock. The decision of admission was made in 13,89% of cases while 86,11% of cases were managed in an ambulatory manner. This study provides relevant information of the Pediatric Assessment Triangle as a useful tool to identify and classify the severity of a pediatric emergency in our hospital(AU)

Cell cycle deregulation and TP53 and RAS mutations are major events in poorly differentiated and undifferentiated thyroid carcinomas.

BACKGROUND: Anaplastic thyroid carcinomas (ATCs) are among the most lethal malignancies, for which there is no effective treatment. OBJECTIVE: In the present study, we aimed to elucidate the molecular alterations contributing to ATC development and to identify novel therapeutic targets. DESIGN: We profiled the global gene expression of five ATCs and validated differentially expressed genes by quantitative RT-PCR in an independent set of tumors. In a series of 26 ATCs, we searched for pathogenic alterations in genes involved in the most deregulated cellular processes, including the hot spot regions of RAS, BRAF, TP53, CTNNB1 (ß-catenin), and PIK3CA genes, and, for the first time, a comprehensive analysis of components involved in the cell cycle [cyclin-dependent kinase (CDK) inhibitors (CDKI): CDKN1A (p21(CIP1)); CDKN1B (p27(KIP1)); CDKN2A (p14(ARF), p16(INK4A)); CDKN2B (p15(INK4B)); CDKN2C (p18(INK4C))], cell adhesion (AXIN1), and proliferation (PTEN). Mutational analysis was also performed in 22 poorly differentiated thyroid carcinomas (PDTCs). RESULTS: Expression profiling revealed that ATCs were characterized by the underexpression of epithelial components and the up regulation of mesenchymal markers and genes from TGF-ß pathway, as well as, the overexpression of cell cycle-related genes. In accordance, the up regulation of the SNAI2 gene, a TGF-ß-responsive mesenchymal factor, was validated. CDKN3, which prevents the G1/S transition, was significantly up regulated in ATCs and PDTCs and aberrantly spliced in ATCs. Mutational analysis showed that most mutations were present in TP53 (42% of ATCs; 27% of PDTCs) or RAS (31% of ATCs; 18% of PDTCs). TP53 and RAS alterations showed evidence of mutual exclusivity (P = .0354). PIK3CA, PTEN, and CDKI mutations were present in 14%-20% of PDTCs, and in 10%-14% of ATCs. BRAF, CTNNB1, and AXIN1 mutations were rarely detected. CONCLUSION: Overall, this study identified crucial roles for TP53, RAS, CDKI, and TGF-ß pathway, which may represent feasible therapeutic targets for ATC and PDTC treatment.

Female gout: age and duration of the disease determine clinical presentation.

OBJECTIVE: This study aimed to compare data and associated diseases between women and men with gout paired for age and duration of the disease. METHODS: Consecutive patients from outpatient gout clinics of 2 rheumatology departments were included in this case-control study. We identified 37 women with gout diagnosis and paired them by age and duration of the disease with 37 men with gout (American College of Rheumatology criteria). Variables were clinical data, associated diseases, and renal function evaluated by 3 methods: creatinine clearance, modification of diet in renal disease, and Cockcroft-Gault. RESULTS: Mean (SD) age was 54.47 (15.13) years in women versus 53.52 (15.23) years in males, and mean (SD) age at onset 46.77 (16.63) years versus 45.62 (16.16) years in women and men, respectively. Hypertension was found in 26 (73%) of 37 women and in 27 (70%) of 37 men, previous diuretics was found in only 1 man, and no significant differences were found between women and men in gout or associated metabolic diseases. Females had lower creatinine clearance than males did (49.8 [29.7] vs. 67.1 [35.5] mL/min, P = 0.039). But, when it was calculated by methods considering sex, there were no significant differences (Cockcroft-Gault 66.4 [37.6] vs. 78.8 [43.8] mL/min [P = 0.2] and modification of diet in renal disease 73.8 [64.6] vs. 73.1 [35.0] mL/min [P = 0.9], females vs. males, respectively). Thirteen women (35%) were premenopausal at onset, 2 had familial history of gout, and 2 had history of lithiasis; other variables were not different from postmenopausal women. CONCLUSIONS: Factors previously associated to female gout seem to be more related to age than to sex or to the disease itself. In our country, patients with gout (males and females) are younger at onset. Gender should be considered to evaluate renal function in females with gout. One third of our female patients with gout were premenopausal and had unexpected higher frequency of lithiasis; no other differences with postmenopausal women were found.

Suplemento de calcio en gestantes multiparas: con antecedentes de trastornos hipertensivos como factor predictivo para su aparición / Supplement of calcium in multiparous gestating with antecedents of hypertensive disorder as predictive factor for the its apparition

El propósito de la presente investigación es conocer la importancia que tiene el calcio como factor preventivo de la hipertensión arterial gestacional en embarazadas multíparas. Determinar la influencia del calcio en la prevención de la hipertensión arterial gestacional en embarazadas multíparas. Establecer los posibles mecanismos por los que el calcio actúa en la prevención de la hipertensión arterial gestacional. Informar a médicos y estudiantes de Medicina acerca de los medios para la prevención de la HTA gestacional utilizando un suplemento de calcio. Señalar las consecuencias de una ingesta inadecuada de calcio en la dieta de la mujer embarazada

Prevención médica a los empleados de galvanoplastia: estudio y enfoque actual / Medical prevention to the galvanoplasty employer: study and actual focussing

Experimentar en el medio físico del trabajo, ya que estamos acostumbrados a recibir información sin estar en contacto directo con un trabajador que por su necesidad de subsistir se expone a una serie de riesgos que comprometen su salud física y mental. Para constatar que las empresas ven al individuo sólo como recurso humano, para acrecentar sus riquezas sin considerar con medidas preventivas y educación el bienestar y la adaptación del trabajo al hombre. En menos escala, consideramos que aun el mismo trabajador no coopera con las medidas mínimas por exceptisismo. El poder a través de este trabajo apoyar con una extensa bibliografía; los riesgos de enfermedades ocupacionales y de accidentes en el área laboral de la industria del Cromo, de puntos de vista distintos, como lo es la Medicina, de Ingenieria, las Ciencias Sociales, las Estadísticas, Psicología, Toxicología, etc., a los cuales está sometido el hombre. Permitir intercambiar ideas entre los estudiantes, trabajar en grupo y en particular nosotros que fue a las afuera de la UCV, cambiando un poco los esquemas

La adolescencia: cambios progresivos del niño al adulto / The adolescence: progressive changes of child a adutl

La adolescencia ese período de transición entre la infancia y la madurez, constituye al parecer uno de los puntos ciegos de la visión médica del hombre, en la que aparentemente el niño se hace adulto sin que medie para ello ningún tipo de cambio progresivo. ¿Acaso las enfermedades tienen su mayor incidencia en este período de transformación física y mental son diferentes a las del niño y a las del adulto?; y de ser así, ¿estaremos listos para atenderlas y enfrentarlas de la mejor forma posible?

Diabetes mellitus en la infancia: repercusión con el entorno familiar / Diabetes mellitus in the infance: repercussion with family environment

Debido a que la DMID es una enfermedad crónica, que al afectar tempranamente a los niños cambia radicalmente sus vidas (2), se pretende relacionar el entorno familiar como un posible factor de riesgo para la aceptación de su enfermedad (1) lo cual se traduciría en un mejor o peor control metabólico de la Diabetes (1,2,3). Con este estudio se pretende probar si un niño sometido a situaciones de stress familiar tiende a presentar mayor descontrol en el metabolismo de los carbohidratos, con lo cual aumentan sus posibilidades de complicaciones (4). Se escogieron las edades comprendidas entre los seis y doce años debido a que en edades inferiores hay pocos casos (7), y a partir de los doce años hay cambios naturales, debido a que la hormona de crecimiento, hace que aumenten los niveles de glucosa en sangre por lo que se puede obtener el porcentaje de hemoglobina glicosilada en sangre elevada (4,5). Consideramos importante determinar la influencia de la situación familiar para poder catalogar a esos niños como de alto riesgo para un descontrol metabólico y de alguna manera seguirlos más de cerca para prevenir complicaciones

Adolescencia: un problema actual: una aproximación a la realidad del adolescente venezolano / Adolescence: an actual problem: an approximation to the reality of venezuelan adolescent

El período de la adolescencia tiene una morbilidad propia, diferente a la del niño y a la del adulto, y es por eso que decidimos realizar un estudio retrospectivo de las 5 primeras causas de consulta en los adolescentes. La adolescencia, ese período de transición entre la infancia y la madurez, constituye al parecer uno de los puntos ciegos de la visión médica del hombre, en la que aparentemente el niño se hace adulto sin que medie para ello ningún tipo de cambio progresivo. ¿Acaso las enfermedades tienen su mayor incidencia en este período de transformación física y mental son diferentes a las del niño y a las del adulto?; y de ser así, ¿estaremos listos para atender y enfrentarlas de la mejor forma posible?. Con la mirada fija en este objetivo, iniciamos una evaluación estadística. Sin embargo, tan noble propósito no soportó el embate inicial de la realidad, en la que un sistema de archivo y registro anacrónico e ineficaz constituyeron el obstáculo insalvable. De este modo, tuvimos que cambiar nuestro objetivo principal. Así, prescindiendo de los datos estadísticos previos, diseñamos una encuesta para adolescentes con edades comprendidas entre los 12 y 17 años inclusive, que aborda de una manera general, temas de interes como: sexo y embarazo, drogadicción, relación con los padres, depresión y suicidio, actividades personales y accidentes entre otros; apoyándonos en un marco teórico que nos nutre e informa, tratando de esta manera de plantear una aproximación a la problemática del adolescente. No obstante, si con este trabajo logramos despertar un mínimo de interés por pequeño que este sea respecto al adolescente, consideraremos cubierta con creces, la esencia de nuestro objetivo principal