Cardiovascular rhythmicity in overweight and obese children / Ritmicidade cardiovascular em crianças com sobrepeso e obesidade

Abstract Introduction: Obesity is thought to play a role in the disruption of cardiac rhythmicity in obese children, but this is mostly an unexplored field of investigation. We aimed to evaluate the impact of overweight and obesity on circadian and ultradian cardiovascular rhythmicity of prepubertal children, in comparison with normal weight counterparts. Methods: We performed a cross sectional study of 316 children, followed in the birth cohort Generation XXI (Portugal). Anthropometrics and 24-hour ambulatory blood pressure were measured and profiles were examined with Fourier analysis for circadian and ultradian blood pressure (BP) and heart rate (HR) rhythms. Results: Overweight/obese children presented more frequently a non-dipping BP pattern than normal weight counterparts (31.5% vs. 21.6%, p = 0.047). The prevalence of 24-hour mean arterial pressure (MAP) and 8-hour HR rhythmicity was significantly lower in obese children (79.3% vs. 88.0%, p = 0.038 and 33.3% vs. 45.2%, p = 0.031, respectively). The prevalence of the remaining MAP and HR rhythmicity was similar in both groups. No differences were found in the median values of amplitudes and acrophases of MAP and HR rhythms. Discussion: The alterations found in rhythmicity suggest that circadian and ultradian rhythmicity analysis might be sensitive in detecting early cardiovascular dysregulations, but future studies are needed to reinforce our findings and to better understand their long-term implications.

Resumo Introdução: Acredita-se que a obesidade desempenhe um papel na desregulação da ritmicidade cardíaca em crianças obesas, mas esse é um campo de investigação ainda pouco explorado. O objetivo deste trabalho foi avaliar o impacto do sobrepeso e da obesidade na ritmicidade cardiovascular circadiana e ultradiana de crianças pré-púberes, em comparação com crianças com peso normal. Métodos: Realizamos um estudo transversal com 316 crianças, acompanhadas na coorte de nascimentos Geração XXI (Portugal). Foram medidos dados antropométricos e a pressão arterial ambulatorial de 24 horas, e os perfis foram examinados com uma análise de Fourier para ritmos circadianos e ultradianos de pressão arterial (PA) e frequência cardíaca (FC). Resultados: Crianças com sobrepeso/obesidade apresentaram mais frequentemente um padrão de PA não-dipper em comparação com crianças com peso normal (31,5% vs. 21,6%; p = 0,047). A prevalência da pressão arterial média (PAM) de 24 horas e da ritmicidade da FC de 8 horas foi significativamente menor em crianças obesas (79,3% vs. 88,0%; p = 0,038 e 33,3% vs. 45,2%; p = 0,031, respectivamente). A prevalência das restantes ritmicidades da PAM e da FC foi semelhante em ambos os grupos. Não foram encontradas diferenças nos valores medianos das amplitudes e acrofases dos ritmos de PAM e FC. Discussão: As alterações encontradas na ritmicidade sugerem que a análise da ritmicidade circadiana e ultradiana pode ser sensível na detecção de desregulações cardiovasculares precoces, mas são necessários novos estudos para reforçar nossos achados e entender melhor suas implicações a longo prazo.

Seizure onset patterns predict outcome after stereo-electroencephalography-guided laser amygdalohippocampotomy.

OBJECTIVE: Stereotactic laser amygdalohippocampotomy (SLAH) is an appealing option for patients with temporal lobe epilepsy, who often require intracranial monitoring to confirm mesial temporal seizure onset. However, given limited spatial sampling, it is possible that stereotactic electroencephalography (stereo-EEG) may miss seizure onset elsewhere. We hypothesized that stereo-EEG seizure onset patterns (SOPs) may differentiate between primary onset and secondary spread and predict postoperative seizure control. In this study, we characterized the 2-year outcomes of patients who underwent single-fiber SLAH after stereo-EEG and evaluated whether stereo-EEG SOPs predict postoperative seizure freedom. METHODS: This retrospective five-center study included patients with or without mesial temporal sclerosis (MTS) who underwent stereo-EEG followed by single-fiber SLAH between August 2014 and January 2022. Patients with causative hippocampal lesions apart from MTS or for whom the SLAH was considered palliative were excluded. An SOP catalogue was developed based on literature review. The dominant pattern for each patient was used for survival analysis. The primary outcome was 2-year Engel I classification or recurrent seizures before then, stratified by SOP category. RESULTS: Fifty-eight patients were included, with a mean follow-up duration of 39 ± 12 months after SLAH. Overall 1-, 2-, and 3-year Engel I seizure freedom probability was 54%, 36%, and 33%, respectively. Patients with SOPs, including low-voltage fast activity or low-frequency repetitive spiking, had a 46% 2-year seizure freedom probability, compared to 0% for patients with alpha or theta frequency repetitive spiking or theta or delta frequency rhythmic slowing (log-rank test, p = .00015). SIGNIFICANCE: Patients who underwent SLAH after stereo-EEG had a low probability of seizure freedom at 2 years, but SOPs successfully predicted seizure recurrence in a subset of patients. This study provides proof of concept that SOPs distinguish between hippocampal seizure onset and spread and supports using SOPs to improve selection of SLAH candidates.

AR cooperates with SMAD4 to maintain skeletal muscle homeostasis.

Androgens and androgen-related molecules exert a plethora of functions across different tissues, mainly through binding to the transcription factor androgen receptor (AR). Despite widespread therapeutic use and misuse of androgens as potent anabolic agents, the molecular mechanisms of this effect on skeletal muscle are currently unknown. Muscle mass in adulthood is mainly regulated by the bone morphogenetic protein (BMP) axis of the transforming growth factor (TGF)-ß pathway via recruitment of mothers against decapentaplegic homolog 4 (SMAD4) protein. Here we show that, upon activation, AR forms a transcriptional complex with SMAD4 to orchestrate a muscle hypertrophy programme by modulating SMAD4 chromatin binding dynamics and enhancing its transactivation activity. We challenged this mechanism of action using spinal and bulbar muscular atrophy (SBMA) as a model of study. This adult-onset neuromuscular disease is caused by a polyglutamine expansion (polyQ) in AR and is characterized by progressive muscle weakness and atrophy secondary to a combination of lower motor neuron degeneration and primary muscle atrophy. Here we found that the presence of an elongated polyQ tract impairs AR cooperativity with SMAD4, leading to an inability to mount an effective anti-atrophy gene expression programme in skeletal muscle in response to denervation. Furthermore, adeno-associated virus, serotype 9 (AAV9)-mediated muscle-restricted delivery of BMP7 is able to rescue the muscle atrophy in SBMA mice, supporting the development of treatments able to fine-tune AR-SMAD4 transcriptional cooperativity as a promising target for SBMA and other conditions associated with muscle loss.

Is there a Link between Non Melanoma Skin Cancer and Hydrochlorothiazide?

AIMS: Here in we evaluated the association between the use of Hydrochlorothiazide (HCTZ) and the risk of NMSC both, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BACKGROUND: Even though the use of HCTZ is not linked with the development of serious adverse drug reactions, non-melanoma skin cancer (NMSC) has been reported in patients treated with the drug in recent years, most likely due to its photosensitizing ability. OBJECTIVE: To evaluate the statistically significant difference (P<0.05) in the development of NMSC between HCTZ users and non-users and the correlation (P<0.05) between HCTZ use and NMSC. METHODS: We performed a retrospective study on patients referred to general practitioners who developed skin cancer or NMSC whether or not they were treated with antihypertensive drugs. Controls were matched with the test by age and sex. We calculated odds ratios (ORs) for skin cancer and NMSC associated with hydrochlorothiazide using conditional logistic regression. RESULTS: We enrolled 19,320 patients in the present study, out of a total of 10,110 (52.3%) who were treated with antihypertensive drugs. Of 10,110 patients, 3,870 were treated with HCTZ (38.3%). During the study, we failed to report an increased risk of NMSC in HCTZ-treated vs. untreated patients. Gender stratification revealed an OR for NMSC of 1.36 for men and 0.56 for women. We did not find a dose-response relationship between HCTZ use and NMSC. CONCLUSION: In the present study, we failed to report an association between the use of HCTZ and the development of NMSC.

Prenatal alcohol exposure affects renal function in overweight schoolchildren: birth cohort analysis.

BACKGROUND: Prenatal ethanol exposure has been shown to reduce nephron endowment in animal models, but the effect of alcohol during human pregnancy on postnatal kidney function has not been explored. We aim to investigate the potential association of maternal alcohol consumption during pregnancy with the offspring renal function, considering potential confounding by intrauterine growth and children's current nutritional status. METHODS: Prospective longitudinal study in a random sample of 1093 children from a population-based birth cohort. Anthropometrics and estimated glomerular filtration rate (eGFR) were assessed at 7 years of age. Multiple linear regression models were fitted, adjusting for child's gender, age, birthweight, and maternal age, education, prepregnancy nutritional status, and smoking. RESULTS: Thirteen percent of mothers consumed alcohol during pregnancy. At 7 years of age, eGFR was significantly lower in children with prenatal alcohol exposure (134 ± 17 vs.138 ± 16 mL/min/1.73m2, p = 0.014). The effect was dose dependent and only present in overweight and obese children, among whom adjusted eGFR was -6.6(-12.0 to -1.1)mL/min/1.73m2 and -11.1(-21.3 to -1.2)mL/min/1.73m2 in those exposed to ≤ 40 g and to > 40 g of alcohol per week, respectively, compared to no consumption (ptrend = 0.002). CONCLUSIONS: Prenatal alcohol exposure has a dose-dependent adverse effect on renal function at school age in overweight and obese children.

El valor del informe pericial caligráfico emitido por un laboratorio acreditado / The value of the caligraphic expert report issued by an accredited laboratory

La mejora constante en el desarrollo y funcionamiento de los laboratorios es una máxima que deben tener todos presentes. En este sentido, al menos en la última década, los laboratorios forenses van implementando en su sistema de gestión las innovaciones que incorpora cualquier otro tipo de empresas u organizaciones como serían los aspectos relativos al personal, a través de normas sobre seguridad e higiene en el trabajo, cuestiones medioambientales dada la preocupación creciente en la sociedad sobre el deterioro medioambiental que se está acrecentando de forma alarmante y que se manifiesta de diversa constante dentro de lo que conocemos como "cambio climático", y por último, la implementación de un sistema de gestión de la calidad, con el fin de exteriorizar un imagen altamente positiva y obtener de esta forma ventajas competitivas sobre otro tipo de empresas que operan en el mismo ramo o sector. Este último aspecto resulta especialmente significativo para los ensayos que, sobre distintas ramas científicas, son realizados por los laboratorios forenses, ya que contribuye a fortalecer todo el proceso secuencial analítico seguido y consecuentemente las conclusiones alcanzadas en los análisis realizados...(AU)

Optimization of photocrosslinkable resin components and 3D printing process parameters.

The role of 3D printing in the biomedical field is growing. In this context, photocrosslink-based 3D printing procedures for resorbable polymers stand out. Despite much work, more studies are needed on photocuring stereochemistry, new resin additives, new polymers and resin components. As part of these studies it is vital to present the logic used to optimize the amount of each resin constituent and how that effects printing process parameters. The present manuscript aims to analyze the effects of poly(propylene fumarate) (PPF) resin components and their effect on 3D printing process parameters. Diethyl fumarate (DEF), bisacylphosphine oxide (BAPO), Irgacure 784, 2-hydroxy-4-methoxybenzophenone (HMB) and, for the first time, in biomedical 3D printing, ethyl acetate (EA), were the resin components under investigation in this study. Regarding printing process parameters, Exposure Time, Voxel Depth, and Overcuring Depth were the parameters studied. Taguchi Design of Experiments was used to search for the effect of varying these resin constituent concentrations and 3D printing parameters on the curing behavior of 3D printable PPF resins. Our results indicate that resins with higher polymer cross-link density, especially those with a higher content of PPF, are able to be printed at higher voxel depth and with greater success (i.e., high yield). High voxel depth, as long as it does not sacrifice required resolution, is desirable as it speeds printing. Nevertheless, the overall process is governed by the correct setup of the voxel depth in relation to overcuring depth. In regards to resin biocompatibility, it was observed that EA is more effective than DEF, the material we had previously relied on. Our preliminary in vitro cytotoxicity tests indicate that the use of EA does not reduce scaffold biocompatibility as measured by standard cytotoxicity testing (i.e., ISO 10993-5). We demonstrate a workpath for resin constituent concentration optimization through thin film tests and photocrosslinkable process optimization. STATEMENT OF SIGNIFICANCE: We report here the results of a study of photo-crosslinkable polymer resin component optimization for the 3D printing of resorbable poly(propylene fumarate) (PPF) scaffolds. Resin additives are initially optimized for PPF thin film printing. Once those parameters have been optimized the 3D printing process parameters for PPF objects with complex, porous shapes can be optimized. The design of experiments to optimize both polymer thin films and complex porous resorbable polymer scaffolds is important as a guess and check, or in some cases a systematic method, are very likely to be too time consuming to accomplish. Previously unstudied resin components and process parameters are reported.

Screening of Additive Manufactured Scaffolds Designs for Triple Negative Breast Cancer 3D Cell Culture and Stem-Like Expansion.

Breast cancer stem cells (BCSCs) are tumor-initiating cells responsible for metastasis and tumor reappearance, but their research is limited by the impossibility to cultivate them in a monolayer culture. Scaffolds are three-dimensional (3D) cell culture systems which avoid problems related with culturing BCSC. However, a standardized scaffold for enhancing a BCSC population is still an open issue. The main aim of this study is to establish a suitable poly (lactic acid) (PLA) scaffold which will produce BCSC enrichment, thus allowing them to be studied. Different 3D printing parameters were analyzed using Taguchi experimental design methods. Several PLA scaffold architectures were manufactured using a Fused Filament Fabrication (FFF) 3D printer. They were then evaluated by cell proliferation assay and the configurations with the highest growth rates were subjected to BCSC quantification by ALDH activity. The design SS1 (0.2 mm layer height, 70% infill density, Zigzag infill pattern, 45° infill direction, and 100% flow) obtained the highest proliferation rate and was capable of enhancing a ALDH+ cell population compared to 2D cell culture. In conclusion, the data obtained endorse the PLA porous scaffold as useful for culturing breast cancer cells in a microenvironment similar to in vivo and increasing the numbers of BCSCs.

Design of a Scaffold Parameter Selection System with Additive Manufacturing for a Biomedical Cell Culture.

Open-source 3D printers mean objects can be quickly and efficiently produced. However, design and fabrication parameters need to be optimized to set up the correct printing procedure; a procedure in which the characteristics of the printing materials selected for use can also influence the process. This work focuses on optimizing the printing process of the open-source 3D extruder machine RepRap, which is used to manufacture poly(ε-caprolactone) (PCL) scaffolds for cell culture applications. PCL is a biocompatible polymer that is free of toxic dye and has been used to fabricate scaffolds, i.e., solid structures suitable for 3D cancer cell cultures. Scaffold cell culture has been described as enhancing cancer stem cell (CSC) populations related to tumor chemoresistance and/or their recurrence after chemotherapy. A RepRap BCN3D+ printer and 3 mm PCL wire were used to fabricate circular scaffolds. Design and fabrication parameters were first determined with SolidWorks and Slic3r software and subsequently optimized following a novel sequential flowchart. In the flowchart described here, the parameters were gradually optimized step by step, by taking several measurable variables of the resulting scaffolds into consideration to guarantee high-quality printing. Three deposition angles (45°, 60° and 90°) were fabricated and tested. MCF-7 breast carcinoma cells and NIH/3T3 murine fibroblasts were used to assess scaffold adequacy for 3D cell cultures. The 60° scaffolds were found to be suitable for the purpose. Therefore, PCL scaffolds fabricated via the flowchart optimization with a RepRap 3D printer could be used for 3D cell cultures and may boost CSCs to study new therapeutic treatments for this malignant population. Moreover, the flowchart defined here could represent a standard procedure for non-engineers (i.e., mainly physicians) when manufacturing new culture systems is required.

Feasibility of using a dose-area product ratio as beam quality specifier for photon beams with small field sizes.

PURPOSE: To investigate the feasibility of using the ratio of dose-area product at 20 cm and 10 cm water depths (DAPR20,10) as a beam quality specifier for radiotherapy photon beams with field diameter below 2 cm. METHODS: Dose-area product was determined as the integral of absorbed dose to water (Dw) over a surface larger than the beam size. 6 MV and 10 MV photon beams with field diameters from 0.75 cm to 2 cm were considered. Monte Carlo (MC) simulations were performed to calculate energy-dependent dosimetric parameters and to study the DAPR20,10 properties. Aspects relevant to DAPR20,10 measurement were explored using large-area plane-parallel ionization chambers with different diameters. RESULTS: DAPR20,10 was nearly independent of field size in line with the small differences among the corresponding mean beam energies. Both MC and experimental results showed a dependence of DAPR20,10 on the measurement setup and the surface over which Dw is integrated. For a given setup, DAPR20,10 values obtained using ionization chambers with different air-cavity diameters agreed with one another within 0.4%, after the application of MC correction factors accounting for effects due to the chamber size. DAPR20,10 differences among the small field sizes were within 1% and sensitivity to the beam energy resulted similar to that of established beam quality specifiers based on the point measurement of Dw. CONCLUSIONS: For a specific measurement setup and integration area, DAPR20,10 proved suitable to specify the beam quality of small photon beams for the selection of energy-dependent dosimetric parameters.

Relationship between the mothers' nutritional status with that of a child population from São Tomé Principe, "Africa" / Avaliação entre o estado nutricional materno e o de uma população infantil de São Tomé e Príncipe "África"

Abstract Objectives: analyse the relation between the nutritional status of children with 0 to 60 months in São Tome and Principe (STP) and their mothers. Methods: characterization of the nutritional status of 1,169 children for the weight / length ratio (W/L) (≤24months) and Body Mass Index (BMI) for age (>24months) and their mothers. The Chi Square or Fisher tests were used for the study on the relation between the nutritional status of the mother and children, as appropriate. Results: fifty-five percent (55%) of the children are female (median = 21 months). There was a high percentage of global acute malnutrition in the children aged0≤24months (30.2%) and 24≤60months (22%) as well as global chronic malnutrition (32% and 41.1% respectively). We observed a high percentage of overweight /obese mothers (31.6%), with 16.5% of them being of a low height. We observed a significantly higher percentage of children with global acute malnutrition 47.5%) when compared with that which was reported for children of normal mothers (27.9%) or overweight /obese (22%) (p<0,001) mothers. Conclusions: It was observed a high prevalence of acute and chronic global malnutrition in the children studied and a high prevalence of overweight /obese mothers. We observed a statistically significant association between maternal and acute global malnutrition of the children.

Resumo Objetivos: analisar a relação entre o estado de nutrição materno e o de crianças dos 0 aos 60 meses em São Tomé e Príncipe (STP). Métodos: caracterizou-se o estado de nutrição de 1.169 crianças pelo Índice Peso/Comprimento (P/C) (≤24meses) e Índice de Massa Corporal (IMC) para a idade (>24meses) e o estado de nutrição das mães (IMC) A associação entre o estado de nutrição materno e o das crianças foi testada pelo teste do qui-quadrado ou exato de Fisher, conforme apropriado. Resultados: do total da amostra analisada, a maior parte é representada por crianças do sexo feminino (55%). Observa-se média de idade de 25,2±18 meses (mediana 21 meses). Observou-se uma elevada percentagem de desnutrição aguda global nas crianças de 0≤24meses (30,2%) e de 24 ≤60 meses (22,0%), bem como de desnutrição crônica global (32,0% e 41,1% respetivamente). Entre as mães, observou-se elevado percentual de sobrepeso/obesidade (31,6%) e de baixa estatura (16,5%). Das crianças estudadas, 47,5% têm desnutrição aguda global, comparativamente à prevalência em crianças de mães eutróficas (27,9%) ou de mães com sobrepeso/obesidade (22%) (p<0,001). Conclusões: Observou-se elevada prevalência de desnutrição global aguda e crônica nas crianças estudadas e elevada prevalência de sobrepeso/obesidade maternas. A desnutrição global aguda dos filhos esteve associada à desnutrição materna.

Lysosomal acid lipase deficiency: A hidden disease among cohorts of familial hypercholesterolemia?

BACKGROUND: Lysosomal acid lipase deficiency (LALD) is an autosomal recessive disorder and an unrecognized cause of dyslipidemia. Patients usually present with dyslipidemia and altered liver function and mutations in LIPA gene are the underlying cause of LALD. OBJECTIVE: The aim of this study was to investigate LALD in individuals with severe dyslipidemia and/or liver steatosis. METHODS: Coding, splice regions, and promoter region of LIPA were sequenced by Sanger sequencing in a cohort of mutation-negative familial hypercholesterolemia (FH) patients (n = 492) and in a population sample comprising individuals with several types of dyslipidemia and/or liver steatosis (n = 258). RESULTS: This study led to the identification of LALD in 4 children referred to the Portuguese FH Study, all with a clinical diagnosis of FH. Mild liver dysfunction was present at the age of FH diagnosis; however, a diagnosis of LALD was not considered. No adults at the time of referral have been identified with LALD. CONCLUSION: LALD is a life-threatening disorder, and early identification is crucial for the implementation of specific treatment to avoid premature mortality. FH cohorts should be investigated to identify possible LALD patients, who will need appropriate treatment. These results highlight the importance of correctly identifying the etiology of the dyslipidemia.

Association of maternal characteristics and behaviours with 4-year-old children's dietary patterns.

This study examined the association of family and maternal characteristics with preschool children's dietary patterns. Trained interviewers evaluated subsample 3422 mothers and children enrolled in the population-based birth cohort Generation XXI (Porto, Portugal, 2005-2006). Maternal characteristics and behaviours (exercise, smoking habits, diet and child-feeding practices) and family characteristics were evaluated. Maternal diet was classified by a dietary score, and children's dietary patterns were identified by latent class analysis. Odds ratios (OR) and confidence intervals (95% CI) were estimated by multinomial regression models. The analysis was based on a framework with four conceptual levels: maternal socio-economic position (SEP) at 12 years, maternal socio-economic and demographic characteristics at child's delivery, family characteristics and maternal behaviours at child's 4 years. Three dietary patterns were identified in children: high in energy-dense foods (EDF); low in foods typically consumed at main meals and intermediate in snacks (Snacking); higher in healthy foods; and lower in unhealthy ones (Healthier, reference). Lower maternal SEP had an overall effect on children's diet (low vs. high SEP; EDF, OR = 1.76, 95% CI: 1.42-2.18; Snacking, OR = 1.73, 95% CI: 1.27-2.35), while maternal education was directly associated with it (≤9 vs. >12 schooling years, EDF, OR = 2.19, 95% CI: 1.70-2.81; Snacking, OR = 2.22, 95% CI: 1.82-3.55). Children whose mothers had worse dietary score were significantly more likely to follow unhealthier patterns (first vs. fourth quartile; EDF, OR = 9.94, 95% CI: 7.35-13.44, P-trend < 0.001; Snacking, OR = 4.21, 95% CI: 2.94-6.05, P-trend < 0.001). Maternal diet was the key factor associated with children's diet, above and beyond socio-economic and demographic characteristics, accounting for one-third of the determination coefficient of the fully adjusted model. At preschool age, interventions should give a particular focus on maternal diet and low SEP groups.

Estudio preliminar sobre el comportamiento de Aedes albopictus de la region central de Venezuela a insecticidas químicos / Preliminary study on the behavior of Aedes albopictus from the central region of Venezuela to chemical insecticides

Aedes albopictus es un competente vector del virus chikungunya, zika y de la mayor parte de los virus de encefalitis equina, capaz de transmitir al menos 24 arbovirus, susceptible a la infeccion (vertical y horizontalmente) por los serotipos del virus dengue. El objetivo fue realizar un estudio preliminar sobre el comportamiento frente a insecticidas organosinteticos de Ae. albopictus de diferentes localidades de tres estados centrales del pais, durante el periodo 2012-2014. Se realizaron pruebas biologicas con botellas tratadas con insecticidas, segun el metodo del CDC e igualmente evaluacion bioquimica para identificar los mecanismos de detoxificacion enzimaticos in vitro y mecanismos de resistencia in vivo con el sinergista butoxido de piperonilo (PB). Todas las cepas evaluadas presentaron sensibilidad al DDT (200 µg/mL) y cuatro de ellas a lambdacialotrina (6,25 µg/mL), solo una, Santos Michelena (SM) presento valores de sobrevivencia. Tambien esto fue observado con: malation (100 µg/mL) con una mortalidad en 30 minutos de 42,6% para Carabobo; 46,2% Distrito Capital (DC); 69,6% Zamora y 75,5% Mario Briceno Iragorry (MBI), solo resulto sensible SM. En cuanto a fenitrotion se encontraron valores de sobrevivencia con mortalidades en 30 minutos de 72,2%; para Carabobo, 30,7% DC y 45,8% MBI; solo expresaron sensibilidad Zamora y SM. En las cepas Carabobo y DC se observo el efecto sinergico FS = 3 y FS = 1,3, respectivamente. Se presume que los valores de sobrevivencia encontrados para insecticidas organofosforados pudiera asociarse con el incremento de esterasas alfa (a) y beta (b), en menor medida por la acetilcolinesterasa insensible (AChei) y las oxidasas con la sobrevivencia a lambdacialotrina en la cepa SM, lo cual podria comprobarse en estudios futuros a realizarse sobre resistencia a insecticidas. Los resultados encontrados en el presente trabajo, constituyen la base para su inicio a corto plazo en Ae. albopictus de Venezuela y la region, a fin de contribuir en la eficacia de las medidas de control quimico de esta especie de importancia medica.

Aedes albopictus is a competent vector of chikungunya virus, zika and most of the equine virus, capable of transmitting at least 24 arboviruses, susceptible to infection (vertically and horizontally) by serotypes of the dengue virus encephalitis. The objective was to conduct a preliminary study on the behavior against Ae. albopictus organosintetic insecticides from different locations in three central states of the country during the period 2012-2014. Bioassays with insecticide-treated bottles were performed according to the method of the CDC and also biochemical evaluation to identify the mechanisms of detoxification enzyme in vitro and in vivo mechanisms of resistance to the synergist piperonyl butoxide (PB). All strains tested showed sensitivity to DDT (200 µg/mL) and four of them lambdacyhalothrin (6.25 µg/mL), only one, Santos Michelena (SM) presented values of survival. This was also observed: malathion (100 µg/mL) with a mortality time (30 min) of 42.6% for Carabobo; 46.2% Capital District (DC); Zamora 69.6% and 75.5% Mario Briceno Iragorry (MBI) was sensitive only SM. As fenitrothion survival values encountered in the mortalities time (30 min) 72.2%; for Carabobo, 30.7% and 45.8% MBI DC; only expressed sensitivity Zamora and SM. In DC strains Carabobo and the synergistic effect was observed FS = 3 and FS = 1.3, respectively.It is presumed that the survival values found for organophosphate insecticides may be associated with increased esterase alpha (a) and beta (b), to a lesser extent insensitive acetylcholinesterase (ACHEI) and oxidases with survival to lambdacialotrine in strain SM , which could be verified in future studies to be carried out on insecticides resistance. The results found in the present work, constitute the basis for its short-term start in Ae. albopictus from Venezuela and the region, in order to contribute to the effectiveness of chemical control measures of this species of medical importance.

Normalization of glomerular filtration rate in obese children.

BACKGROUND: Glomerular filtration rate (GFR) is conventionally indexed to body surface area (BSA), but this may lead to biased results when applied to subjects of abnormal body size. The aim of our study was to examine the impact of normalization to the BSA and alternative body size descriptors on measured and estimated GFR in overweight and obese children. METHODS: This was a cross-sectional study of 313 children aged 8-9 years old. GFR was measured by 24-h creatinine clearance (CrCl) and additionally estimated from serum creatinine and cystatin C (CysC) using the combined Zappitelli formula, both as absolute values and adjusted to various body size descriptors. The results were compared between 163 normal-weight, 89 overweight and 61 obese children. RESULTS: Compared to the normal-weight children, mean absolute GFR (both measured and estimated) was higher in the overweight and obese children, whereas BSA-adjusted GFR was lower. Linear regression models fitted in normal-weight children revealed equally close associations between absolute GFR and squared height, ideal body weight (IBW) and BSA derived from IBW. Normalization of GFR to the IBW-derived BSA completely eliminated the discrepancy between absolute and BSA-indexed GFR in overweight and obese children. CONCLUSIONS: Indexing of GFR to BSA calculated from the ideal-rather than actual-body weight is a promising approach to avoid overcorrection when studying obese children. Further studies should assess the accuracy of this approach across the full range of age and BMI distribution.

Decreased renal function in overweight and obese prepubertal children.

BACKGROUND: Obesity is a potentially modifiable risk factor for the development and progression of kidney disease, both in adults and children. We aim to study the association of obesity and renal function in children, by comparing estimated glomerular filtration rate (eGFR) in nonoverweight and overweight/obese children. Secondarily, we aim to evaluate the accuracy of equations on eGFR estimation when compared to 24-h urinary creatinine clearance (CrCl). METHODS: Cross-sectional study of 313 children aged 8-9 y, followed in the birth cohort Generation XXI (Portugal). Creatinine and cystatin C, GFR estimated by several formulas and CrCl were compared in 163 nonoverweight and 150 overweight/obese, according to World Health Organization growth reference. RESULTS: Overweight/obese children had significantly lower eGFR, estimated by all methods, except for CrCl and revised Schwartz formula. Despite all children having renal function in the normal range, eGFR decreased significantly with BMI z-score (differences ranging from -4.3 to -1.1 ml/min/1.73 m(2) per standard deviation of BMI). The Zappitelli combined formula presented the closest performance to CrCl, with higher correlation coefficients and higher accuracy values. CONCLUSION: Young prepubertal children with overweight/obesity already present significantly lower GFR estimations that likely represent some degree of renal impairment associated with the complex deleterious effects of adiposity.

Comparison between small radiation therapy electron beams collimated by Cerrobend and tubular applicators.

The purpose of this study was to compare the dosimetric properties of small field electron beams shaped by circular Cerrobend blocks and stainless steel tubular applicators. Percentage depth dose curves, beam profiles, and output factors of small-size circular fields from 2 to 5 cm diameter, obtained either by tubular applicators and Cerrobend blocks, were measured for 6, 10, and 15 MeV electron beam energies. All measurements were performed using a PTW microDiamond 60019 premarket prototype. An overall similar behavior between the two collimating systems can be observed in terms of PDD and beam profiles. However, Cerrobend collimators produce a higher bremsstrahlung background under irradiation with high-energy electrons. In such irradiation condition, larger output factors are observed for tubular applicators. Similar dosimetric properties are observed using circular Cerrobend blocks and stainless steel tubular applicators at lower beam energies. However, Cerrobend collimators allow the delivery of specific beam shapes, conformed to the target area. On the other hand, in high-energy irradiation conditions, tubular applicators produce a lower bremsstrahlung contribution, leading to lower doses outside the target volume. In addition, the higher output factors observed at high energies for tubular applicators lead to reduced treatment times.

Aleitamento materno e caracterização dos hábitos alimentares na primeira infância: experiência de São Tomé e Príncipe / Maternal breastfeeding and the characterization of feeding habits in early infancy: the experience of São Tomé e Príncipe

Avaliação da amamentação, da diversificação e frequência alimentar, em crianças de São Tomé e Príncipe (STP). Métodos: trata-se de uma amostra constituída por 1285 crianças. O protocolo incluiu a prevalência do aleitamento materno exclusivo (AME) e Total (AMT), início da diversificação alimentar (DA) e um questionário de frequência alimentar. O tratamento estatístico foi efetuado no SPSS®. Os resultados foram apresentados de acordo com o total da amostra. Resultados: 45,5 por cento são do sexo feminino e a média de idades 26±18 meses. 46,6 por cento fez AME até aos 6 meses (média 5±2). A média de AMT foi 12±7 meses e o início da DA aos 6±3 meses (mediana=6), sendo as farinhas e a canja de peixe os primeiros alimentos oferecidos. 42 por cento das crianças são incluídas na dieta familiar aos 7±3 meses (mediana=6). Elevada porcentagem de crianças nunca ingere: leite de vaca (74 por cento) ou iogurte (40 por cento), contrariamente ao elevado consumo de óleo alimentar (34 por cento) e açúcar (33 por cento). A idade média de iniciação da cerveja é aos 18±12 meses e vinho de palma 13±10 meses. Conclusões: observa-se uma elevada prevalência de AME e uma precoce introdução da DA. Embora existam recursos alimentares disponíveis, não há informação/ formação adequada para elaborar um plano alimentar saudável durante a infância...

To evaluate breastfeeding and the frequency and diversification of feeding, in children in São Tomé e Príncipe (STP). Methods: the sample comprised 1,285 children. The protocol included the prevalence of exclusive (EMB) and total (TMB) maternal breastfeeding, the onset of nutritional diversification (ND) and a questionnaire on the frequency of feeding. The statistics were processed using SPSS®. The results were presented in terms of the total sample. Results: 45.5 percent of the babies were female and the mean age 26±18 months. 46.6 percent were given EMB up to the age of six months (mean 5±2). The mean for TMB was 12±7 months and the onset of ND at 6±3 months (median=6), with corn flour and fish soup being the first solid foods offered. 42 percent ate the same as the rest of the family at 7±3 months (median=6). High percentages of children never ingested cow's milk (74 percent) or yogurt (40 percent), in contrast to the high consumption of cooking oil (34 percent) and sugar (33 percent). The mean age for beginning to drink beer was 18±12 months and for beginning to drink palm wine 13±10 months. Conclusions: There was a high prevalence of EMB and early introduction of ND. Although nutritional resources are available, there is no adequate information or training on how to draw up a healthy eating plan for infants...

Hypercholesterolemia--a disease with expression from childhood.

INTRODUCTION: Hypercholesterolemia results from an alteration, genetic or acquired, in lipoprotein metabolism. Evidence that hypercholesterolemia is associated with the atherosclerotic process from childhood justifies the screening of high-risk children and initiation of therapy at preschool ages. OBJECTIVE: To assess children referred for pediatric consultations due to hypercholesterolemia. METHODS: Children and adolescents referred for pediatric consultations with a diagnosis of hypercholesterolemia were enrolled. Information on family history and clinical, anthropometric and biochemical parameters was recorded and, when appropriate, molecular study was performed. RESULTS: A total of 168 children were assessed. Forty-six presented a familial hypercholesterolemia phenotype and in 22 of these, a mutation in the low-density lipoprotein (LDL) receptor gene was identified. The lipid profile of the group with mutations showed significantly higher values of total and non-high-density lipoprotein (HDL) cholesterol compared to the group without mutations (total cholesterol 316.5±75.9 mg/dl vs. 260.9±42,0 mg/dl; non-HDL cholesterol 268.3±72.6 mg/dl vs. 203.5±43.9 mg/dl; p<0.05). Of the total, 55 were prescribed pharmacological therapy and the others underwent diet and exercise interventions only. A greater reduction in LDL cholesterol was observed in individuals under pharmacological therapy compared to those prescribed diet and exercise only (30.3% vs. 18.1%). Drug side effects were insignificant. CONCLUSION: It is possible to maintain a normal lipid profile in most individuals with familial hypercholesterolemia in order to reduce the risk of early onset of atherosclerosis, which is associated with serious cardiovascular complications from childhood.

Evaluación de la eficacia de drogas antihelmínticas para el control de Trichuris trichiura y otras helmintiasis en el estado Aragua, Venezuela / Evaluation of the efficacy of antihelmintic drugs for the control of Trichuris trichiura and other helminthic diseases in the state of Aragua, Venezuela

Un ensayo clínico de cuatro brazos fue llevado a cabo en 14 comunidades del estado Aragua para evaluar cuatro esquemas de tratamientos antihelmínticos para geohelmintos: Mebendazol y albendazol como monoterapias y cada una de estas drogas en combinación con ivermectina como terapias combinadas. Los tratamientos fueron administrados posteriormente a un examen coproparsitoscópico inicial, con reevaluaciones a los 7 y 21 días. Quedó en evidencia que las tasas de curación observadas a los 7 días posteriores al tratamiento, a favor de los esquemas combinados, particularmente la combinación albendazol + ivermectina (χ2 = 10,85; P < 0,0009), pero no se reflejaron a los 21 días después de la administración de los tratamientos y ningún esquema demostró una eficacia superior. Trichuris trichiura aún responde satisfactoriamente a los tratamientos convencionales. A pesar de la similitud en la eficacia de las monoterapias y terapias combinadas, el porcentaje de pacientes curados con T. trichiura solo o con infecciones mixtas fue elevada (> 93%). Las uncinarias fueron curadas en 100% (cero huevos en heces), seguido de A. lumbricoides (98,2%) y las infecciones mixtas de T. trichiura + A. lumbricoides + uncinarias (100%). La reducción porcentual de huevos por gramo de heces fue de 100% para las uncinarias, 89,3% para A. lumbricoides y 81,7% para T. trichiura. Las tasas de fracasos fueron bajas para los cuatro esquemas terapéuticos: mebendazol (5,14%), albendazol (6,20%), albendazol + ivermectina (2,02%) y mebendazol + ivermectina (2,22%). El grupo de edad de 0 a 9 años registró el mayor número de fracasos terapéuticos (n = 13). Quizás convendría emplear esquemas combinados en casos de fracasos terapéuticos. Pero, surge la duda si se está evidenciando la posibilidad de resistencia a estos medicamentos, dado que la mayoría de los fracasos terapéuticos se observaron en pacientes con bajas cargas parasitarias que bien podrían revertirse en el tiempo.

A four-arm clinical trial was carried out in 14 communities in the State of Aragua to evaluate four antihelminthics treatments, as monotherapy and combined treatments for soil-transmitted helminthiasis: Mebendazole, albendazole and each of these drugs in combination with ivermectin. Treatments were given after an initial stool specimens were obtained for examination, with two sequential stool reevaluations on days 7 and 21. Cure rates (zero eggs in stools) at day 7 after treatments were favourable for combined treatments, specially albendazole + ivermectin (χ2 = 10.85; P < 0.0009), which was not reflected by day 21 since no treatment showed any superior efficacy. Trichuris trichiura still responds satisfactorily to conventional treatments offered by the national Programme for the Fight against Anclyostomiasis and other Intestinal Parasites. Notwithstanding the similarities of monotherapy and combined treatments efficacy, the percentage of patients cured with T. trichiura solely or with mixed infections was high (> 93%). Hookworm infections were cured a 100% (zero eggs found in feces), followed by A. lumbricoides (98.2%) and mixed infections by T. trichiura + A. lumbricoides + hookworms (100%). However, the mean egg reduction percent was also a 100% for hookworms, 89.3% for A. lumbricoides and 81.7% for T. trichiura. The rates of treatment failure were limited, albendazole 6.20%, mebendazole 5.14%, for the combination of albendazole + ivermectin 2.02% and for mebendazole + ivermectine 2.22%. The majority of treatment failures were seen in the 0-9 age group. It is perhaps convenient to use combined schemes in cases of treatment failure. But, there is doubt as to whether there is the possibility of resistance to these drugs given that the majority of treatment failures observed in patients with low intensity infections which might be subdued in time.