Benefits of sunlight: Vitamin D deficiency might increase the risk of sudden unexpected death in epilepsy

Epilepsy is the most common serious neurological condition and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. information concerning risk factors for SUDEP is conflicting, but high seizure frequency is a potential risk factor. Additionally, potential pathomechanisms for SUDEP are unknown, but it is very probable that cardiac arrhythmias during and between seizures or transmission of epileptic activity to the heart via the autonomic nervous system potentially play a role. In parallel, studies have shown a link between vitamin D dysfunction and epilepsy. Moreover, several evidences in the literature suggest an association between low vitamin D and seizures, indicating the possibility of anticonvulsant properties of this hormone. Quite interesting, a growing body of data suggests that low vitamin D levels may adversely affect cardiovascular health, directly associated with death from heart failure and sudden cardiac death. In view of the above findings, our research group focused in this review article that SUDEP, at least in some cases, could be related with low vitamin D levels. (C) 2009 Elsevier Ltd. All rights reserved.

HYPOTHALAMIC COCAINE- AND AMPHETAMINE-REGULATED TRANSCRIPT AND CORTICOTROPHIN RELEASING FACTOR NEURONS ARE STIMULATED BY EXTRACELLULAR VOLUME AND OSMOTIC CHANGES

Several studies suggest that hypothalamic cocaine- and amphetamine-regulated transcript (CART) may interact with the hypothalamic-pituitary-adrenal (HPA) axis in the control of neuroendocrine function and may also participate in cardiovascular regulation. Therefore, this study aimed to evaluate, in experimental models of isotonic (I-EVE) and hypertonic (H-EVE) extracellular volume expansion and water deprivation (WD), the activation of CART- and corticotrophin releasing factor (CRF)-immunoreactive neurons, as well as the relative expression of CART and CRF mRNAs in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. Both H-EVE (0.30M NaCl, 2mL/100g of body weight, in 1 minute) and 24 hours of WD significantly increased plasma sodium concentrations, producing, respectively, either an increase or a decrease in extracellular volume. I-EVE (0.15M NaCl, 2mL/100g of body weight, in 1 minute) evoked a significant increase in the circulating volume accompanied by unaltered plasma concentrations of sodium. CART-expressing neurons of both magnocellular and parvocellular hypothalamic divisions were activated to produce Fos in response to H-EVE but not in response to I-EVE. Furthermore, increased expression of CART mRNA was found in the PVN of H-EVE but not I-EVE rats. These data show for the first time that EVE not only activates hypothalamic CRF neurons but also increases CRF mRNA expression in the PVN. In contrast, WD increases the number of CART-immunoreactive neurons activated to produce Fos in the PVN and SON but does not change the number of neurons double labeled for Fos and CRF or expression of CRF mRNA in the PVN. These findings provided new insights into the participation of CART in diverse processes within the PVN and SON, including its possible involvement in activation of the HPA axis and cardiovascular regulation in response to changes in extracellular volume and osmolality. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Temporal distribution of trauma deaths: Quality of trauma care in a developing country

Background: Examination of the epidemiology and timing of trauma deaths has been deemed a useful method to evaluate the quality of trauma care. Objective: The purpose of this study was to evaluate the quality of trauma care in a regional trauma system and in a university hospital in Brazil by comparing the timing of deaths in the studied prehospital and in-hospital settings to those published for trauma systems in other areas. Methods: We analyzed the National Health Minister`s System of Deaths Information for the prehospital mortality and we retrospectively collected the demographics, timelines, and trauma severity scores of all in-hospital patients who died after admission through the Emergency Unit of Hospital das Clinicas de Ribeirao Preto between 2000 and 2001. Results. During the study period, there were 787 trauma fatalities in the city: 448 (56.9%) died in the prehospital setting and 339 (43.1%) died after being admitted to a medical facility. In 2 years, 238 trauma deaths occurred in the studied hospital, and we found a complete clinical set of data for 224 of these patients. The majority of deaths in the prehospital setting were caused by penetrating injuries (66.7%), whereas in-hospital mortality was mainly because of blunt traumas (59.1%). The largest number of in-hospital deaths occurred beyond 72 hours of stay (107 patients-47%). Conclusions: The region studied showed some deficiencies in prehospital and in-hospitals settings, in particular in the critical care and short-term follow-up of trauma patients when compared with the literature. Particularly, the late mortality may be related to training and human resources deficiency. Based on the timeline of trauma deaths, we can suggest that the studied region needs improvements in the prehospital trauma system and in hospital critical care.

Obesity due to Melanocortin 4 Receptor (MC4R) Deficiency Is Associated with Increased Linear Growth and Final Height, Fasting Hyperinsulinemia, and Incompletely Suppressed Growth Hormone Secretion

Context: Melanocortin receptor 4 (MC4R) deficiency is characterized by increased linear growth greater than expected for the degree of obesity. Objective: The objective of the investigation was to study the somatotroph axis in obese MC4R-deficient patients and equally obese controls. Patients and Methods: We obtained anthropometric measurements and insulin concentrations in 153 MC4R-deficient subjects and 1392 controls matched for age and severity of obesity. We measured fasting IGF-I, IGF-II, IGF binding protein (IGFBP)-1, IGFBP-3, and acid-labile subunit levels in a subset of 33 MC4R-deficient patients and 36 control subjects. We examined pulsatile GH secretion in six adult MC4R-deficient subjects and six obese controls. Results: Height so score was significantly greater in MC4R-deficient children under 5 yr of age compared with controls (mean +/- SEM: 2.3 +/- 0.06 vs. 1.8 +/- 0.04, P < 0.001), an effect that persisted throughout childhood. Final height (cm) was greater in MC4R-deficient men (mean +/- SEM 173 +/- 2.5 vs. 168 +/- 2.1, P < 0.001) and women (mean 165 +/- 2.1 vs. 158 +/- 1.9, P < 0.001). Fasting IGF-I, IGF-II, acid-labile subunit, and IGFBP-3 concentrations were similar in the two groups. GH levels were markedly suppressed in obese controls, but pulsatile GH secretion was retained in MC4R deficiency. The mean maximal GH secretion rate per burst (P < 0.05) and mass per burst (P < 0.05) were increased in MC4R deficiency, consistent with increased pulsatile and total GH secretion. Fasting insulin levels were markedly elevated in MC4R-deficient children. Conclusions: In MC4R deficiency, increased linear growth in childhood leads to increased adult final height, greater than predicted by obesity alone. GH pulsatility is maintained in MC4R deficiency, a finding consistent with animal studies, suggesting a role for MC4R in controlling hypothalamic somatostatinergic tone. Fasting insulin levels are significantly higher in children carrying MC4R mutations. Both of these factors may contribute to the accelerated growth phenotype characteristic of MC4R deficiency. (J Clin Endocrinol Metab 96: E181-E188, 2011)

Prevalence and risk factors of metabolic syndrome in Brazilian and Italian obese adolescents: a comparison study

Background: Metabolic syndrome (MS) prevalence between different populations in obese adolescents is scanty to date. Objective: To compare the MS prevalence and related risk factors in Brazilian and Italian obese adolescents. Methods: A total of 509 adolescents (110 Brazilian, 399 Italian), aged 15-19 years. Anthropometric characteristics, triglycerides (TG), total, low-density lipoprotein (LDL)-, high-density lipoprotein (HDL)-cholesterol, fasting plasma glucose (FPG), insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and blood pressure were measured. Results: Age, body mass index (BMI) and BMI z-score were not significantly different between the two subgroups. BMI z-score, TG, FPG, HOMA-IR and systolic blood pressure (SBP) were significantly higher in boys than in girls both in Brazilian and Italian adolescents, while HDL-cholesterol levels were lower in boys than in girls. No significant differences were observed in BMI, LDL and total-cholesterol and DBP in two genders and groups. Insulin, FPG, HOMA-IR and TG were significantly higher, while LDL-cholesterol and SBP were significantly lower in Brazilian than in Italian subjects, both in males and females. HDL and total-cholesterol and diastolic blood pressure (DBP) were not significantly different between the two subgroups and genders. MS prevalence was higher in Brazilian than in Italian obese boys (34.8 vs. 23.6%, p < 0.001) and girls (15.6 vs. 12.5%, p < 0.01). The most frequently altered parameter was HOMA-IR both in subjects with MS (100% in Brazilian and 81.8% in Italian) and without MS (42.9% and 11.7%). Conclusion: Metabolic syndrome represents a worldwide emerging health problem in different ethnical populations, the alterations of the risk factors related to MS (different in their prevalence between different subgroups) being strictly linked to the degree of obesity.

Asymmetrical changes in lumbar sympathetic nerve activity following stimulation of the sciatic nerve in rat

Noxious stimulation of the leg increases hind limb blood flow (HBF) to the ipsilateral side and decreases to the contralateral in rat. Whether or not this asymmetrical response is due to direct control by sympathetic terminals or mediated by other factors such as local metabolism and hormones remains unclear. The aim of this study was to compare responses in lumbar sympathetic nerve activity, evoked by stimulation of the ipsilateral and contralateral sciatic nerve (SN). We also sought to determine the supraspinal mechanisms involved in the observed responses. In anesthetized and paralyzed rats, intermittent electrical stimulation (1 mA, 0.5 Hz) of the contralateral SN evoked a biphasic sympathoexcitation. Following ipsilateral SN stimulation, the response is preceded by an inhibitory potential with a latency of 50 ms (N=26). Both excitatory and inhibitory potentials are abolished following cervical Cl spinal transection (N=6) or bilateral microinjections of muscimol (N=6) in the rostral ventrolateral medulla (RVLM). This evidence is suggestive that both sympathetic potentials are supraspinally mediated in this nucleus. Blockade of RVLM glutamate receptors by microinjection of kynurenic acid (N=4) selectively abolished the excitatory potential elicited by ipsilateral SN stimulation. This study supports the physiological model that activation of hind limb nociceptors evokes a generalized sympathoexcitation, with the exception of the ipsilateral side where there is a withdrawal of sympathetic tone resulting in an increase in HBF. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.

The universal newborn hearing screening in Brazil: From identification to intervention

Objective: The objective of the study is to investigate the results of the newborn hearing screening program carried out in a Public Hospital in Brazil, in the first 3 years regarding: (1) the prevalence of hearing impairment; (2) the influence of the universal hearing screening program on the age at which the diagnosis of hearing loss is defined; (3) the cost effectiveness of the program; (4) the outcomes, in terms of the age in which the hearing rehabilitation started. Methods: A descriptive study of the first 3 years after starting the universal newborn hearing screening in a Public Hospital of Bauru, Sao Paulo state, Brazil. The screening method consists of a two-stage screening approach with transient otoacoustic emissions (TOAE), conducted by an audiologist. If the outcome in the second-stage screening is REFER, the infant is submitted to diagnostic follow-up testing and intervention at the Audiology and Speech Pathology Clinic at the University of Sao Paulo, campus of Bauru. The evaluation of the costs of the universal newborn hearing screening program per each screened newborn (around 4000/year) was done based on a proposal by the National Center for Hearing Assessment and Management, of the Utah State University, United States of America. Results: 11,466 newborns were submitted to hearing screening, corresponding to 90.52% of the living newborns. The prevalence of sensorineural hearing loss was 0.96:1000. Of the 11 children with sensorineural hearing loss, eight children received hearing aids and five started the therapeutic process before the age of 1. Currently, four children between the ages of 11 months and 2 years old were submitted to cochlear implant surgery. The cost of hearing screening was US$7.00 and the annual cost of the universal newborn hearing screening program was US$26,940.47. Conclusion: The hospital-based universal newborn hearing screening carried out through the Brazilian National Health System is viable, with promising results. However, in a country such as Brazil, which presents large socio-economic differences, the same type of analyses should be performed in several regions, so as to take into account specific aspects, to implement the newborn hearing screening along with the Public System. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Population-Based Multicentric Survey of Hepatitis B Infection and Risk Factor Differences among Three Regions in Brazil

This multicentric population-based study in Brazil is the first national effort to estimate the prevalence of hepatitis B (HBV) and risk factors in the capital cities of the Northeast. Central-West, and Federal Districts (2004-2005). Random multistage cluster sampling was used to select persons 13-69 years of age. Markers for HBV were tested by enzyme-linked immunosorbent assay. The HBV genotypes were determined by sequencing hepatitis B surface antigen (HBsAg). Multivariate analyses and simple catalytic model were performed. Overall. 7,881 persons were inculded < 70% were not vaccinated. Positivity for HBsAg was less than 1% among non-vaccinated persons and genotypes A, D, and F co-circulated. The incidence of infection increased with age with similar force of infection in all regions. Males and persons having initiated sexual activity were associated with HBV infection in the two settings: healthcare jobs and prior hospitalization were risk factors in the Federal District. Our survey classified these regions as areas with HBV endemicity and highlighted the risk factors differences among the settings.

Structural changes in the epithelium of the small intestine and immune cell infiltration of enteric ganglia following acute mucosal damage and local inflammation

An acute enteritis is commonly followed by intestinal neuromuscular dysfunction, including prolonged hyperexcitability of enteric neurons. Such motility disorders are associated with maintained increases in immune cells adjacent to enteric ganglia and in the mucosa. However, whether the commonly used animal model, trinitrobenzene sulphonate (TNBS)-induced enteritis, causes histological and immune cell changes similar to human enteric neuropathies is not clear. We have made a detailed study of the mucosal damage and repair and immune cell invasion following intralumenal administration of TNBS. Intestines from untreated, sham-operated and TNBS-treated animals were examined at 3 h to 56 days. At 3 h, the mucosal surface was completely ablated, by 6 h an epithelial covering was substantially restored and by 1 day there was full re-epithelialisation. The lumenal epithelium developed from a squamous cell covering to a fully differentiated columnar epithelium with mature villi at about 7 days. Prominent phagocytic activity of enterocytes occurred at 1-7 days. A surge of eosinophils and T lymphocytes associated with the enteric nerve ganglia occurred at 3 h to 3 days. However, elevated immune cell numbers occurred in the lamina propria of the mucosa until 56 days, when eosinophils were still three times normal. We conclude that the disruption of the mucosal surface that causes TNBS-induced ileitis is brief, a little more than 6 h, and causes a transient immune cell surge adjacent to enteric ganglia. This is much briefer than the enteric neuropathy that ensues. Ongoing mucosal inflammatory reaction may contribute to the persistence of enteric neuropathy.

Immunohistochemical analysis of neuron types in the mouse small intestine

The definition of the nerve cell types of the myenteric plexus of the mouse small intestine has become important, as more researchers turn to the use of mice with genetic mutations to analyze roles of specific genes and their products in enteric nervous system function and to investigate animal models of disease. We have used a suite of antibodies to define neurons by their shapes, sizes, and neurochemistry in the myenteric plexus. Anti-Hu antibodies were used to reveal all nerve cells, and the major subpopulations were defined in relation to the Hu-positive neurons. Morphological Type II neurons, revealed by anti-neurofilament and anti-calcitonin gene-related peptide antibodies, represented 26% of neurons. The axons of the Type II neurons projected through the circular muscle and submucosa to the mucosa. The cell bodies were immunoreactive for choline acetyltransferase (ChAT), and their terminals were immunoreactive for vesicular acetylcholine transporter (VAChT). Nitric oxide synthase (NOS) occurred in 29% of nerve cells. Most were also immunoreactive for vasoactive intestinal peptide, but they were not tachykinin (TK)-immunoreactive, and only 10% were ChAT-immunoreactive. Numerous NOS terminals occurred in the circular muscle. We deduced that 90% of NOS neurons were inhibitory motor neurons to the muscle (26% of all neurons) and 10% (3% of all neurons) were interneurons. Calretinin immunoreactivity was found in a high proportion of neurons (52%). Many of these had TK immunoreactivity. Small calretinin neurons were identified as excitatory neurons to the longitudinal muscle (about 20% of neurons, with ChAT/calretinin/+/- TK chemical coding). Excitatory neurons to the circular muscle (about 10% of neurons) had the same coding. Calretinin immunoreactivity also occurred in a proportion of Type II neurons. Thus, over 90% of neurons in the myenteric plexus of the mouse small intestine can be currently identified by their neurochemistry and shape.

Diagnostic reference levels for the most frequent radiological examinations carried out in Brazil

Objectives. A large-scale survey of doses to patients undergoing the most frequent radiological examinations was carried out in health services in Sao Paulo (347 radiological examinations per 1 000 inhabitants), the most populous Brazilian state. Methods. A postal dosimetric kit with thermoluminescence dosimeters was used to evaluate the entrance surface dose (ESD) to patients. A stratified sampling technique applied to the national health database furnished important data on the distribution of equipment and the annual number of examinations. Chest, head (skull and sinus), and spine (cervical, thoracic, and lumbar) examinations were included in the trial. A total of 83 rooms and 868 patients were included, and 1 415 values of ESD were measured. Results. The data show large coefficients of variation in tube charge, giving rise to large variations in ESD values. Also, a series of high ESD values associated with unnecessary localizing fluoroscopy were detected. Diagnostic reference levels were determined, based on the 75th percentile (third quartile) of the ESD distributions. For adult patients, the diagnostic reference levels achieved are very similar to those obtained in international surveys. However, the situation is different for pediatric patients: the ESD values found in this survey are twice as large as the international recommendations for chest radiographs of children. Conclusions. Despite the reduced number of ESD values and rooms for the pediatric patient group, it is recommended that practices in chest examinations be revised and that specific national reference doses and image quality be established after a broader survey is carried out.

Bayesian density estimation using Skew Student-t-Normal mixtures

We present a Bayesian approach for modeling heterogeneous data and estimate multimodal densities using mixtures of Skew Student-t-Normal distributions [Gomez, H.W., Venegas, O., Bolfarine, H., 2007. Skew-symmetric distributions generated by the distribution function of the normal distribution. Environmetrics 18, 395-407]. A stochastic representation that is useful for implementing a MCMC-type algorithm and results about existence of posterior moments are obtained. Marginal likelihood approximations are obtained, in order to compare mixture models with different number of component densities. Data sets concerning the Gross Domestic Product per capita (Human Development Report) and body mass index (National Health and Nutrition Examination Survey), previously studied in the related literature, are analyzed. (c) 2008 Elsevier B.V. All rights reserved.