[Violence against children and adolescents with disabilities: narratives with guardianship councilors]. / Violência contra crianças e adolescentes com deficiência: narrativas com conselheiros tutelares.

The article is based on Thompson's indepth hermeneutics with emphasis on meanings produced from narrative analysis of 15 guardianship councilors, seeking to interpret the significance of the councilor's function and ensuring the rights of children and adolescents with disabilities. The conclusion drawn is that certain generic discourses on this theme are presented as an inflexible core which reinforces the invisibility of the population and renders it more vulnerable. At the other extreme, the generic category of being "special" highlights the difficulties of the guardianship councilor in seeking strategies in the institutional network (health, leisure, education) for ensuring the rights and needs of this segment and their families, when failing to differentiate between the various categories of disability. Finally, the acquisition of knowledge by counselors related to this clientele depends greatly on the proximity of these counselors to health institutions that contribute in formulating strategies for guaranteeing rights that form networks. The situations of vulnerability to which counselors are exposed in the relationship between their mandate to respond to the violations suffered by the juvenile segment, and impotence to resolve them are stressed.

Violência contra crianças e adolescentes com deficiência: narrativas com conselheiros tutelares / Violence against children and adolescents with disabilities: narratives with guardianship councilors

Artigo focado na hermenêutica de profundidade de Thompson com recorte nos sentidos produzidos a partir da análise narrativa com 15 conselheiros tutelares visando interpretar os sentidos da função de conselheiro na garantia dos direitos de crianças e adolescentes com deficiência. Conclui-se que determinados discursos genéricos sobre este tema funcionam como um núcleo duro que reforça a invisibilidade desse público e o torna mais vulnerável. No outro extremo a categoria genérica "especial" fala das dificuldades do conselheiro tutelar em buscar na rede institucional (saúde, lazer, educação) estratégias dessas garantias e das necessidades deste segmento e de suas famílias, ao deixar de diferenciar as diversas categorias de deficiências. Por fim, as aquisições de conhecimento, por alguns conselheiros, relacionadas a essa clientela se dá muito em função da proximidade com instituições de saúde que contribuem na construção de estratégias de garantia de direitos que formam redes. Destacamos as situações de vulnerabilidade a que estão expostos os conselheiros na relação entre o mandato de responder às violações sofridas pelo segmento infanto-juvenil, e a impotência resolutiva.

The article is based on Thompson's indepth hermeneutics with emphasis on meanings produced from narrative analysis of 15 guardianship councilors, seeking to interpret the significance of the councilor's function and ensuring the rights of children and adolescents with disabilities. The conclusion drawn is that certain generic discourses on this theme are presented as an inflexible core which reinforces the invisibility of the population and renders it more vulnerable. At the other extreme, the generic category of being "special" highlights the difficulties of the guardianship councilor in seeking strategies in the institutional network (health, leisure, education) for ensuring the rights and needs of this segment and their families, when failing to differentiate between the various categories of disability. Finally, the acquisition of knowledge by counselors related to this clientele depends greatly on the proximity of these counselors to health institutions that contribute in formulating strategies for guaranteeing rights that form networks. The situations of vulnerability to which counselors are exposed in the relationship between their mandate to respond to the violations suffered by the juvenile segment, and impotence to resolve them are stressed.

The critical path from pump to pancreas: the impact of FDA regulation on the development of a closed-loop diabetes management system.

Breakthrough medical tools and technologies are rapidly becoming available in countries across the world, but cannot be purchased in the United States, where these innovative products still await FDA approval. The artificial pancreas is a prime example of such medical technologies, as one of these device systems has been available in over 40 countries outside of the United States for more than 3 years. The term "artificial pancreas" refers to any one of a group of closed-loop device systems designed to protect type 1 diabetics against dangerous diabetes episodes, while also reducing the risk of diabetes-related complications by enabling tighter glycemic control. The following paper will provide an overview of diabetes, a brief history of diabetes management, the technological challenges of creating a fully functional closed-loop diabetes management system, and the role of FDA in the development of the artificial pancreas.

Functional consequences of sulfhydryl modification of the γ-aminobutyric acid transporter 1 at a single solvent-exposed cysteine residue.

The aims of this study were to optimize the experimental conditions for labeling extracellularly oriented, solvent-exposed cysteine residues of γ-aminobutyric acid transporter 1 (GAT1) with the membrane-impermeant sulfhydryl reagent [2-(trimethylammonium)ethyl]methanethiosulfonate (MTSET) and to characterize the functional and pharmacological consequences of labeling on transporter steady-state and presteady-state kinetic properties. We expressed human GAT1 in Xenopus laevis oocytes and used radiotracer and electrophysiological methods to assay transporter function before and after sulfhydryl modification with MTSET. In the presence of NaCl, transporter exposure to MTSET (1-2.5 mM for 5-20 min) led to partial inhibition of GAT1-mediated transport, and this loss of function was completely reversed by the reducing reagent dithiothreitol. MTSET treatment had no functional effect on the mutant GAT1 C74A, whereas the membrane-permeant reagents N-ethylmaleimide and tetramethylrhodamine-6-maleimide inhibited GABA transport mediated by GAT1 C74A. Ion replacement experiments indicated that MTSET labeling of GAT1 could be driven to completion when valproate replaced chloride in the labeling buffer, suggesting that valproate induces a GAT1 conformation that significantly increases C74 accessibility to the extracellular fluid. Following partial inhibition by MTSET, there was a proportional reduction in both the presteady-state and steady-state macroscopic signals, and the functional and pharmacological properties of the remaining signals were indistinguishable from those of unlabeled GAT1. Therefore, covalent modification of GAT1 at C74 results in completely nonfunctional as well as electrically silent transporters.

Comparison of clinical and angiographic prognostic risk scores in patients with acute coronary syndromes: Analysis from the Acute Catheterization and Urgent Intervention Triage StrategY (ACUITY) trial.

BACKGROUND: Several prognostic risk scores have been developed for patients with coronary artery disease, but their comparative use in patients with non-ST-segment elevation acute coronary syndromes (NSTEACS) undergoing percutaneous coronary intervention (PCI) has not been examined. We therefore investigated the accuracy of the Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score, Clinical Synergy Between PCI With Taxus and Cardiac Surgery score (CSS), New Risk Stratification (NERS) score (NERS), Age, Creatinine, Ejection Fraction (ACEF) score, Global Registry for Acute Coronary Events (GRACE) score, and Thrombolysis in Myocardial Infarction (TIMI) score for risk assessment of 1-year mortality, cardiac mortality, myocardial infarction, target vessel revascularization, and stent thrombosis in patients with NSTEACS undergoing PCI. METHODS: The 6 scores were determined in 2,094 patients with NSTEACS treated with PCI enrolled in the angiographic substudy of the ACUITY trial. The prognostic accuracy of the 6 scores was assessed using the c statistic for discrimination and the Hosmer-Lemeshow test for calibration. The index of separation and net reclassification improvement (NRI) were also determined. RESULTS: Scores incorporating clinical and angiographic variables (CSS and NERS) showed the best tradeoff between discrimination and calibration for most end points, with the best discrimination for all end points and good calibration for most of them. The CSS had the best index of separation for most ischemic endpoints and displayed an NRI for cardiac death and myocardial infarction (MI) compared to the other scores, whereas NERS displayed an NRI for all-cause death and target vessel revascularization. The 3 scores-CSS, NERS, and SYNTAX-were the only scores to have both good discrimination and calibration for cardiac mortality. CONCLUSIONS: In patients with NSTEACS undergoing PCI, risk scores incorporating clinical and angiographic variables had the highest predictive accuracy for a broad spectrum of ischemic end points.

Corticotropin-releasing hormone and pro-opiomelanocortin gene expression in female monkeys with differences in sensitivity to stress.

BACKGROUND/AIMS: The expressions of corticotropin-releasing hormone (CRH) and pro-opiomelanocortin (POMC) were assessed in brain tissue collected from nonstressed female cynomolgus monkeys previously categorized as highly stress resilient (HSR), medium stress resilient (MSR), or stress sensitive (SS) with respect to stress-induced anovulation. METHODS: In situ hybridization and quantitative image analysis was used to measure mRNAs coding for CRH in the hypothalamic paraventricular nucleus (PVN) and thalamic center median-subfascicular complex (CM-Sf). Then, CRH neurons in the PVN were immunostained and the area of immunostaining was measured. Also, CRH fibers were immunostained in the central nucleus of the amygdala and the area of immunostaining was obtained. Finally, POMC mRNA expression was characterized in the hypothalamic infundibular nucleus. The groups were compared with ANOVA and Student-Newman-Keul's (SNK) post hoc comparison. RESULTS: CRH mRNA was significantly elevated in the caudal PVN in the MSR and SS animals compared to HSR animals (p < 0.05, SNK). There was a significant increase in average and total CRH-positive area in the MSR and SS groups compared to the HSR group (p < 0.05, SNK). There was also a significant increase in CRH volume in the MSR and SS groups compared to the HSR group (p < 0.05, SNK). In the CM-Sf, the average CRH optical density was significantly higher in the MSR and SS groups than in the HSR group (p < 0.05, SNK). In the central nucleus of the amygdala, the area of CRH fiber staining was significantly higher in the SS group than in the MSR or HSR groups (p < 0.05, SNK). There was no difference between the groups in POMC mRNA expression in the mediobasal hypothalamus. CONCLUSION: Macaques that exhibit immediate suppression of reproductive function upon stress are considered stress sensitive. These animals have elevated CRH in the hypothalamus and limbic structures, which may play a role in suppressing the hypothalamic-gonadal axis upon stress initiation.

Hypothalamic expression of serotonin 1A, 2A and 2C receptor and GAD67 mRNA in female cynomolgus monkeys with different sensitivity to stress.

Like women, female cynomolgus monkeys show differential sensitivity to stress-induced reproductive dysfunction. A combined social and metabolic stress (mild diet+moderate exercise+relocation) will rapidly induce anovulation in a third of female cynomolgus monkeys (stress-sensitive; SS); a third will ovulate once and then become anovulatory (medium stress-resilient; MSR) and a third are highly stress-resilient (HSR) and exhibit normal menstrual cycles through two stressed menstrual cycles. In a non-stressed menstrual cycle, SS animals have lower levels of estrogen and progesterone, lower activity of the serotonin system and lower expression of genes related to the serotonin system in the dorsal raphe nucleus. In this study, we examined the expression of 5HT1A, 5HT2A, 5HT2C receptors and GAD67 in the hypothalamus of SS, HSR and MSR monkeys using in situ hybridization. SS monkeys exhibited higher expression of 5HT2A mRNA in the paraventricular nucleus (PVN), higher expression of 5HT2C and GAD67 in the infundibulum, as well as higher expression of GAD67 in the posterior hypothalamus (PH), compared with HSR monkeys. However, the expression of 5HT1A mRNA in the ventromedial nucleus (VMN) was not different between groups. We speculate that the serotonin and GABA systems may be altered in the stress-response and reproductive-related circuits of SS monkeys, and may be participating in altering the sensitivity of the reproductive system to stress in these individuals.

Serotonin in microdialysate from the mediobasal hypothalamus increases after progesterone administration to estrogen primed macaques.

Estrogen and progesterone act on gene and protein expression in serotonin neurons in a manner that suggests serotonin neurotransmission should increase. However, measurement of extracellular serotonin in macaques was lacking. Elevated prolactin secretion can be an indicator of increased serotonergic function and prolactin is increased by combined estrogen and progesterone treatment. We examined extracellular serotonin by microdialysis in a well-characterized macaque model of steroid-induced prolactin secretion. Monkeys were fitted with 2 guide tubes directed to the arcuate nucleus of the hypothalamus. Samples (75 microl/15-minute interval) were obtained via a tether-swivel device through sample lines into an adjoining room. Serotonin was measured with a modified commercial enzyme linked immunoassay (ELISA) kit. Fenfluramine infused through the probe (300 microM for 2 h; n=2 trials) or administered intravenously (2.5 mg/kg; n=2 trials) caused a marked increase in extracellular serotonin and verified the efficacy of the procedure. Three monkeys were maintained with an estrogen implant for 2 weeks. Each monkey was injected with 20 mg of progesterone s.c. in oil at 1500 h; microdialysis was initiated the next morning and samples were obtained for 24 h. There was a significant increase in serotonin between 40 and 43 h after the progesterone injection (P<0.001, ANOVA). Serotonin averaged 59+/-1 pg/sample from 18-30 h post-progesterone injection, and averaged 76+/-2 pg/sample from 30-48 h post-progesterone injection (P<0.0001; t-test). Since the increase in serotonin is delayed by approximately 40 h after progesterone-injection, we speculate that the action of progesterone may involve either nuclear progestin receptors or membrane progestin receptors.

A second tryptophan hydroxylase isoform, TPH-2 mRNA, is increased by ovarian steroids in the raphe region of macaques.

Recently, a second gene that codes for the rate-limiting enzyme in serotonin synthesis was found in brain, named tryptophan hydroxylase-2 (TPH-2). We sequenced overlapping segments (251 and 510 bp) of 5' monkey TPH-2 and questioned whether TPH-2 is regulated by estrogen (E) and progesterone (P) in serotonin neurons of macaques. Monkey TPH-2 was 97% homologous to human TPH-2 and 65% homologous to monkey TPH-1 in the coding region. Spayed monkeys were administered placebo, E-only, P-only, or E + P for 1 month via Silastic implants (n = 4/treatment) and the midbrain was utilized for TPH-2 in situ hybridization (ISH). Additional monkeys (n = 3/treatment) were used to determine the relative abundance of TPH-2 mRNA with quantitative (q) RT-PCR. In the ISH assay, all of the hormone treatments caused a significant and similar increase in TPH-2 mRNA optical density (fourfold; P < 0.004) and positive pixel area (twofold; P < 0.002) over spayed controls. Treatment with E or E + P for 1 month increased the relative abundance of TPH-2 mRNA over spayed controls in the qRT-PCR assay (ANOVA P < 0.05 and P < 0.007, respectively). In conclusion, ovarian steroids stimulate TPH-2 mRNA expression, which could in turn cause an increase in serotonin synthesis. This would impact many of the neural functions that are governed by serotonin.

Incentivo ao aleitamento materno no Município do Rio de Janeiro: avaliaçäo das condiçöes de eficiência dos serviços

O presente trabalho tem como objetivo comunicar a experiência do comitê de aleitamento Materno da Sóperj (Cam/Soperj), na aplicaçäo de um novo instrumento de avaliaçäo das práticas de saúde vinculadas a promoçäo e facilitaçäo do aleitamento materno no âmbito hospitalar do Município do Rio de Janeiro. Foram analisadas as práticas ligadas a Assistência Pré-Natal, Assistência ao Parto e Puerpério Imediato e Assistência Pós-Parto atribuindo pontos aos itens de planta física, equipamento, pessoal, procedimentos, interaçäo entre os Serviços e atividades programadas. Os autores concluíram que em relaçäo ao incentivo ao Aleitamento, a Assitência Pré-Natal foi considerada deficiente (85%) dos serviços) devido, principalmente ao despreparo da Equipe de Saúde. A Assistência ao Parto foi considerada regular (50% dos serviços). A Assistência Pós-Natal foi considerada deficiente (75% dos serviços). De todas as instituiçöes analisadas, as de pior desempenho foram as Universitárias