Associação entre exposição ao material particulado e internações por doenças respiratórias em crianças

The aim of this study was to estimate the association between exposure to particulate matter less than 2.5 microns in diameter and hospitalization for respiratory diseases. It was an ecological time series study with daily indicators of hospitalization for respiratory diseases in children up to 10 years, living in Piracicaba, SP, Southeastern Brazil, between August 1, 2011 and July 31, 2012. We used generalized additive model for the Poisson regression. The relative risks were RR = 1.008; 95%CI 1.001; 1.016 for lag 1 and RR = 1.009; 95%CI 1.001; 1.017 for lag 3. The increment of 10 mu g/m(3) in particulate matter less than 2.5 microns in diameter implies increase in relative risk between 7.9 and 8.6 percentage points. In conclusion, exposure to particulate matter less than 2.5 microns in diameter was associated with hospitalization for respiratory diseases in children.

Correlation between sleep and quality of life in cerebral palsy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Qualidade de vida em portadores de paralisia cerebral: associação com nível funcional e aspectos sócio-demográficos

Pós-graduação em Saúde Coletiva - FMB

There is no difference in nitric oxide metabolites and neonatal outcome between premature infants born to pre-eclamptic and those born to normotensive women

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cumulative long-term safety, efficacy and patient-reported outcomes in children with juvenile idiopathic arthritis treated with intravenous abatacept: up to 7 years of treatment

The long-term efficacy and safety of intravenous abatacept in patients (pts) with juvenile idiopathic arthritis (JIA) have been reported previously from the Phase III AWAKEN trial ([1, 2]). Here, we report efficacy, safety and pt-reported outcomes from the open-label, long-term extension (LTE) of AWAKEN, with up to 7 years of follow-up. Pts entered the LTE if they were JIA ACR 30 non-responders (NR) at the end of the 4-month lead-in period (abatacept only), or if they received abatacept or placebo (pbo) in the 6-month double-blind (DB) period. The Child Health Questionnaire was used to evaluate health-related quality of life (HRQoL); physical (PhS) and psychosocial (PsS) summary and pain scores were analyzed. Pain was assessed by parent global assessment using a 100 mm visual analog scale. Efficacy and HRQoL evaluations are reported up to Day 1765 (~ Year 5.5). Safety is presented for the cumulative period (lead-in, DB and LTE), for all pts who received abatacept during the LTE. Of the 153 pts entering the LTE (58 from DB abatacept group, 59 from DB pbo group, 36 NR), 69 completed the trial (29 abatacept, 27 pbo, 13 NR). For pts treated in the LTE, mean (range) exposure to abatacept was 53.6 (5.6–85.6) months. During the LTE, incidence rates of AEs and serious AEs per 100 pt-years were 209.1 and 5.6. Thirty pts (19.6%) had serious AEs; most were unrelated and were musculoskeletal (8.5%) or infectious events (6.5%). No malignancy was reported. There was one death (accidental; unrelated). At Day 169, JIA ACR 50 and 70 response rates were 79.3% and 55.2% in the abatacept group, and 52.5% and 30.5% in the pbo group; 31.0% and 10.2% of pts in the abatacept and pbo groups, respectively, had inactive disease. By Day 1765, JIA ACR 50 and 70 response rates were 93.9% and 78.8% in the abatacept group, and 80.0% and 63.3% in the pbo group; 51.5% and 33.3% had inactive disease. In the NR group, 69.2% and 53.8% of pts achieved JIA ACR 50 and 70 responses at Day 1765, and 30.8% had inactive disease. In pts who entered the LTE, mean baseline PhS scores were below the range for healthy children (abatacept 30.2, pbo 31.0, NR 29.5). At Day 169, 38.3% of pts had reached a PhS score >50 ((1). By the end of the LTE, 43.5% of pts had reached a PhS score >50. At baseline, mean PsS scores for those who entered the LTE were slightly lower than the mean for healthy children (abatacept 43.5, pbo 44.2, NR 47.0). At Day 169, 54.9% of pts had a PsS score >50 (1). By Day 1765, 58.1% of pts had reached a PsS score >50. At baseline, the mean pain score was 42.9. By Day 169, 13.9% of pts were considered pain free (pain score = 0); this was maintained over the LTE (1).

Inquérito sobre a qualidade de vida relacionada à saúde em crianças e adolescentes portadores de artrites idiopáticas juvenis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Association between risk behaviors and adiposity indicators in adolescents from Southern Brazil: A methodological approach

The aim of this study was to analyze the association between risk behaviors and adiposity indicators in adolescents and to discuss some methodological aspects related to this relationship. We evaluated 1,321 adolescents (55.2% female) aged 10-16 years. Relative body fat (%fat) by measurement of triceps and subscapular skinfold thickness and waist circumference (WC) were used as total and central adiposity indicators, respectively. Physical inactivity, time spent in front of the TV, the consumption of soda and/or chocolate, alcohol, and tobacco smoking were analyzed as risk behaviors. Information about the socioeconomic status (categorized into three levels) and nutritional status of the mother (overweight or normal weight) were used as adjustment factors in the analyses of prevalence ratio (PR) of the outcomes and their associated 95% confidence intervals (95% CI). The chi-square test and Poisson regression were used for statistical analyses. Low associations were found between risk behaviors and adiposity indicators. Tobacco smoking was the most positively correlated behavior with adiposity in girls (%fat: PR = 1.61; 95% CI = 1.04-2.47; WC: PR = 1.90; 95% CI = 1.17-3.08) and in adolescents whose mothers were normal weight (%fat: PR = 2.31; 95% CI = 1.33-4.03; WC: PR: 2.31; CI: 1.19-4.46). Additionally, as an important methodological issue, we highlighted the assessment of risk behaviors in adolescents as crucial to producing more robust evidence on the subject. Of the investigated behaviors, we concluded that tobacco smoking is the behavior most associated with adiposity indicators.

South Carolina Home Economics Association Records - Accession 22

This collection is a valuable source on home economics history in South Carolina during the twentieth century. While there is information on the SCHEA from its beginning in 1914 to 1980, the actual records do not start until 1920. An outline of what the South Carolina Home Economics Association was doing from 1914 to 1920, is provided in the “historical file” (see Box 1, folders 1 to 4). The inclusive dates for a particular series may vary and, for most series, the records are incomplete. The collection contains all the records normally created by an organization, including constitutions, correspondence, minutes, reports, handbooks, etc. A wide variety of research topics could be developed from the records, including the SCHEA’s impact on the legislative process in South Carolina (e.g. the passage of the bill for the enrichment of cornmeal and grits in 1943), its cooperation and relationship with relief agencies in the state and its role in improving child health during the 1930s.

EMERGENT CONDITIONAL RELATIONS IN A GO/NO-GO PROCEDURE: FIGURE-GROUND AND STIMULUS-POSITION COMPOUND RELATIONS

Past research has demonstrated emergent conditional relations using a go/no-go procedure with pairs of figures displayed side-by-side on a computer screen. The present Study sought to extend applications Of this procedure. In Experiment, 1, we evaluated whether emergent conditional relations Could be demonstrated when two-component stimuli were displayed in figure-ground relationships-abstract figures displayed on backgrounds of different colors. Five normal)), capable adults participated. During training, each two-component stimulus Was presented successively. Responses emitted in the presence of some Stimulus pairs (A1B1, A2B2, A3B3, B1C1, B2C2 and B3C3) were reinforced, whereas responses emitted in the presence of other pairs (A1B2, A1B3, A2B1, A2B3, A3B1, A3B2, B1C2, B1C3, B2C1, B2C3, B3C1 and B3C2) were not. During tests, new configurations (AC and CA) were presented, thus emulating structurally the matching-to-sample tests employed in typical equivalence Studies. All participants showed emergent relations consistent with stimulus equivalence during testing. In Experiment 2, we systematically replicated the procedures with Stimulus compounds consisting Of four figures (A1, A2, C1 and C2) and two locations (left - B1 and right - 132). A,11 6 normally capable adults exhibited emergent stimulus-stimulus relations. Together, these experiments show that the go/no-go procedure is a potentially useful alternative for Studying emergent. conditional relations when matching-to-sample is procedurally cumbersome or impossible to use.

OBSERVING BEHAVIOR AND ATYPICALLY RESTRICTED STIMULUS CONTROL

Restricted stimulus control refers to discrimination learning with atypical limitations in the range of controlling stimuli or stimulus features In the study reported here 4 normally capable individuals and 10 individuals with Intellectual disabilities (ID) performed two-sample delayed matching to sample Sample stimulus observing was recorded with an eye tracking apparatus High accuracy scores indicated stimulus control by both sample stimuli for the 4 nondisabled participants and 4 participants with ID and eye tracking data showed reliable observing of all stimuli Intermediate accuracy scores indicated restricted stimulus control for the remaining 6 participants Their eye tracking data showed that errors were related to failures to observe sample stimuli and relatively brief observing durations Five of these participants were then given interventions designed to improve observing behavior For 4 participants the interventions resulted initially in elimination of observing failures increased observing durations and Increased accuracy For 2 of these participants contingencies sufficient to maintain adequate observing were not always sufficient to maintain high accuracy subsequent procedure modifications restored It however For the 5th participant initial improvements in observing were not accompanied by improved accuracy in apparent Instance of observing without attending accuracy improved only after an additional intervention that imposed contingencies on observing behavior Thus interventions that control observing behavior seem necessary but may not always be sufficient for the remediation of restricted stimulus control

Evidence of the Importance of the First Intracellular Loop of Prokineticin Receptor 2 in Receptor Function

Prokineticin receptors (PROKR) are G protein-coupled receptors (GPCR) that regulate diverse biological processes, including olfactory bulb neurogenesis and GnRH neuronal migration. Mutations in PROKR2 have been described in patients with varying degrees of GnRH deficiency and are located in diverse functional domains of the receptor. Our goal was to determine whether variants in the first intracellular loop (ICL1) of PROKR2 (R80C, R85C, and R85H) identified in patients with hypogonadotropic hypogonadism interfere with receptor function and to elucidate the mechanisms of these effects. Because of structural homology among GPCR, clarification of the role of ICL1 in PROKR2 activity may contribute to a better understanding of this domain across other GPCR. The effects of the ICL1 PROKR2 mutations on activation of signal transduction pathways, ligand binding, and receptor expression were evaluated. Our results indicated that the R85C and R85H PROKR2 mutations interfere only modestly with receptor function, whereas the R80C PROKR2 mutation leads to a marked reduction in receptor activity. Cotransfection of wild-type (WT) and R80C PROKR2 showed that the R80C mutant could exert a dominant negative effect on WT PROKR2 in vitro by interfering with WT receptor expression. In summary, we have shown the importance of Arg80 in ICL1 for PROKR2 expression and demonstrate that R80C PROKR2 exerts a dominant negative effect on WT PROKR2. (Molecular Endocrinology 26: 1417-1427, 2012)

Three Postpartum Antiretroviral Regimens to Prevent Intrapartum HIV Infection

BACKGROUND The safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in infants of mothers with human immunodeficiency virus (HIV) infection who did not receive antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated three ART regimens in such infants. METHODS Within 48 hours after their birth, we randomly assigned formula-fed infants born to women with a peripartum diagnosis of HIV type 1 (HIV-1) infection to one of three regimens: zidovudine for 6 weeks (zidovudine-alone group), zidovudine for 6 weeks plus three doses of nevirapine during the first 8 days of life (two-drug group), or zidovudine for 6 weeks plus nelfinavir and lamivudine for 2 weeks (three-drug group). The primary outcome was HIV-1 infection at 3 months in infants uninfected at birth. RESULTS A total of 1684 infants were enrolled in the Americas and South Africa (566 in the zidovudine-alone group, 562 in the two-drug group, and 556 in the three-drug group). The overall rate of in utero transmission of HIV-1 on the basis of Kaplan-Meier estimates was 5.7% (93 infants), with no significant differences among the groups. Intrapartum transmission occurred in 24 infants in the zidovudine-alone group (4.8%; 95% confidence interval [CI], 3.2 to 7.1), as compared with 11 infants in the two-drug group (2.2%; 95% CI, 1.2 to 3.9; P=0.046) and 12 in the three-drug group (2.4%; 95% CI, 1.4 to 4.3; P=0.046). The overall transmission rate was 8.5% (140 infants), with an increased rate in the zidovudine-alone group (P=0.03 for the comparisons with the two-and three-drug groups). On multivariate analysis, zidovudine monotherapy, a higher maternal viral load, and maternal use of illegal substances were significantly associated with transmission. The rate of neutropenia was significantly increased in the three-drug group (P < 0.001 for both comparisons with the other groups). CONCLUSIONS In neonates whose mothers did not receive ART during pregnancy, prophylaxis with a two-or three-drug ART regimen is superior to zidovudine alone for the prevention of intrapartum HIV transmission; the two-drug regimen has less toxicity than the three-drug regimen. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] and others; ClinicalTrials.gov number, NCT00099359.)

Análise de mutações nos genes TAC3 e TACR3 em pacientes com distúrbios puberais centrais idiopáticos

OBJETIVO: Investigar a presença de variantes nos genes TAC3 e TACR3, os quais codificam a NKB e seu receptor (NK3R), respectivamente, em uma coorte de pacientes com distúrbios puberais centrais idiopáticos. SUJEITOS E MÉTODOS: Duzentos e trinta e sete pacientes foram estudados: 114 com puberdade precoce central (PPC), 73 com hipogonadismo hipogonadotrófico isolado normósmico (HHI) e 50 com retardo constitucional do crescimento e desenvolvimento (RCCD). O grupo controle consistiu de 150 indivíduos brasileiros que apresentaram desenvolvimento puberal normal. O DNA genômico foi extraído de sangue periférico, e as regiões codificadoras dos genes TAC3 e TACR3 foram amplificadas e sequenciadas automaticamente. RESULTADOS: Uma variante (p.A63P) foi identificada na NKB, e quatro variantes, p.G18D, p.L58L (c.172C>T), p.W275X e p.A449S, foram identificadas no NK3R, as quais foram ausentes no grupo controle. A variante p.A63P foi identificada em uma menina com PPC, e a variante p.A449S, em uma menina com RCCD. As variantes previamente descritas, p.G18D, p.L58L e p.W275X, foram identificadas em três indivíduos com HHI normósmico do sexo masculino não relacionados. CONCLUSÃO: Variantes raras nos genes TAC3 e TACR3 foram identificadas em pacientes com distúrbios puberais centrais idiopáticos. Mutações de perda de função no gene TACR3 foram associadas com o fenótipo de HHI normósmico. Arq Bras Endocrinol Metab. 2012;56(9):646-52

Cerebral White Matter Oxidation and Nitrosylation in Young Rodents With Kaolin-Induced Hydrocephalus

Hydrocephalus is associated with reduced blood flow in periventricular white matter. To investigate hypoxic and oxidative damage in the brains of rats with hydrocephalus, kaolin was injected into the cisterna magna of newborn 7- and 21-day-old Sprague-Dawley rats, and ventricle size was assessed by magnetic resonance imaging at 7, 21, and 42 days of age. In-situ evidence of hypoxia in periventricular capillaries and glial cells was shown by pimonidazole hydrochloride binding. Biochemical assay of thiobarbituric acid reaction and immunohistochemical detection of malondialdehyde and 4-hydroxy-2-nonenal indicated the presence of lipid peroxidation in white matter. Biochemical assay of nitrite indicated increased nitric oxide production. Nitrotyrosine immunohistochemistry showed nitrosylated proteins in white matter reactive microglia and astrocytes. Activities of the antioxidant enzymes catalase and glutathione peroxidase were not increased, and altered hypoxia-inducible factor 1 alpha was not detected by quantitative reverse transcription-polymerase chain reaction. Cerebral vascular endothelial growth factor expression determined by quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay was not changed, but vascular endothelial growth factor immunoreactivity was increased in reactive astrocytes of hydrocephalic white matter. To determine if nitric oxide synthase is involved in the pathogenesis, we induced hydrocephalus in 7-day-old wild-type and neuronal nitric oxide synthase-deficient mice. At 7 days, the wild-type and mutant mice exhibited equally severe ventriculomegaly and no behavioral differences, although increased glial fibrillary acidic protein was less in the mutant mice. We conclude that hypoxia, via peroxidation and nitrosylation, contributes to brain changes in young rodents with hydrocephalus and that compensatory mechanisms are negligible.

Infantile Encephaloneuromyopathy and Defective Mitochondrial Translation Are Due to a Homozygous RMND1 Mutation

Defects of mitochondrial protein synthesis are clinically and genetically heterogeneous. We previously described a male infant who was born to consanguineous parents and who presented with severe congenital encephalopathy, peripheral neuropathy, myopathy, and lactic acidosis associated with deficiencies of multiple mitochondrial respiratory-chain enzymes and defective mitochondrial translation. In this work, we have characterized four additional affected family members, performed homozygosity mapping, and identified a homozygous splicing mutation in the splice donor site of exon 2 (c.504+1G>A) of RMND1 (required for meiotic nuclear division-1) in the affected individuals. Fibroblasts from affected individuals expressed two aberrant transcripts and had decreased wild-type mRNA and deficiencies of mitochondrial respiratory-chain enzymes. The RMND1 mutation caused haploinsufficiency that was rescued by overexpression of the wild-type transcript in mutant fibroblasts; this overexpression increased the levels and activities of mitochondrial respiratory-chain proteins. Knockdown of RMND1 via shRNA recapitulated the biochemical defect of the mutant fibroblasts, further supporting a loss-of-function pathomechanism in this disease. RMND1 belongs to the sif2 family, an evolutionary conserved group of proteins that share the DUF155 domain, have unknown function, and have never been associated with human disease. We documented that the protein localizes to mitochondria in mammalian and yeast cells. Further studies are necessary for understanding the function of this protein in mitochondrial protein translation.