The effect of active and passive maternal smoking before and during pregnancy on neonatal weight at birth

IntroductionSmoking during pregnancy is a risk factor for adverse pregnancy outcomes. Data on the correlation between passive maternal smoking and pregnancy outcomes remain limited. We investigated the effect of active smoking and environmental tobacco smoke (ETS) during pregnancy on neonatal birthweight, including the risk for low birthweight (LBW).Material and methodsThe study was conducted between 2010 and 2012. A group of 8625 women were surveyed during postpartum hospitalization. Outcome measures included mean birthweight of newborns. Additionally, odds ratios with confidence intervals were calculated to investigate the risk for LBW in active and passive smoking groups of mothers.ResultsLower birthweight (46 g – 307 g; p < 0.05) and a higher risk for LBW (OR = 1.35, 95% CI: 1.05–1.75; p < 0.05) were observed in all infants born to smoking mothers. A negative effect of ETS in pregnancy on the reduction of mean birthweight was also found. Additionally, we analyzed the cumulative effect of active and passive smoking on neonatal birthweight. A statistically significant reduction in neonatal weight at birth was found in a group of women who smoked actively and passively during pregnancy (130 g; p < 0.05).ConclusionsSmoking is associated with decreased birthweight and in a group of active smoking mothers increased risk for LBW. This effect is dose-dependent and is also present in a group of women who smoked before pregnancy. There is also a cumulative effect of active smoking and ETS causing decreased neonatal birthweight and increased risk for low birthweight.     

Mutations in the planar cell polarity gene, Fuzzy, are associated with neural tube defects in humans

Neural tube defects (NTDs) are a heterogeneous group of common severe congenital anomalies which affect 1-2 infants per 1000 births. Most genetic and/or environmental factors that contribute to the pathogenesis of human NTDs are unknown. Recently, however, pathogenic mutations of VANGL1 and VANGL2 genes have been associated with some cases of human NTDs. Vangl genes encode proteins of the planar cell polarity (PCP) pathway that regulates cell behavior during early stages of neural tube formation. Homozygous disruption of PCP genes in mice results in a spectrum of NTDs, including defects that affect the entire neural axis (craniorachischisis), cranial NTDs (exencephaly) and spina bifida. In this paper, we report the dynamic expression of another PCP gene, Fuzzy, during neural tube formation in mice. We also identify non-synonymous Fuzzy amino acid substitutions in some patients with NTDs and demonstrate that several of these Fuzzy mutations affect formation of primary cilia and ciliary length or affect directional cell movement. Since Fuzzy knockout mice exhibit both NTDs and defective primary cilia and Fuzzy is expressed in the emerging neural tube, we propose that mutations in Fuzzy may account for a subset of NTDs in humans.     

Antimanic-like effect of tamoxifen is not reproduced by acute or chronic administration of medroxyprogesterone or clomiphene

Tamoxifen, a protein kinase C (PKC) inhibitor and antiestrogenic drug, has clinical antimanic effects and blocks psychostimulant-induced hyperlocomotion. Medroxyprogesterone (MPA), which has antiestrogenic effects, also exerts some clinical benefits in female manic patients and partially blocks amphetamine-induced hyperlocomotion, indicating that the antiestrogenic effect of tamoxifen could contribute to its antimanic effect. The present study evaluated the effect of acute and chronic (21 day) treatment of two antiestrogenic drugs, MPA and clomiphene (an estrogenic receptor antagonist), on methylphenidate (MPH, 5.0mg/kg)-induced hyperlocomotion in mice, an animal model of mania. Acute and chronic tamoxifen administration was used as a positive control. Acute and chronic tamoxifen (1.0mg/kg) administration blocked MPH-induced hyperlocomotion. Acute and chronic MPA (acute: 3.0 or 6.0mg/kg; chronic: 3.0mg/kg) and clomiphene (acute: 1.5 or 3.0mg/kg; chronic: 1.5mg/kg) treatment did not alter MPH-induced hyperlocomotion. These results indicate that tamoxifen exerts antimanic-like effects, and reduced estrogenic activity does not have antimanic-like effects in this psychostimulant-induced hyperlocomotion model. Therefore, the antiestrogenic effect of tamoxifen likely does not contribute to its antimanic effect, which may instead be related to its effect on PKC activity. Therefore, PKC inhibition may be associated with the antimanic effect of mood stabilizers.     

Presence of tropical spastic paraparesis/human T-cell lymphotropic virus type 1-associated myelopathy (TSP/HAM)-like among HIV-1-infected patients

Human immunodeficiency virus type 1 (HIV‐1) and human T‐cell lymphotropic virus types 1 and 2 (HTLV‐1 and ‐2) are retroviruses that share similar routes of transmission and some individuals may have a dual infection. These co‐infected subjects may be at increased risk for tropical spastic paraparesis/HTLV‐1‐associated myelopathy (TSP/HAM)‐like. To study the prevalence of tropical spastic paraparesis/HTLV‐1‐associated myelopathy (TSP/HAM) among co‐infected HIV‐1/HTLV‐1 subjects. Since July 1997, our group has been following a cohort to study the interaction of HTLV with HIV and/or hepatitis C virus (HCV), as well as HTLV‐1‐only infected asymptomatic carriers or those already presenting with TSP/HAM. During these 9 years, 296 HTLV‐1‐infected individuals were identified from a total of 538 patients who were referred to our clinic at the Institute of Infectious Diseases “Emílio Ribas,” in São Paulo, Brazil. All subjects were evaluated by two neurologists, blinded to the HTLV status. TSP/HAM diagnosis was based on Kagoshima diagnostic criteria. Results: A total of 38 HIV‐1/HTLV‐1 co‐infected subjects were identified in this cohort: Twenty‐six had already been diagnosed with AIDS and 12 remained asymptomatic. Six of 38 co‐infected subjects (18%) were diagnosed as having TSP/HAM and also AIDS, and for 5 of them TSP/HAM was their first illness. One additional incident case was diagnosed after 2 years of follow‐up. No modifications on HIV‐1 viral load was seen. In contrast, the co‐infected with TSP/HAM‐like group showed higher HTLV‐1 proviral load (505 ± 380 vs. 97 ± 149 copies/10⁴ PBMC, P = 0.012) than asymptomatic co‐infected subjects, respectively. The incidence of myelopathy among HIV‐1/HTLV‐1 co‐infected subjects is probably higher than among patients infected only with HTLV‐1, and related to a higher HTLV‐1 proviral load. Thus, HTLV‐1/2 screening should be done for all HIV‐1‐infected patients in areas where HTLV‐1 infection is endemic. J. Med. Virol. 80:392–398, 2008. © 2008 Wiley‐Liss, Inc.     

Decreased proportions of CD4 + IL17+/CD4 + CD25 + CD127− and CD4 + IL17+/CD4 + CD25 + CD127 − FoxP3+ T cells in children with autoimmune thyroid diseases*

Until now, altered balance of Th1 and Th2 immune cells has been postulated to play an important role in the pathogenesis of autoimmune thyroid diseases (AITD). However, recent studies on thyroid diseases have suggested a new role for Th17 cells that have been classified as a new lineage, distinct from Th1, Th2 and Treg cells. Despite wide interest, the role of Th17 cells in the pathogenesis of inflammatory and autoimmune diseases is still debated. The aim of the study was to estimate the proportions of Th17/Treg T cells in peripheral blood from patients with Graves’ disease (GD; n?=?29, mean age 15.4?±?5.1 years), Hashimoto’s thyroiditis (HT; n?=?39, mean age 15.2?±?4.1 years) and in healthy controls (n?=?49, mean age 14.8?±?3 years). Polychromatic flow cytometry and several fluorochrome-conjugated monoclonal antibodies were applied to delineate Th17 and Treg cells. The analysis of Th17/Treg T cell proportions in peripheral blood from patients with Graves’ disease revealed significantly lower ratios of CD4?+?IL17+/CD4?+?CD25?+?CD127???(p?p?p?p?R?=?0.71, p?R?=?0.72, p?R?=?0.66, p?相似文献   

Escherichia coli lipopolysaccharide may affect the endothelial barrier and IL-10 expression of apolipoprotein B100-pulsed dendritic cells

Atherogenesis is associated with chronic gut infections; however, the mechanisms are not clear. The aim of the study was to determine whether lipopolysaccharide of E. coli (E. coli LPS) may affect endothelial barrier and modify IL-10 expression in dendritic cells (DCs). Human umbilical vein endothelial cells (HUVECs) and monocyte-derived DCs were treated with E. coli LPS, apolipoprotein B100 (ApoB100) and 7-ketocholesterol (7-kCH) – harmful oxidized form of cholesterol. The effect of E. coli LPS, 7-kCH and ApoB100 on the barrier functions of HUVECs in real-time cell electric impedance sensing system (RTCA-DP) was assessed. Furthermore, the effect of 7-kCH and ApoB100 on barrier functions of HUVECs co-cultured with DCs previously treated with LPS was analyzed. Both E. coli LPS and 7-kCH decreased barrier functions of HUVECs and reduced tight junction protein mRNA expression, whereas ApoB100 increased endothelial barrier. In DCs, ApoB100 and E. coli LPS decreased IL-10 mRNA expression. In HUVECs co-cultured with DCs treated with LPS and subsequently pulsed with ApoB100 or 7-kCH, IL-10 mRNA expression was lower. E. coli LPS-exposed DCs diminished the protective effect of ApoB100 on endothelial integrity and led to the decrease in occludin mRNA expression. LPS potentially derived from gut microflora may destabilize endothelial barrier together with oxidized cholesterol and intensify the immunogenicity of ApoB100.     

Use of a human factors approach to uncover informatics needs of nurses in documentation of care

PurposeThe success of health information technology implementations is often tied to the impact the technical system will have on the work of the clinicians using them. Considering the role of nurses in healthcare, it is shocking that there is a lack of evaluations of nursing information systems in the literature. Here we report on how a human factors approach can be used to address barriers and facilitators to use of the nursing information system (NIS). Human factors engineering (HFE) approaches provide the theoretical and methodological underpinning to address these socio-technical issues.MethodsThis study investigated the use of an NIS, a module of the electronic health record (EHR) previously implemented throughout the hospital system. The study took place in two hospitals (760 beds and 300 beds) within a three-hospital health system. Earlier in the year, the NIS was implemented throughout the health system. We applied a scenario-based evaluation technique in order to understand the barriers and facilitators to nurse use of the NIS as part of improving the healthcare delivery system. The scenarios were designed to have the nurses interact with the major components of the NIS. The research team developed the standardized scenarios to cover the major functions of the system.ResultsTwelve nurses completed the study and results show that documentation within the NIS was hindered by several aspects of the interface. This paper discusses the themes associated with the usability of the NIS interface analyzing them using usability heuristics. The team also identified facilitators to use and proposed avenues to support or enhance these facilitators.ConclusionsThis study examined the use of an NIS to standardize care and documentation in nursing. It used scenario-based usability testing, applying the “think-aloud” protocol technique to assess the use of the NIS in documenting patient care. This method of usability evaluation exposed an understanding of how nurses use the NIS and their perspective on the system. We hypothesize that this method will offer key insights into how the usability of the NIS not only impacts use but also informs redesign opportunities. In addition, this is one of the few rigorous studies of NIS and provides direction and recommendations for informaticians, developers and nurse decision makers.     

Tissue mosaicism,FMR1 expression and intellectual functioning in males with fragile X syndrome

Fragile X syndrome (FXS) is caused by hypermethylation of the FMR1 promoter due to the full mutation expansion (full mutation [FM]: CGG ≥ 200 repeats) and silencing of FMR1. Assessment of mosaicism for active-unmethylated alleles has prognostic utility. This study examined relationships between FMR1 methylation in different tissues with FMR1 messenger ribonucleic acid (mRNA) and intellectual functioning in 87 males with FXS (1.89–43.17 years of age). Methylation sensitive Southern blot (mSB) and Methylation Specific-Quantitative Melt Aanalysis (MS-QMA) were used to examine FMR1 methylation. FMR1 mRNA levels in blood showed strong relationships with FMR1 methylation assessed using MS-QMA in blood (n = 68; R² = 0.597; p = 1.4 × 10⁻¹⁰) and buccal epithelial cells (BEC) (n = 62; R² = 0.24; p = 0.003), with these measures also showing relationships with intellectual functioning scores (p < 0.01). However, these relationships were not as strong for mSB, with ~40% of males with only FM alleles that were 100% methylated and non-mosaic by mSB, showing methylation mosaicism by MS-QMA. This was confirmed through presence of detectable levels of FMR1 mRNA in blood. In summary, FMR1 methylation levels in blood and BEC examined by MS-QMA were significantly associated with FMR1 mRNA levels and intellectual functioning in males with FXS. These relationships were not as strong for mSB, which underestimated prevalence of mosaicism.     

DASH Diet as a Proposal for Improvement in Cellular Immunity and Its Association with Metabolic Parameters in Persons with Overweight and Obesity

The development of obesity entails a chronic low-grade inflammatory state with increased pro-inflammatory cells, mainly in visceral adipose tissue (VAT). Additionally, dietary patterns have an influence on the regulation of chronic inflammation. Dietary Approaches to Stop Hypertension (DASH) include foods with an anti-inflammatory profile and that have positive impacts on body composition (BC), suggesting improvements in inflammatory processes. Objective: To analyze the impact of the DASH diet on cellular immunity, anthropometric, biochemical and BC parameters in patients with overweight and obesity, who could present metabolic syndrome. Methodology: Lymphocyte subpopulations, biochemical parameters, anthropometric parameters, and BC before and 8 weeks after intervention with the DASH diet in persons with overweight and obesity were measured. Results: Fifty-nine young adults participated in the study. After the intervention, no significant changes in biochemical parameters were observed, although a significant decrease in nearly all of the anthropometric and BC variables was found: waist circumference (p < 0.001), percentage and kilograms of fat (p < 0.001 and p < 0.025, respectively), VAT (p < 0.020), and weight (p < 0.001), as well as total lymphocytes and double-positive TCD4+ cells. A relation between changes in leukocyte subpopulations (monocytes, natural killer, helper and cytotoxic lymphocytes, and naive TCD4+ cells) and metabolic improvements (glucose, triglycerides, total cholesterol and LDL-c) was also found. Conclusions: The DASH diet promotes positive changes in lymphocyte subpopulations, anthropometric parameters and BC in persons with overweight and obesity. Future studies should elucidate the cellular and molecular mechanisms through which the DASH diet produces inmunometabolic improvement.