Parenting practices in pregnancy smokers compared to non smokers

BACKGROUND: The present investigation compared parenting practices in a sample of preschoolers whose mothers reported smoking during pregnancy versus those who did not. METHODS: A sample of n = 216, 3.0- to 5.11-year-old children, participants in an ongoing longitudinal study, was separated into those reportedly exposed to smoking in utero and those who were not. Parenting practices were compared between the two groups, using T-tests and exact logistic regressions. Multiple linear regressions and multivariate logistic regressions were used to examine the association between smoking status and parenting, controlling for variables also known to be associated with parenting practices. RESULTS: Current study findings suggest that smoking during pregnancy is associated with harsh parenting practices. CONCLUSIONS: Study results highlight the possible role of parenting in disruptive outcomes well-known in toddlers exposed to nicotine in utero and have implications for targeting early interventions in these populations

High Adherence Is Necessary to Realize Health Gains from Water Quality Interventions

BACKGROUND: Safe drinking water is critical for health. Household water treatment (HWT) has been recommended for improving access to potable water where existing sources are unsafe. Reports of low adherence to HWT may limit the usefulness of this approach, however. METHODS AND FINDINGS: We constructed a quantitative microbial risk model to predict gains in health attributable to water quality interventions based on a range of assumptions about pre-treatment water quality; treatment effectiveness in reducing bacteria, viruses, and protozoan parasites; adherence to treatment interventions; volume of water consumed per person per day; and other variables. According to mean estimates, greater than 500 DALYs may be averted per 100,000 person-years with increased access to safe water, assuming moderately poor pre-treatment water quality that is a source of risk and high treatment adherence (>90% of water consumed is treated). A decline in adherence from 100% to 90% reduces predicted health gains by up to 96%, with sharpest declines when pre-treatment water quality is of higher risk. CONCLUSIONS: Results suggest that high adherence is essential in order to realize potential health gains from HWT

The estimated economic burden of genital herpes in the United States. An analysis using two costing approaches

BACKGROUND: Only limited data exist on the costs of genital herpes (GH) in the USA. We estimated the economic burden of GH in the USA using two different costing approaches. METHODS: The first approach was a cross-sectional survey of a sample of primary and secondary care physicians, analyzing health care resource utilization. The second approach was based on the analysis of a large administrative claims data set. Both approaches were used to generate the number of patients with symptomatic GH seeking medical treatment, the average medical expenditures and estimated national costs. Costs were valued from a societal and a third party payer's perspective in 1996 US dollars. RESULTS: In the cross-sectional study, based on an estimated 3.1 million symptomatic episodes per year in the USA, the annual direct medical costs were estimated at a maximum of $984 million. Of these costs, 49.7$214 million. The analysis of 1,565 GH cases from the claims database yielded a minimum national estimate of $283 million direct medical costs. CONCLUSIONS: GH appears to be an important public health problem from the health economic point of view. The observed difference in direct medical costs may be explained with the influence of compliance to treatment and possible undersampling of subpopulations in the claims data set. The present study demonstrates the validity of using different approaches in estimating the economic burden of a specific disease to the health care system

Contribution of Cystine-Glutamate Antiporters to the Psychotomimetic Effects of Phencyclidine

Altered glutamate signaling contributes to a myriad of neural disorders, including schizophrenia. While synaptic levels are intensely studied, nonvesicular release mechanisms, including cystine–glutamate exchange, maintain high steady-state glutamate levels in the extrasynaptic space. The existence of extrasynaptic receptors, including metabotropic group II glutamate receptors (mGluR), pose nonvesicular release mechanisms as unrecognized targets capable of contributing to pathological glutamate signaling. We tested the hypothesis that activation of cystine–glutamate antiporters using the cysteine prodrug N-acetylcysteine would blunt psychotomimetic effects in the rodent phencyclidine (PCP) model of schizophrenia. First, we demonstrate that PCP elevates extracellular glutamate in the prefrontal cortex, an effect that is blocked by N-acetylcysteine pretreatment. To determine the relevance of the above finding, we assessed social interaction and found that N-acetylcysteine reverses social withdrawal produced by repeated PCP. In a separate paradigm, acute PCP resulted in working memory deficits assessed using a discrete trial t-maze task, and this effect was also reversed by N-acetylcysteine pretreatment. The capacity of N-acetylcysteine to restore working memory was blocked by infusion of the cystine–glutamate antiporter inhibitor (S)-4-carboxyphenylglycine into the prefrontal cortex or systemic administration of the group II mGluR antagonist LY341495 indicating that the effects of N-acetylcysteine requires cystine–glutamate exchange and group II mGluR activation. Finally, protein levels from postmortem tissue obtained from schizophrenic patients revealed significant changes in the level of xCT, the active subunit for cystine–glutamate exchange, in the dorsolateral prefrontal cortex. These data advance cystine–glutamate antiporters as novel targets capable of reversing the psychotomimetic effects of PCP

Walkability and self-rated health in primary care patients

BACKGROUND: The objective of this study was to investigate the relationship between perceived walkability and overall self-rated health among patients who use community-based clinics. METHODS: A cross-sectional survey was distributed to a convenience sample in three community clinics. Forms were completed by 793 clinic patients. Multiple logistic regression analysis was to control for the effects of demographic variables and lifestyles. RESULTS: Perceiving the availability of places to walk was related to better self-rated health. The most important places were work (OR = 3.2), community center (OR = 3.12), park (OR = 2.45) and day care (OR = 2.05). Respondents who said they had zero (OR = .27) or one (OR = .49) place to walk were significantly less healthy than persons who said they had five or more places to walk. CONCLUSION: Persons who perceived that they had no place to walk were significantly less healthy than persons who thought they had at least one place to walk (OR = .39). Support for walkable neighborhoods and education of patients about options for walking may be in the best interests of community medicine patients

Facilitative parenting and children's social, emotional and behavioural adjustment

Facilitative parenting (FP) supports the development of children’s social and emotional competence and effective peer relationships. Previous research has shown that FP discriminates between children bullied by peers from children who are not bullied, according to reports of teachers. This study investigates the association between FP and children’s social, emotional and behavioral problems, over and above the association with dysfunctional parenting (DP). 215 parents of children aged 5–11 years completed questionnaires about parenting and child behavior, and children and teachers completed measures of child bullying victimization. As predicted, FP accounted for variance in teacher reports of children’s bullying victimization as well as parent reports of children’s social and emotional problems and prosocial behavior better than that accounted for by DP. However for children’s reports of peer victimization the whole-scale DP was a better predictor than FP. Contrary to predictions, FP accounted for variance in conduct problems and hyperactivity better than DP. When analyses were replicated substituting subscales of dysfunctional and FP, a sub-set of FP subscales including Warmth, Supports Friendships, Not Conflicting, Child Communicates and Coaches were correlated with low levels of problems on a broad range of children’s adjustment problems. Parent–child conflict accounted for unique variance in children’s peer victimization (teacher report), peer problems, depression, emotional problems, conduct problems and hyperactivity. The potential relevance of FP as a protective factor for children against a wide range of adjustment problems is discussed

Protein Diffusion in Mammalian Cell Cytoplasm

We introduce a new method for mesoscopic modeling of protein diffusion in an entire cell. This method is based on the construction of a three-dimensional digital model cell from confocal microscopy data. The model cell is segmented into the cytoplasm, nucleus, plasma membrane, and nuclear envelope, in which environment protein motion is modeled by fully numerical mesoscopic methods. Finer cellular structures that cannot be resolved with the imaging technique, which significantly affect protein motion, are accounted for in this method by assigning an effective, position-dependent porosity to the cell. This porosity can also be determined by confocal microscopy using the equilibrium distribution of a non-binding fluorescent protein. Distinction can now be made within this method between diffusion in the liquid phase of the cell (cytosol/nucleosol) and the cytoplasm/nucleoplasm. Here we applied the method to analyze fluorescence recovery after photobleach (FRAP) experiments in which the diffusion coefficient of a freely-diffusing model protein was determined for two different cell lines, and to explain the clear difference typically observed between conventional FRAP results and those of fluorescence correlation spectroscopy (FCS). A large difference was found in the FRAP experiments between diffusion in the cytoplasm/nucleoplasm and in the cytosol/nucleosol, for all of which the diffusion coefficients were determined. The cytosol results were found to be in very good agreement with those by FCS

Formation and Toxicity of Soluble Polyglutamine Oligomers in Living Cells

Aggregation and cytotoxicity of mutant proteins containing an expanded number of polyglutamine (polyQ) repeats is a hallmark of several diseases, including Huntington's disease (HD). Within cells, mutant Huntingtin (mHtt) and other polyglutamine expansion mutant proteins exist as monomers, soluble oligomers, and insoluble inclusion bodies (IBs). Determining which of these forms constitute a toxic species has proven difficult. Recent studies support a role for IBs as a cellular coping mechanism to sequester levels of potentially toxic soluble monomeric and oligomeric species of mHtt.When fused to a fluorescent reporter (GFP) and expressed in cells, the soluble monomeric and oligomeric polyglutamine species are visually indistinguishable. Here, we describe two complementary biophysical fluorescence microscopy techniques to directly detect soluble polyglutamine oligomers (using Htt exon 1 or Htt(ex1)) and monitor their fates in live cells. Photobleaching analyses revealed a significant reduction in the mobilities of mHtt(ex1) variants consistent with their incorporation into soluble microcomplexes. Similarly, when fused to split-GFP constructs, both wildtype and mHtt(ex1) formed oligomers, as evidenced by the formation of a fluorescent reporter. Only the mHtt(ex1) split-GFP oligomers assembled into IBs. Both FRAP and split-GFP approaches confirmed the ability of mHtt(ex1) to bind and incorporate wildtype Htt into soluble oligomers. We exploited the irreversible binding of split-GFP fragments to forcibly increase levels of soluble oligomeric mHtt(ex1). A corresponding increase in the rate of IBs formation and the number formed was observed. Importantly, higher levels of soluble mHtt(ex1) oligomers significantly correlated with increased mutant cytotoxicity, independent of the presence of IBs.Our study describes powerful and sensitive tools for investigating soluble oligomeric forms of expanded polyglutamine proteins, and their impact on cell viability. Moreover, these methods should be applicable for the detection of soluble oligomers of a wide variety of aggregation prone proteins

Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis.

Molecular, genetic and pathological evidence suggests that deficits in GABAergic parvalbumin-positive interneurons contribute to schizophrenia pathophysiology through alterations in the brain's excitation-inhibition balance that result in impaired behaviour and cognition. Although the factors that trigger these deficits are diverse, there is increasing evidence that they converge on a common pathological hub that involves NMDA receptor hypofunction and oxidative stress. These factors have been separately linked to schizophrenia pathogenesis, but evidence now suggests that they are mechanistically interdependent and contribute to a common schizophrenia-associated pathology