Awareness, Knowledge, and Travel-Related Risk Factors for Zika Virus Among Latinas Attending a Federally Qualified Health Center in Rural North Carolina.

BACKGROUND The Zika virus (ZIKV) epidemic that began in 2015 presented a risk for ZIKV infection among persons who traveled to ZIKV-affected countries. Latinas in North Carolina and their sexual partners may be exposed to ZIKV when traveling to these regions.METHODS We administered a cross-sectional survey, measuring ZIKV risk and knowledge, to a convenience sample of 262 reproductive-age Latinas attending a Federally Qualified Health Center in rural North Carolina. We described ZIKV risk and knowledge in the sample, and compared responses between those who were pregnant or recently pregnant, and those who were not pregnant. We further identified factors associated with 1) awareness of ZIKV and 2) high knowledge of ZIKV sequelae and prevention among those who were aware of ZIKV, using log-binomial regression.RESULTS Two-thirds of participants had ever heard of ZIKV, which was positively associated with educational attainment. Most participants aware of ZIKV had moderate/high knowledge of ZIKV transmission (92.5%) and symptoms (73.2%), but knowledge of preventing sexual and congenital transmission was limited. Travel was infrequent among pregnant or recently pregnant participants (5.4%) and their partners (7.1%). Despite low risk for ZIKV infection, participants were willing to practice ZIKV prevention.LIMITATIONS Our study is limited by a lack of generalizability to Latinas in other regions of the country, self-reporting bias, and lack of survey validation as an indicator of English language proficiency.CONCLUSIONS Providers should identify patients likely to become pregnant and travel to high-risk areas, inquire about partner travel history, and offer culturally appropriate ZIKV risk counseling.

Computational investigation of the photochemical deoxygenation of thiophene-S-oxide and selenophene-Se-oxide.

CASSCF and multireference MP2 calculations were carried out on thiophene-S-oxide (TO) and selenophene-Se-oxide (SeO), comparing the energies of the ground state to the first two electronically excited singlet and triplet states, using constrained optimizations and multiple fixed S-O or Se-O distances. For both molecules, one of the two triplet states smoothly dissociates to yield O((3)P) with little or no barrier. Single point calculations are consistent with the same phenomenon occurring for dibenzothiophene-S-oxide (DBTO). This provides an explanation for the inefficient unimolecular photochemical dissociation of O((3)P) from DBTO despite a phosphorescence energy below that of S-O dissociation, i.e., that S-O scission probably occurs from a spectroscopically unobserved triplet (T2) state.

A tale of two factors: what determines the rate of progression in Huntington's disease? A longitudinal MRI study.

Over the past several years, increased attention has been devoted to understanding regionally selective brain changes that occur in Huntington's disease and their relationships to phenotypic variability. Clinical progression is also heterogeneous, and although CAG repeat length influences age of onset, its role, if any, in progression has been less clear. We evaluated progression in Huntington's disease using a novel longitudinal magnetic resonance imaging analysis. Our hypothesis was that the rate of brain atrophy is influenced by the age of onset of Huntington's disease. We scanned 22 patients with Huntington's disease at approximately 1-year intervals; individuals were divided into 1 of 3 groups, determined by the relative age of onset. We found significant differences in the rates of atrophy of cortex, white matter, and subcortical structures; patients who developed symptoms earlier demonstrated the most rapid rates of atrophy compared with those who developed symptoms during middle age or more advanced age. Rates of cortical atrophy were topologically variable, with the most rapid changes occurring in sensorimotor, posterior frontal, and portions of the parietal cortex. There were no significant differences in the rates of atrophy in basal ganglia structures. Although both CAG repeat length and age influenced the rate of change in some regions, there was no significant correlation in many regions. Rates of regional brain atrophy seem to be influenced by the age of onset of Huntington's disease symptoms and are only partially explained by CAG repeat length. These findings suggest that other genetic, epigenetic, and environmental factors play important roles in neurodegeneration in Huntington's disease.

Altered white matter microstructure in the corpus callosum in Huntington's disease: implications for cortical "disconnection".

The corpus callosum (CC) is the major conduit for information transfer between the cerebral hemispheres and plays an integral role in relaying sensory, motor and cognitive information between homologous cortical regions. The majority of fibers that make up the CC arise from large pyramidal neurons in layers III and V, which project contra-laterally. These neurons degenerate in Huntington's disease (HD) in a topographically and temporally selective way. Since any focus of cortical degeneration could be expected to secondarily de-afferent homologous regions of cortex, we hypothesized that regionally selective cortical degeneration would be reflected in regionally selective degeneration of the CC. We used conventional T1-weighted, diffusion tensor imaging (DTI), and a modified corpus callosum segmentation scheme to examine the CC in healthy controls, huntingtin gene-carriers and symptomatic HD subjects. We measured mid-sagittal callosal cross-sectional thickness and several DTI parameters, including fractional anisotropy (FA), which reflects the degree of white matter organization, radial diffusivity, a suggested index of myelin integrity, and axial diffusivity, a suggested index of axonal damage of the CC. We found a topologically selective pattern of alterations in these measures in pre-manifest subjects that were more extensive in early symptomatic HD subjects and that correlated with performance on distinct cognitive measures, suggesting an important role for disrupted inter-hemispheric transfer in the clinical symptoms of HD. Our findings provide evidence for early degeneration of commissural pyramidal neurons in the neocortex, loss of cortico-cortical connectivity, and functional compromise of associative cortical processing.

Cerebral cortex and the clinical expression of Huntington's disease: complexity and heterogeneity.

The clinical phenotype of Huntington's disease (HD) is far more complex and variable than depictions of it as a progressive movement disorder dominated by neostriatal pathology represent. The availability of novel neuro-imaging methods has enabled us to evaluate cerebral cortical changes in HD, which we have found to occur early and to be topographically selective. What is less clear, however, is how these changes influence the clinical expression of the disease. In this study, we used a high-resolution surface based analysis of in vivo MRI data to measure cortical thickness in 33 individuals with HD, spanning the spectrum of disease and 22 age- and sex-matched controls. We found close relationships between specific functional and cognitive measures and topologically specific cortical regions. We also found that distinct motor phenotypes were associated with discrete patterns of cortical thinning. The selective topographical associations of cortical thinning with clinical features of HD suggest that we are not simply correlating global worsening with global cortical degeneration. Our results indicate that cortical involvement contributes to important symptoms, including those that have been ascribed primarily to the striatum, and that topologically selective changes in the cortex might explain much of the clinical heterogeneity found in HD. Additionally, a significant association between regional cortical thinning and total functional capacity, currently the leading primary outcome measure used in neuroprotection trials for HD, establishes cortical MRI morphometry as a potential biomarker of disease progression.

Quantitative tractography metrics of white matter integrity in diffusion-tensor MRI.

We present new quantitative diffusion-tensor imaging (DTI) tractography-based metrics for assessing cerebral white matter integrity. These metrics extend prior work in this area. Tractography models of cerebral white matter were produced from each subject's DTI data. The models are a set of curves (e.g., "streamtubes") derived from DTI data that represent the underlying topography of the cerebral white matter. Nine metrics were calculated in whole brain tractography models and in three "tracts-of-interest": transcallosal fibers and the left and right cingulum bundles. The metrics included the number of streamtubes and several other based on the summed length of streamtubes, including some that were weighted by scalar anisotropy metrics and normalized for estimated intracranial volume. We then tested whether patients with subcortical ischemic vascular disease (i.e., vascular cognitive impairment or VCI) vs. healthy controls (HC) differed on the metrics. The metrics were significantly lower in the VCI group in whole brain and in transcallosal fibers but not in the left or right cingulum bundles. The metrics correlated significantly with cognitive functions known to be impacted by white matter abnormalities (e.g., processing speed) but not with those more strongly impacted by cortical disease (e.g., naming). These new metrics help bridge the gap between DTI tractography and scalar analytical methods and provide a potential means for examining group differences in white matter integrity in specific tracts-of-interest.

Exposure to oral contraceptives increases the risk for development of inflammatory bowel disease: a meta-analysis of case-controlled and cohort studies.

BACKGROUND: The oral contraceptive pill (OCP) is a widely used method of contraception. There have been conflicting studies linking the use of OCPs to the development of inflammatory bowel disease (IBD). The intent of this meta-analysis is to better define the association between OCP exposure and the risk for development of IBD. METHODS: A thorough search of multiple databases, including Scopus, Cochrane, MEDLINE/PubMed, and CINAHL, and abstracts from major gastroenterology meetings was performed (October, 2016). Studies reporting the development of IBD in patients with or without previous exposure to OCP, compared with healthy controls, were included. A meta-analysis was completed using the Mantel-Haenszel model to evaluate the risk of developing IBD in the setting of previous OCP exposure. RESULTS: In a complete analysis of 20 studies, there appeared to be over a 30% increased risk for the development of IBD in patients exposed to OCP compared with patients not exposed to OCP [odds ratio (OR): 1.32, 95% confidence interval (CI): 1.17-1.49, P<0.001, I=14%]. More specifically, there was a 24% higher risk for developing Crohn's disease (OR: 1.24, 95% CI: 1.09-1.40, P<0.001; I=38%) and a 30% higher risk for developing ulcerative colitis (OR: 1.30, 95% CI: 1.13-1.49, I=26%) in patients exposed to OCP compared with those not exposed to the medication. CONCLUSION: The use of OCP is associated with an increased risk for development of Crohn's disease and ulcerative colitis in the genetically susceptible host. The total duration, dose of OCP exposure, and the risk for development of IBD need to be better characterized.

The reaction of flavanols with nitrous acid protects against N-nitrosamine formation and leads to the formation of nitroso derivatives which inhibit cancer cell growth.

Studies have suggested that diets rich in polyphenols such as flavonoids may lead to a reduced risk of gastrointestinal cancers. We demonstrate the ability of monomeric and dimeric flavanols to scavenge reactive nitrogen species derived from nitrous acid. Both epicatechin and dimer B2 (epicatechin dimer) inhibited nitrous acid-induced formation of 3-nitrotyrosine and the formation of the carcinogenic N-nitrosamine, N-nitrosodimethylamine. The reaction of monomeric and dimeric epicatechin with nitrous acid led to the formation of mono- and di-nitroso flavanols, whereas the reaction with hesperetin resulted primarily in the formation of nitrated products. Although, epicatechin was transferred across the jejunum of the small intestine yielding metabolites, its nitroso form was not absorbed. Dimer B2 but not epicatechin monomer inhibited the proliferation of, and triggered apoptosis in, Caco-2 cells. The latter was accompanied by caspase-3 activation and reductions in Akt phosphorylation, suggesting activation of apoptosis via inhibition of prosurvival signaling. Furthermore, the dinitroso derivative of dimer B2, and to a lesser extent the dinitroso-epicatechin, also induced significant toxic effects in Caco-2 cells. The inhibitory effects on cellular proliferation were paralleled by early inhibition of ERK 1/2 phosphorylation and later reductions in cyclin D1 levels, indicating modulation of cell cycle regulation in Caco-2 cells. These effects highlight multiple routes in which dietary derived flavanols may exert beneficial effects in the gastrointestinal tract.

Does exposure to isotretinoin increase the risk for the development of inflammatory bowel disease? A meta-analysis.

BACKGROUND: Isotretinoin is a treatment option for severe nodulocystic acne. However, its use has inconsistently been associated with the development of inflammatory bowel disease (IBD). This meta-analysis aims to elucidate the association between isotretinoin exposure and the risk for IBD. METHODS: A comprehensive search of PubMed/MEDLINE, CINAHL, the Cochrane database, and Google Scholar was performed (July 2015). All studies on the development of IBD in patients with or without prior exposure to isotretinoin, along with control participants, were included. Meta-analysis was carried out using the Mantel-Haenszel random effect model to assess the risk for IBD in the context of prior isotretinoin exposure. RESULTS: In a pooled analysis of six research studies, there was no increased risk of developing IBD in patients exposed to isotretinoin compared with patients not exposed to isotretinoin [odds ratio (OR) 1.08, 95% confidence interval (CI) 0.82, 1.42, P=0.59]. Furthermore, there was no increased risk of developing Crohn's disease (OR 0.98, 95% CI 0.62, 1.55, P=0.93, I(2)=62%) or ulcerative colitis (OR 1.14, 95% CI 0.79, 1.63, P=0.49, I(2)=44%) in patients exposed to isotretinoin compared with those not exposed to the medication. CONCLUSION: Isotretinoin exposure is not associated with an increased risk of developing both ulcerative colitis and Crohn's disease.

Complexity and heterogeneity: what drives the ever-changing brain in Huntington's disease?

Significant advances are being made in our understanding of basic pathophyiological and biochemical mechanisms that cause Huntington's disease (HD). There is increasing reason to believe that pathologic alterations occur in the brain for years before symptoms manifest. The "classic" hallmark of neuropathology in HD is selective neurodegeneration in which vulnerable populations of neurons degenerate while less vulnerable populations are spared. While the earliest and most striking neuropathologic changes have been found in the neostriatum, neuronal loss has been identified in many other regions of the brain. We report topologically selective, early, and progressive changes in the cortex, striatum, extrastriatal brain structures, and white matter throughout the spectrum of disease. Our growing understanding of HD underscores the reality that points to the complexity of HD. A single, well-defined, genetic mutation causes a cascade of events whose final result is an aggregate insult of the homeostatic process. We explore possible explanations for the selective vulnerability of the brain in HD. The ultimate goal in HD is to develop disease-modifying therapies that will prevent the onset of clinical symptoms in those individuals who are at risk and slow the progression of symptoms in those individuals already affected with symptoms. Understanding changes in brain morphometry and their relationship to clinical symptoms may provide important and new insights into basic pathophysiological mechanisms at play in the disease.