Skin Cancer and UV Exposure-Related Behaviors Among Appalachian and Non-Appalachian Adults

Introduction: Appalachian communities experience elevated rates of cancer incidence and mortality relative to other regions in the U.S. Specifically, melanoma mortality rates are higher in Appalachia compared to the national average, despite comparable incidence rates. Purpose: To examine differences in self-reported history of skin cancer and prevalence of two UV exposure behaviors between Appalachian and non-Appalachian adults in a nationally representative sample. Methods: Data are from four cross-sectional cycles of the Health Information National Trends Survey (2011–2014) (N=14,451). We examined sunscreen use and tanning bed use, and self-reported history of melanoma and non-melanoma skin cancer. Descriptive and weighted multivariable analyses were conducted to examine sunscreen and tanning bed use, controlling for sociodemographic characteristics. Results: Approximately 8% of the study sample resided in Appalachia (n=1,015). Self-reported melanoma (0.6%) and non-melanoma (3.2%) skin cancer histories were low among Appalachians and did not differ statistically from non-Appalachians (p\u3e0.05). Only 21.2% of Appalachians reported using sunscreen often or always when going outside for more than one hour on a warm, sunny day compared to 27.4% of non-Appalachians (p\u3c0.05). In separate multivariable logistic regressions, Appalachians reported lower odds of sunscreen use compared to non-Appalachian (OR=0.76, p=0.04), but there were no regional differences in tanning bed use (OR=1.48, p=0.23) when controlling for sociodemographics and general health status. Implications: Appalachians had comparable histories of self-reported melanoma and non-melanoma skin cancer but were less likely to report sunscreen use than non-Appalachians. Enhanced communication efforts to promote sunscreen use and other UV protection behaviors in Appalachia may be valuable

KIF5A and the contribution of susceptibility genotypes as a predictive biomarker for multiple sclerosis

There is increasing interest in the development of multiple sclerosis (MS) biomarkers that reflect central nervous system tissue injury to determine prognosis. We aimed to assess the prognostic value of kinesin superfamily motor protein KIF5A in MS by measuring levels of KIF5A in cerebrospinal fluid (CSF) combined with analysis of single nucleotide polymorphisms (SNPs; rs12368653 and rs703842) located within a MS susceptibility gene locus at chromosome 12q13–14 region. Enzyme-linked immunosorbent assay was used to measure KIF5A in CSF obtained from two independent biobanks comprising non-inflammatory neurological disease controls (NINDC), clinically isolated syndrome (CIS) and MS cases. CSF KIF5A expression was significantly elevated in progressive MS cases compared with NINDCs, CIS and relapsing–remitting MS (RRMS). In addition, levels of KIF5A positively correlated with change in MS disease severity scores (EDSS, MSSS and ARMSSS), in RRMS patients who had documented disease progression at 2-year clinical follow-up. Copies of adenine risk alleles (AG/AA; rs12368653 and rs703842) corresponded with a higher proportion of individuals in relapse at the time of lumbar puncture (LP), higher use of disease-modifying therapies post LP and shorter MS duration. Our study suggests that CSF KIF5A has potential as a predictive biomarker in MS and further studies into the potential prognostic value of analysing MS susceptibility SNPs should be considered

Aggregate blood pressure responses to serial dietary sodium and potassium intervention: Defining responses using independent component analysis

BACKGROUND: Hypertension is a complex trait that often co-occurs with other conditions such as obesity and is affected by genetic and environmental factors. Aggregate indices such as principal components among these variables and their responses to environmental interventions may represent novel information that is potentially useful for genetic studies. RESULTS: In this study of families participating in the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) Study, blood pressure (BP) responses to dietary sodium interventions are explored. Independent component analysis (ICA) was applied to 20 variables indexing obesity and BP measured at baseline and during low sodium, high sodium and high sodium plus potassium dietary intervention periods. A “heat map” protocol that classifies subjects based on risk for hypertension is used to interpret the extracted components. ICA and heat map suggest four components best describe the data: (1) systolic hypertension, (2) general hypertension, (3) response to sodium intervention and (4) obesity. The largest heritabilities are for the systolic (64 %) and general hypertension (56 %) components. There is a pattern of higher heritability for the component response to intervention (40–42 %) as compared to those for the traditional intervention responses computed as delta scores (24 %–40 %). CONCLUSIONS: In summary, the present study provides intermediate phenotypes that are heritable. Using these derived components may prove useful in gene discovery applications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12863-015-0226-8) contains supplementary material, which is available to authorized users

Theory for Metal Hydrides with Switchable Optical Properties

Recently it has been discovered that lanthanum, yttrium, and other metal hydride films show dramatic changes in the optical properties at the metal-insulator transition. Such changes on a high energy scale suggest the electronic structure is best described by a local model based on negatively charged hydrogen (H$^-$) ions. We develop a many-body theory for the strong correlation in a H$^-$ ion lattice. The metal hydride is described by a large $U$-limit of an Anderson lattice model. We use lanthanum hydride as a prototype of these compounds, and find LaH$_3$ is an insulator with a substantial gap consistent with experiments. It may be viewed either as a Kondo insulator or a band insulator due to strong electron correlation. A H vacancy state in LaH$_3$ is found to be highly localized due to the strong bonding between the electron orbitals of hydrogen and metal atoms. Unlike the impurity states in the usual semiconductors, there is only weak internal optical transitions within the vacancy. The metal-insulator transition takes place in a band of these vacancy states.Comment: 18 pages, 16 figures and 6 tables. Submitted to PR

Reduced expression of mitochondrial fumarate hydratase in progressive multiple sclerosis contributes to impaired in vitro mesenchymal stromal cell-mediated neuroprotection

BACKGROUND: Cell-based therapies for multiple sclerosis (MS), including those employing autologous bone marrow-derived mesenchymal stromal cells (MSC) are being examined in clinical trials. However, recent studies have identified abnormalities in the MS bone marrow microenvironment. OBJECTIVE: We aimed to compare the secretome of MSC isolated from control subjects (C-MSC) and people with MS (MS-MSC) and explore the functional relevance of findings. METHODS: We employed high throughput proteomic analysis, enzyme-linked immunosorbent assays and immunoblotting, as well as in vitro assays of enzyme activity and neuroprotection. RESULTS: We demonstrated that, in progressive MS, the MSC secretome has lower levels of mitochondrial fumarate hydratase (mFH). Exogenous mFH restores the in vitro neuroprotective potential of MS-MSC. Furthermore, MS-MSC expresses reduced levels of fumarate hydratase (FH) with downstream reduction in expression of master regulators of oxidative stress. CONCLUSIONS: Our findings are further evidence of dysregulation of the bone marrow microenvironment in progressive MS with respect to anti-oxidative capacity and immunoregulatory potential. Given the clinical utility of the fumaric acid ester dimethyl fumarate in relapsing–remitting MS, our findings have potential implication for understanding MS pathophysiology and personalised therapeutic intervention

Oxidative stress-related biomarkers in multiple sclerosis:a review

Aim: To provide an up-to-date review of oxidative stress biomarkers in multiple sclerosis and thus identify candidate molecules with greatest promise as biomarkers of diagnosis, disease activity or prognosis. Method: A semi-systematic literature search using PubMed and other databases. Results: Nitric oxide metabolites, superoxide dismutase, catalase, glutathione reductase, inducible nitric oxide synthase, protein carbonyl, 3-nitrotyrosine, isoprostanes, malondialdehyde and products of DNA oxidation have been identified across multiple studies as having promise as diagnostic, therapeutic or prognostic markers in MS. Conclusion: Heterogeneity of study design, particularly patient selection, limits comparability across studies. Further cohort studies are needed, and we would recommend promising markers be incorporated into future clinical trials to prospectively validate their potential

The Streptococcus mutans Cid and Lrg systems modulate virulence traits in response to multiple environmental signals

The tight control of autolysis by Streptococcus mutans is critical for proper virulence gene expression and biofilm formation. A pair of dicistronic operons, SMU.575/574 (lrgAB) and SMU.1701/1700 (designated cidAB), encode putative membrane proteins that share structural features with the bacteriophage-encoded holin family of proteins, which modulate host cell lysis during lytic infection. Analysis of S. mutans lrg and cid mutants revealed a role for these operons in autolysis, biofilm formation, glucosyltransferase expression and oxidative stress tolerance. Expression of lrgAB was repressed during early exponential phase and was induced over 1000-fold as cells entered late exponential phase, whereas cidAB expression declined from early to late exponential phase. A two-component system encoded immediately upstream of lrgAB (LytST) was required for activation of lrgAB expression, but not for cid expression. In addition to availability of oxygen, glucose levels were revealed to affect lrg and cid transcription differentially and significantly, probably through CcpA (carbon catabolite protein A). Collectively, these findings demonstrate that the Cid/Lrg system can affect several virulence traits of S. mutans, and its expression is controlled by two major environmental signals, oxygen and glucose. Moreover, cid/lrg expression is tightly regulated by LytST and CcpA