Entry and Fusion of Emerging Paramyxoviruses

Paramyxoviruses are a family of non-segmented RNA viruses that includes major human pathogens such as measles virus and respiratory syncytial virus (RSV) and significant animal viruses like rinderpest. In recent years, several new paramyxoviruses have been identified, further increasing the breadth and importance of this viral family. While many elements of the fusion and entry mechanisms of these recently identified pathogens are conserved, there are interesting differences, including variations in receptor binding, cell tropism, fusion (F) protein proteolytic activation, and triggering of membrane fusion. Thus, study of their entry mechanisms has highlighted the diversity of these critical events in the family

Population Based Study of 12 Autoimmune Diseases in Sardinia, Italy: Prevalence and Comorbidity

BACKGROUND: The limited availability of prevalence data based on a representative sample of the general population, and the limited number of diseases considered in studies about co-morbidity are the critical factors in study of autoimmune diseases. This paper describes the prevalence of 12 autoimmune diseases in a representative sample of the general population in the South of Sardinia, Italy, and tests the hypothesis of an overall association among these diseases. METHODS: Data were obtained from 21 GPs. The sample included 25,885 people. Prevalence data were expressed with 95% Poisson C.I. The hypothesis of an overall association between autoimmune diseases was tested by evaluating the co-occurrence within individuals. RESULTS: Prevalence per 100,000 are: 552 rheumatoid arthritis, 124 ulcerative colitis, 15 Crohn's disease, 464 type 1 diabetes, 81 systemic lupus erythematosus, 124 celiac disease, 35 myasthenia gravis, 939 psoriasis/psoriatic arthritis, 35 systemic sclerosis, 224 multiple sclerosis, 31 Sjogren's syndrome, and 2,619 autoimmune thyroiditis. An overall association between autoimmune disorders was highlighted. CONCLUSIONS: The comparisons with prevalence reported in current literature do not show outlier values, except possibly for a few diseases like celiac disease and myasthenia gravis. People already affected by a first autoimmune disease have a higher probability of being affected by a second autoimmune disorder. In the present study, the sample size, together with the low overall prevalence of autoimmune diseases in the population, did not allow us to examine which diseases are most frequently associated with other autoimmune diseases. However, this paper makes available an adequate control population for future clinical studies aimed at exploring the co-morbidity of specific pairs of autoimmune disease

English Language Proficiency and Geographical Proximity to a Safety Net Clinic as a Predictor of Health Care Access

Studies suggest that proximity to a safety net clinic (SNC) promotes access to care among the uninsured. Distance-based barriers to care may be greater for people with limited English proficiency (LEP), compared to those who are English proficient (EP), but this has not been explored. We assessed the relationship between distance to the nearest SNC and access in non-rural uninsured adults in California, and examined whether this relationship differs by language proficiency. Using the 2005 California Health Interview Survey and a list we compiled of California’s SNCs, we calculated distance between uninsured interviewee residence and the exact address of the nearest SNC. Using multivariate regression to adjust for other relevant characteristics, we examined associations between this distance and interviewee’s probability of having a usual source of health care (USOC) and having visited a physician in the prior 12 months. To examine differences by language proficiency, we included interactions between distance and language proficiency. Uninsured LEP adults living within 2 miles of a SNC were 9.3% less likely than their EP counterparts to have a USOC (P = 0.046). Further, distance to the nearest SNC was inversely associated with the probability of having a USOC among LEP, but not among EP; consequently, the difference between LEP and EP in the probability of having a USOC widened with increasing distance to the nearest SNC. There was no difference between LEP and EP adults living within 2 miles of a SNC in likelihood of having a physician visit; however, as with USOC, distance to the nearest SNC was inversely associated with the probability of having a physician visit among LEP but not EP. The effect sizes diminished, but remained significant, when we included county fixed effects in the models. Having LEP is a barrier to health care access, which compounds when combined with increased distance to the nearest SNC, among uninsured adults. Future studies should explore potential mechanisms so that appropriate interventions can be implemented

Characterizing low affinity epibatidine binding to α4β2 nicotinic acetylcholine receptors with ligand depletion and nonspecific binding

<p>Abstract</p> <p>Background</p> <p>Along with high affinity binding of epibatidine (<it>K</it>_d1≈10 pM) to α4β2 nicotinic acetylcholine receptor (nAChR), low affinity binding of epibatidine (<it>K</it>_d2≈1-10 nM) to an independent binding site has been reported. Studying this low affinity binding is important because it might contribute understanding about the structure and synthesis of α4β2 nAChR. The binding behavior of epibatidine and α4β2 AChR raises a question about interpreting binding data from two independent sites with ligand depletion and nonspecific binding, both of which can affect equilibrium binding of [³H]epibatidine and α4β2 nAChR. If modeled incorrectly, ligand depletion and nonspecific binding lead to inaccurate estimates of binding constants. Fitting total equilibrium binding as a function of total ligand accurately characterizes a single site with ligand depletion and nonspecific binding. The goal of this study was to determine whether this approach is sufficient with two independent high and low affinity sites.</p> <p>Results</p> <p>Computer simulations of binding revealed complexities beyond fitting total binding for characterizing the second, low affinity site of α4β2 nAChR. First, distinguishing low-affinity specific binding from nonspecific binding was a potential problem with saturation data. Varying the maximum concentration of [³H]epibatidine, simultaneously fitting independently measured nonspecific binding, and varying α4β2 nAChR concentration were effective remedies. Second, ligand depletion helped identify the low affinity site when nonspecific binding was significant in saturation or competition data, contrary to a common belief that ligand depletion always is detrimental. Third, measuring nonspecific binding without α4β2 nAChR distinguished better between nonspecific binding and low-affinity specific binding under some circumstances of competitive binding than did presuming nonspecific binding to be residual [³H]epibatidine binding after adding a large concentration of cold competitor. Fourth, nonspecific binding of a heterologous competitor changed estimates of high and low inhibition constants but did not change the ratio of those estimates.</p> <p>Conclusions</p> <p>Investigating the low affinity site of α4β2 nAChR with equilibrium binding when ligand depletion and nonspecific binding are present likely needs special attention to experimental design and data interpretation beyond fitting total binding data. Manipulation of maximum ligand and receptor concentrations and intentionally increasing ligand depletion are potentially helpful approaches.</p

Evaluation of groundwater quality and its suitability for drinking and agricultural use in Thanjavur city, Tamil Nadu, India

As groundwater is a vital source of water for domestic and agricultural activities in Thanjavur city due to lack of surface water resources, groundwater quality and its suitability for drinking and agricultural usage were evaluated. In this study, 102 groundwater samples were collected from dug wells and bore wells during March 2008 and analyzed for pH, electrical conductivity, temperature, major ions, and nitrate. Results suggest that, in 90% of groundwater samples, sodium and chloride are predominant cation and anion, respectively, and NaCl and CaMgCl are major water types in the study area. The groundwater quality in the study site is impaired by surface contamination sources, mineral dissolution, ion exchange, and evaporation. Nitrate, chloride, and sulfate concentrations strongly express the impact of surface contamination sources such as agricultural and domestic activities, on groundwater quality, and 13% of samples have elevated nitrate content (>45 mg/l as NO3). PHREEQC code and Gibbs plots were employed to evaluate the contribution of mineral dissolution and suggest that mineral dissolution, especially carbonate minerals, regulates water chemistry.Groundwater suitability for drinking usage was evaluated by the World Health Organization and Indian standards and suggests that 34% of samples are not suitable for drinking. Integrated groundwater suitability map for drinking purposes was created using drinking water standards based on a concept that if the groundwater sample exceeds any one of the standards, it is not suitable for drinking. This map illustrates that wells in zones 1, 2, 3, and 4 are not fit for drinking purpose. Likewise, irrigational suitability of groundwater in the study region was evaluated, and results suggest that 20% samples are not fit for irrigation. Groundwater suitability map for irrigation was also produced based on salinity and sodium hazards and denotes that wells mostly situated in zones 2 and 3 are not suitable for irrigation. Both integrated suitability maps for drinking and irrigation usage provide overall scenario about the groundwater quality in the study area. Finally, the study concluded that groundwater quality is impaired by man-made activities, and proper management plan is necessary to protect valuable groundwater resources inThanjavur city

HPV vaccine decision making in pediatric primary care: a semi-structured interview study

<p>Abstract</p> <p>Background</p> <p>Despite national recommendations, as of 2009 human papillomavirus (HPV) vaccination rates were low with < 30% of adolescent girls fully vaccinated. Research on barriers to vaccination has focused separately on parents, adolescents, or clinicians and not on the decision making process among all participants at the point of care. By incorporating three distinct perspectives, we sought to generate hypotheses to inform interventions to increase vaccine receipt.</p> <p>Methods</p> <p>Between March and June, 2010, we conducted qualitative interviews with 20 adolescent-mother-clinician triads (60 individual interviews) directly after a preventive visit with the initial HPV vaccine due. Interviews followed a guide based on published HPV literature, involved 9 practices, and continued until saturation of the primary themes was achieved. Purposive sampling balanced adolescent ages and practice type (urban resident teaching versus non-teaching). Using a modified grounded theory approach, we analyzed data with NVivo8 software both within and across triads to generate primary themes.</p> <p>Results</p> <p>The study population was comprised of 20 mothers (12 Black, 9 < high school diploma), 20 adolescents (ten 11-12 years old), and 20 clinicians (16 female). Nine adolescents received the HPV vaccine at the visit, eight of whom were African American. Among the 11 not vaccinated, all either concurrently received or were already up-to-date on Tdap and MCV4. We did not observe systematic patterns of vaccine acceptance or refusal based on adolescent age or years of clinician experience. We identified 3 themes: (1) Parents delayed, rather than refused vaccination, and when they expressed reluctance, clinicians were hesitant to engage them in discussion. (2) Clinicians used one of two strategies to present the HPV vaccine, either presenting it as a routine vaccine with no additional information or presenting it as optional and highlighting risks and benefits. (3) Teens considered themselves passive participants in decision making, even when parents and clinicians reported including them in the process.</p> <p>Conclusions</p> <p>Programs to improve HPV vaccine delivery in primary care should focus on promoting effective parent-clinician communication. Research is needed to evaluate strategies to help clinicians engage reluctant parents and passive teens in discussion and measure the impact of distinct clinician decision making approaches on HPV vaccine delivery.</p