Association between the ACCN1 gene and multiple sclerosis in Central East Sardinia

Multiple genome screens have been performed to identify regions in linkage or association with Multiple Sclerosis (MS, OMIM 126200), but little overlap has been found among them. This may be, in part, due to a low statistical power to detect small genetic effects and to genetic heterogeneity within and among the studied populations. Motivated by these considerations, we studied a very special population, namely that of Nuoro, Sardinia, Italy. This is an isolated, old, and genetically homogeneous population with high prevalence of MS. Our study sample includes both nuclear families and unrelated cases and controls. A multi-stage study design was adopted. In the first stage, microsatellites were typed in the 17q11.2 region, previously independently found to be in linkage with MS. One significant association was found at microsatellite D17S798. Next, a bioinformatic screening of the region surrounding this marker highlighted an interesting candidate MS susceptibility gene: the Amiloride-sensitive Cation Channel Neuronal 1 (ACCN1) gene. In the second stage of the study, we resequenced the exons and the 3' untranslated (UTR) region of ACCN1, and investigated the MS association of Single Nucleotide Polymorphisms (SNPs) identified in that region. For this purpose, we developed a method of analysis where complete, phase-solved, posterior-weighted haplotype assignments are imputed for each study individual from incomplete, multi-locus, genotyping data. The imputed assignments provide an input to a number of proposed procedures for testing association at a microsatellite level or of a sequence of SNPs. These include a Mantel-Haenszel type test based on expected frequencies of pseudocase/pseudocontrol haplotypes, as well as permutation based tests, including a combination of permutation and weighted logistic regression analysis. Application of these methods allowed us to find a significant association between MS and the SNP rs28936 located in the 3' UTR segment of ACCN1 with p = 0.0004 (p = 0.002, after adjusting for multiple testing). This result is in tune with several recent experimental findings which suggest that ACCN1 may play an important role in the pathogenesis of MS.     

Secular trends of obesity and cardiovascular risk factors in a Mediterranean population

Objective: To evaluate time trends of obesity, abdominal obesity, and cardiovascular risk factors (CRFs) according to BMI and waist circumference (WC) categories in a Mediterranean population. Research Methods and Procedures: Subjects were Spanish men (n = 2383) and women (n = 2525) 25 to 74 years old, examined in 1994 to 1995 and 1999 to 2000 in two independent population‐based cross‐sectional surveys in the northeast of Spain. Lifestyle measures, CRFs, and anthropometric variables were analyzed. Results: Over the 5 years of the study, mean age‐standardized BMI increased by 1.0 units in men and by 0.8 units in women. At the same time the prevalence of obesity increased from 15.4% to 21.9% in men and from 15.4% to 21.4% in women. An upward trend was observed for WC and abdominal obesity (WC > 102 cm in men and WC > 88 cm in women) only in men. The proportion of men and women with hypercholesterolemia, diabetes, and low high‐density lipoprotein‐cholesterol plasma concentration remained stable within BMI and WC categories. The proportion of hypertension and smoking in obese men significantly increased from 1995 to 2000. Discussion: The 5‐year increase in BMI and WC is of considerable magnitude in the present population, although several CRFs remained stable within BMI and WC categories.     

Adiponectin and ghrelin levels and body size in normoglycemic Filipino, African-American, and white women

Objective: Prior studies have reported ethnic differences in adiponectin and ghrelin, but few have assessed the role of body size in normoglycemic women. We compared fasting adiponectin and ghrelin concentrations in normoglycemic 40‐ to 80‐year‐old Filipino, African‐American, and white women. Methods: Participants included women from the Rancho Bernardo Study (n = 143), the University of California‐San Diego Filipino Women's Health Study (n = 136), and the Health Assessment Study of African‐American Women (n = 212). A 2‐hour oral glucose tolerance test was administered; glucose, insulin, lipid, and anthropometric measurements were obtained. Fasting adiponectin and ghrelin were measured by radioimmunoassay. Results: Whites and Filipinas had similar BMI (23.7 and 24.3 kg/m², respectively), waist girth (75.6 and 77.2 cm, respectively), and total body fat (27.4 and 28.5%, respectively); African‐Americans had significantly larger BMI (28.8 kg/m²), waist girth (86.3 cm), and body fat (39.6%, p < 0.0001). Adiponectin was lower in Filipinas (8.90 µg/mL) and African‐Americans (9.67 µg/mL) compared with whites (15.6 µg/mL, p < 0.001) after adjusting for age, homeostasis model assessment of insulin resistance (HOMA‐IR), and waist‐to‐hip ratio. Compared with whites, Filipinas (β = ?5.06, p < 0.0001) and African‐Americans (β = ?6.85, p < 0.0001) had significantly lower adiponectin levels after adjusting for age, waist‐to‐hip ratio, HOMA‐IR, triglycerides, high‐density lipoprotein (HDL) cholesterol, exercise, and alcohol use. Ghrelin was significantly lower in Filipinas compared with African‐Americans (1146.9 vs. 1412.2 pg/mL, p < 0.001), and this observation persisted in multivariable analysis (β = ?245.4, p < 0.0001). Ghrelin levels did not differ between whites (1356.9 pg/mL) and either ethnic group. Discussion: Normoglycemic Filipino and African‐American women had significantly lower adiponectin concentrations than white women, and Filipinas had lower ghrelin levels than African‐Americans, independently of body size or indices of insulin resistance or lipids.     

Differences in variation of human immunodeficiency virus type 1 sequences from Henan and Shanghai regions of China

Illegally paid blood donation was a risk factor for HIV acquisition exclusively in Henan and Hubei Provinces of China, and not in Shanghai. Nucleotide sequences in the gag and env genes of HIV-1 were compared between isolates from Henan and Shanghai regions of China to test whether an expected higher degree of a common source of infections from this unique blood donation transmission risk would be evident as decreased variation among Henan isolates in an exploratory cross-sectional analysis. Among 38 isolates studied, 23 of 23 (100%) from Henan and 8 of 15 (54%) from Shanghai were subtype B. In addition, fewer sequence differences were found in gp41 of subtype B isolates from Henan than from Shanghai isolates. Further studies with additional controls are therefore warranted to confirm the role of the degree of a common source of infections in differences in HIV variation across populations. Fundation items: The Vanderbilt-Meharry Center for AIDS Research (P30 AI 54999); R.T.D (R01 AI 29193); Start Fund of Ministry of Education of China (for Hong-zhou LU, 2004BA719A10).     

Ethnobotanical notes about some uses of medicinal plants in Alto Tirreno Cosentino area (Calabria, Southern Italy)

The present zootherapeutic study describes the traditional knowledge related to the use of different animals and animal-derived products as medicines by the Saharia tribe reside in the Shahabad and Kishanganj Panchayat Samiti's of Baran district of Rajasthan, India. A field survey was conducted from April to June 2006 by performing interview through structured questionnaire with 21 selected respondents, who provided information regarding use of animals and their products in folk medicine. A total of 15 animal species were recorded and they are used for different ethnomedical purposes, including cough, asthma, tuberculosis, paralysis, earache, herpes, weakness, muscular pain etc. The zootherapeutic knowledge was mostly based on domestic animals, but some protected species like the peacock (Pavo cristatus,), hard shelled turtle (Kachuga tentoria), sambhar (Cervus unicolor) were also mentioned as medicinal resources. We would suggest that this kind of neglected traditional knowledge should be included into the strategies of conservation and management of faunistic resources. Further studies are required for experimental validation to confirm the presence of bioactive compounds in these traditional remedies and also to emphasize more sustainable use of these resources.     

A novel factor XI missense mutation (Val371Ile) in the activation loop is responsible for a case of mild type II factor XI deficiency

Coagulation factor XI (FXI) is the zymogen of a serine protease that, when converted to its active form, contributes to blood coagulation through proteolytic activation of factor IX. FXI deficiency is typically an autosomal recessive disorder, characterized by bleeding symptoms mainly associated with injury or surgery. Of the more than 100 FXI gene mutations reported in FXI-deficient patients, most are associated with a proportional decrease in FXI functional and immunologic levels (type I defects), whereas only a few mutations leading to the presence of dysfunctional molecules in plasma have been molecularly analyzed to date (type II deficiencies). We report the functional and molecular characterization of a missense mutation (Val371Ile) identified, in the heterozygous state, in a 25-year-old Italian male with mild FXI deficiency. Laboratory analysis revealed reduced functional FXI levels (34%), but normal antigen levels (102%), distinctive of a type II defect. Given the proximity of Val371 to the FXI activation site, a possible interference with zymogen activation was postulated. Expression experiments of the FXI-Val371Ile recombinant protein, followed by activation assays, showed both a different time course in FXI activation and a slight delay in factor IX activation by thrombin-activated FXI.     

National mass drug administration costs for lymphatic filariasis elimination

Background

Because lymphatic filariasis (LF) elimination efforts are hampered by a dearth of economic information about the cost of mass drug administration (MDA) programs (using either albendazole with diethylcarbamazine [DEC] or albendazole with ivermectin), a multicenter study was undertaken to determine the costs of MDA programs to interrupt transmission of infection with LF. Such results are particularly important because LF programs have the necessary diagnostic and treatment tools to eliminate the disease as a public health problem globally, and already by 2006, the Global Programme to Eliminate LF had initiated treatment programs covering over 400 million of the 1.3 billion people at risk.

Methodology/Principal Findings

To obtain annual costs to carry out the MDA strategy, researchers from seven countries developed and followed a common cost analysis protocol designed to estimate 1) the total annual cost of the LF program, 2) the average cost per person treated, and 3) the relative contributions of the endemic countries and the external partners. Costs per person treated ranged from $0.06 to $2.23. Principal reasons for the variation were 1) the age (newness) of the MDA program, 2) the use of volunteers, and 3) the size of the population treated. Substantial contributions by governments were documented – generally 60%–90% of program operation costs, excluding costs of donated medications.

Conclusions/Significance

MDA for LF elimination is comparatively inexpensive in relation to most other public health programs. Governments and communities make the predominant financial contributions to actual MDA implementation, not counting the cost of the drugs themselves. The results highlight the impact of the use of volunteers on program costs and provide specific cost data for 7 different countries that can be used as a basis both for modifying current programs and for developing new ones.     

Urine profiling by SELDI-TOF/MS: monitoring of the critical steps in sample collection, handling and analysis

The topic of this study is the impact of several pre-analytical and analytical variables on proteomic profiling of human urine by surface enhanced laser desorption/ionization time of flight-mass spectrometry (SELDI-TOF-MS) in healthy subjects. Urine storage at room temperature caused a progressive degradation of proteins, which was prevented by the addition of protease inhibitors only up to 2 h from the collection. The timing of collection over the day had only a minor impact on protein profile, although influencing the intensity of peaks. Repeated freeze/thaw cycles (up to five) did not affect either the number or the intensity of the peaks. A comparison of the protein profile from eight different healthy individuals showed fairly consistent inter-subject similarities, along with between-subject differences, which were markedly dependent on the sex and the type of ProteinChip array used. The addition of a variety of denaturing agents improved the quality of the spectra with all the chips tested (CM10, Q10 and H50), but not with the copper-coated IMAC-30 chip. Finally, SPA matrix allowed to achieve a better performance of SELDI-TOF/MS spectrum, as compared with CHCA, regardless of the ProteinChip array used and even in the low m/z range (2500-10,000). In conclusion, we suggest that a careful choice of a number of pre-analytical and analytical conditions is required to accomplish and define a unifying protocol for the analysis of human urine by SELDI-TOF/MS, in physiological and in pathological states.