Loss of ovarian hormones increases salt-sensitivity in normotensive women

Salt sensitivity (SS) is associated with an elevated risk of developing hypertension(HTN) and is an independent risk factor for cardiovascular (CV) morbidity and mortality. Cross-sectional studies have suggested that postmenopausal women are more salt sensitive than premenopausal women. The purpose of the present study was to investigate prospectively the prevalence of SS among healthy premenopausal women and determine whether the loss of ovarian hormones increases SS.

Role of gene methylation in antitumor immune response: Implication for tumor progression

Cancer immunosurveillance theory has emphasized the role of escape mechanisms in tumor growth. In this respect, a very important factor is the molecular characterization of the mechanisms by which tumor cells evade immune recognition and destruction. Among the many escape mechanisms identified, alterations in classical and non-classical HLA (Human Leucocyte Antigens) class I and class II expression by tumor cells are of particular interest. In addition to the importance of HLA molecules, tumor-associated antigens and accessory/co-stimulatory molecules are also involved in immune recognition. The loss of HLA class I antigen expression and of co-stimulatory molecules can occur at genetic, transcriptional and post-transcriptional levels. Epigenetic defects are involved in at least some mechanisms that preclude mounting a successful host-antitumor response involving the HLA system, tumor-associated antigens, and accessory/co-stimulatory molecules. This review summarizes our current understanding of the role of methylation in the regulation of molecules involved in the tumor immune response.

Malnutrition prevalence in hospitalized elderly diabetic patients.

Background & aims: Malnutrition prevalence is unknown among elderly patients with diabetes mellitus. Our objectives were to determine malnutrition prevalence in elderly in patients with diabetes, and to describe their impact on prognosis. Methods: An observational multicenter study was conducted in 35 Spanish hospitals. Malnutrition was assessed with the Mini Nutritional Assessment (MNA) tool. Patients were followed until discharge. Results: 1,090 subjects were included (78 ± 7.1 years; 50% males). 39.1% had risk of malnutrition, and 21.2% malnutrition. A 15.5% of the malnourished subjects and 31.9 % of those at risk had a BMI =?30 kg/m2. In multivariate analysis, female gender (OR = 1.38; 95% CI: 1.19- 1.11), age (OR = 1.04; 95% CI: 1.02-1.06) and presence of diabetic complications (OR = 1.97; 95% CI: 1.52-2.56) were associated with malnutrition. Length of stay (LOS) was longer in at-risk and malnourished patients than in well-nourished (12.7 ± 9.9 and 15.7 ± 12.8 days vs 10.7 ± 9.9 days; p < 0.0001). After adjustment by age and gender, MNA score (OR = 0.895; 95% CI 0.814-0.985) and albumin (OR = 0.441; 95% CI 0.212-0.915) were associated with mortality. MNA score was associated with the probability of home discharge (OR = 1.150; 95% CI 1.084-1.219). Conclusion: A high prevalence of malnutrition among elderly in patients with diabetes was observed, regardless of BMI. Malnutrition, albumin, and MNA score were related to LOS, mortality and home discharge.

Fine mapping and functional analysis of the multiple sclerosis risk gene CD6.

CD6 has recently been identified and validated as risk gene for multiple sclerosis (MS), based on the association of a single nucleotide polymorphism (SNP), rs17824933, located in intron 1. CD6 is a cell surface scavenger receptor involved in T-cell activation and proliferation, as well as in thymocyte differentiation. In this study, we performed a haptag SNP screen of the CD6 gene locus using a total of thirteen tagging SNPs, of which three were non-synonymous SNPs, and replicated the recently reported GWAS SNP rs650258 in a Spanish-Basque collection of 814 controls and 823 cases. Validation of the six most strongly associated SNPs was performed in an independent collection of 2265 MS patients and 2600 healthy controls. We identified association of haplotypes composed of two non-synonymous SNPs [rs11230563 (R225W) and rs2074225 (A257V)] in the 2(nd) SRCR domain with susceptibility to MS (P max(T) permutation = 1×10(-4)). The effect of these haplotypes on CD6 surface expression and cytokine secretion was also tested. The analysis showed significantly different CD6 expression patterns in the distinct cell subsets, i.e. - CD4(+) naïve cells, P = 0.0001; CD8(+) naïve cells, P<0.0001; CD4(+) and CD8(+) central memory cells, P = 0.01 and 0.05, respectively; and natural killer T (NKT) cells, P = 0.02; with the protective haplotype (RA) showing higher expression of CD6. However, no significant changes were observed in natural killer (NK) cells, effector memory and terminally differentiated effector memory T cells. Our findings reveal that this new MS-associated CD6 risk haplotype significantly modifies expression of CD6 on CD4(+) and CD8(+) T cells.