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Background: Oral anticoagulant therapy (OAT) with a vitamin K antagonist (VKA) is the choice of treatment for preventing thromboembolism in patients with mechanical heart valve prosthesis (MHP). The percentage of time in the therapeutic range (TTR%) expresses the OAT quality. We planned a case-control study in order to determine vitamin K1 plasmatic concentrations in MHP patients and to correlate these with TTR%. Materials and Methods: Of 756 MHP patients receiving OAT, 125 patients (61 younger than 65 years, and 64 older than 65 years) and 120 healthy blood donors, matched for sex and age, were enrolled in the study. All subjects completed a living questionnaire regarding diet, and underwent blood collection. Vegetable and fruit intake was categorized as optimal or suboptimal, and the high-performance liquid chromatography method was used to determine vitamin K1 levels. Results: Neither the patients nor controls had been taking vitamin supplements prior to the start of the study. The median vitamin K1 level was 290 pg/L in 72 controls with optimal intake, and 274 pg/L in 48 controls with suboptimal intake, while the median vitamin K1 level in MHP patients with optimal intake was 409 pg/L, significantly higher ( p < 0.001) than the 133.5 pg/L in patients with suboptimal intake. Vitamin K1 concentration in MHP patients appears to be linked to an age-related threshold: in patients younger than 65 years of age, the median vitamin K1 level was 431 pg/L, significantly higher ( p < 0.05) than the 290 pg/L in patients older than 65 years of age. No clear relation was found between vitamin K1 levels and TTR% (Pearson = 0.14). However, patients with vitamin K1 >160 pg/L showed a TTR% >60 %. Among patients younger than 65 years, subjects with vitamin K1 >160 pg/L showed a median TTR of 66 %, this being significantly higher ( p < 0.001) than the 46 % level shown by patients with vitamin K1 <160 pg/L. Conclusions: Vitamin K1 concentrations in MHP patients seem to be related to both diet and age. [ABSTRACT FROM AUTHOR]

Throughout the manuscript the units of plasma vitamin K1 concentration which previously read [ABSTRACT FROM AUTHOR]

Background: LRRK2 mutations are common in familial and sporadic Parkinson's disease (PD) cases., Objective: We present a screening of the most frequently mutated exons of LRRK2 in Calabrian population., Methods: Eighty-eight PD patients diagnosed according to standard criteria, underwent screening for LRRK2 mutations in exons 19, 21, 24, 25, 27, 29, 31, 32, 33, 35, 38, 40, 41, and 48., Results: Eight LRRK2 variations were identified in nine patients affected by PD, including three novel missense variations (p.Phe1227Leu, p.Gly1520Ala, p.Ile2020Ser) and five previously identified mutations (p.Ala1151Thr, IVS31+3A>G, p.Arg1514Gln, p.Gly2019Ser, p.Thr2356Ile). LRRK2 frequency mutations were approximately 10.2% in all PD patients, 12% in familial, 8% in sporadic cases. The p.Gly2019Ser mutation was found in 2.3% of the total cohort and in 3.2% of sporadic cases. The clinical features of LRRK2-associated with PD in our patients were similar to those of idiopathic PD although most LRRK2 mutated patients presented with bradykinesia instead of tremor; 33.3% developed dementia., Conclusions: We identified three novel LRRK2 mutations and reported a higher frequency in Calabria compared to previously reported data possibly due to the relative genetic isolation of the Calabrian population. These findings contribute to the understanding of the role of LRKK2 variations in PD and provide additional genetic insight into this disease.

The gene encoding the inducible form of Nitric Oxide Synthase (NOS2A) has been considered with interest in the evaluation of the genetic predisposition to Multiple Sclerosis (MS). The aim of the present study was to address the possible contribution of two microsatellites repeats of the NOS2A promoter region - (CCTTT)(n) and (AAAT)(n) - to MS susceptibility. One hundred and thirteen Italian patients with clinically definite RRMS and 237 age and sex matched healthy controls from Calabria (South Italy) were studied. The distribution analysis of the markers frequencies showed that the (CCTTT)(14) allele was found in 11.5% of the RRMS patients and in 25.3% of the healthy subjects, with a statistically significant difference (chi(2)=8.843, p=0.003). This data seems to confer a significant protection against MS (OR=0.348; 95% CI=0.174-0.693, corrected for age and gender). No association with MS susceptibility was observed for the bi-allelic (AAAT)(n) microsatellite. In conclusion, we found that the NOS2A (CCTTT)(14) allele was detected more frequently in the control group than in the RRMS patients, thus confirming the scientific interest on this marker.

Lymphocyte and monocyte brain infiltration determines inflammation in multiple sclerosis. The trafficking of these cells into the CNS results from the VLA-4 binding with its ligand on brain endothelial cells. MS patients treated with an antibody against the alpha-4 subunit, which inhibits this interaction, prevents brain lesion development. We investigated the association between VLA-4 gene polymorphisms and MS in a study on 275 patients and 255 controls. No differences were detected, thus suggesting that these polymorphisms are not a significant genetic risk factor for susceptibility to MS in Italy.