Prevalence of pharmacogenomic variants affecting the efficacy of clopidogrel therapy in the Hispanic Community Health Study/Study of Latinos cohort

Purpose: Although clopidogrel is the most widely used oral P2Y12 receptor antagonist, up to 10% of acute coronary syndrome patients treated with clopidogrel will experience a recurrent myocardial infarction and 2-3% will experience stent thrombosis within 1 year. The purpose of this research is to describe the prevalence of pharmacogene variants associated with clopidogrel responsiveness (CYP2C19, B4GALT2, ABCB1, PON1, CES1 and P2RY12) in Hispanic/Latino patients of diverse backgrounds. Methods: Minor allele frequencies of nine variants from participants of Hispanic Community Health Study/Study of Latinos were compared between subpopulations as well as to continental ancestry references using z-test for independent proportions. Results: MAFs for six out of nine variants differed between Caribbean and Mainland subpopulations (p < 0.05). Compared with European reference group, MAFs of ABCB1, CES1 and PON1 were higher in Hispanic Community Health Study/Study of Latinos, whereas B4GALT2 and CYP2C19∗2 and ∗17 were lower. Conclusion: Significant differences in the prevalence of most pharmacogenomic variants related to clopidogrel response provide a foundation to better inform ongoing and future clinical studies of clopidogrel pharmacogenetics in the US Hispanic/Latino populations

Conservative treatment of idiopathic scoliosis according to FITS concept: presentation of the method and preliminary, short term radiological and clinical results based on SOSORT and SRS criteria

<p>Abstract</p> <p>Background</p> <p>Conservative scoliosis therapy according to the FITS Concept is applied as a unique treatment or in combination with corrective bracing. The aim of the study was to present author's method of diagnosis and therapy for idiopathic scoliosis FITS-Functional Individual Therapy of Scoliosis and to analyze the early results of FITS therapy in a series of consecutive patients.</p> <p>Methods</p> <p>The analysis comprised separately: (1) single structural thoracic, thoracolumbar or lumbar curves and (2) double structural scoliosis-thoracic and thoracolumbar or lumbar curves. The Cobb angle and Risser sign were analyzed at the initial stage and at the 2.8-year follow-up. The percentage of patients improved (defined as decrease of Cobb angle of more than 5 degrees), stable (+/- 5 degrees), and progressed (increase of Cobb angle of more than 5 degrees) was calculated. The clinical assessment comprised: the Angle of Trunk Rotation (ATR) initial and follow-up value, the plumb line imbalance, the scapulae level and the distance from the apical spinous process of the primary curve to the plumb line.</p> <p>Results</p> <p>In the Group A: (1) in single structural scoliosis 50,0% of patients improved, 46,2% were stable and 3,8% progressed, while (2) in double scoliosis 50,0% of patients improved, 30,8% were stable and 19,2% progressed. In the Group B: (1) in single scoliosis 20,0% of patients improved, 80,0% were stable, no patient progressed, while (2) in double scoliosis 28,1% of patients improved, 46,9% were stable and 25,0% progressed.</p> <p>Conclusion</p> <p>Best results were obtained in 10-25 degrees scoliosis which is a good indication to start therapy before more structural changes within the spine establish.</p

Physical therapy intervention studies on idiopathic scoliosis-review with the focus on inclusion criteria1

<p>Abstract</p> <p>Background</p> <p>Studies investigating the outcome of conservative scoliosis treatment differ widely with respect to the inclusion criteria used. This study has been performed to investigate the possibility to find useful inclusion criteria for future prospective studies on physiotherapy (PT).</p> <p>Materials and methods</p> <p>A PubMed search for outcome papers on PT was performed in order to detect study designs and inclusion criteria used.</p> <p>Results</p> <p>Real outcome papers (start of treatment in immature samples/end results after the end of growth; controlled studies in adults with scoliosis with a follow-up of more than 5 years) have not been found. Some papers investigated mid-term effects of exercises, most were retrospective, few prospective and many included patient samples with questionable treatment indications.</p> <p>Conclusion</p> <p>There is no outcome paper on PT in scoliosis with a patient sample at risk for being progressive in adults or in adolescents followed from premenarchial status until skeletal maturity. However, papers on bracing are more frequently found and bracing can be regarded as evidence-based in the conservative management and rehabilitation of idiopathic scoliosis in adolescents.</p

Anti-angiogenic effect of high doses of ascorbic acid

Pharmaceutical doses of ascorbic acid (AA, vitamin C, or its salts) have been reported to exert anticancer activity in vitro and in vivo. One proposed mechanism involves direct cytotoxicity mediated by accumulation of ascorbic acid radicals and hydrogen peroxide in the extracellular environment of tumor cells. However, therapeutic effects have been reported at concentrations insufficient to induce direct tumor cell death. We hypothesized that AA may exert anti-angiogenic effects. To test this, we expanded endothelial progenitor cells (EPCs) from peripheral blood and assessed, whether or not high dose AA would inhibit EPC ability to migrate, change energy metabolism, and tube formation ability. We also evaluated the effects of high dose AA on angiogenic activities of HUVECs (human umbilical vein endothelial cells) and HUAECs (human umbilical arterial endothelial cells). According to our data, concentrations of AA higher than 100 mg/dl suppressed capillary-like tube formation on Matrigel for all cells tested and the effect was more pronounced for progenitor cells in comparison with mature cells. Co-culture of differentiated endothelial cells with progenitor cells showed that there was incorporation of EPCs in vessels formed by HUVECs and HUAECs. Cell migration was assessed using an in vitro wound healing model. The results of these experiments showed an inverse correlation between AA concentrations relative to both cell migration and gap filling capacity. Suppression of NO (nitric oxide) generation appeared to be one of the mechanisms by which AA mediated angiostatic effects. This study supports further investigation into non-cytotoxic antitumor activities of AA

Grotte des Perrats (Agris, Charente)

87 pagesRapport de fouille programmée pluriannuelle, rapport intermédiaire 200

Hispanic adults with type 2 diabetes mellitus using lipid-lowering agents have better periodontal health than non-users

Background: Recent studies suggest that lipid-lowering agents (LLA) may reduce chronic periodontitis, but it is unknown whether this benefit extends to people with type 2 diabetes (T2D). Objective: We assessed the association between LLA use and periodontitis in Hispanic adults with T2D. Design: This was a cross-sectional observational study. Methods: We assessed the association of LLA use and periodontal parameters in 253 Puerto Ricans 40–65 years with T2D who participated in the Lipid-Lowering agents use in Periodontitis and Diabetes Study study. Participants were classified as (a) none- or 4 years. The primary outcome consists of a tertile percent of sites with probing pocket depth (PPD) ⩾ 4 mm and the secondary outcome includes tertiles of percent sites with clinical attachment loss (CAL) ⩾ 4 mm. Multinomial logistic regression models adjusted for age, gender, smoking status, education, waist circumference, glycosylated hemoglobin A1C (HbA1c), bleeding on probing, examiner, and anti-inflammatory agents were used to estimate the association. Results: LLA (92.5%, statins) was used by 52% of participants. LLA use 1–4 years was associated with lower odds of PPD ⩾ 4 mm (OR: 0.22, p   =  0.005; high versus low tertile) or lower odds of CAL ⩾ 4 mm (OR: 0.33, p   =  0.02, middle versus low tertile), compared to those with LLA minimal or no use. This association was lost for participants who used LLA for >4 years. LLA users for >4 years with periodontal disease had elevated HbA1c (OR: 1.36, p   =  0.05). Conclusion: The use of LLA for 1–4 years was associated with lower values of periodontal parameters versus minimal LLA use. This association was not present among people using LLA > 4 years users, but these participants had poorer glycemic control compared to other participants. In this cross-sectional study, the finding that LLA use 1- 4 years is associated with lower values of periodontal parameters of severity in T2D individuals may help clarify some of the controversies regarding the benefit of these medications in this population

LANFEX: A field and modeling study to improve our understanding and forecasting of radiation fog

Fog is a high-impact weather phenomenon affecting human activity, including aviation, transport, and health. Its prediction is a longstanding issue for weather forecast models. The success of a forecast depends on complex interactions among various meteorological and topographical parameters; even very small changes in some of these can determine the difference between thick fog and good visibility. This makes prediction of fog one of the most challenging goals for numerical weather prediction. The Local and Nonlocal Fog Experiment (LANFEX) is an attempt to improve our understanding of radiation fog formation through a combined field and numerical study. The 18-month field trial was deployed in the United Kingdom with an extensive range of equipment, including some novel measurements (e.g., dew measurement and thermal imaging). In a hilly area we instrumented flux towers in four adjacent valleys to observe the evolution of similar, but crucially different, meteorological conditions at the different sites. We correlated these with the formation and evolution of fog. The results indicate new quantitative insight into the subtle turbulent conditions required for the formation of radiation fog within a stable boundary layer. Modeling studies have also been conducted, concentrating on high-resolution forecast models and research models from 1.5-km to 100-m resolution. Early results show that models with a resolution of around 100 m are capable of reproducing the local-scale variability that can lead to the onset and development of radiation fog, and also have identified deficiencies in aerosol activation, turbulence, and cloud micro- and macrophysics, in model parameterizations

A Novel Admixture-Based Pharmacogenetic Approach to Refine Warfarin Dosing in Caribbean Hispanics.

AIM:This study is aimed at developing a novel admixture-adjusted pharmacogenomic approach to individually refine warfarin dosing in Caribbean Hispanic patients. PATIENTS & METHODS:A multiple linear regression analysis of effective warfarin doses versus relevant genotypes, admixture, clinical and demographic factors was performed in 255 patients and further validated externally in another cohort of 55 individuals. RESULTS:The admixture-adjusted, genotype-guided warfarin dosing refinement algorithm developed in Caribbean Hispanics showed better predictability (R2 = 0.70, MAE = 0.72mg/day) than a clinical algorithm that excluded genotypes and admixture (R2 = 0.60, MAE = 0.99mg/day), and outperformed two prior pharmacogenetic algorithms in predicting effective dose in this population. For patients at the highest risk of adverse events, 45.5% of the dose predictions using the developed pharmacogenetic model resulted in ideal dose as compared with only 29% when using the clinical non-genetic algorithm (p<0.001). The admixture-driven pharmacogenetic algorithm predicted 58% of warfarin dose variance when externally validated in 55 individuals from an independent validation cohort (MAE = 0.89 mg/day, 24% mean bias). CONCLUSIONS:Results supported our rationale to incorporate individual's genotypes and unique admixture metrics into pharmacogenetic refinement models in order to increase predictability when expanding them to admixed populations like Caribbean Hispanics. TRIAL REGISTRATION:ClinicalTrials.gov NCT01318057