Association of leukocyte DNA methylation changes with dietary folate and alcohol intake in the EPIC study.

BACKGROUND: There is increasing evidence that folate, an important component of one-carbon metabolism, modulates the epigenome. Alcohol, which can disrupt folate absorption, is also known to affect the epigenome. We investigated the association of dietary folate and alcohol intake on leukocyte DNA methylation levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Leukocyte genome-wide DNA methylation profiles on approximately 450,000 CpG sites were acquired with Illumina HumanMethylation 450K BeadChip measured among 450 women control participants of a case-control study on breast cancer nested within the EPIC cohort. After data preprocessing using surrogate variable analysis to reduce systematic variation, associations of DNA methylation with dietary folate and alcohol intake, assessed with dietary questionnaires, were investigated using CpG site-specific linear models. Specific regions of the methylome were explored using differentially methylated region (DMR) analysis and fused lasso (FL) regressions. The DMR analysis combined results from the feature-specific analysis for a specific chromosome and using distances between features as weights whereas FL regression combined two penalties to encourage sparsity of single features and the difference between two consecutive features. RESULTS: After correction for multiple testing, intake of dietary folate was not associated with methylation level at any DNA methylation site, while weak associations were observed between alcohol intake and methylation level at CpG sites cg03199996 and cg07382687, with qval = 0.029 and qval = 0.048, respectively. Interestingly, the DMR analysis revealed a total of 24 and 90 regions associated with dietary folate and alcohol, respectively. For alcohol intake, 6 of the 15 most significant DMRs were identified through FL. CONCLUSIONS: Alcohol intake was associated with methylation levels at two CpG sites. Evidence from DMR and FL analyses indicated that dietary folate and alcohol intake may be associated with genomic regions with tumor suppressor activity such as the GSDMD and HOXA5 genes. These results were in line with the hypothesis that epigenetic mechanisms play a role in the association between folate and alcohol, although further studies are warranted to clarify the importance of these mechanisms in cancer.

Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort.

Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1 = 1.26; 95% CI 1.00-1.58; Ptrend = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1 = 1.29; 95% CI 1.02-1.62; Ptrend = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.

[Adenosine deaminase is useful for the diagnosis of peritoneal tuberculosis in patients with end-stage renal failure]. / Le dosage d'adénosine déaminase est utile pour le diagnostic de tuberculose péritonéale chez le patient dialysé

INTRODUCTION: End-stage renal failure patients are particularly at risk for tuberculosis, especially for peritoneal tuberculosis. Microbiological diagnosis remains hazardous in many cases. CASE REPORT: We report on a case of peritoneal tuberculosis in an end-stage renal failure patient. The diagnosis was suspected on the basis of adenosine deaminase dosage in peritoneal fluid, allowing an early presumptive treatment and a favourable outcome with a 3 years follow-up. DISCUSSION: The measurement of adenosine deaminase activity in ascites represents a diagnostic advance in tuberculous peritonitis among end-stage renal failure patients.

Long-term persistence of the spatial organization of temperature fluctuation lifetime in turbulent air avalanches.

It has been recently proposed that some natural phenomena, such as sunspot occurrence, can be represented by a modulated Markov jitter, which is a high-frequency Markov signal multiplied by a long-term component. The two parameters of this model can be estimated using a nonlinear method based on absolute derivatives. This analysis is applied here to a different physical system: the temperature time series measured during air avalanches in the vertical access pit of an underground quarry. The thermal fluctuations associated with these turbulent flows, driven by the external temperature forcing, actually appear as another practical realization of a modulated Markov jitter. One parameter of the model provides the lifetime of the temperature fluctuations, which can be estimated as a function of time and position. The obtained lifetime is of the order of 10 to 25 min , and is remarkably constant in time for each sensor, independently of the amplitude of the forcing. Furthermore, a significant and persistent spatial structure is observed, revealing a long-term intrinsic organization of the turbulent air flows in the pit. Such a stable spatial organization may reflect a general feature of turbulent phenomena.

Dynamics of air avalanches in the access pit of an underground quarry.

Temperature measurements have been performed in the vertical access pit of an underground quarry. During autumn, air avalanches induce an initial thermal feedback and a stationary mixing state characterized by spatially coherent broad-band fluctuations with a standard deviation of about 0.2 degrees C, linearly increasing with the inside-minus-outside temperature difference. Phase changes of water are shown to contribute to the onset condition, the feedback, and the stationary mixing state. This experiment may give insight on turbulent thermal and compositional convection with nonadiabatic boundaries.

[Blood levels of homocysteine by high pressure liquid chromatography and comparison with two other techniques]. / Dosage de l'homocysteéine plasmatique par chromatographie liquide haute performance et comparaison à deux autres techniques.

Cardio-vascular diseases are the most common cause of death in industrialized countries. A new marker has emerged among offending risk factors in the past few years: homocysteine. This sulphured amino-acid is an important intermediate in transsulphuration and remethylation reactions of methionine's metabolism. We proposed to evaluate a home made method of determination for this parameter by high performance liquid chromatography (HPLC) and to compare it to fluorescence polarization immunoassay technique (FPIA) and to gaz phase chromatography (CG-SM). This method associated with good sensibility and precision remain much less expensive than FPIA technique.

[In vitro activity of six beta-lactams against 295 strains of enterobacteriaceae and P. aeruginosa isolated from neutropenic patients]. / Activité in vitro de six beta-lactamines vis-à-vis de 295 souches d'entérobactéries et P. aeruginosa isolées chez des patients neutropéniques.

The in vitro activity of two new beta-lactam agents, cefpirome (CPO) and cefepime (FEP), was investigated against 295 Gram-negative bacilli (250 enterobacteriaceae and 45 P. aeruginosa) isolated from neutropenic patients. They were compared with ceftazidime (CAZ), piperacillin-tazobactam (TZP), imipenem (IPM) and cefotaxime (CTX). All enterobacteriacae were susceptible to IPM, 16 strains were intermediately susceptible or resistant to CAZ (1 strain of E. coli, 4 of Morganella morganii and 11 of Enterobacter. The 250 strains of enterobacteriacea were susceptible to FEP (MIC < 1 mg/l) and only one strain among them was intermediately susceptible to CPO. Among 45 strains of P. aeruginosa, 21 strains were susceptible to CPO, 30 to FEP, 31 to TZP, 32 to CAZ and 34 to IPM. All the strains were inhibited by less than 32 mg/l of FEP and IPM.

[Evaluation of soluble bacterial antigens detected by electrosyneresis in infectious diseases in children]. / Evaluation de la recherche d'antigènes bactériens solubles par électrosynérèse en pathologie infectieuse de l'enfant.

The diagnostic interest of the search for soluble bacterial antigens, using counter-current immunoelectrophoresis (CIE) has been evaluated in 109 children hospitalized with acute infection. In meningitis, CIE was well correlated with cerebrospinal fluid (CSF) culture and allowed a rapid diagnostic orientation in 82% of meningitis which were confirmed by classical bacteriology (CIE has to be performed using CSF and concentrated urine). False positive results were observed with type B meningococcus, especially on urine samples. In respiratory infections, the search for soluble antigens was of no interest except for focal pneumonitis; in that case, CIE was more frequently positive (35%) than blood culture (28%) and led to a 31% increase of correct diagnosis (CIE must be performed using concentrated urine). Serum and pleural fluid investigations were less sensitive. CIE was not useful in case of upper respiratory or nonfocal broncho-pulmonary infection, due to its very low efficiency.

[Detection of peripheral diabetic neuropathy. A reappraisal of electrophysiological data]. / Dépistage des neuropathies diabétiques périphériques. Réévaluation des paramètres électrophysiologiques.

In addition to motor and sensory nerve conduction, monosynaptic triceps surae reflex, amplitude of median nerve voltage and response of extensor digitorum brevis and soleus muscles were investigated in 29 diabetic patients. These parameters were altered earlier than motor and sensory nerve conduction, which considerably increased the incidence of subclinical peripheral neuropathy (90% of the patients). It was also found that sensory fibers were affected earlier than motor fibers. The electrically detected neuropathy correlated with duration of diabetes and control of glycaemia.

[Results of a cooperative study of bromazepam involving 3.401 ambulatory psychiatric patients and 8.191 patients from general practice (author's transl)]. / Bilan de l'étude coopérative du bromazépam portant sur 3.401 observations de psychiatrie ambulatoire et 8.191 observations de médecine praticienne.

The value of this study lies in the large number of patients treated by general practitioners who accepted to follow a very strict protocol. Statistical analysis of the results was performed with the help of a computer. This is probably the first time that an anxiolytic drug is investigated in that way. A fairly accurate clinical profile of the anxious patient could be drawn from a total of 11.592 cases, including distribution by sex and age, characteristics of the anxiety and symptoms by which it is expressed or accompanied, evaluation of the symptoms by the patients themselves, and nosological context. The results recorded confirm the quality of the anxiolytic effects of bromazepam in all forms of anxiety, with the additional benefit of relief from anxiety-induced inhibitions. Precise information was obtained concerning the optimal dosage and duration of treatment and the incidence of untoward reactions.