Cross-calibration of a combined electrostatic and time-of-flight analyzer for energy- and charge-state-resolved spectrometry of tin laser-produced plasma.

We present the results of the calibration of a channeltron-based electrostatic analyzer operating in time-of-flight mode (ESA-ToF) using tin ions resulting from laser-produced plasma, over a wide range of charge states and energies. Specifically, the channeltron electron multiplier detection efficiency and the spectrometer resolution are calibrated, and count rate effects are characterized. With the obtained overall response function, the ESA-ToF is shown to accurately reproduce charge-integrated measurements separately and simultaneously obtained from a Faraday cup (FC), up to a constant factor the finding of which enables absolute cross-calibration of the ESA-ToF using the FC as an absolute benchmark. Absolute charge-state-resolved ion energy distributions are obtained from ns-pulse Nd:YAG-laser-produced microdroplet tin plasmas in a setting relevant for state-of-the-art extreme ultraviolet nanolithography.

Implementation of a multilevel, multicomponent intervention for obesity control in Native American communities (OPREVENT2): challenges and lessons learned.

OPREVENT2 was a multilevel, multicomponent (MLMC) adult obesity prevention that sought to improve access and demand for healthier food and physical activity opportunities in six Native American communities in the Southwest and Midwest. OPREVENT2 worked with worksites, food stores, schools (grades 2-6), through social media and mailings, and with a local community action committee (CAC), in each of the three intervention communities, and was implemented in six phases. We conducted a process evaluation to assess implementation of each intervention component in terms of reach, dose delivered and fidelity. Implementation of each component was classified as high, medium or low according to set standards, and reported back at the end of each phase, allowing for improvements. The school and worksite components were implemented with high reach, dose delivered and fidelity, with improvement over time. The school program had only moderate reach and dose delivered, as did the social media component. The CAC achieved high reach and dose delivered. Overall, study reach and dose delivered reached a high implementation level, whereas fidelity was medium. Great challenges exist in the consistent implementation of MLMC interventions. The detailed process evaluation of the OPREVENT2 trial allowed us to carefully assess the relative strengths and limitations of each intervention component.

[Organophosphorus poisoning: Towards enzymatic treatments]. / Intoxication aux organophosphorés : vers des traitements enzymatiques.

Organophosphorus compounds (OP) are toxic molecules developed as insecticides and chemical warfare nerve agents (CWNAs). Most OP are neurotoxic and act as nervous system disruptors by blocking cholinergic transmission. They are therefore responsible for many poisonings worldwide. OP toxicity may result either from acute or chronic exposure, and their poisoning effect were evaluated using several animal models. These latter were also used for evaluating the efficacy of antidotes. Strategies based on enzymes that can trap (stoichiometric bioscavengers) or degrade (catalytic bioscavengers) OP, were particularly studied since they allow effective decontamination, without toxicity or environmental impact. This review summarizes the results obtained in vivo with enzymes through three levels: prophylaxis, treatment and external decontamination. The efficiency of enzymatic treatments in different animal models is presented and the relevance of these models is also discussed for a better extrapolation to humans.

Implementation of B'More Healthy Communities for Kids: process evaluation of a multi-level, multi-component obesity prevention intervention.

B'More Healthy Communities for Kids was a multi-level, multi-component obesity prevention intervention to improve access, demand and consumption of healthier foods and beverages in 28 low-income neighborhoods in Baltimore City, MD. Process evaluation assesses the implementation of an intervention and monitor progress. To the best of our knowledge, little detailed process data from multi-level obesity prevention trials have been published. Implementation of each intervention component (wholesaler, recreation center, carryout restaurant, corner store, policy and social media/text messaging) was classified as high, medium or low according to set standards. The wholesaler component achieved high implementation for reach, dose delivered and fidelity. Recreation center and carryout restaurant components achieved medium reach, dose delivered and fidelity. Corner stores achieved medium reach and dose delivered and high fidelity. The policy component achieved high reach and medium dose delivered and fidelity. Social media/text messaging achieved medium reach and high dose delivered and fidelity. Overall, study reach and dose delivered achieved a high implementation level, whereas fidelity achieved a medium level. Varying levels of implementation may have balanced the performance of an intervention component for each process evaluation construct. This detailed process evaluation of the B'More Healthy Communities for Kids allowed the assessment of implementation successes, failures and challenges of each intervention component.

[Decontamination of organophosphorus compounds: Towards new alternatives]. / La décontamination des organophosphorés : vers de nouvelles alternatives.

Organophosphorus coumpounds (OP) are toxic chemicals mainly used for agricultural purpose such as insecticides and were also developed and used as warfare nerve agents. OP are inhibitors of acetylcholinesterase, a key enzyme involved in the regulation of the central nervous system. Chemical, physical and biological approaches have been considered to decontaminate OP. This review summarizes the current and emerging strategies that are investigated to tackle this issue with a special emphasis on enzymatic remediation methods. During the last decade, many studies have been dedicated to the development of biocatalysts for OP removal. Among these, recent reports have pointed out the promising enzyme SsoPox isolated from the archaea Sulfolobus solfataricus. Considering both its intrinsic stability and activity, this hyperthermostable enzyme is highly appealing for the decontamination of OP.

Thyroid endocrine status of wild European eels (Anguilla anguilla) in the Loire (France). Relationships with organic contaminant body burdens.

In teleost fish, thyroid function is involved in various critical physiological processes. Given the complexity of the hypothalamo-pituitary-thyroid (HPT) axis, a large number of genes and proteins can be the potential target of endocrine-disrupting compounds (EDCs). The aim of this study was to evaluate, in yellow and silver European eels (Anguilla anguilla), potential effects of EDCs on thyroid status by analyzing the associations between EDC body burdens and thyroid hormones (THs). In yellow individuals, greater free T3/T4 ratios (FT3/FT4) and lower plasma FT4 levels were associated with greater concentrations of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), as highlighted by significant correlations with many congeners. Few positive relationships with alkylphenols were noticed. In contrast, silver eels usually exhibited less significant correlations between THs and contaminant loads. Expression of a series of genes involved in the HPT axis was also investigated in the silver individuals. Concerning mRNA expression in silver females, some main correlations were noticed: thyroid-stimulating hormone (TSHß) gene expression was significantly correlated to numerous PCBs, and hepatic mRNA levels of deiodinase 2 (Deio 2) were negatively correlated to 2-hydroxyfluorene (2-OHF) and 2-naphtol (2-OHNa). Thyroid receptor (TRα and TRß) mRNA levels exhibited weak negative correlations with some PBDEs in silver females and males. Hepatic vitellogenin (Vtg) mRNA levels were detected in all silver males but at lower levels than in silver females. In males, Vtg mRNA levels were positively associated to FT4/TT4. In silver females, strong positive correlations were found between congeners of PCBs, PBDEs and PFAS suggesting potential estrogenic effects. Overall, the observed results indicate that several organic contaminants, mainly dl-, ndl-PCBs and PBDEs, could be associated with changes in thyroid homeostasis in these fish, via direct or indirect interactions with peripheral deiodination, metabolism of T4 and mechanisms involved in TSHß, Deio 2 and Vtg gene transcription.

Occurrence of POPs and other persistent organic contaminants in the European eel (Anguilla anguilla) from the Loire estuary, France.

The chemical contamination of the Loire estuary by three classes of persistent organic pollutants (POPs): the polychlorinated biphenyls (PCBs), the polybrominated diphenyl ethers (PBDEs) and the perfluorinated and polyfluorinated alkyl substances (PFAS), and three families of organic contaminants, the alkylphenols (APs), the polycyclic aromatic hydrocarbon metabolites (OH-PAHs) and the bisphenol A (BPA) were investigated in the muscles and bile of European eel (Anguilla anguilla). Yellow eels (n=30) were caught in three different points along the estuary to highlight variations between sites and sources of contaminations. Silver eels (n=15) were also studied to compare contaminant impregnation between different life stages of the species. Average concentrations in the muscles of the eel ranged between: 857 and 4358 ng/gLW for the PCBs, 26 and 46 ng/gLW for the PBDEs, 130 and 1293 ng/gLW for the PFAS; and in bile: 31 and 286 µg/g protein for the APs, 9 and 26 µg/g protein for the OH-PAHs and ND-1213 µg/g protein for the BPA. Among PCBs, PCB 153 (40% contribution to the sum of PCBs) was predominant in all eel muscles. PBDE 47 (60%) was the most predominant PBDE congeners, while perfluorooctanesulfonic acid (85%) was the most widely detected PFAS. For APs, 4p-nonylphenol (91%) was the most abundant and for the OH-PAHs, it was 1OH-Pyrene (63%). All the eels exceeded the environmental quality standards (EQS) for biota for the PBDEs and about 75% were higher than the EQS specific to PFOS. Finally, 20% of the analyzed eels presented TEQ concentrations above the maximum limits for lipid-rich species. These results supplied new data on the occurrence, levels, and patterns of 53 organic chemicals in the eels from the Loire estuary and they highlighted the need of further investigations focused notably on the potential effects of these chemicals on this species and their analysis in the water and sediments of the estuary.

Dioxin-like, non-dioxin like PCB and PCDD/F contamination in European eel (Anguilla anguilla) from the Loire estuarine continuum: spatial and biological variabilities.

To characterize the eel contamination by dioxin-like (dl) and non dioxin-like (ndl) polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), sixty-two eels from the Loire estuary (France) were analyzed. PCB contamination significantly increased from glass eel stage (3.71 ± 1.85 and 15.2 ± 4.2 ng g(-1) dw) to other life stages (for yellow eels: 62.8 ± 34.4 and 382 ± 182 ng g(-1) dw; for silver eels: 93.7 ± 56.3 and 463 ± 245 ng g(-1) dw respectively for dl and ndl-PCBs). An inter-site variability based on PCB levels and profiles was observed among the three studied sites. For glass eels, the profile was mainly characterized by less chlorinated PCBs contrary to the other eels, displaying a different bioaccumulation pathway. Overall, the contamination level in the eels from this estuary was shown to be low for PCDD/Fs and intermediate for dl and ndl-PCBs, compared to other international/national areas. However, more than 60% of the studied silver eels displayed higher values for PCDD/F and dl-PCB WHO2005 TEQ than the EU permissible level of 10 pg g(-1) ww. This statement suggests a potential exposure to PCBs through eel consumption, especially with silver eels, and also points out apparent contamination that could eventually affect the reproductive success of the species.

Hypertension management in patients with renal cell cancer treated with anti-angiogenic agents.

Inhibitors of the vascular endothelial growth factor (vegf-is) signalling pathway have fundamentally changed the treatment of metastatic renal cell carcinoma (mrcc). Hypertension is one of the most common side effects of vegf-is and has been reported with almost every vegf-i used for treatment to date. The exact mechanism of vegf-i-induced hypertension appears complex and multifactorial, and it remains to be fully explained. No randomized clinical trials are available to guide the management of hypertension during vegf-i treatment in mrcc patients. The guiding principles suggested here summarize the consensus of opinions on the diagnosis and management of vegf-i-induced hypertension during treatment of mrcc obtained from an expert working group composed of 4 Canadian medical oncologists and 5 Canadian hypertension specialists. The Canadian Hypertension Education Program guidelines, available literature, and expert opinion were used to develop the guiding principles.

Poster - Thur Eve - 38: Review of couch parameters using an FMEA.

To improve patient safety during positioning, we undertook a systematic review of the processes used by our center to obtain couch positions. We used a Failure Mode and Effects Analysis (FMEA) framework and fifteen different possible failures were identified and rated. The three major failures were 1) Loss of planned couch position and bias from the previous day's couch position, 2) DICOM origin or isocenter is different between two plans (imaging or treatment), and 3) Patient shift in opposite direction than intended. The main effect of these failures was to cause an override of couch parameters. Based on these results, we modified our processes, introduced new QA and software checks and developed new tolerance tables so as to improve system robustness and increase our success rate at catching failures before they can affect the patient. It has been a year since we made these modifications. Based on our results, we have reduced the number of overrides at our center from a maximum of 20.5% to a maximum of 6.3%, with an average at 4% of daily treatments. Our results suggest that FMEA is an effective tool in improving treatment quality that could be used in other centers.

[Knowledge transfer and implementation of clinical practice guidelines. Experience of the Canadian Hypertension Education Program]. / Le transfert des connaissances et la mise en oeuvre de lignes directrices de pratique Expérience du Programme d'Education Canadien sur l'Hypertension.

For the last 10 years, the update of guidelines for the treatment of hypertension in Canada is part of an annual process. This national strategy called the Canadian Hypertension Education Program (CHEP) has an organizational structure which allows not only to revise guidelines using an evidence-based scientific process but also to facilitate the implementation and the dissemination of the recommendations to the various healthcare professionals (doctors, pharmacists, nurses, etc.). As part of this process, the CHEP is also measuring different outcomes which could estimate the impact of its interventions. Recent data clearly show an improvement of the screening of hypertension as well as the quality of antihypertensive treatment (increase in the number of new prescriptions and of the percentage of subjects treated with 2 antihypertensive agents or more) in Canada. Finally, recent Canadian data showing a reduction of the cardiovascular complications attributable to hypertension suggest a possible link of causality with the implementation of the CHEP. This article will describe the functioning of the CHEP with its various strategies aiming at a better management of hypertension in Canada.

Age-related effects of methionine-enriched diet on plasma homocysteine concentration and methylation of hepatic DNA in rats.

In the present study we determined the age-related effect of methionine-enriched diet, a model of hyperhomocysteinemia, on the level of plasma homocysteine and hepatic global DNA methylation in rats. Feeding methionine diet to middle-aged rats for only 14 days resulted in a significant increase in plasma homocysteine level and DNA hypomethylation. In contrast, feeding the methionine-containing diet for 2 weeks to juvenile or post-pubertal animals did not alter the level of plasma homocysteine or hepatic DNA methylation. Supplementation of the methionine-enriched diet with vitamins B6, B12 and folic acid prevented both hepatic DNA hypomethylation and an increase of plasma homocysteine concentration in the middle-aged rats. These findings indicate that the elevated level of plasma homocysteine may be indicative of much broader and deeper alterations in intracellular methylation dysfunction, and suggest that dietary enrichment with B-vitamins is essential for the metabolism of homocysteine, especially in adult animals.

Development and evaluation of a PCR method for detection of the Clostridium difficile toxin B gene in stool specimens.

A PCR assay detecting Clostridium difficile toxin B gene in stool specimens was compared to the cytotoxicity assay as the reference standard for the diagnosis of C. difficile antibiotic-associated diarrhea (CDAD). Overall, 118 stool samples were tested. All of the specimens that were negative by the cytotoxicity assay (59 out of 118) were also negative by the PCR method (specificity of 100%). Of the 59 cytotoxin-positive samples, 54 were PCR positive (sensitivity of 91.5%). This PCR method is promising for rapid diagnosis of CDAD.

Anomalous dispersion and superluminal group velocity in a coaxial photonic crystal: theory and experiment.

We demonstrate that coaxial cables with a periodic impedance exhibit dispersion properties specific to photonic crystals, albeit on a much lower frequency scale. Highly superluminal (>2c) pulse propagation is observed near the photonic band gap at 10 MHz. The influence of group velocity dispersion and crystal length on the traveling speed and shape of a Gaussian pulse are discussed. Results compare favorably with a simple multilayer theory and a coupled-mass model of the structure.

Yield of smear, culture and amplification tests from repeated sputum induction for the diagnosis of pulmonary tuberculosis.

OBJECTIVES: To assess the yield of repeated sputum induction for the diagnosis of active tuberculosis in patients who do not produce spontaneous sputum, or with smear-negative spontaneous samples. METHODS: Induced sputum was examined with fluorescent microscopy, two amplification methods (PCR Amplicor MTB, and MTD2), and cultured for mycobacteria using liquid (Bactec 12B) and Lowenstein-Jensen media. Bronchoscopy and collection of other specimens were performed at the discretion of the treating physician. RESULTS: A total of 1115 sputum inductions performed in 500 patients without adverse events yielded an adequate specimen in 1113 (99.8%), and microbiological confirmation in 43 of 44 (98%) culture-positive active TB cases. Yield increased with repeated sputum induction. The cumulative yield for acid-fast bacilli smear and mycobacterial culture was 64% and 70% respectively for one, 81% and 91% for two, 91% and 99% for three, and 98% and 100% for four induced samples. Yield of PCR also increased with the greater number of induced samples tested. CONCLUSIONS: Repeated sputum induction could considerably improve diagnostic accuracy for pulmonary TB.

Blood S-adenosylmethionine concentrations and lymphocyte methylenetetrahydrofolate reductase activity in diabetes mellitus and diabetic nephropathy.

The erythrocyte concentrations of the body's chief physiologic methyl donor S-adenosylmethionine (SAM) and of its metabolite and inhibitor S-adenosylhomocysteine (SAH), the plasma concentrations of total homocysteine (tHcy), and the activity of N(5,10) methylenetetrahydrofolate reductase (MTHFR) in lymphocytes were determined in healthy subjects and patients with diabetes mellitus without complications and at various stages of diabetic nephropathy, categorized according to the degree of progression of the disease. These groups were as follows: 1, control; 2, diabetics with no complications; 3, patients with albuminuria; 4, patients with an elevated plasma creatinine; and 5, patients on dialysis. No parameter studied exhibited significant differences between the type 1 and the type 2 diabetics. In control subjects, the blood concentrations of SAM were proportional to the activity of MTHFR; in diabetics, it was not. Consistent with previous observations, progression of nephropathy was accompanied by increased concentrations of tHcy. Increased erythrocyte concentrations of SAH, decreased erythrocyte concentrations of SAM, SAM/SAH ratios, and lymphocyte MTHFR activity also accompanied disease progression. The blood concentrations of SAH paralleled those of tHcy, while the concentrations of SAM showed a bimodal relationship with those of tHcy. These results provide further evidence that alterations in the blood concentrations of SAM and related compounds are abnormal in patients with diabetes, particularly in those with nephropathy. The deficiency of SAM may lead to methyl deficiencies, which may contribute to the high morbidity and mortality in patients with diabetic nephropathy. We have also demonstrated a decrease in lymphocyte MTHFR activity in patients with advanced nephropathy, suggesting that hyperhomocysteinemia in these patients may be due to a generalized metabolic abnormality. Further studies are needed to determine the pathogenesis of these abnormalities and whether they are present in renal failure due to causes other than diabetes or whether they are specific to diabetic nephropathy.

Effects of nebivolol and atenolol on insulin sensitivity and haemodynamics in hypertensive patients.

OBJECTIVES: To compare the effects of nebivolol and atenolol in 25 ambulatory hypertensive patients with impaired glucose tolerance. DESIGN: Clinic and ambulatory blood pressure, insulin sensitivity (euglycemic-hyperinsulinemic clamp), glucose tolerance (intravenous glucose tolerance test), systemic and regional haemodynamics were measured after 4 weeks of placebo and after each 16-week treatment period in a double-blind, crossover fashion. RESULTS: Nebivolol and atenolol similarly reduced (P< 0.001) clinic and ambulatory blood pressure by approximately 15/10 mmHg, systolic and diastolic. Clinic and ambulatory heart rate was reduced to a greater extent (P < 0.01) by atenolol than nebivolol. Atenolol was associated with an approximately 20% reduction in insulin sensitivity (insulin-induced glucose disposal rate/mean insulin concentration ratio, P < 0.01) and an approximately 10% reduction in glucose disappearance rate (K-value, P < 0.05), whereas these variables were not significantly modified with nebivolol. Cardiac output was reduced similarly (P < 0.05) by both drugs at rest but forearm blood flow, forearm vascular resistance or total peripheral resistance were unaffected. A significant inverse correlation coefficient between cardiac output and insulin sensitivity was found at baseline, suggesting that a compensatory increase in systemic blood flow occurs in hypertensive patients with progressively more marked insulin resistance. This relationship was unaffected by nebivolol but was lost with atenolol. CONCLUSIONS: These results indicate that insulin sensitivity was not modified significantly by nebivolol, whereas it was reduced by atenolol, although blood pressure was decreased to the same extent by both drugs. Neither drug induced systemic or forearm vasodilatation but the inverse relationship between cardiac output and insulin sensitivity was preserved with nebivolol but not with atenolol.

Increasing levels of dietary homocystine with carotid endarterectomy produced proportionate increases in plasma homocysteine and intimal hyperplasia.

PURPOSE: The role that homocysteine may play in post-carotid endarterectomy (CEA) restenosis due to intimal hyperplasia is not well understood. This study was designed to investigate the effects of different levels of dietary homocystine on: (1) plasma homocysteine; (2) post-CEA intimal hyperplasia; and (3) levels of the methyl donor S-adenosylmethionine (SAM) and its counterpart S-adenosylhomocysteine (SAH) in the homocysteine pathway. METHODS: Male rats were fed specialized diets for 2 weeks pre- and post-CEA. Groups included control (0 homocystine added, n=9), 1.5 (1.5 g/kg homocystine added, n=10), 3.0 (3.0 g/kg homocystine added, n=9), and 4.5 (4.5 g/kg homocystine added, n=11). The rats underwent a surgical carotid endarterectomy. Endpoints included; plasma homocysteine, intimal hyperplasia, replicative index using with alpha-SM actin and BrdU, hepatic SAM levels, SAH levels, and the hepatic activities of methylenetetrahydrofolate reductase (MTHFR) and cystathionine beta-synthase (CBS). RESULTS: Increasing dietary homocystine produced a proportionate increase in plasma homocysteine and an increase in intimal hyperplasia. Regression analysis of plasma homocysteine levels and intimal hyperplasia showed a significant correlation (r=0.71,P=0.003). Plasma homocysteine levels above 15 microM were associated with significant increases in intimal hyperplasia above 6.5% (P=0.04). Elevation of plasma homocysteine levels to moderate levels (5-25 microM) resulted in significant post-CEA intimal hyperplasia. Cellular analysis of the area of intimal hyperplasia in all diet groups showed comparable amounts of cells positive for alpha-SM actin. However, with increasing levels of dietary homocystine and plasma homocysteine there was an increase in replicative index (P<0.001) as determined by BrdU staining. Increasing dietary homocystine increased plasma homocysteine and was followed by increases in the replicative index thus producing increased intimal hyperplasia and lumenal stenosis. In hepatic measurements the 1.5 and 3.0 g/kg homocystine diets caused: increased liver activity of MTHFR (P=0.03) and decreased hepatic levels of SAM, SAH and SAM/SAH ratios compared to controls. Homocystine treatment did not cause significant alterations in CBS levels (P=0.992). These studies also showed no correlation of the MTHFR and CBS enzymes with plasma homocysteine levels or intimal hyperplasia. However, hepatic levels of SAM showed significant negative correlations with plasma homocysteine (r=-0.58; P=0.006) and with BrdU percentages of cellular proliferation (r=-0.69; P=0.06). CONCLUSION: The degree of post-CEA intimal hyperplasia in a rat model is directly related to the plasma level of homocysteine. The hyperplastic effects of homocysteine may be mediated in part by a physiological insufficiency of methyl donors as shown by decreases in SAM. Thus, increasing levels of plasma homocysteine enhanced and accelerated the smooth muscle cell response after CEA which led to increased intimal hyperplasia and lumenal stenosis.

Blood determinations of S-adenosylmethionine, S-adenosylhomocysteine, and homocysteine: correlations with diet.

An increasing number of both clinical and experimental studies have shown an association between deficiencies of the dietary sources of physiological methyl groups and cancer formation. The critical metabolic intermediate in a determination of methylation status is S-adenosylmethionine (SAM), the body's chief physiological methyl donor. The present study examined the erythrocyte levels of SAM and of its demethylated metabolite S-adenosylhomocysteine (SAH) in 66 normal subjects (33 men and 33 women), whose blood had been drawn at days 0, 7 and 14 of an experimental period during which they were fed a fixed diet. The plasma levels of homocysteine (HCys) were also determined in the same individuals at the same time points. In addition, the subjects had completed a food frequency questionnaire (FFQ) describing their usual dietary habits before being placed on the dietary regimen. The blood levels of SAM, SAH, and HCys were compared with the dietary intakes of folate, vitamin B(6), fats, and calories, both prior to using the FFQ and during the experimental period. The results indicated that the intraindividual differences were very low, but the interindividual differences were large for the values of SAM, SAH, SAM:SAH ratios, and HCys. Interestingly, the blood levels of SAM and HCys were higher in men than in women and generally showed the expected correlations with folate intake i.e., positive for SAM and negative for HCys. The intakes of folate (276 microg/days) and B(6) (1.87 mg/days) during the 2-week experimental period were relatively low compared with the usual intakes of these vitamins (375 and 2.06 mg/day for folate and B(6), respectively) but correlated well with each other during both periods of the study. Surprisingly, both men and women showed a significant rise in erythrocyte SAM:SAH ratios as a function of age. In addition, the combined results from men and women, even adjusted for gender, showed significant correlations between HCys and both weight and body mass index. On the other hand, during the experimental period of the study, blood SAM levels were inversely correlated with the intakes of both fat and calories when the data for both men and women were combined and adjusted for gender. The blood determinations of SAM and related compounds showed a high degree of reproducibility over time and thus appear to provide a practical marker of methylation status for the assessment of cancer risk from dietary, environmental, and genetic factors.