DNA methylation is an epigenetic modification critical to normal genome regulation and development. The vitamin folate is a key source of the one carbon group used to methylate DNA. Because normal mammalian development is dependent on DNA methylation, there is enormous interest in assessing the potential for changes in folate intake to modulate DNA methylation both as a biomarker for folate status and as a mechanistic link to developmental disorders and chronic diseases including cancer. This review highlights the role of DNA methylation in normal genome function, how it can be altered, and the evidence of the role of folate/folic acid in these processes.
Periconceptional intake of folic acid is known to reduce a woman’s risk of having an infant affected by a neural tube birth defect (NTD). National programs to mandate fortification of food with folic acid have reduced the prevalence of NTDs worldwide. Uncertainty surrounding possible unintended consequences has led to concerns about higher folic acid intake and food fortification programs. This uncertainty emphasizes the need to continually monitor fortification programs for accurate measures of their effect and the ability to address concerns as they arise. This review highlights the history, effect, concerns, and future directions of folic acid food fortification programs.
Objective To determine an optimal population red blood cell (RBC) folate concentration for the prevention of neural tube birth defects. Design Bayesian model. Setting Data from two population based studies in China.Participants 247 831 participants in a prospective community intervention project in China (1993-95) to prevent neural tube defects with 400 μg/day folic acid supplementation and 1194 participants in a population based randomized trial to evaluate the effect of folic acid supplementation on blood folate concentration among Chinese women of reproductive age.
Background— In the United States and Canada, folic acid fortification of enriched grain products was fully implemented by 1998. The resulting population-wide reduction in blood homocysteine concentrations might be expected to reduce stroke mortality if high homocysteine levels are an independent risk factor for stroke. Methods and Results— In this population-based cohort study with quasi-experimental intervention, we used segmented log-linear regression to evaluate trends in stroke-related mortality before and after folic acid fortification in the United States and Canada and, as a comparison, during the same period in England and Wales, where fortification is not required. Average blood folate concentrations increased and homocysteine concentrations decreased in the United States after fortification. The ongoing decline in stroke mortality observed in the United States between 1990 and 1997 accelerated in 1998 to 2002 in nearly all population strata, with an overall change from −0.3% (95% CI, −0.7 to 0.08) to −2.9 (95% CI, −3.5 to −2.3) per year ( P =0.0005). Sensitivity analyses indicate that changes in other major recognized risk factors are unlikely to account for the reduced number of stroke-related deaths in the United States. The fall in stroke mortality in Canada averaged −1.0% (95% CI, −1.4 to −0.6) per year from 1990 to 1997 and accelerated to −5.4% (95% CI, −6.0 to −4.7) per year in 1998 to 2002 ( P ≤0.0001). In contrast, the decline in stroke mortality in England and Wales did not change significantly between 1990 and 2002. Conclusions— The improvement in stroke mortality observed after folic acid fortification in the United States and Canada but not in England and Wales is consistent with the hypothesis that folic acid fortification helps to reduce deaths from stroke.
The NHANES has monitored folate status of the U.S. population from prefortification (1988-1994) to postfortification (1999-2010) by measuring serum and RBC folate concentrations. The Bio-Rad radioassay (BR) was used from 1988 to 2006, and the microbiologic assay (MBA) was used from 2007 to 2010. The MBA produces higher concentrations than the BR and is considered to be more accurate. Thus, to bridge assay differences and to examine folate trends over time, we adjusted the BR results to be comparable to the MBA results. Postfortification, assay-adjusted serum and RBC folate concentrations were 2.5 times and 1.5 times prefortification concentrations, respectively, and showed a significant linear trend (P < 0.001) to slightly lower concentrations during 1999-2010. The postfortification prevalence of low serum (<10 nmol/L) or RBC (<340 nmol/L) folate concentrations was ≤ 1%, regardless of demographic subgroup, compared with 24% for serum folate and 3.5% for RBC folate prefortification, with substantial variation among demographic subgroups. The central 95% reference intervals for serum and RBC folate varied by demographic subgroup during both pre- and postfortification periods. Age and dietary supplement use had the greatest effects on prevalence estimates of low folate concentrations during the prefortification period. In summary, the MBA-equivalent blood folate concentrations in the U.S. population showed first a sharp increase from pre- to postfortification, then showed a slight decrease (17% for serum and 12% for RBC folate) during the 12-y postfortification period. The MBA-equivalent pre- and postfortification reference concentrations will inform countries that plan folic acid fortification or that need to evaluate its impact.
The west European subspecies of house mouse (Mus musculus domesticus) has gained much of its current widespread distribution through commensalism with humans. This means that the phylogeography of M. m. domesticus should reflect patterns of human movements. We studied restriction fragment length polymorphism (RFLP) and DNA sequence variations in mouse mitochondrial (mt) DNA throughout the British Isles (328 mice from 105 localities, including previously published data). There is a major mtDNA lineage revealed by both RFLP and sequence analyses, which is restricted to the northern and western peripheries of the British Isles, and also occurs in Norway. This distribution of the 'Orkney' lineage fits well with the sphere of influence of the Norwegian Vikings and was probably generated through inadvertent transport by them. To form viable populations, house mice would have required large human settlements such as the Norwegian Vikings founded. The other parts of the British Isles (essentially most of mainland Britain) are characterized by house mice with different mtDNA sequences, some of which are also found in Germany, and which probably reflect both Iron Age movements of people and mice and earlier development of large human settlements. MtDNA studies on house mice have the potential to reveal novel aspects of human history.
The daily and within-day variation in udder temperature was monitored in dairy cows (n = 10) using infrared thermography (IRT). The initial assessment and prediction of udder surface temperature variation would hopefully form the basis for future development of an early detection method for mastitis. Our initial objective was to determine the magnitude and pattern of udder temperature variation. To accomplish this, we measured daily fluctuations in udder temperature and the influence of environmental factors upon these values in non-mastitic cows. Udder temperature rose significantly after an exercise period (P < 0.05). Withinday monitoring of udder temperature demonstrated there was a distinct circadian rhythm. Lag regression analysis showed that previous daily udder temperatures together with environmental temperature parameters could successfully predict current udder temperature with a high degree of accuracy. The variation between predicted and actual udder temperature was within the detectable range for an inflammatory response. Infrared thermography shows promise in its application if coupled with environmental temperature monitoring as an early detection method for mastitis.Key words: Thermography, dairy cattle, environment, temperature Berry, R. J., Kennedy, A. D., Scott, S. L., Kyle, B. L. et Schaefer, A. L. 2003. Détermination de la variation quotidienne de la température à la surface du pis des vaches laitières par thermographie infrarouge : utilité potentielle pour le dépistage de la mammite. Can. J. Anim. Sci. 83: 687-693. Les auteurs ont examiné la variation quotidienne et intra-quotidienne de la température du pis des vaches laitières (n = 10) par thermographie infrarouge (TI). En effet, une première évaluation et la prévision subséquente de la température à la surface du pis pourraient aboutir à l'élaboration d'une technique de dépistage précoce de la mammite. L'objectif initial consistait à établir l'ampleur d'une telle variation et ses particularités. Pour cela, les auteurs ont mesuré les fluctuations quotidiennes de la température du pis et l'influence de divers facteurs environnementaux chez des vaches ne souffrant pas de la mammite. La température du pis grimpe sensiblement (P < 0,05) après une période d'activité. Dans la journée, elle suit un rythme nettement circadien. L'analyse de régression avec retard indique qu'on pourrait utiliser la température du jour antérieur et les paramètres de la température ambiante pour prévoir la température courante avec une grande précision. L'écart entre la température prévue du pis et la température réelle est assez faible pour qu'on détecte une inflammation. La TI est une technique prometteuse pour le dépistage précoce de la mammite si on la combine à la surveillance des paramètres de la température ambiante.
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