Insulin and glycolysis dependency of cardioprotection by nicotinamide riboside.

Decreased nicotinamide adenine dinucleotide (NAD+) levels contribute to various pathologies such as ageing, diabetes, heart failure and ischemia-reperfusion injury (IRI). Nicotinamide riboside (NR) has emerged as a promising therapeutic NAD+ precursor due to efficient NAD+ elevation and was recently shown to be the only agent able to reduce cardiac IRI in models employing clinically relevant anesthesia. However, through which metabolic pathway(s) NR mediates IRI protection remains unknown. Furthermore, the influence of insulin, a known modulator of cardioprotective efficacy, on the protective effects of NR has not been investigated. Here, we used the isolated mouse heart allowing cardiac metabolic control to investigate: (1) whether NR can protect the isolated heart against IRI, (2) the metabolic pathways underlying NR-mediated protection, and (3) whether insulin abrogates NR protection. NR protection against cardiac IRI and effects on metabolic pathways employing metabolomics for determination of changes in metabolic intermediates, and 13C-glucose fluxomics for determination of metabolic pathway activities (glycolysis, pentose phosphate pathway (PPP) and mitochondrial/tricarboxylic acid cycle (TCA cycle) activities), were examined in isolated C57BL/6N mouse hearts perfused with either (a) glucose + fatty acids (FA) ("mild glycolysis group"), (b) lactate + pyruvate + FA ("no glycolysis group"), or (c) glucose + FA + insulin ("high glycolysis group"). NR increased cardiac NAD+ in all three metabolic groups. In glucose + FA perfused hearts, NR reduced IR injury, increased glycolytic intermediate phosphoenolpyruvate (PEP), TCA intermediate succinate and PPP intermediates ribose-5P (R5P) / sedoheptulose-7P (S7P), and was associated with activated glycolysis, without changes in TCA cycle or PPP activities. In the "no glycolysis" hearts, NR protection was lost, whereas NR still increased S7P. In the insulin hearts, glycolysis was largely accelerated, and NR protection abrogated. NR still increased PPP intermediates, with now high 13C-labeling of S7P, but NR was unable to increase metabolic pathway activities, including glycolysis. Protection by NR against IRI is only present in hearts with low glycolysis, and is associated with activation of glycolysis. When activation of glycolysis was prevented, through either examining "no glycolysis" hearts or "high glycolysis" hearts, NR protection was abolished. The data suggest that NR's acute cardioprotective effects are mediated through glycolysis activation and are lost in the presence of insulin because of already elevated glycolysis.

Survey of selected pathogens in free-ranging pinnipeds in Uruguay.

Marine mammals, regarded as sentinels of aquatic ecosystem health, are exposed to different pathogens and parasites under natural conditions. We surveyed live South American fur seals Arctocephalus australis and South American sea lions Otaria flavescens in Uruguay for Leptospira spp., canine distemper virus (CDV), Mycobacterium spp., Toxoplasma gondii, and Neospora caninum. Samples were collected from 2007 to 2013. The seroprevalence of Leptospira spp. was 37.6% positive, 50.9% negative, and 11.5% suspect for A. australis (n = 61) while for O. flavescens (n = 12) it was 67% positive, 25% negative, and 8% suspect. CDV RNA was not detected in any of the analyzed samples. Most animals tested seropositive to tuberculosis antigens by WiZo ELISA (A. australis: 29/30; O. flavescens: 20/20); reactivity varied with a novel ELISA test (antigens MPB70, MPB83, ESAT6 and MPB59). Seroprevalence against N. caninum and T. gondii was 6.7 and 13.3% positive for O. flavescens and 0 and 2.2% positive for A. australis respectively. To evaluate possible sources of infection for pinnipeds, wild rats Rattus rattus and semi-feral cats Felis catus were also tested for Leptospira spp. and T. gondii respectively. Water samples tested for Leptospira revealed saprofitic L. bioflexa. Pathogenic Leptospira were detected in the kidneys of 2 rats, and cats tested positive for T. gondii (100%). These results represent a substantial contribution to the study of the health status of wild pinnipeds in Uruguay.

Are low and high utilization related to the way GPs manage their practices? An observational study.

BACKGROUND: General practice care plays a key role in keeping healthcare effective and cost-efficient. However, variation in the utilization rates of practices may reveal variation in practice performance. Our research goal is to investigate whether the socio-demographic profile of the patients' area of residence and practice organization characteristics influence the low or high utilization of general practice care. METHODS: Data on the utilization of general practice care were derived from the electronic health records of 232 general practices participating in the NIVEL Primary Care Database for the year 2013. Census data for the year 2013 were matched with the postal code of the patients. A small area estimation (SAE) technique was used to calculate the estimated utilization rate for general practice care per practice based on the socio-demographic profile of the patients' area of residence. Subsequently, the actual utilization rates were compared to the estimated rates per practice. Linear regression analysis was used to link the differences between the actual and estimated utilization rates to practice organization characteristics. RESULTS: The socio-demographic profile of the patients' area of residence accounted for 25.7% of the estimated utilization rates per practice. Practice organization characteristics accounted for 19.3% of the difference between the actual utilization rates and the estimated rates. Practices had higher utilization rates than estimated when a practice was a dual practice, when it employed female GPs, when it employed other healthcare providers and/or when it offered more services related to a disease management programme. CONCLUSION: We found that utilization rates of general practice care can be partially explained by the socio-demographic profile of the patients' area of residence, but also by practice organization characteristics. Insight into these factors provides both GPs and the other stakeholders involved in the organization of general practice care with information to help reflect on the utilization of care.

Innovation in dental education: The "On-the-Fly" approach to simultaneous development, implementation and evidence collection.

INTRODUCTION: This study outlines an approach for education innovation and addresses the ambivalence between evidence-based and non-evidence-based conditions. The "on-the-fly" approach was described as involving implementation during the development of an innovation for dental education. MATERIALS AND METHODS: The process of designing and implementing cutting-edge technology of the MOOG Simodont Dental Trainer (DT) whilst systematically collecting evidence illustrates the "on-the-fly" approach. RESULTS: Using the "on-the-fly" approach for developing, implementing and collecting evidence simultaneously in an academic environment appears feasible in serving both the professionals, users and developers and system designers. During the implementation of the new technology, growing evidence stepwise strengthened its position; therefore, showing stakeholders that evidence was used to improve the technology seemed to support and increase acceptance of the new technology. CONCLUSIONS: When pioneering an innovative technology in a specialty field, the development stage often precedes evidence for its effectiveness. Consciously choosing the "on-the-fly" approach clarifies to stakeholders in advance about the lack of evidence in an innovation and the need of their support to collect such evidence for improvement and in order to facilitate implementation.

Effect of students' determination of testing time on their test performance.

This article investigates whether giving students control over preparing for and the moment of taking a test affects their test results in comparison with when the school is in control of the amount of training followed by a predetermined test moment. The students participated in training for manual dexterity. After the training, the students performed a test. The results of the test were stored in a database. Students from the group with freedom to select the moment of the test performed much better than those in the other group who did not have the freedom to select the moment for the test, with significantly fewer students requiring three attempts to pass the test. The fact that students when given the responsibility to develop manual skills performed better than when guided by the policy of the school is hopeful in the sense that students can learn in an early stage of their study to take responsibility for learning.

Collaboration of general practitioners and exercise providers in promotion of physical activity a written survey among general practitioners.

BACKGROUND: General practitioners have an ideal position to motivate inactive patients to increase their physical activity. Most patients are able to exercise in regular local facilities outside the health care setting. The purpose of this study was to get insight into general practitioners perceptions and current practices regarding referral of patients to local exercise facilities. Furthermore, collaboration with exercise providers in the community was investigated, and motivators and barriers for referral. METHODS: A written questionnaire sent to a representative random sample of 800 Dutch general practitioners. Descriptive statistics and Chi(2) tests were used. RESULTS: All responding general practitioners (340) recommend their patients to take more exercise when necessary and 87 % say to refer patients sometimes. Limited motivation of the patient (44 %) and reduced health status (34 %) are the most mentioned barriers for advising patients to increase physical activity. When referred, most patients are send to a physical therapist (69 %) but also local exercise facilities were mentioned (54 %). The most important barrier for referring patients to local exercise activities are patients limited financial possibilities (46 %). Restricted knowledge of local exercise- or sport facilities was an additional barrier (19 %). There is little structural collaboration between general practitioners and exercise providers, but when collaboration exists general practitioners refer more often. Positive experiences of patients (67 %), affordable offers (59 %) and information of local exercise facilities (46 %) are seen as important promoting factors for referral. Although 32 % of the general practitioners think that good collaboration would be stimulating, regular meetings with sports and exercise providers were considered the least important for increasing referral (3 %). CONCLUSIONS: Dutch physicians have a positive attitude towards stimulating physical activity but referral to local exercise facilities is low. Referral is partly hindered by restricted knowledge of local exercise facilities. Although general practitioners think that collaboration is important for physical activity promotion, it should not cost them much extra time. A coordinator with knowledge of the local situation can facilitate contacts between GP practices and sports providers.

Short- and long-term effects of real-time medication monitoring with short message service (SMS) reminders for missed doses on the refill adherence of people with Type 2 diabetes: evidence from a randomized controlled trial.

AIMS: To investigate short- and long-term effects of real-time monitoring medication use combined with short message service (SMS) reminders for missed doses on refill adherence to oral anti-diabetic medication. METHODS: A randomized controlled trial with two intervention groups and one control group involving 161 participants with Type 2 diabetes with suboptimal adherence. For 6 months, participants in the SMS group (n = 56) were monitored and received SMS reminders if they missed their medication. Participants in the non-SMS group (n = 48) were only monitored. The control group (n = 57) was not exposed to any intervention. Primary outcome measure was refill adherence to oral anti-diabetic medication. Multi-level regression analyses were performed to examine intervention effects on adherence between and within groups after 1 and 2 years of follow-up. RESULTS: At baseline, mean refill adherence was comparable between the groups. After 1 year, adherence in the SMS group was significantly higher than in the control group (79.5% vs. 64.5%; P < 0.001) and showed a significant improvement from baseline (+16.3%; P < 0.001). Mean adherence in the non-SMS group reached 73.1% (+7.3%; P < 0.05), but did not differ from the control group (P = 0.06). After 2 years, the improved adherence in the SMS group persisted and remained significantly higher than in the control group (80.4% vs. 68.4%; P < .01), contrary to the non-SMS group whose adherence approached baseline level again (65.5%). CONCLUSIONS: This study shows the long-term effectiveness of real-time medication monitoring combined with SMS reminders in improving refill adherence. This new reminder system can strengthen the self-management of people with diabetes.

Low risk of late intracranial complications in mild traumatic brain injury patients using oral anticoagulation after an initial normal brain computed tomography scan: education instead of hospitalization.

BACKGROUND AND PURPOSE: Mild traumatic brain injury (mTBI) is a common neurological disorder. Whether oral anticoagulation (OAC) use is a risk factor for secondary deterioration in mTBI patients after a normal computed tomography (CT) scan is unclear. Therefore data were retrospectively collected on patients with mTBI who used OAC to determine the incidence of secondary clinical deterioration after an initial normal head CT scan. METHODS: This was a retrospective single-centre patient record study. All patients with an mTBI who presented at the emergency department between January 2007 and October 2011 were selected. Inclusion criteria were mTBI and at least 1 week of OAC use resulting in an international normalized radio > 1.1. CT scans were re-evaluated for this study. RESULTS: A total of 211 mTBI patients using OAC and with an initial CT scan without abnormalities were included in the analysis. In five patients a secondary deterioration was found. One patient developed a subdural hematoma after 15 h of clinical observation. The other four patients became symptomatic between 2 and 28 days after trauma. CONCLUSIONS: A low risk of secondary deterioration within 24 h in mTBI patients taking OAC with a normal first head CT scan was found. Our study does not support the recommendation of the current guidelines that these patients should be clinically observed for at least 24 h. The fact that in our series the majority of secondary deteriorations occurred between 2 and 28 days after trauma underscores the importance of patient instructions upon discharge from the hospital.

Dietetic treatment lowers body mass index in overweight patients: an observational study in primary health care.

BACKGROUND: Greater insight into the effectiveness of usual dietetic care will contribute to the ongoing development of dietetic services. The present study examined the change in body mass index (BMI) in overweight patients after dietetic treatment in primary care, the sources of variability and factors associated with BMI change. METHODS: This population-based observational study was based on data from a Dutch registration network of dietitians in primary health care. Data were derived from electronic medical records concerning 3960 overweight adult patients (BMI ≥ 25 kg m⁻²) who received usual care from 32 registered dietitians between 2006 and 2012. Multilevel linear regression analyses were conducted. RESULTS: Patients' BMI significantly (P < 0.001) decreased by 0.94 kg m⁻² on average during treatment. An additional reduction of 0.8 kg m⁻² was observed in patients treated for longer than 6 months. BMI decreased by 0.06 kg m⁻² for each additional unit in initial BMI above 31.6. Most (97%) variability in BMI change was attributed to patients and 3% to dietitians. Part of the variance between patients (11%) and dietitians (30%) was explained by patient sociodemographic characteristics, nutrition-related health aspects, initial body weight and treatment duration. CONCLUSIONS: Dietetic treatment in primary care lowers BMI in overweight patients. Patients' change in BMI was rather similar between dietitians. Greater BMI reductions were observed in those with a high initial BMI and those treated for at least 6 months. Future research is necessary to study the long-term effects of weight loss after treatment by primary healthcare dietitians, especially because many patients drop out of treatment prematurely.

Lazy sunday afternoons: the negative impact of interruptions in patients' daily routine on adherence to oral antidiabetic medication. A multilevel analysis of electronic monitoring data.

PURPOSE: Considerable variability in adherence over time exists. The aim of this study was to investigate to what extent deviations from the prescribed regimen in type 2 diabetes patients can be explained by characteristics of the individual 'medication intake moments' and the patient. METHODS: Medication intake of 104 non-adherent type 2 diabetes patients from 37 community pharmacies was electronically monitored for 6 months. The primary outcome measures were: (1) whether or not the intake occurred and (2) whether or not the intake occurred within the agreed-upon time period (correct timing). Multilevel logistic regression analyses were performed to account for the nested structure of the data. RESULTS: Medication intakes in the evening and during weekends and holidays were more likely to be incorrectly timed and also more likely to be completely missed. Irrespective of timing, most intakes occurred in the mornings of Monday through Thursday (96 %), and least intakes occurred on Saturday evening (82 %). Correctly timed intakes most often occurred on Monday and Tuesday mornings (61 %) in contrast to Sunday evenings (33 %). A patient's medication regimen was significantly associated with adherence. CONCLUSION: Based on our results, among patients who already have difficulties in taking their oral antidiabetic medication, interruptions in the daily routine negatively influence the intake of their medication. Professionals need to be aware of this variation in adherence within patients. As regular medication intake is important to maintain glycaemic control, healthcare professionals and patients should work together to find strategies that prevent deviations from the prescribed regimen at these problematic dosing times.

Polyglucosan body density in the aged mouse hippocampus is controlled by a novel modifier locus on chromosome 1.

Aging can be associated with the accumulation of hypobranched glycogen molecules (polyglucosan bodies, PGBs), particularly in astrocytes of the hippocampus. While PGBs have a detrimental effect on cognition in diseases such as adult polyglucosan body disease and Lafora disease, the underlying mechanism and clinical relevance of age-related PGB accumulation remains unknown. Here, we have investigated the genetic basis and functional impact of age-related PGB accumulation in 32 fully sequenced BXD-type strains of mice which exhibit a 400-fold variation in PGB burden in 16-18 month old females. We mapped a major locus controlling PGB density in the hippocampus to chromosome 1 at 72-75 Mb (linkage of 4.9 -logP), which we defined as the Pgb1 locus. To identify potentially causal gene variants within Pgb1, we generated extensive hippocampal transcriptome datasets and identified two strong candidate genes for which mRNA correlates with PGB density-Smarcal1 and Usp37. In addition, both Smarcal1 and Usp37 contain non-synonymous allele variations likely to impact protein function. A phenome-wide association analysis highlighted a trans-regulatory effect of the Pgb1 locus on expression of Hp1bp3, a gene known to play a role in age-related changes in learning and memory. To investigate the potential impact of PGBs on cognition, we performed conditioned fear memory testing on strains displaying varying degrees of PGB burden, and a phenome-wide association scan of ~12,000 traits. Importantly, we did not find any evidence suggesting a negative impact of PGB burden on cognitive capacity. Taken together, we have identified a major modifier locus controlling PGB burden in the hippocampus and shed light on the genetic architecture and clinical relevance of this strikingly heterogeneous hippocampal phenotype.

[The Simodont in dental education]. / De Simodont in het onderwijs.

The Simodont is a virtual learning environment for students of dentistry which is intended to expand and optimize the preparation ofstudents for the treatment ofpatients so that the transition in education from pre-clinic to clinic is reduced. The Simodont makes it possible to offer students more realistic clinical problems. In that way, students can practice much more extensively than they can in the pre-clinic on phantom heads. The Simodont also provides a safe learning environment in which unlimited mistakes can be made without unfortunate consequencesfor the student and patient. The simulator is coordinated with reading material on a computer, which makes it possible to integrate techniques and theory in dental education. Virtual teeth, with and without pathology, have been created for application in the Simodont, to allow unlimited possibilities for practice. The future possibilities for the Simodont offer many opportunities for students in dental education, for supplementary and post-graduate education andfor the re-integration of dentists in their profession.

Comparison of real-time PCR techniques to cytotoxigenic culture methods for diagnosing Clostridium difficile infection.

In the past decade, the incidence of Clostridium difficile infections (CDI) with a more severe course has increased in Europe and North America. Assays that are capable of rapidly diagnosing CDI are essential. Two real-time PCRs (LUMC and LvI) targeting C. difficile toxin genes (tcdB, and tcdA and tcdB, respectively) were compared with the BD GeneOhm PCR (targeting the tcdB gene), using cytotoxigenic culture as a gold standard. In addition, a real-time PCR targeting the tcdC frameshift mutation at position 117 (Δ117 PCR) was evaluated for detecting toxigenic C. difficile and the presence of PCR ribotype 027 in stool samples. In total, 526 diarrheal samples were prospectively collected and included in the study. Compared with those for cytotoxigenic culture, sensitivity, specificity, positive predicted value (PPV), and negative predicted value (NPV) were for PCR LUMC 96.0%, 88.0%, 66.0%, and 98.9%, for PCR LvI 100.0%, 89.4%, 69.7%, and 100.0%, for PCR Δ117 98.0%, 90.7%, 71.9%, and 99.5%, and for PCR BD GeneOhm 88.3%, 96.9%, 86.5%, and 97.4%. Compared to those with feces samples cultured positive for C. difficile type 027, the sensitivity, specificity, PPV, and NPV of the Δ117 PCR were 95.2%, 96.2%, 87.0%, and 98.7%. We conclude that all real-time PCRs can be applied as a first screening test in an algorithm for diagnosing CDI. However, the low PPVs hinder the use of the assays as stand-alone tests. Furthermore, the Δ117 PCR may provide valuable information for minimizing the spread of the epidemic C. difficile PCR ribotype 027.

Spectral sidebands on a narrow-bandwidth optical probe as a broad-bandwidth THz pulse diagnostic.

Broad-bandwidth THz-domain electro-magnetic pulses are typically diagnosed through temporal electro-optic (EO) cross-correlation with an optical probe pulse. Single-shot time-domain measurements of the THz waveform involve complex setups at a bandwidth coverage limited by the probe bandwidth. Here we present an EO-based diagnostic directly in the spectral domain, relying on THz-induced optical sidebands on a narrow-bandwidth optical probe. Experiments are conducted with a 0.11-THz-bandwidth optical probe and a broadband source (0-8 THz detection bandwidth) rich in spectral features. The validity of the sideband diagnostic concept, its spectral resolution, sideband amplitude, and the effects of probe timing are studied. For probe pulses longer than the THz pulse, the sideband technique proves an accurate single-shot spectral diagnostic, with advantages in setup simplicity and bandwidth coverage no longer limited by the laser bandwidth.

Multiple pathways towards achieving a living income for different types of smallholder tree-crop commodity farmers.

Many sources indicate that smallholder tree-crop commodity farmers are poor, but there is a paucity of data on how many of them are poor and the depth of poverty. The living income concept establishes the net annual income required for a household in a place to afford a decent standard of living. Based on datasets on smallholder cocoa and tea farmers in Ghana, Ivory Coast and Kenya and literature, we conclude that a large proportion of such farmers do not have the potential to earn a living income based on their current situation. Because these farmers typically cultivate small farm sizes and have low capacity to invest and to diversify, there are no silver bullets to move them out of poverty. We present an assessment approach that results in insights into which interventions can be effective in improving the livelihoods of different types of farmers. While it is morally imperative that all households living in poverty are supported to earn a living income, the assessment approach and literature indicate that focussing on short- to medium-term interventions for households with a low likelihood of generating a living income could be: improving food security and health, finding off-farm and alternative employment, and social assistance programmes. In the long term, land governance policies could address land fragmentation and secure rights. Achieving living incomes based on smallholder commodity production requires more discussion and engagement with farmers and their household members and within their communities, coordination between all involved stakeholders, sharing lessons learnt and data.

Relatedness of human and animal Clostridium difficile PCR ribotype 078 isolates determined on the basis of multilocus variable-number tandem-repeat analysis and tetracycline resistance.

Totals of 102 and 56 Clostridium difficile type 078 strains of human and porcine origins, respectively, from four European countries were investigated by an optimized multilocus variable-number tandem-repeat analysis (MLVA) and for tetracycline susceptibility. Eighty-five percent of all isolates were genetically related, irrespective of human or porcine origin. Human strains were significantly more resistant to tetracycline than porcine strains. All tetracycline-resistant strains contained the Tn916-like transposon harboring the tet(M) gene. We conclude that strains from human and porcine origins are genetically related, irrespective of the country of origin. This may reflect a lack of diversity and/or common source.

Long-term effectiveness of exercise therapy in patients with osteoarthritis of the hip or knee: a randomized controlled trial comparing two different physical therapy interventions.

OBJECTIVE: To determine if behavioral graded activity (BGA) results in better long-term effectiveness (5 years after inclusion) than usual exercise therapy (UC; usual care) in patients with osteoarthritis (OA) of the hip or knee. METHOD: Long-term follow-up study of a single blind cluster randomized trial comparing BGA and UC. One hundred and forty-nine patients out of the 200 included were followed until 60 months' follow-up. Primary outcome measures were pain, physical function, and patient global assessment. Furthermore, patient-oriented physical function, physical performance, health care utilization and the number of joint replacement surgeries were assessed. Assessments took place at 3, 9, 15 and 60 months' follow-up. Data were analyzed according to intent-to-treat principle. RESULTS: Both treatments showed beneficial within-groups effects in the long-term. In patients with knee OA no differences between treatments were found on the short-, mid-long and long-term. In patients with hip OA significant differences in favor of BGA were found at 3 months' (pain and physical performance) and 9 months' follow-up (pain, physical function, patients global assessment and patient-oriented physical function). Furthermore, UC resulted in patients with hip OA in more joint replacement surgeries compared to BGA (hazard ratio [HR], 2.87; 95% confidence interval [CI], 1.1; 7.3). CONCLUSION: No differences between treatment groups were found in the long-term on the primary outcome measures. Although more research is needed to confirm the study findings, the results indicate that BGA reduces the risk for joint replacement surgeries compared to UC in patients with hip OA, which probably can be explained by better outcome in favor of BGA in the short- and mid-long-term.

Clostridium difficile is not associated with outbreaks of viral gastroenteritis in the elderly in the Netherlands.

The coincidental increase in norovirus outbreaks and Clostridium difficile infection (CDI) raised the question of whether these events could be related, e.g. by enhancing spread by diarrhoeal disease outbreaks. Therefore, we studied the prevalence of C. difficile in outbreaks of viral gastroenteritis in nursing homes for the elderly and characterised enzyme immunoassay (EIA)-positive stool samples. Stool samples from nursing home residents (n = 752) in 137 outbreaks of viral aetiology were investigated by EIA for the presence of C. difficile toxins. Positive samples were further tested by a cell neutralisation cytotoxicity test, a second EIA and culture. Cultured isolates were tested for the presence of toxin genes, the production of toxins and characterised by 16S rRNA polymerase chain reaction (PCR) and sequencing. Twenty-four samples (3.2%) tested positive in the EIA. Of these 24 positive samples, only two were positive by cytotoxicity and three by a second EIA. Bacterial culture of 21 available stool samples yielded a toxinogenic C. difficile PCR ribotype 001 in one patient sample only. In conclusion, we found no evidence in this retrospective study for an association between viral gastroenteritis outbreaks and C. difficile. The high rate of false-positive EIA samples emphasises the need for second confirmation tests to diagnose CDI.

Controlled study on folate status following folic acid supplementation and discontinuation in women of child-bearing age.

BACKGROUND: To decrease the incidence of neural tube defects, active efforts are currently undertaken to promote folic acid (FA) intake among women. In 2003, the Food and Drug Administration approved the proposal of introducing an oral contraceptive (OC) and FA combination pill. It is unknown whether these pills will reduce neural tube defect incidence for couples who do not become pregnant soon after discontinuation. We studied FA kinetics up to 12 weeks discontinuation of eight weeks 500 microg/d FA in 27 healthy Dutch women of child-bearing age. METHODS: In this controlled study, women were assigned to an intervention group (n = 13) or a control group (n = 14). The total study duration was 20 weeks, during which the subjects had to give blood on nine occasions (week -8 [baseline], -4, 0, 1, 2, 3, 4, 8 and 12) for analyses of serum and erythrocyte folate, and plasma total homocysteine. The intervention group received 500 microg/d FA during the first eight weeks, and discontinued the intake from weeks 0 to 12. No supplements were supplied to the control group. RESULTS: Serum folate and plasma total homocysteine returned to baseline after 12 weeks of FA discontinuation, erythrocyte folate did not. CONCLUSION: An FA/OC combination pill seems to be of value for only a minor portion of women. Active efforts to stimulate women of child-bearing age to take FA remain essential.