Vitamin C-related nutrient-nutrient and nutrient-gene interactions that modify folate status.

PURPOSE: Folate-related nutrient-nutrient and nutrient-gene interactions modify disease risk; we therefore examined synergistic relationships between dietary folic acid, vitamin C and variant folate genes with respect to red cell folate status. METHODS: Two hundred and twelve subjects were examined using chemiluminescent immunoassay, PCR and food frequency questionnaire to determine red cell and serum folate, 14 folate gene polymorphisms, dietary folate (natural and synthetic) and vitamin C. RESULTS: When examined independently, synthetic PteGlu correlates best with red cell folate at higher levels of intake (p = 0.0102), while natural 5CH(3)-H(4)-PteGlu(n) correlates best with red cell folate at lower levels of intake (p = 0.0035). However, dietary vitamin C and 5CH(3)-H(4)-PteGlu(n) interact synergistically to correlate with red cell folate at higher levels of intake (p = 0.0005). No interaction between dietary vitamin C and PteGlu was observed. This 'natural' nutrient-nutrient interaction may provide an alternative to synthetic PteGlu supplementation that is now linked to adverse phenomena/health outcomes. On its own, vitamin C also correlates with red cell folate (p = 0.0150) and is strongly influenced by genetic variation in TS, MTHFR and MSR, genes critical for DNA and methionine biosynthesis that underpin erythropoiesis. Similarly, dietary vitamin C and 5CH(3)-H(4)-PteGlu(n) act synergistically to modify red cell folate status according to variation in folate genes: of note, heterozygosity for 2R3R-TS (p = 0.0181), SHMT (p = 0.0046) and all three MTHFR SNPs (p = 0.0023, 0.0015 and 0.0239 for G1793A, C677T and A1298C variants, respectively) promote a significant association with red cell folate. Again, all these genes are critical for nucleic acid biosynthesis. Folate variants with the strongest independent effect on folate status were C677T-MTHFR (p = 0.0004) and G1793A-MTHFR (p = 0.0173). CONCLUSIONS: 5CH(3)-H(4)-PteGlu(n) assimilation and variant folate gene expression products may be critically dependent on dietary vitamin C.

Interferon treatment for chronic hepatitis C: a family impact study.

Hepatitis C virus is estimated to affect 170 million people worldwide. Infection can lead to cirrhosis, liver failure, or liver cancer. Hepatitis C is unique among chronic illnesses, in that potentially curative treatment is available. Therapy is of prolonged duration and associated with multiple physiological and psychological side effects. These side effects have the potential to impact not only the individual receiving therapy but also their family and the day-to-day functioning of the family unit.This paper describes data and findings obtained from a family impact study instigated to explore the repercussions of interferon treatment for chronic hepatitis C on family life, from both the perspectives of individuals who had received treatment and their family members. An exploratory study was conducted using semi-structured focus groups.Findings reveal the treatment impacted on physical, emotional, relational, and financial domains. The major themes identified were resilience, loss, hardship, anger and irritability, and secrecy. The side-effect profile of therapy exerted significant and previously unforeseen impacts on family relationships, both negatively and positively. Treatment receivers tended to view their experiences as having more adverse impact, while family members, although affected, demonstrated considerable resilience and coping.

Midwives' personal use of complementary and alternative medicine (CAM) influences their recommendations to women experiencing a post-date pregnancy.

Complementary and Alternative Medicine (CAM) have increasingly been used by pregnant women with a steady rise in interest by midwives. Literature describing CAM and self-help options midwives recommend to women experiencing a post-date pregnancy is sparse. This study aimed to investigate if Australian midwives' personal CAM use impacts on discussions and recommendations of CAM/Self-help strategies. METHODOLOGY/DESIGN: A survey of a national midwifery association midwifery members (n=3,552) was undertaken at a midwifery conference (October 2015) and via e-bulletins (November 2015-March 2016). The self-administered survey included questions on what self-help and CAM strategies midwives discuss and recommend to women with a post-date pregnancy, midwives' confidence levels on discussing or recommending CAM, midwives' own personal use of CAM. FINDINGS: A total of 571 registered midwives completed the survey (16%). Demographics (age, years as a midwife, state of residence) reflected Australian midwives and the midwifery association membership. Most respondents discuss (91.2%) and recommend (88.6%) self-help/CAM strategies to women with a post-date pregnancy. The top five CAM recommended were Acupuncture (65.7%), Acupressure (58.1%), Raspberry Leaf (52.5%), Massage (38.9%) and Hypnosis/Calmbirthing/Hypnobirthing (35.7%). Midwives were more likely to discuss strategies if they personally used CAM (p<.001), were younger (p<.001) or had worked less years as midwives (p=.004). Midwives were more likely to recommend strategies if they used CAM in their own pregnancies (p=.001). CONCLUSION: Midwives' personal use of CAM influenced their discussions and recommendations of CAM/self-help strategies to women experiencing a post-date pregnancy. This study has implications for inclusion of CAM in midwifery education curricula.

Design, rationale and feasibility of a multidimensional experimental protocol to study early life stress.

There is a rapidly accumulating body of evidence regarding the influential role of early life stress (ELS) upon medical and psychiatric conditions. While self-report instruments, with their intrinsic limitations of recall, remain the primary means of detecting ELS in humans, biological measures are generally limited to a single biological system. This paper describes the design, rationale and feasibility of a study to simultaneously measure neuroendocrine, immune and autonomic nervous system (ANS) responses to psychological and physiological stressors in relation to ELS. Five healthy university students were recruited by advertisement. Exclusion criteria included chronic medical conditions, psychotic disorders, needle phobia, inability to tolerate pain, and those using anti-inflammatory medications. They were clinically interviewed and physiological recordings made over a two-hour period pre, during and post two acute stressors: the cold pressor test and recalling a distressing memory. The Childhood Trauma Questionnaire and the Parental Bonding Index were utilised to measure ELS. Other psychological measures of mood and personality were also administered. Measurements of heart rate, blood pressure, respiratory rate, skin conductance, skin blood flow and temporal plasma samples were successfully obtained before, during and after acute stress. Participants reported the extensive psychological and multisystem physiological data collection and stress provocations were tolerable. Most (4/5) participants indicated a willingness to return to repeat the protocol, indicating acceptability. Our protocol is viable and safe in young physically healthy adults and allows us to assess simultaneously neuroendocrine, immune and autonomic nervous system responses to stressors in persons assessed for ELS.

A feasibility randomised controlled trial of acupressure to assist spontaneous labour for primigravid women experiencing a post-date pregnancy.

OBJECTIVE: this Australian feasibility study aimed to determine; the willingness of women experiencing a post-date pregnancy to participate in a randomised controlled trial (RCT) of acupressure and compliance with the study protocol. The study also aimed to determine the effect size of the primary outcome in order to calculate a sample size for a future appropriately powered RCT. DESIGN: a two-arm randomised controlled trial. Staff providing clinical care were blinded to group allocation unless the participant disclosed study participation. SETTING: maternity services at two outer metropolitan public hospitals in New South Wales, Australia PARTICIPANTS: sixty seven healthy primigravid women experiencing a singleton cephalic pregnancy at 40 weeks±2 days gestation were assessed as eligible to participate and were provided with study information. INTERVENTION: both groups received standard clinical care, with the intervention group also receiving verbal and written instructions on the self-administration of three acupoints (Spleen 6, Large Intestine 4, and Gall Bladder 21) to be used until spontaneous or induced labour began. MEASUREMENTS: assessment of feasibility included determining recruitment rate and acceptability of an RCT for a CAM modality, and acupressure treatment compliance, via participant surveys. The primary clinical outcome was spontaneous onset of labour. FINDINGS: from the 67 women eligible during the timeframe for the study, 44 women (65.6%) agreed to participate and were randomised. There was no statistically significant difference in rate of spontaneous onset of labour (50% acupressure vs 41% control). Twenty nine participant surveys were returned (65.9%). In the intervention group there was a high compliance with the acupressure protocol (83%) and the use of the three acupoints (94%). CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: this feasibility study revealed that pregnant women are interested in the use of CAM, and acupressure in particular, for the initiation of labour. Most women found it acceptable to be randomised to receive the intervention. While the 9% difference in the primary outcome was not statistically significant it is the best estimate of the treatment effect for calculating a sample size of 994 for a future RCT with 80% power, alpha 0.05. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ANZCTR:12613000145707.

Genetic Variation in Glutamate Carboxypeptidase II and Interaction with Dietary Natural Vitamin C May Predict Risk for Adenomatous Polyp Occurrence.

BACKGROUND: The C1561T variant of the glutamate carboxypeptidase II (GCPII) gene is critical for natural methylfolylpolyglutamte (methylfolate) absorption, and has been associated with perturbations in folate metabolism and disease susceptibility. However, little is known on C1561T-GCPII as a risk factor for colorectal cancer. Therefore, this study examined whether C1561T-GCPII influences folate metabolism and adenomatous polyp occurrence. MATERIALS AND METHODS: 164 controls and 38 adenomatous polyp cases were analysed to determine blood folate and plasma homocysteine (Hcy) level, dietary intake of natural methylfolate, synthetic pteroylglutamic acid (PteGlu), vitamin C and C1561T-GCPII genotype. RESULTS: In controls and cases, 7.3 and 18.4 percent of subjects respectively, were found to have the CT genotype, increasing the risk for adenomatous polyp occurrence 2.86 times (95% CI:1.37-8.0, p=0.035). Total dietary folate, methylfolate and PteGlu intake and the level of erythrocyte folate and plasma Hcy did not predict the occurrence of an adenomatous polyp. However, dietary natural vitamin C intake was associated with adenomatous polyp risk within C1561T-GCPII CT genotype subjects (p=0.037). CONCLUSIONS: The findings suggest that C1561T-GCPII variation may be associated with risk for adenomatous polyp, and vitamin C may modify risk by interacting with the variant gene, its expression product and/or folate substrates.

Gene-Nutrient Interaction between Folate and Dihydrofolate Reductase in Risk for Adenomatous Polyp Occurrence: A Preliminary Report.

Folate and related gene variants are significant risk factors in the aetiology of colorectal cancer. Dihydrofolate reductase (DHFR) is critical in the metabolism of synthetic folic acid (pteroylmonoglutamatamic, PteGlu) to tetrahydrofolate following absorption. Therefore, the 19bp deletion variant of DHFR may lead to the alteration of folate-related colorectal disease susceptibility. This study examined the association between PteGlu and 19bp del-DHFR, and adenomatous polyp (AP) occurrence, an antecedent of colorectal cancer. A total of 199 subjects (162 controls and 37 AP cases) were analysed to determine dietary intake of total folate, natural methylfolate and synthetic PteGlu, level of erythrocyte folate and plasma homocysteine (tHcy), and genotype of 19bp del-DHFR. Dietary folate intake, erythrocyte folate, tHcy and 19bp del-DHFR variants did not independently predict the occurrence of AP. However, a gene-nutrient interaction was observed when subjects were stratified according to dietary folate intake. In subjects with a folate intake above the median value due to significant dietary PteGlu content, the presence of the 19bp-deletion allele decreased the risk for AP (OR=0.35, 95% CI: 0.13-0.97). However, such association was not evident in individuals with a folate intake below the median value. In conclusion, the finding suggests that folate nutrition and 19bp del-DHFR variation may interact to modify AP risk.

Methylation diet and methyl group genetics in risk for adenomatous polyp occurrence.

PURPOSE: The aim of this study is to explore whether a methylation diet influences risk for adenomatous polyps (AP) either independently, or interactively with one-carbon metabolism-dependent gene variants, and whether such a diet modifies blood homocysteine, a biochemical phenotype closely related to the phenomenon of methylation. METHODS: 249 subjects were examined using selective fluorescence, PCR and food frequency questionnaire to determine homocysteine, nine methylation-related gene polymorphisms, dietary methionine, 5-methyltetrahydrofolate, vitamins B6 and B12. RESULTS: 1). Both dietary methionine and 5-methyltetrahydrofolate intake are significantly associated with plasma homocysteine. 2). Dietary methionine is related to AP risk in 2R3R-TS wildtype subjects, while dietary B12 is similarly related to this phenotype in individuals heterozygous for C1420T-SHMT, A2756G-MS and 844ins68-CBS, and in those recessive for 2R3R-TS. 3). Dietary methionine has a marginal influence on plasma homocysteine level in C1420T-SHMT heterozygotes, while B6 exhibits the same effect on homocysteine in C776G-TCN2 homozygote recessive subjects. Natural 5-methyltetrahydrofolate intake is interesting: Wildtype A1298C-MTHFR, heterozygote C677T-MTHFR, wildtype A2756G-MS and recessive A66G-MSR individuals all show a significant reciprocal association with homocysteine. 4). Stepwise regression of all genotypes to predict risk for AP indicated A2756G-MS and A66G-MSR to be most relevant (p = 0.0176 and 0.0408 respectively). Results were corrected for age and gender. CONCLUSION: A methylation diet influences methyl group synthesis in the regulation of blood homocysteine level, and is modulated by genetic interactions. Methylation-related nutrients also interact with key genes to modify risk of AP, a precursor of colorectal cancer. Independent of diet, two methylation-related genes (A2756G-MS and A66G-MSR) were directly associated with AP occurrence.

Factors that may influence midwives work-related stress and burnout.

RESEARCH QUESTION: To determine the incidence and level of work-related stress and burnout in midwives and contributing and protective demographic factors that may influence those levels. PARTICIPANTS AND METHOD: All registered midwives (152) working in two public hospital maternity units within the same health service district in NSW completed the Maslach Burnout Inventory Human Services Survey and a demographic survey including care model, shift work, lifestyle data and exercise level. FINDINGS: There was a response rate of 36.8% with 56 (56/152) midwives completing the surveys. Almost two thirds (60.7%) of midwives in this sample experienced moderate to high levels of emotional exhaustion, a third (30.3%) scoring low personal accomplishment and a third (30.3%) experiencing depersonalization related to burnout. Significant differences were found among groups of midwives according to years in the profession, shifts worked, how many women with multiple psychosocial issues were included in the midwife's workload and the midwife's uptake of physical exercise. Those midwives who had spent longer in the profession and exercised scored low burnout levels. CONCLUSION: The impact of years in the profession, shifts worked, how many women with multiple psychosocial issues were included in their workload and the midwife's level of exercise significantly affected how these midwives dealt with burnout and provided care for women. As the response rate was low, and the study cannot be generalised to the entire midwifery workforce but provides important insights for further research. Understanding factors related to burnout can benefit health care institutions financially and in terms of human costs, especially in view of consistent international shortages of midwives.

TAS2R38 bitter taste genetics, dietary vitamin C, and both natural and synthetic dietary folic acid predict folate status, a key micronutrient in the pathoaetiology of adenomatous polyps.

Taste perception may influence dietary preferences and nutrient intakes contributing to diet-related disease susceptibility. This study examined bitter taste genetics and whether variation in the TAS2R38 gene at three polymorphic loci (A49P, V262A and I296V) could alter dietary and systemic folate levels and dietary vitamin C intake, and whether a nutrigenetic circuit existed that might link bitter taste, folate/antioxidant status and risk for a colonic adenomatous polyp. TAS2R38 diplotype predicted bitter taste (PROP) phenotype (p value <0.00001) and red cell folate status (p=0.0179) consistent with the diplotype that has the broadest range of bitter perception (AVI/PAV) also possessing the highest average red cell folate value. However, TAS2R38 diplotype did not predict dietary intake of methylfolic acid, pteroylmonoglutamic acid or total folic acid. Neither did it predict dietary intake of vitamin C. Despite this, intake of dietary folate predicts red cell folate with analysis pointing to a key nutrient-nutrient interaction between vitamin C intake and systemic folate status. Analysis of 38 patients with an adenomatous polyp and 164 controls showed that individually, dietary nutrient intake, nutrient status and taste diplotype did not influence polyp risk. However, red cell folate status (in individuals below the population median value) did interact with bitter taste diplotype (AVI/PAV) to predict polyp risk (p=0.0145). Furthermore, synthetic folic acid (below median intake) was statistically associated with adenoma occurrence (p=0.0215); individuals with adenomatous polyps had a 1.77× higher intake than controls. Additionally, stepwise regression taking account of all dietary nutrients showed a tight relationship between methylfolic acid (but not pteroylmonoglutamic acid) intake and red cell folate level in those with a low folate status and occurrence of an adenomatous polyp (p=0.0039). These findings point to a role for folate in the pathoaetiology of adenomatous polyps, with the natural and synthetic vitamers not necessarily having the same biological effect.

The development of a tool to assess levels of stress and burnout.

OBJECTIVE: To pilot test the reliability and validity of a newly developed tool measuring nursing and midwifery staff stress and burnout. DESIGN: Descriptive survey. SETTING: Public hospital, aged care facility and university. SUBJECTS: For the pilot study a total of forty-nine (n = 49) nurses and midwives, selected by convenience sampling, were sent an initial pilot questionnaire. The return rate was seventy per cent initially and the return rate on the second mail out was forty-nine per cent. MAIN OUTCOME MEASURE: To determine reliability and validity of a new tool that explores nurses' and midwives' perceptions of stress, burnout and control over their working environment. RESULTS: Face validity, test-retest reliability, internal consistency and principal component analysis were established. Overall Cronbach's alpha was 0.87 indicating good internal consistency for the stress/ burnout element of the questionnaire. The test-retest reliability intraclass correlation coefficient reported 0.30 - 0.90 for all six sub scales which were developed for both parts of the questionnaire. CONCLUSION: The pilot study indicates that it is possible to construct a valid and reliable instrument to assess nurses' and midwives' perception of stress and burnout.