Thought Leader Perspectives on the Benefits, Barriers, and Enablers for Routinely Collected Electronic Health Data to Support Professional Development: Qualitative Study.

BACKGROUND: Hospitals routinely collect large amounts of administrative data such as length of stay, 28-day readmissions, and hospital-acquired complications; yet, these data are underused for continuing professional development (CPD). First, these clinical indicators are rarely reviewed outside of existing quality and safety reporting. Second, many medical specialists view their CPD requirements as time-consuming, having minimal impact on practice change and improving patient outcomes. There is an opportunity to build new user interfaces based on these data, designed to support individual and group reflection. Data-informed reflective practice has the potential to generate new insights about performance, bridging the gap between CPD and clinical practice. OBJECTIVE: This study aims to understand why routinely collected administrative data have not yet become widely used to support reflective practice and lifelong learning. METHODS: We conducted semistructured interviews (N=19) with thought leaders from a range of backgrounds, including clinicians, surgeons, chief medical officers, information and communications technology professionals, informaticians, researchers, and leaders from related industries. Interviews were thematically analyzed by 2 independent coders. RESULTS: Respondents identified visibility of outcomes, peer comparison, group reflective discussions, and practice change as potential benefits. The key barriers included legacy technology, distrust with data quality, privacy, data misinterpretation, and team culture. Respondents suggested recruiting local champions for co-design, presenting data for understanding rather than information, coaching by specialty group leaders, and timely reflection linked to CPD as enablers to successful implementation. CONCLUSIONS: Overall, there was consensus among thought leaders, bringing together insights from diverse backgrounds and medical jurisdictions. We found that clinicians are interested in repurposing administrative data for professional development despite concerns with underlying data quality, privacy, legacy technology, and visual presentation. They prefer group reflection led by supportive specialty group leaders, rather than individual reflection. Our findings provide novel insights into the specific benefits, barriers, and benefits of potential reflective practice interfaces based on these data sets. They can inform the design of new models of in-hospital reflection linked to the annual CPD planning-recording-reflection cycle.

Defects in NLRP6, autophagy and goblet cell homeostasis are associated with reduced duodenal CRH receptor 2 expression in patients with functional dyspepsia.

Functional dyspepsia (FD) affects up to 15% of the population and is characterised by recurring upper gastrointestinal (GI) symptoms occurring in the absence of clinically identifiable pathology. Psychological stress is a key factor associated with the onset of FD and locally acting hypothalamic-pituitary-adrenal (HPA) axis hormones have been implicated in GI motility and barrier dysfunction. Recent pre-clinical work has identified mechanistic pathways linking corticotropin-releasing hormone (CRH) with the innate epithelial immune protein NLRP6, an inflammasome that has been shown to regulate GI mucus secretion. We recruited twelve FD patients and twelve healthy individuals to examine whether dysregulation of hypothalamic-pituitary adrenal (HPA) axis hormones and altered NLRP6 pathways were evident in the duodenal mucosa. Protein expression was assessed by immunoblot and immunohistochemistry in D2 duodenal biopsies. Plasma HPA axis hormones were assayed by ELISA and enteroid and colorectal cancer cell line cultures were used to verify function. FD patients exhibited reduced duodenal CRH-receptor 2, compared to non-GI disease controls, indicating a dysregulation of duodenal HPA signalling. The loss of CRH-receptor 2 correlated with reduced NLRP6 expression and autophagy function, processes critical for maintaining goblet cell homeostasis. In accordance, duodenal goblet cell numbers and mucin exocytosis was reduced in FD patients compared to controls. In vitro studies demonstrated that CRH could reduce NLRP6 in duodenal spheroids and promote mucus secretion in the HT29-MTX-E12 cell line. In conclusion, FD patients exhibit defects in the NLRP6-autophagy axis with decreased goblet cell function that may drive symptoms of disease. These features correlated with loss of CRH receptor 2 and may be driven by dysregulation of HPA signalling in the duodenum of FD patients.

Biophysical evidence to support and extend the vitamin D-folate hypothesis as a paradigm for the evolution of human skin pigmentation.

OBJECTIVE: To test the "vitamin D-folate hypothesis for the evolution of human skin pigmentation." METHODS: Total ozone mapping spectrometer (TOMS) satellite data were used to examine surface UV-irradiance in a large (n = 649) Australian cross-sectional study population. Genetic analysis was used to score vitamin D- and folate-related gene polymorphisms (n = 22), along with two pigmentation gene variants (IRF4-rs12203592/HERC2-rs12913832). Red cell folate and vitamin D3 were measured by immunoassay and HPLC, respectively. RESULTS: Ultraviolet radiation (UVR) and pigmentation genes interact to modify blood vitamin levels; Light skin IRF4-TT genotype has greatest folate loss while light skin HERC2-GG genotype has greatest vitamin D3 synthesis (reflected in both TOMS and seasonal data). UV-wavelength exhibits a dose-response relationship in folate loss within light skin IRF4-TT genotype (305 > 310 > 324 > 380 nm). Significant vitamin D3 photosynthesis only occurs within light skin HERC2-GG genotype, and is maximal at 305 nm. Three dietary antioxidants (vitamins C, E, and ß-carotene) interact with UVR and pigmentation genes preventing oxidative loss of labile reduced folate vitamers, with greatest benefit in light skin IRF4-TT subjects. The putative photosensitiser, riboflavin, did not sensitize red cell folate to UVR and actually afforded protection. Four genes (5xSNPs) influenced blood vitamin levels when stratified by pigmentation genotype; MTHFR-rs1801133/rs1801131, TS-rs34489327, CYP24A-rs17216707, and VDR-ApaI-rs7975232. Lightest IRF4-TT/darkest HERC2-AA genotype combination (greatest folate loss/lowest vitamin D3 synthesis) has 0% occurrence. The opposing, commonest (39%) compound genotype (darkest IRF4-CC/lightest HERC2-GG) permits least folate loss and greatest synthesis of vitamin D3 . CONCLUSION: New biophysical evidence supports the vitamin D-folate hypothesis for evolution of skin pigmentation.

Factors associated with the development of acute general surgical pathology in medical inpatients.

BACKGROUND: Medical inpatients can develop acute general surgical conditions. However, this is rare. The presence of multiple acute pathologies delays diagnosis and these patients have poorer prognoses. AIM: To determine the incidence, risk factors and prognosis of medical inpatients developing acute general surgical conditions. METHODS: A single-centre retrospective case-control study was conducted over 1 year in the United Kingdom. Medical patients developing acute surgical pathology were identified using the local referral system. For each case, two controls were selected from a pool of medical inpatients receiving no general surgical input during their admission. Patient records were used to collect hospital admission details, demographic and laboratory data. Univariate analysis and multivariable analysis were performed. RESULTS: The study included 42 cases and 84 controls. The incidence of general surgical pathology in medical inpatients was 2.3/1000 admissions/year. In multivariate analysis, risk factors associated with developing general surgical pathology were previous abdominal surgery (odds ratio (OR) =3.68; 95% confidence interval (CI): 1.43 to 9.48; P = 0.007) and doubling from baseline creatinine (OR = 18.9; 95% CI: 2.57 to 139; P = 0.004). Patients with surgical pathology had longer inpatient stays (22.8 vs 9.4 days; P < 0.001) and a higher inpatient mortality (23.8% vs 7.1%; P = 0.011). Development of surgical pathology was strongly associated with mortality (OR = 4.06; 95% CI: 1.36 to 12.1). CONCLUSION: The development of acute surgical pathology in medical inpatients is rare but associated with longer inpatient stays and higher mortality. We have identified risk-factors associated with the development of surgical pathology, which can be used to identify patients at risk of surgical pathology.

What makes a model prescriber? A documentary analysis.

INTRODUCTION: In recent years, the authority to prescribe medications in healthcare has expanded to include pharmacists, nurses and Allied Healthcare Professionals. Subsequently, the quantity of guidelines describing appropriate prescribing practice has increased. Despite this, the literature notes a lack of consensus regarding the overall qualities of a good prescriber. The aim of this study was to attempt to define what makes a model prescriber in practice, regardless of professional background. METHODS: A documentary analysis of UK-based and international prescribing practice guidelines was performed. Data analysis was conducted through a constructivist grounded theory approach to enable concepts to be identified from the data itself without the use of pre-defined categories. RESULTS: A total of 13 guideline documents were analysed. Overall, four core categories of a model prescriber in practice were identified: Knowledgeable: including that of disease and drug properties; Safe: relating to appropriate drug quantities and treatment-monitoring; Good Communicators: with both patients and colleagues; Contemporary: through enhancing knowledge and skills. CONCLUSIONS: These four categories can serve as a definition of a high-level prescriber and as an additional tool for prescribing educators to evaluate the extent their curriculum develops and assesses the core qualities needed by their students to be high-level prescribers in practice.

Bitter and sweet taste perception: relationships to self-reported oral hygiene habits and oral health status in a survey of Australian adults.

BACKGROUND: Oral health, an essential part of general health and well-being, is influenced by multiple factors, including oral hygiene habits and dietary factors. Dietary preferences are influenced by variation in taste perceptions and threshold tasting. Polymorphisms in specific genes for sweet and bitter taste receptors and bitter taste perception have been associated with dental caries. However, taste is complex with multiple receptors, each with multiple potential polymorphisms contributing to taste perception as well as social, cultural, and environmental influences. Additionally, these association studies have been conducted in restricted cohorts (e.g., children only). Furthermore, outcomes have been limited to dental caries and studies between taste perception and oral hygiene habits have not been completed. METHODS: A cross-sectional online survey was conducted to investigate the relationships between bitter and sweet taste perception (liking and intensity of index food items), self-reported oral hygiene habits and oral health (n = 518). RESULTS: Higher mean intensity scores for bitter (16-21%) and sweet (< 5%-60%) were seen with higher frequencies of oral hygiene habits (brushing, use of mouthwash, chewing gum and tongue cleaning). Lower mean bitter liking scores (18-21%) were seen with higher frequencies of oral hygiene habits (brushing, mouthwash use, floss use and chewing gum). Sweet liking scores varied by reported frequency of mouthwash use and flossing only, with mixed patterns of variance. Mean bitter and sweet intensity perception scores varied with the number of dental caries ((13-20% higher in those with 3 or more caries, compared to none). CONCLUSIONS: While there were numerous relationships identified between liking and perception of sweet and bitter and oral health outcomes, the magnitude and direction of associations varied by outcome. The direction of the associations cannot be inferred due to the cross-sectional nature of the study. The demonstrated relationships justify further future investigations, which could help better understand if taste liking and perception is impacted by oral hygiene and health, or vice versa. This could be important in understanding the causation and progression of oral health diseases or the development of novel therapeutics for oral health.

The impact of inflammatory bowel disease on sexual health in men: A scoping review.

AIMS AND OBJECTIVES: To review the literature on the impact of inflammatory bowel disease on the sexual health of men and make recommendations for nursing practice and research. BACKGROUND: Inflammatory bowel disease is a chronic condition of the gastrointestinal tract, causing symptoms that may impact upon sexual health. Specialist nurses are well positioned to assess and manage sexual health, but there is a lack of clinical guidance, especially in relation to men. DESIGN: A systematic scoping review following the Arksey and O'Malley (International Journal of Social Research Methodology, 8, 2005, 19) framework reported in line with the PRISMA-ScR checklist (Tricco et al., Annals of Internal Medicine, 169, 2018, 467). METHODS: OVID MEDLINE ALL [R], OVID EMBASE [R], OVID PsychINFO, EBSCO CINAHL Complete, The Cochrane Library and ProQuest were searched. Inclusion and exclusion criteria were applied independently by two reviewers. Data were extracted, charted and summarised from eligible studies. RESULTS: Thirty-one studies met the inclusion criteria. These were synthesised under three categories: mediators, moderators and descriptors of sexual health. Depression, disease activity and surgery were the most commonly cited disease-related factors to affect sexual health in men. The most commonly used assessment tool was The International Index of Erectile Function. Descriptors of function included frequency of intercourse, libido and the ability to maintain a desired sexual role. CONCLUSIONS: The effect of inflammatory bowel disease on sexual health in men involves a complex interaction of physical and psychosocial factors. Researchers must explore areas outside of erectile function to understand how the disease impacts sexuality, sexual well-being and masculinity. This can be achieved through qualitative exploration of patient, partner and health professional experiences. RELEVANCE TO CLINICAL PRACTICE: A holistic nursing assessment of men with inflammatory bowel disease should include sexual health. Developing understanding of how the disease influences sexual interaction and expression will facilitate support that is relevant, accessible and of value to men living with the disease.

Early lifecycle UV-exposure calibrates adult vitamin D metabolism: Evidence for a developmentally originated vitamin D homeostat that may alter related adult phenotypes.

OBJECTIVES: Within the Developmental Origins of Adult Disease (DOHaD) model, early life environmental exposures can confer a long-term legacy on human health. This mechanism may be adaptive or maladaptive depending on lifestyle circumstances. This article examines the role of first trimester UV-exposure on late-life vitamin D levels, and potentially related adaptive and maladaptive phenotypes (height and osteoporosis respectively). METHODS: Six hundred and forty nine subjects were examined for vitamin D2 and D3 (HPLC) and height (stadiometer). Osteoporosis was assessed with an extensive medical history questionnaire. RESULTS: Solar irradiance over the first 90 days postconception correlated positively with late-life vitamin D3 (R2 = .0140; P = .0082; ß = .1075), but not vitamin D2 levels. It also correlated positively with female adult height (R2 = .170; P = .0103; ß = .1291) and negatively with the occurrence of female osteoporosis (P = .0495). All data were adjusted for age and gender as appropriate (unadjusted data also provided). From a contemporary perspective, vitamin D levels varied significantly according to season of blood sampling as might be predicted (P = .0009). CONCLUSIONS: Increased solar irradiance/UV exposure during the first trimester of pregnancy calibrates adult vitamin D metabolism, which is an important hormone in maintaining calcium balance. This may explain how very early lifecycle UV exposure can influence skeletal development (adult height) and modify risk for the skeletal degenerative disorder osteoporosis. The data demonstrate humans are tuned to the world (exposome) in ways we have not yet fully considered, and which are entrained at the earliest phase of the lifecycle.

Frequency of folate-related polymorphisms varies by skin pigmentation.

OBJECTIVES: Folate-mediated 1-carbon transfer processes are vital in human health but are susceptible to independent and interactive influences of genetic variance and environmental exposures. Evidence suggests folate levels may be impacted by genetic variance and environmental UVR, with the effect of UVR levels influenced in part by degree of skin pigmentation. Folate-related genes are also influenced by UVR levels; however, the potential relationship between key folate-related genes and skin pigmentation has not yet been explored. The purpose of this study was to examine potential associations between frequencies of key folate variants and degree of skin pigmentation. METHODS: Association between population prevalence of 17 variants in 9 folate-related genes (MTRR, MTR, MTHFR, CBS, SHMT1, MTHFD1, RFC1, BHMT, TYMS) and the Fitzpatrick skin phototype of populations was assessed via collation of genotypic data from ALFRED (Allele Frequency Database) and 1000 Genomes databases. RESULTS: A significant association between variant frequency and Fitzpatrick phototype was observed for 16 of 17 examined variants (P < .0029 Bonferroni corrected significance threshold in all cases). CONCLUSIONS: These findings demonstrate novel relationships between skin color and folate-related genes, with trends suggesting folate genotypes are selected to maintain homeostasis in the folate system under differing UVR conditions.

Vitamin D and folate: A reciprocal environmental association based on seasonality and genetic disposition.

OBJECTIVES: The purpose of this study was (1) to elucidate any reciprocal seasonal relationship that might exist between red cell folate (RCF) and serum vitamin D3 Levels; (2) to explore whether folate-related gene variants that influence/alter DNA-thymidylate and methyl group biosynthesis modify any associations detected in objective 1; and (3) to consider whether these processes might influence reproductive success consistent with the "folate-vitamin D-UV hypothesis of skin pigmentation" evolutionary model. METHODS: A large (n = 649) Australian cross-sectional study population was examined. Polymerase chain reaction (PCR)/Restriction fragment length polymorphism (RFLP) analysis was used to genotype C677T-MTHFR, C1420T-SHMT, T401C-MTHFD and 2R > 3R-TS. RCF was measured by chemiluminescent immunoassay and vitamin D2 and D3 by HPLC. RESULTS: RCF and photosynthesized vitamin D3 , but not RCF and dietary vitamin D2 , exhibit a significant reciprocal association in spring and summer. Three folate genes (C677T-MTHFR, C1420T-SHMT, and 2R > 3R-TS) strengthen this effect in spring, and another (T401C-MTHFD) in summer. Effects are seasonal, and do not occur over the whole year. CONCLUSIONS: Findings are consistent with what might be required for the "folate-vitamin D-UV hypothesis of skin pigmentation" model. It suggests genetic influence in provision of one-carbon units by 5,10-methylene-H4 folate, may be an important factor in what appears to be a clear seasonal relationship between vitamin D3 and folate status.

Standard setting in Australian medical schools.

BACKGROUND: Standard setting of assessment is critical in quality assurance of medical programs. The aims of this study were to identify and compare the impact of methods used to establish the passing standard by the 13 medical schools who participated in the 2014 Australian Medical Schools Assessment Collaboration (AMSAC). METHODS: A survey was conducted to identify the standard setting procedures used by participating schools. Schools standard setting data was collated for the 49 multiple choice items used for benchmarking by AMSAC in 2014. Analyses were conducted for nine schools by their method of standard setting and key characteristics of 28 panel members from four schools. RESULTS: Substantial differences were identified between AMSAC schools that participated in the study, in both the standard setting methods and how particular techniques were implemented. The correlation between the item standard settings data by school ranged from - 0.116 to 0.632. A trend was identified for panel members to underestimate the difficulty level of hard items and overestimate the difficulty level of easy items for all methods. The median derived cut-score standard across schools was 55% for the 49 benchmarking questions. Although, no significant differences were found according to panel member standard setting experience or clinicians versus scientists, panel members with a high curriculum engagement generally had significantly lower expectations of borderline candidates (p = 0.044). CONCLUSION: This study used a robust assessment framework to demonstrate that several standard setting techniques are used by Australian medical schools, which in some cases use different techniques for different stages of their program. The implementation of the most common method, the Modified Angoff standard setting approach was found to vary markedly. The method of standard setting used had an impact on the distribution of expected minimally competent student performance by item and overall, with the passing standard varying by up to 10%. This difference can be attributed to the method of standard setting because the ASMSAC items have been shown over time to have consistent performance levels reflecting similar cohort ability. There is a need for more consistency in the method of standard setting used by medical schools in Australia.

Undiagnosed pancreatic exocrine insufficiency and chronic pancreatitis in functional GI disorder patients with diarrhea or abdominal pain.

BACKGROUND AND AIM: A previous UK study showed that 6.1% of patients with diarrhea-predominant irritable bowel syndrome (IBS-D) had evidence of severe pancreatic exocrine insufficiency (PEI), but these findings need replication. We aimed to identify the prevalence of PEI based on fecal elastase stool testing in consecutive outpatients presenting with chronic unexplained abdominal pain and/or diarrhea and/or IBS-D. METHODS: Patients aged over 40 years presenting to hospital outpatient clinics from six sites within Australia with unexplained abdominal pain and/or diarrhea for at least 3 months and/or IBS-D were studied. Patients completed validated questionnaires and donated a stool sample in which elastase concentration was measured by ELISA. A concentration of < 100 mcg/g stool represented severe and < 200 mcg/g mild to moderate PEI. Patients whose fecal elastase was < 200 mcg/g underwent testing for pancreatic pathology with an endoscopic ultrasound or abdominal CT. RESULTS: Two hundred eighteen patients (mean age of 60 years, 29.4% male) were studied. PEI was found in 4.6% (95% CI 2.2-8.3%) (n = 10), with five patients (2.3% (95% CI 0.8-5.3%) having severe PEI. Only male sex and heavy alcohol use were significantly associated with abnormal versus normal pancreatic functioning. Of seven patients who underwent endoscopic ultrasound or CT, two had features indicative of chronic pancreatitis. CONCLUSION: One in 50 patients with IBS-D or otherwise unexplained abdominal pain or diarrhea have an abnormal fecal elastase, but unexpected pancreatic insufficiency was detected in only a minority of these. This study failed to confirm the high prevalence of PEI among patients with unexplained GI symptoms previously reported.

UV-associated decline in systemic folate: implications for human nutrigenetics, health, and evolutionary processes.

OBJECTIVES: The purpose of this study was to examine whether UV exposure alters folate status according to C677T-MTHFR genotype, and to consider the relevance of this to human health and the evolutionary model of skin pigmentation. METHODS: Total Ozone Mapping Spectrometer (TOMS) satellite data were used to examine surface UV-irradiance, as a marker of UV exposure, in a large (n = 649) Australian cross-sectional study population. PCR/RFLP analysis was used to genotype C677T-MTHFR. RESULTS: Overall, cumulative UV-irradiance (42 and 120 days pre-clinic) was significantly negatively related to red cell folate (RCF) levels. When the cohort was stratified by MTHFR-C677T genotype, the relationship between UV-irradiance (42 days pre-clinic) and RCF remained significant only in the cohorts containing carriers of the T allele. Statistically significant z-score statistics and interaction terms from genotype and UV-irradiance (p-interaction) demonstrated that genotype did modify the effect of UV-irradiance on RCF, with the largest effect of UV being demonstrated in the 677TT-MTHFR subjects. CONCLUSIONS: Data provide strong evidence that surface UV-irradiance reduces long-term systemic folate levels, and that this is influenced by the C677T-MTHFR gene variant. We speculate this effect may be due to 677TT-MTHFR individuals containing more 5,10CH2 -H4 PteGlu, and that this folate form may be particularly UV labile. Since UV-irradiance lowers RCF in an MTHFR genotype-specific way, there are likely implications for human health and the evolution of skin pigmentation.

VDR gene methylation as a molecular adaption to light exposure: Historic, recent and genetic influences.

OBJECTIVES: The vitamin D receptor (VDR) is a member of the nuclear receptor family of transcription factors. We examined whether degree of VDR gene methylation acts as a molecular adaptation to light exposure. We explored this in the context of photoperiod at conception, recent UV irradiance at 305 nm, and gene-latitude effects. METHODS: Eighty subjects were examined for VDR gene-CpG island methylation density. VDR gene variants were also examined by PCR-RFLP. RESULTS: Photoperiod at conception was significantly positively related to VDR methylation density, explaining 17% of the variance in methylation (r2 = 0.17; P = .001). Within this model, photoperiod at conception and plasma 25(OH)D independently predicted methylation density at the VDR-CpG island. Recent UV exposure at 305 nm led to a fivefold increase in mean methylation density (P = .02). Again, UV exposure and plasma 25(OH)D independently predicted methylation density at the VDR-CpG island. In the presence of the BsmI mutant allele, methylation density was increased (P = .01), and in the presence of the TaqI or FokI mutant allele, methylation density was decreased (P = .007 and .04 respectively). Multivariate modelling suggests plasma 25(OH)D, photoperiod at conception, recent solar irradiance, and VDR genotype combine as independent predictors of methylation at the VDR-CpG island, explaining 34% of the variance in methylation (R2 = 0.34, P < .0001). CONCLUSIONS: Duration of early-life light exposure and strength of recent irradiance, along with latitudinal genetic factors, influence degree of VDR gene methylation consistent with this epigenetic phenomenon being a molecular adaptation to variation in ambient light exposure. Findings contribute to our understanding of human biology.

Vitamin D Receptor Polymorphisms Relate to Risk of Adenomatous Polyps in a Sex-Specific Manner.

Vitamin D receptor (VDR) gene polymorphisms may influence risk for adenomatous polyps (AP), a benign precursor to colon cancer, via modulation of vitamin D sensitive pathways, including cell proliferation and differentiation. However, results have been mixed and any association remains contentious. Failure to clinically exclude the presence of (AP in control cohorts may contribute to the lack of consensus. Therefore, we assessed the role of the FokI, BsmI, ApaI, and TaqI VDR polymorphisms in modifying risk for AP, adjusting for a range of dietary and lifestyle variables. Blood was collected from colonoscopy patients (n = 258) and VDR polymorphisms assessed by restriction fragment length polymorphism. Dietary habits were estimated from food frequency questionnaires. Odds ratios for AP were calculated by genotype, stratified by sex, and adjusted for age, lifestyle, and dietary factors. FokI was associated with modified risk for AP in males, whereas the BsmI/ApaI/TaqI haplotype was associated with modified risk in females. No interaction was found between VDR variants and vitamin D intake. This study offers novel insight into the potential for VDR genetics to contribute to risk for AP and is the first to demonstrate a sex-specific relationship between these polymorphisms and risk for AP.

Sex-dependent association between erythrocyte n-3 PUFA and type 2 diabetes in older overweight people.

The association between n-3 PUFA intake and type 2 diabetes (T2D) is unclear, and studies relating objective biomarkers of n-3 PUFA consumption to diabetic status remain limited. The aim of this study was to determine whether erythrocyte n-3 PUFA levels (n-3 index; n-3I) are associated with T2D in a cohort of older adults (n 608). To achieve this, the n-3I (erythrocyte %EPA+%DHA) was determined by GC and associated with fasting blood glucose; HbA1c; and plasma insulin. Insulin resistance (IR) was assessed using the homeostatic model assessment of insulin resistance (HOMA--IR). OR for T2D were calculated for each quartile of n-3I. In all, eighty-two type 2 diabetic (46·3 % female; 76·7 (sd 5·9) years) and 466 non-diabetic (57·9 % female; 77·8 (sd 7·1) years) individuals were included in the analysis. In overweight/obese (BMI≥27 kg/m2), the prevalence of T2D decreased across ascending n-3I quartiles: 1·0 (reference), 0·82 (95 % CI 0·31, 2·18), 0·56 (95 % CI 0·21, 1·52) and 0·22 (95 % CI 0·06, 0·82) (P trend=0·015). A similar but non-significant trend was seen in overweight men. After adjusting for BMI, no associations were found between n-3I and fasting blood glucose, HbA1c, insulin or HOMA-IR. In conclusion, higher erythrocyte n-3 PUFA status may be protective against the development of T2D in overweight women. Further research is warranted to determine whether dietary interventions that improve n-3 PUFA status can improve measures of IR, and to further elucidate sex-dependent differences.

Is the long case dead? 'Uh, I don't think so': the Uh/Um Index.

Current tools for clinical assessment are tedious and time-consuming, particularly the dreadful long case. There is a need for novel instruments that incorporate other aspects of competence. We propose such a method, namely the Uh/Um Index. Our innovation paper describes the rationale for using speech dysfluency and occurrences of filler words such as 'uh' and 'um' as a proxy for competence. This appears to have won initial support from senior clinicians in our institution. Additional research is needed (non-restricted grants are welcomed) to establish rigorous standard setting and to fund our attendance at overseas conferences to make the Uh/Um Index the new buzzword in medical education.

The role of vitamins and minerals in modulating the expression of microRNA.

A growing number of studies in recent years have highlighted the importance of molecular nutrition as a potential determinant of health and disease. In particular, the ability of micronutrients to regulate the final expression of gene products via modulation of transcription and translation is now being recognised. Modulation of microRNA (miRNA) by nutrients is one pathway by which nutrition may mediate gene expression. miRNA, a class of non-coding RNA, can directly regulate gene expression post-transcriptionally. In addition, miRNA are able to indirectly influence gene expression potential at the transcriptional level via modulation of the function of components of the epigenetic machinery (DNA methylation and histone modifications). These mechanisms interact to form a complex, bi-directional regulatory circuit modulating gene expression. Disease-specific miRNA profiles have been identified in multiple disease states, including those with known dietary risk factors. Therefore, the role that nutritional components, in particular, vitamins and minerals, play in the modulation of miRNA profiles, and consequently health and disease, is increasingly being investigated, and as such is a timely subject for review. The recently posited potential for viable exogenous miRNA to enter human blood circulation from food sources adds another interesting dimension to the potential for dietary miRNA to contribute to gene modulation.

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.