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Aims: To create a summative document containing aims, objectives and methods that can be used for the training of healthcare professionals in inpatient diabetes care., Methods: A four-stage approach was introduced for the ward-based teaching of inpatient diabetes care at the University of the West Indies, Cave Hill over the 2014-2015 academic year. Within this approach, 55 students (100%) submitted aims, objectives and methods to support two 2-h, ward-based sessions. This was guided by brief instructions and access to a copy of the Endocrine Society Clinical Practice Guideline on the management of non-critical, non-perioperative inpatient diabetes. Conceptual content analysis was used to convert submissions into a unifying document., Results: Six themes emerged from students' submissions: diagnosis; assessment and investigation of diabetes and its complications; planning individualized care and pharmacological management; hypoglycaemia management, including severe hypoglycaemia; patient education; discharge planning; and multidisciplinary teamwork. Students were primarily interested in patient management and treatment using higher-level objectives and active learning methods., Conclusions: This study produced comprehensive, student-generated, and hence student-centred, aims, objectives and methods for inpatient diabetes care with objectives appropriately set for higher cognitive levels of learning. This material can be used to guide teaching or for further development into a curriculum. This is the first known publication of content that could be used in a ward-based inpatient diabetes curriculum., (© 2015 Diabetes UK.)

A limestone mine in Ohio has had instability problems that have led to massive roof falls extending to the surface. This study focuses on the role that weak, moisture-sensitive floor has in the instability issues. Previous NIOSH research related to this subject did not include analysis for weak floor or weak bands and recommended that when such issues arise they should be investigated further using a more advanced analysis. Therefore, to further investigate the observed instability occurring on a large scale at the Ohio mine, FLAC3D numerical models were employed to demonstrate the effect that a weak floor has on roof and pillar stability. This case study will provide important information to limestone mine operators regarding the impact of weak floor causing the potential for roof collapse, pillar failure, and subsequent subsidence of the ground surface.

Background: Postoperative ileus (POI) has a significant impact on patient wellbeing, and with a 15% incidence in colectomy patients costs US hospitals >$1.3 billion per year. Although some causative mechanisms have been identified, little is known about what places patients at risk for ileus. We aimed to identify factors that independently influence the development of POI., Materials and Methods: Patients who underwent elective surgery between 2011 and 2012 were identified from the colectomy-specific American College of Surgeons National Surgical Quality Improvement Program database. Descriptive statistics were calculated, and demographics, comorbidities, preoperative treatments, and operative characteristics were evaluated as risk factors using multivariate analyses., Results: A total of 9734 patients were included in this analysis; 1364 (14%) were found to have POI. Patients who developed an ileus were more likely to develop any postoperative complication, to be readmitted, and require reoperation compared with patients without POI. In addition, we identified 13 independent risk factors for POI., Conclusions: Five modifiable risk factors for development of POI were identified as follows: smoking, weight loss, preoperative oral antibiotics, mechanical bowel preparation, and surgical approach. These identifications provide insight into possible targets for preoperative modification, which may lead to improvements in patients' quality of life and influence outcomes such as postoperative complications, readmission, and reoperation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The central nervous system continues to develop during gestation and after birth, and folate is an essential nutrient in this process. Folate deficiency and folate receptor alpha autoantibodies (FRα-AuAb) have been associated with pregnancy-related complications and neurodevelopmental disorders. In this pilot study, we investigated the effect of exposure to FRα antibodies (Ab) during gestation (GST), the pre-weaning (PRW), and the post weaning (POW) periods on learning and behavior in adulthood in a rat model. In the open field test and novel object recognition task, which examine locomotor activity and anxiety-like behavior, deficits in rats exposed to Ab during gestation and pre-weaning (GST+PRW) included more time spent in the periphery or corner areas, less time in the central area, frequent self-grooming akin to stereotypy, and longer time to explore a novel object compared to a control group; these are all indicative of increased levels of anxiety. In the place avoidance tasks that assess learning and spatial memory formation, only 30% of GST+PRW rats were able to learn the passive place avoidance task. None of these rats learned the active place avoidance task indicating severe learning deficits and cognitive impairment. Similar but less severe deficits were observed in rats exposed to Ab during GST alone or only during the PRW period, suggesting the extreme sensitivity of the fetal as well as the neonatal rat brain to the deleterious effects of exposure to Ab during this period. Behavioral deficits were not seen in rats exposed to antibody post weaning. These observations have implications in the pathology of FRα-AuAb associated with neural tube defect pregnancy, preterm birth and neurodevelopmental disorders including autism.

In this paper, the advantage of using numerical models with the strength reduction method (SRM) to evaluate entry stability in complex multiple-seam conditions is demonstrated. A coal mine under variable topography from the Central Appalachian region is used as a case study. At this mine, unexpected roof conditions were encountered during development below previously mined panels. Stress mapping and observation of ground conditions were used to quantify the success of entry support systems in three room-and-pillar panels. Numerical model analyses were initially conducted to estimate the stresses induced by the multiple-seam mining at the locations of the affected entries. The SRM was used to quantify the stability factor of the supported roof of the entries at selected locations. The SRM-calculated stability factors were compared with observations made during the site visits, and the results demonstrate that the SRM adequately identifies the unexpected roof conditions in this complex case. It is concluded that the SRM can be used to effectively evaluate the likely success of roof supports and the stability condition of entries in coal mines.

Ground control research in underground coal mines has been ongoing for over 50 years. One of the most problematic issues in underground coal mines is roof failures associated with weak shale. This paper will present a historical narrative on the research the National Institute for Occupational Safety and Health has conducted in relation to rock mechanics and shale. This paper begins by first discussing how shale is classified in relation to coal mining. Characterizing and planning for weak roof sequences is an important step in developing an engineering solution to prevent roof failures. Next, the failure mechanics associated with the weak characteristics of shale will be discussed. Understanding these failure mechanics also aids in applying the correct engineering solutions. The various solutions that have been implemented in the underground coal mining industry to control the different modes of failure will be summarized. Finally, a discussion on current and future research relating to rock mechanics and shale is presented. The overall goal of the paper is to share the collective ground control experience of controlling roof structures dominated by shale rock in underground coal mining.

Objective: Dairy products are sources of protein and micronutrients important in a healthy diet. The purpose of the present analysis was to estimate consumption of dairy products by Brazilians and identify contributions of dairy products to nutrient intakes., Design: Dairy consumption data were obtained from 24 h dietary records. Dairy products were defined as milk (including flavoured), cheese and yoghurt. Estimates of dairy product intakes were generated for all individuals, individuals in urban and rural households and for age groups 10-18 years, 19-59 years and ≥60 years. Contributions to nutrient intakes were estimated for the total sample and sub-populations., Setting: Nationwide cross-sectional survey, 2008-2009., Subjects: Nationally representative sample of individuals aged ≥10 years in the Individual Food Intake survey, a component of the Brazilian Household Budget Survey (n 34 003)., Results: Among individuals aged ≥10 years, per capita intake of dairy products was 142 (se 2.1) g/d. Dairy product intake was higher among individuals in urban compared with rural areas and among groups 10-18 years and ≥60 years compared with adults aged 19-59 years. Dairy products accounted for 6.1% of daily energy intake, 7.3% of protein, 16.9% of saturated fat, 11.1% and 4.3% of total and added sugars, respectively, and 10.2-37.9% of daily Ca, vitamin D, P, vitamin A and K., Conclusions: Dairy products were substantial contributors to daily intakes of selected nutrients of concern in Brazil, although mean daily dairy product consumption was less than a typical portion. Education efforts in Brazil to raise awareness about the nutritional role of dairy foods may serve to improve overall diet quality.

Design of rib support systems in U.S. coal mines is based primarily on local practices and experience. A better understanding of current rib support practices in U.S. coal mines is crucial for developing a sound engineering rib support design tool. The objective of this paper is to analyze the current practices of rib control in U.S. coal mines. Twenty underground coal mines were studied representing various coal basins, coal seams, geology, loading conditions, and rib control strategies. The key findings are: (1) any rib design guideline or tool should take into account external rib support as well as internal bolting; (2) rib bolts on their own cannot contain rib spall, especially in soft ribs subjected to significant load-external rib control devices such as mesh are required in such cases to contain rib sloughing; (3) the majority of the studied mines follow the overburden depth and entry height thresholds recommended by the Program Information Bulletin 11-29 issued by the Mine Safety and Health Administration; (4) potential rib instability occurred when certain geological features prevailed-these include draw slate and/or bone coal near the rib/roof line, claystone partings, and soft coal bench overlain by rock strata; (5) 47% of the studied rib spall was classified as blocky-this could indicate a high potential of rib hazards; and (6) rib injury rates of the studied mines for the last three years emphasize the need for more rib control management for mines operating at overburden depths between 152.4 m and 304.8 m.

Background: Although combinations of biologically relevant polymorphic variants affect folate status, most studies have focused on the effects of individual polymorphisms; however, these effects may be altered by interactions between polymorphisms., Objective: We investigated the individual and combined effects of polymorphisms that affect folate transport or metabolism on folate status., Methods: The associations between the methylenetetrahydrofolate reductase (MTHFR) 677C > T, methionine transferase reductase (MTRR) 66A > G, MTRR 524C > T, 5,10-methylenetetrahydrofolate dehydrogenase-5,10-methylenetetrahydrofolate cyclohydrolase-10-formyltetrahydrofolate synthetase (MTHFD1) 1958G > A, MTHFD1 -105C > T, dihydrofolate reductase (DHFR) 19-bp insertion/deletion, and solute carrier family 19A, member 1 (SLC19A1) 80G > A polymorphisms and fasting plasma folate (PF), red cell folate (RCF), and plasma total homocysteine (tHcy) were tested by ANCOVA and Cox regression analysis in 781 Spanish adults., Results: Folate deficiency (PF <7 nmol/L) was observed in 18.8% of the participants. Geometric mean PF (nmol/L) was lower in MTHFR 677TT (10.0; 95% CI: 9.2, 11.9) compared with 677CC (12.4; 95% CI: 11.6, 13.2; P < 0.001). RCF (nmol/L) was lower in MTHFR 677TT (652; 95% CI: 611, 695) compared with 677CC (889; 95% CI: 851, 929; P < 0.001) and in SLC19A1 80AA (776; 95% CI: 733, 822) compared with 80GG (861; 95% CI: 815, 910; P < 0.01). RCF and tHcy (μmol/L) did not differ in MTHFR + MTRR 677TT/524TT compared with 677CC/524CC: 780 (95% CI: 647, 941) compared with 853 (95% CI: 795, 915; P = 0.99) and 10.2 (95% CI: 8.4, 12.3) compared with 8.9 (95% CI: 8.5, 9.4; P = 0.99), respectively. The RR of lowest-tertile RCF (≤680 nmol/L) was 2.1 (95% CI: 1.0, 4.5) for MTHFR + MTRR 677TT/66GG compared with 677CC/66AA, 2.2 (95% CI: 1.2, 4.1) for MTHFR + MTHFD1 677TT/1958AA compared with 677CC/1958GG, 2.9 (95% CI: 1.4, 6.0) for MTHFR + MTHFD1 677TT/-105TT compared with 677CC/-105CC, and 3.5 (95% CI: 1.5, 8.1) for MTHFR + SLC19A1 677TT/80AA compared with 677CC/80GG. Confining the analysis to the MTHFR 677TT genotype, the risk of lowest-tertile RCF was reduced for MTHFR + MTRR 677TT/66GG compared with 677TT/66AA (RR: 0.5; 95% CI: 0.3, 0.9)., Conclusions: Folate status was lower in the MTHFR 677TT and SLC19A1 80AA genotypes compared with corresponding reference genotypes. Low folate status risk associated with the MTHFR 677TT genotype varied depending on its combination with other polymorphisms., (© 2016 American Society for Nutrition.)

Haematopoietic stresses mobilize haematopoietic stem cells (HSCs) from the bone marrow to the spleen and induce extramedullary haematopoiesis (EMH). However, the cellular nature of the EMH niche is unknown. Here we assessed the sources of the key niche factors, SCF (also known as KITL) and CXCL12, in the mouse spleen after EMH induction by myeloablation, blood loss, or pregnancy. In each case, Scf was expressed by endothelial cells and Tcf21(+) stromal cells, primarily around sinusoids in the red pulp, while Cxcl12 was expressed by a subset of Tcf21(+) stromal cells. EMH induction markedly expanded the Scf-expressing endothelial cells and stromal cells by inducing proliferation. Most splenic HSCs were adjacent to Tcf21(+) stromal cells in red pulp. Conditional deletion of Scf from spleen endothelial cells, or of Scf or Cxcl12 from Tcf21+ stromal cells, severely reduced spleen EMH and reduced blood cell counts without affecting bone marrow haematopoiesis. Endothelial cells and Tcf21(+) stromal cells thus create a perisinusoidal EMH niche in the spleen, which is necessary for the physiological response to diverse haematopoietic stresses.

Solid cancer cells commonly enter the blood and disseminate systemically, but are highly inefficient at forming distant metastases for poorly understood reasons. Here we studied human melanomas that differed in their metastasis histories in patients and in their capacity to metastasize in NOD-SCID-Il2rg(-/-) (NSG) mice. We show that melanomas had high frequencies of cells that formed subcutaneous tumours, but much lower percentages of cells that formed tumours after intravenous or intrasplenic transplantation, particularly among inefficiently metastasizing melanomas. Melanoma cells in the blood and visceral organs experienced oxidative stress not observed in established subcutaneous tumours. Successfully metastasizing melanomas underwent reversible metabolic changes during metastasis that increased their capacity to withstand oxidative stress, including increased dependence on NADPH-generating enzymes in the folate pathway. Antioxidants promoted distant metastasis in NSG mice. Folate pathway inhibition using low-dose methotrexate, ALDH1L2 knockdown, or MTHFD1 knockdown inhibited distant metastasis without significantly affecting the growth of subcutaneous tumours in the same mice. Oxidative stress thus limits distant metastasis by melanoma cells in vivo.

Haematopoietic stem cells (HSCs) reside in a perivascular niche but the specific location of this niche remains controversial. HSCs are rare and few can be found in thin tissue sections or upon live imaging, making it difficult to comprehensively localize dividing and non-dividing HSCs. Here, using a green fluorescent protein (GFP) knock-in for the gene Ctnnal1 in mice (hereafter denoted as α-catulin(GFP)), we discover that α-catulin(GFP) is expressed by only 0.02% of bone marrow haematopoietic cells, including almost all HSCs. We find that approximately 30% of α-catulin-GFP(+)c-kit(+) cells give long-term multilineage reconstitution of irradiated mice, indicating that α-catulin-GFP(+)c-kit(+) cells are comparable in HSC purity to cells obtained using the best markers currently available. We optically cleared the bone marrow to perform deep confocal imaging, allowing us to image thousands of α-catulin-GFP(+)c-kit(+) cells and to digitally reconstruct large segments of bone marrow. The distribution of α-catulin-GFP(+)c-kit(+) cells indicated that HSCs were more common in central marrow than near bone surfaces, and in the diaphysis relative to the metaphysis. Nearly all HSCs contacted leptin receptor positive (Lepr(+)) and Cxcl12(high) niche cells, and approximately 85% of HSCs were within 10 μm of a sinusoidal blood vessel. Most HSCs, both dividing (Ki-67(+)) and non-dividing (Ki-67(-)), were distant from arterioles, transition zone vessels, and bone surfaces. Dividing and non-dividing HSCs thus reside mainly in perisinusoidal niches with Lepr(+)Cxcl12(high) cells throughout the bone marrow.

Background: The proportion of obese women is nearly twice the proportion of obese men in Barbados, and physical inactivity may be a partial determinant. Using qualitative interviews and 'semi-structured' participant observation, the aim of this study was to identify modifiable barriers to physical activity and to explore the factors that facilitate physical activity amongst overweight and obese women in this low-resourced setting., Methods: Seventeen women aged 25 to 35 years with a BMI ≥25, purposefully sampled from a population-based cross-sectional study conducted in Barbados, were recruited in 2014 to participate in in-depth semi-structured interviews. Twelve of these women participated in one or more additional participant observation sessions in which the researcher joined and observed a routine activity chosen by the participant. More than 50 hours of participant observation data collection were accumulated and documented in field notes. Thematic content analysis was performed on transcribed interviews and field notes using the software Dedoose., Results: Social, structural and individual barriers to physical activity were identified. Social factors related to gender norms and expectations. Women tended to be active with their female friends rather than partners or male peers, and reported peer support but also alienation. Being active also competed with family responsibilities and expectations. Structural barriers included few opportunities for active commuting, limited indoor space for exercise in the home, and low perceived access to convenient and affordable exercise classes. Several successful strategies associated with sustained activity were observed, including walking and highly social, low-cost exercise groups. Individual barriers related to healthy living strategies included perceptions about chronic disease and viewing physical activity as a possible strategy for desired weight loss but less effective than dieting., Conclusions: It is important to understand why women face barriers to physical activity, particularly in low-resourced settings, and to investigate how this could be addressed. This study highlights the role that gender norms and health beliefs play in shaping experiences of physical activity. In addition, structural barriers reflect a mix of resource-scarce and resource-rich factors which are likely to be seen in a wide variety of developing contexts.

Objective: We describe trends in life expectancy at birth (LE) and between-country LE disparities since 1965, in Latin America and the Caribbean., Methods & Findings: LE trends since 1965 are described for three geographical sub-regions: the Caribbean, Central America, and South America. LE disparities are explored using a suite of absolute and relative disparity metrics, with measurement consensus providing confidence to observed differences. LE has increased throughout Latin America and the Caribbean. Compared to the Caribbean, LE has increased by an additional 6.6 years in Central America and 4.1 years in South America. Since 1965, average reductions in between-country LE disparities were 14% (absolute disparity) and 23% (relative disparity) in the Caribbean, 55% and 51% in Central America, 55% and 52% in South America., Conclusions: LE in Latin America and the Caribbean is exceeding 'minimum standard' international targets, and is improving relative to the world region with the highest human longevity. The Caribbean, which had the highest LE and the lowest between-country LE disparities in Latin America and the Caribbean in 1965-70, had the lowest LE and the highest LE disparities by 2005-10. Caribbean Governments have championed a collaborative solution to the growing burden of non-communicable disease, with 15 territories signing on to the Declaration of Port of Spain, signalling regional commitment to a coordinated public-health response. The persistent LE inequity between Caribbean countries suggests that public health interventions should be tailored to individual countries to be most effective. Between- and within-country disparity monitoring for a range of health metrics should be a priority, first to guide country-level policy initiatives, then to contribute to the assessment of policy success.

Background: Diabetes (DM) is estimated to affect 10-15% of the adult population in the Caribbean. Preventive efforts require population wide measures to address its social determinants. We undertook a systematic review to determine current knowledge about the social distribution of diabetes, its risk factors and major complications in the Caribbean. This paper describes our findings on the distribution by gender., Methods: We searched Medline, Embase and five databases through the Virtual Health Library, for Caribbean studies published between 2007 and 2013 that described the distribution by gender for: known risk factors for Type 2 DM, prevalence of DM, and DM control or complications. PRISMA guidance on reporting systematic reviews on health equity was followed. Only quantitative studies (n>50) were included; each was assessed for risk of bias. Meta-analyses were performed, where appropriate, on studies with a low or medium risk of bias, using random effects models., Results: We found 50 articles from 27 studies, yielding 118 relationships between gender and the outcomes. Women were more likely to have DM, obesity, be less physically active but less likely to smoke. In meta-analyses of good quality population-based studies odds ratios for women vs. men for DM, obesity and smoking were: 1.65 (95% CI 1.43, 1.91), 3.10 (2.43, 3.94), and 0.24 (0.17, 0.34). Three studies found men more likely to have better glycaemic control but only one achieved statistical significance., Conclusion and Implications: Female gender is a determinant of DM prevalence in the Caribbean. In the vast majority of world regions women are at a similar or lower risk of type 2 diabetes than men, even when obesity is higher in women. Caribbean female excess of diabetes may be due to a much greater excess of risk factors in women, especially obesity. These findings have major implications for preventive policies and research.

Purpose: The purpose of this study was to compare pressure ulcer prevention programs in 2 long-term care (LTC) facilities with diverse Information Technology Sophistication (ITS), one with high sophistication and one with low sophistication, and to identify implications for the WOC nurse., Design: Secondary analysis of narrative data obtained from a mixed-methods study., Subjects and Setting: The study setting was 2 LTC facilities in the Midwestern United States. The sample comprised 39 staff from 2 facilities, including 26 from a high-ITS facility and 13 from the low-ITS facility. Respondents included certified nurse assistants, certified medical technicians, restorative medical technicians, social workers, RNs, licensed practical nurses, information technology staff, administrators, and directors., Methods: This study is a secondary analysis of interviews regarding communication and education strategies in 2 LTC agencies. This analysis focused on focus group interviews, which included both direct and nondirect care providers., Results: Eight themes (codes) were identified in the analysis. Three themes are presented individually with exemplars of communication and education strategies. The analysis revealed specific differences between the high-ITS and low-ITS facilities in regard to education and communication involving pressure ulcer prevention. These differences have direct implications for WOC nurses consulting in the LTC setting., Conclusions: Findings from this study suggest that effective strategies for staff education and communication regarding PU prevention differ based on the level of ITS within a given facility. Specific strategies for education and communication are suggested for agencies with high ITS and agencies with low ITS.

Nearly all Americans (97%) report eating candy at least once per year; yet, on a given day, only approximately one-fourth of the US population aged ≥2 y consumes candy. Among all Americans, candy contributes a relatively small proportion of calories, added sugars, and saturated fat to the total diet, and recent research suggests that current levels of candy consumption are not associated with risk of weight gain and cardiovascular disease in children and adults. Providing guidance for the consumption of candy in moderation requires an understanding of various behavioral health-related factors that influence candy consumption. A roundtable of behavioral nutrition experts, researchers, and nutrition educators met to discuss recent data on intakes of candy, health outcomes associated with usual candy intake, and the impact of behavioral strategies, including restriction, education, and environmental awareness, on modifying eating behaviors to achieve moderate intakes of candy. Restricting access to palatable foods, whether self-imposed or by parental control, may have potentially negative consequences. Techniques and insight into how to adopt "moderation" in candy consumption, from effective parental practices to environmental strategies that facilitate behavior change without a high degree of effort, were identified as important next steps toward sustainable dietary guidance related to the role of candy and other treats in a healthy lifestyle., (© 2015 American Society for Nutrition.)

Objective: Multiple studies show that behavioral couples therapy (BCT) is more efficacious than individually based therapy (IBT) for substance use and relationship outcomes among men with alcohol use disorder (AUD). The present study compared BCT with IBT for women with AUD., Method: Participants were women with AUD (N = 105) and their male partners without substance use disorder. Participants were mostly White and in their 40s. Women were randomized to equally intensive treatments consisting of either BCT plus 12-step-oriented IBT or IBT only. Primary outcomes included time line follow-back interview percentage days abstinent (PDA) and Inventory of Drug Use Consequences measure of substance-related problems. Secondary outcomes included the Dyadic Adjustment Scale (DAS), Relationship Happiness Scale (RHS), and Revised Conflict Tactics Scales measure of intimate partner violence (IPV). Outcome data were collected at baseline, posttreatment, and quarterly for 1-year follow-up., Results: Compared with IBT only, BCT plus IBT had significantly better primary outcomes of higher PDA and fewer substance-related problems during the 1-year follow-up period. Compared with IBT only, BCT had significantly higher male RHS during the 1-year follow-up. Women with lower pretreatment DAS had significantly higher DAS following BCT versus IBT, and there was an increasing advantage for BCT on female DAS over the follow-up. IPV was significantly reduced from pretreatment to follow-up, with no differences between treatment conditions., Conclusion: RESULTS showed that BCT for women with AUD was more efficacious than IBT in reducing substance use and substance-related problems and improving partner relationships.

Linear, dibranched and miktoarm amphiphiles containing both hydrophobic and fluorophilic moieties were synthesized and characterized in an attempt to elucidate the relationship between semi-fluorinated amphiphile structure and aggregate behaviour in aqueous solution. For the linear and dibranched amphiphiles, there was an exponential decrease in critical aggregation concentration (CMC) and a logarithmic increase in core microviscosity with increasing length of the fluorocarbon segments; while the miktoarm architecture produced no notable trend in microviscosity or CMC. Furthermore, the linear and dibranched surfactants showed enhanced kinetic stability, dissociating more slowly in the presence of human serum than did either the dibranched or miktoarm amphiphiles. Finally, encapsulation studies with the hydrophobic drug paclitaxel (PTX) showed that the ability to solubilize and retain PTX increased with the presence and with the increasing size of the fluorocarbon moiety for both the linear and dibranched amphiphiles, while no such trend was observed for the miktoarm amphiphiles.

Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR), riboflavin-dependent enzymes, participate in homocysteine metabolism. Reported effects of riboflavin status on the association between the MTHFR 677C>T polymorphism and homocysteine vary, and the effects of the MTRR 66A>G or MTRR 524C>T polymorphisms on homocysteine are unclear. We tested the hypothesis that the effects of the MTHFR 677C>T, MTRR 66A>G and MTRR 524C>T polymorphisms on fasting plasma total homocysteine (tHcy) depend on riboflavin status (erythrocyte glutathionine reductase activation coefficient, optimum: <1.2; marginally deficient: 1.2-1.4; deficient: ≥1.4) in 771 adults aged 18-75 years. MTHFR 677T allele carriers with middle or low tertile plasma folate (<14.7 nmol/L) had 8.2 % higher tHcy compared to the 677CC genotype (p < 0.01). This effect was eliminated when riboflavin status was optimal (p for interaction: 0.048). In the lowest cobalamin quartile (≤273 pmol/L), riboflavin status modifies the relationship between the MTRR 66 A>G polymorphism and tHcy (p for interaction: 0.034). tHcy was 6.6 % higher in MTRR 66G allele carriers compared to the 66AA genotype with marginally deficient or optimal riboflavin status, but there was no difference when riboflavin status was deficient (p for interaction: 0.059). tHcy was 13.7 % higher in MTRR 524T allele carriers compared to the 524CC genotype when cobalamin status was low (p < 0.01), but no difference was observed when we stratified by riboflavin status. The effect of the MTHFR 677C>T polymorphism on tHcy depends on riboflavin status, that of the MTRR 66A>G polymorphism on cobalamin and riboflavin status and that of the MTRR 524C>T polymorphism on cobalamin status.

Objective: To understand decision making concerning adoption and nonadoption of accelerated partial breast radiotherapy (RT) prior to long-term randomized trial evidence., Methods: A total of 36 radiation oncologists and surgeons were recruited through purposive and snowball sampling strategies from September 2010 through January 2013. Semistructured phone interviews were conducted and audio-recorded and lasted 20-45 minutes. Qualitative analysis was conducted using a framework approach, iteratively exploring key concepts and emerging issues raised by subjects. Interviews were transcribed and imported into Atlas.ti v6. Transcripts were independently coded by 3 researchers shortly after each interview, followed by consensus development on each coded transcript. Barriers and facilitators of adoption, practice patterns, and informational/educational sources concerning accelerated partial breast RT were all assessed to determine major themes., Results: Nearly half of physicians were surgeons (47%), and half were radiation oncologists (53%), with 61% overall in urban settings. Twenty-nine of the 36 physicians interviewed used brachytherapy-based partial breast RT. Five major factors were involved in physicians' decisions to adopt accelerated partial breast RT: facilitators encouraging adoption (e.g., enthusiastic colleagues and patient convenience), financial and prestige incentives, pressures to adopt (e.g., potential declines in referrals), judgment concerning acceptable level of scientific evidence, and barriers (e.g., not having appropriate machinery or referral mechanism in place). If technology was adopted, clinical guideline adherence varied., Conclusions: Technology adoption is based on financial and social pressures, along with often-limited scientific evidence and what seems "best" for patients. For technology adoption and diffusion to be rational and evidence-based, we must encourage appropriate financial payment models to curb use outside of research studies and promote development of additional treatment registries until sufficient evidence is gathered., (© The Author(s) 2014.)

Folate is essential for fetal development, and its deficiency during gestation causes behavioural deficits in the offspring. The present study investigated its influence during weaning on brain function in the pups of rats that were put on a folate-deficient (FD) diet on postnatal day (PND) 1. Systemic folate deficiency in pups on the FD diet (n 15) was evident from the dramatically lower hepatic folate concentrations (median 23·7, range 8·1-48·4 ng/mg protein) and higher homocysteine concentrations (median 27·7, range 14·7-45·5 pmol/mg protein), respectively, compared with those of pups on the normal diet (ND; n 9) (median 114·5, range 64·5-158·5 ng/mg protein and median 15·5, range 11·6-18·9 pmol/mg protein) on PND 23. Brain folate concentrations although low were similar in pups on the FD diet (median 10·5, range 5·5-24·5 ng/mg protein) and ND (median 11·1, range 7·1-24·2 ng/mg protein). There was a high accumulation of homocysteine in the brain of FD pups, mostly in the hippocampus (median 58·1, range 40·8-99·7 pmol/mg protein) and cerebellum (median 69·1, range 50·8-126·6 pmol/mg protein), indicating metabolic folate deficiency despite normal brain folate concentrations. Developmental deficits or autistic traits were more frequent in the FD group than in the ND group and repetitive self-grooming occurred, on average, three times (range 1-8) v. once (range 0-3) during 5 min, respectively. Long-term memory or spatial learning and set-shifting deficits affected 12 to 62% of rats in the FD group compared with none in the ND group. Post-weaning folic acid supplementation did not correct these deficits. These observations indicate that folate deficiency during weaning affects postnatal development even when gestational folate supply is normal.

Despite dietary recommendations that have repeatedly underscored the importance of increasing consumption of fruits and vegetables, intakes worldwide are lower than recommended levels. Consequently, the diets of many individuals may be lacking in nutrients and phytonutrients typical of a diet rich in a variety of fruits and vegetables. In the present study, we estimated phytonutrient intakes by adults categorised by sex, level of fruit and vegetable consumption (< 5 v. ≥ 5 servings/d), and geographic diet cluster. Intakes of nine select phytonutrients were estimated from the 2002-4 World Health Survey fruit and vegetable servings intake data (n 198,637), the FAO supply utilisation accounts data, and phytonutrient concentration data obtained from the US Department of Agriculture databases and the published literature. Percentage contributions to each phytonutrient intake from fruit and vegetable sources were also estimated. Estimated intakes of phytonutrients from fruits and vegetables varied across the thirteen geographic diet clusters, reflecting regional differences in both numbers and proportions of fruit and vegetable servings consumed, and the specific types of fruits and vegetables available in the diet. The mean phytonutrient intakes by adults consuming ≥ 5 servings/d of fruits and vegetables were approximately 2- to 6-fold the mean phytonutrient intakes by adults with low fruit and vegetable consumption (< 5 servings/d). In some cases, phytonutrient intakes by adults consuming ≥ 5 servings/d of fruits and vegetables in one geographic diet cluster were lower than the intakes by adults reporting < 5 servings/d in another cluster. The findings from this assessment provide important information regarding the major dietary patterns of phytonutrient intakes across geographic diet clusters.

Adult muscle's exceptional capacity for regeneration is mediated by muscle stem cells, termed satellite cells. As with many stem cells, Wnt/β-catenin signaling has been proposed to be critical in satellite cells during regeneration. Using new genetic reagents, we explicitly test in vivo whether Wnt/β-catenin signaling is necessary and sufficient within satellite cells and their derivatives for regeneration. We find that signaling is transiently active in transit-amplifying myoblasts, but is not required for regeneration or satellite cell self-renewal. Instead, downregulation of transiently activated β-catenin is important to limit the regenerative response, as continuous regeneration is deleterious. Wnt/β-catenin activation in adult satellite cells may simply be a vestige of their developmental lineage, in which β-catenin signaling is critical for fetal myogenesis. In the adult, surprisingly, we show that it is not activation but rather silencing of Wnt/β-catenin signaling that is important for muscle regeneration., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Osteochondral allograft (OCA) transplantation is an effective treatment for defects in the medial femoral condyle (MFC), but the procedure is limited by a shortage of grafts. Lateral femoral condyles (LFCs) differ in geometry from MFCs but may be a suitable graft source. The difference between articular surface locations of the knee can be evaluated with micro-computed tomography imaging and 3-dimensional image analysis., Hypothesis: LFC OCAs inserted into MFC lesions can provide a cartilage surface match comparable with those provided by MFC allografts., Study Design: Controlled laboratory study., Methods: Twenty MFCs and 10 LFCs were divided into 3 groups: 10 MFC recipients (MFCr), 10 MFC donors (MFCd), and 10 LFC donors (LFCd). A 20-mm defect was created in the weightbearing portion of the MFCr. Two grafts, 1 MFCd and 1 LFCd, were implanted sequentially into each MFCr. Micro-computed tomography (μCT) images of the MFCr were acquired and analyzed to compare the topography of the original recipient site with the MFCd- and LFCd-repaired sites. Three-dimensional transformations were defined to register the defect site in the 3 scans of each MFCr. Vertical deviations from each voxel of the graft cartilage surface, relative to the intact recipient cartilage surface, were calculated and assessed as root mean square deviation and percentage graft area that was proud, sunk, and within the "acceptable" distance (±1.00 mm). The effect of repair (with MFC vs with LFC) on each of the surface match parameters is presented as mean ± SD and was assessed by t test: height deviation over area (root mean square, mm), graft area acceptable (%), area unacceptably proud (%), area unacceptably sunk (%), step-off height over circumference (root mean square, mm), graft circumference acceptable (%), circumference unacceptably proud (%), and circumference unacceptably sunk (%). Percentage data were arcsin transformed before statistical testing. An alpha level of 0.05 was used to conclude if variations were statistically significant., Results: MFCr defects were filled with both orthotopic MFCd and nonorthotopic LFCd. Registered μCT images of the MFCr illustrate the cartilage surface contour in the sagittal and coronal planes, in the original intact condyle, as well as after OCA repairs. Specimen-specific surface color maps for the MFCr after implant of the MFCd and after implant of LFCd were generally similar, with some deviation near the edges. On average, the MFCr site exhibited a typical contour, and the MFCd and LFCd were slightly elevated. Both types of OCA-MFCd and LFCd-matched well, showing overall height deviations of 0.63 mm for area and 0.47 mm for step-off, with no significant difference between MFCd and LFCd (P = .92 and .57, respectively) and acceptable deviation based on area (87.6% overall) and step-off (96.7% overall), with no significant difference between MFCd and LFCd (P = .87 and .22, respectively). A small portion of the implant was proud (12.1% of area and 2.6% of circumference step-off height), with no significant difference between MFCd and LFCd (P = .26 and .27, respectively). A very small portion of the implant area and edge was sunk (0.3% of area and 0.6% of circumference), with no significant difference between MFCd and LFCd (P = .29 and .86, respectively)., Conclusion/clinical Relevance: The achievement of excellent OCA surface match with an MFCd or LFCd graft into the common MFCr site suggests that nonorthotopic LFC OCAs are acceptable graft options for MFC defects., (© 2014 The Author(s).)

Studies of the identity and physiological function of mesenchymal stromal cells (MSCs) have been hampered by a lack of markers that permit both prospective identification and fate mapping in vivo. We found that Leptin Receptor (LepR) is a marker that highly enriches bone marrow MSCs. Approximately 0.3% of bone marrow cells were LepR(+), 10% of which were CFU-Fs, accounting for 94% of bone marrow CFU-Fs. LepR(+) cells formed bone, cartilage, and adipocytes in culture and upon transplantation in vivo. LepR(+) cells were Scf-GFP(+), Cxcl12-DsRed(high), and Nestin-GFP(low), markers which also highly enriched CFU-Fs, but negative for Nestin-CreER and NG2-CreER, markers which were unlikely to be found in CFU-Fs. Fate-mapping showed that LepR(+) cells arose postnatally and gave rise to most bone and adipocytes formed in adult bone marrow, including bone regenerated after irradiation or fracture. LepR(+) cells were quiescent, but they proliferated after injury. Therefore, LepR(+) cells are the major source of bone and adipocytes in adult bone marrow., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: This study investigated children of alcoholics' (COAs) exposure to inter-parental conflict before and after their fathers received alcohol treatment and compared exposure levels to a community comparison sample., Method: This study included 67 couples with a treatment-seeking male alcoholic partner and children aged 4-16. The alcoholic fathers and their relationship partners provided data at baseline and at six and twelve month follow-ups. A community comparison sample of 78 couples with children in the target age range completed similar longitudinal assessments. It was hypothesized that treatment of paternal alcoholism would be associated with a decrease in COAs' exposure to conflict, and that among remitted patients exposure to conflict would decrease to the level found in the community sample., Results: Prior to the father's alcohol treatment, the children of the treatment sample were exposed to significantly more conflict between their parents than in the community comparison sample. After the fathers received alcohol treatment, COAs' exposure to conflict significantly decreased at both the six and twelve month follow-ups compared to baseline. Children of remitted alcoholics did not differ significantly in levels of exposure to conflict at six months follow-up compared to the community sample as predicted. However, at twelve months remitted alcoholics reported significantly more exposure to conflict compared to the community sample., Conclusions: Decreased child exposure to parental conflict is a benefit associated with the father's treatment for alcoholism, and it may lead to improvements in COAs' functioning after parental treatment., (Published by Elsevier Ltd.)

Dynamic standing balance is essential to perform functional activities and is included in the treatment of many lower extremity injuries. Physiotherapists utilize many methods to restore standing balance including stability exercises, functional retraining, and manual therapy. The purpose of this study was to investigate the effects of a rearfoot distraction manipulation on dynamic standing balance. Twenty healthy participants (age: 24.4 ± 2.8 years; height: 162.9 ± 37.7 cm; mass: 68.0 ± 4.8 kg; right leg dominant = 20) completed this study. Following familiarization, dynamic standing balance was assessed during: (1) an experimental condition immediately following a rearfoot distraction manipulation, and (2) a control condition. Dominant leg balance was quantified using the Y-balance test which measures lower extremity reach distances. Reach distances were normalized to leg length and measured in the anterior, posteromedial and posterolateral directions. Overall balance was calculated through the summing of all normalized directions. Paired t-tests and Wilcoxon rank tests were used to compare balance scores for parametric and non-parametric data as appropriate. Significance was set at 0.05 a priori. Effect size (ES) was calculated to determine the clinical impact of the manipulation. Increased reach distances (indicating improved balance) were noted following manipulation for overall balance (p = 0.03, ES = 0.26) and in the posteromedial direction (p = 0.01, ES = 0.42). Reach distances did not differ for the anterior (p = 0.11, ES = 0.16) or posterolateral (p = 0.11, ES = 0.25) components. Dynamic standing balance improved after a rearfoot distraction manipulation in healthy participants. It is hypothesized that manual therapy applied to the foot and ankle may be beneficial to augment other therapeutic modalities when working with patients to improve dynamic standing balance., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

To test the hypothesized role of alcohol consumption as a proximal risk factor for partner violence, a within-subjects analysis compared levels of alcohol consumption in violent versus nonviolent conflict events among substance-abusing women and their male partners. Participants were married or cohabiting women (N = 145) who had recently begun a substance abuse treatment program and reported both a violent and a nonviolent relationship conflict event with their male partner in the prior 6 months. The average age was 38, and 83% were White. Male partners did not participate in the study. The female participant provided information about the male partner. Women were interviewed regarding a violent conflict event in which physical violence occurred and a nonviolent conflict event in which psychological aggression occurred without physical violence. The interview assessed quantity of alcohol consumed and use of other drugs prior to each conflict. Alcohol consumption was significantly greater prior to violent versus nonviolent conflict events for all measures of women's alcohol consumption examined: any drinking, heavy drinking, number of drinks in the 12 hr preceding the conflict event, and estimated blood alcohol concentration at time of the event. Male partners' alcohol consumption showed similar results. Use of other drugs in women, but not men, was significantly more likely prior to physical conflicts. These within-subject comparisons help to rule out individual difference explanations for the alcohol-violence association and indicate that the quantity of alcohol consumption is an important proximal risk factor for partner violence in substance-abusing women and their male partners. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Background: Dietary guidance recommends consumption of a nutrient-dense diet containing a variety of fruits. The purpose of this study was to estimate usual nutrient intakes and adequacy of nutrient intakes among adult grapefruit consumers and non-consumers, and to examine associations between grapefruit consumption and select health parameters., Methods: The analysis was conducted with data collected in the National Health and Nutrition Examination Survey (NHANES) 2003-2008. Respondents reporting consumption of any amount of grapefruit or 100% grapefruit juice at least once during the 2 days of dietary recall were classified as grapefruit consumers., Results: Among adults aged 19+ years with 2 days of dietary recall (n=12,789), 2.5% of males and 2.7% of females reported consumption of 100% grapefruit juice or fresh, canned, or frozen grapefruit during the recalls. Grapefruit consumers were less likely to have usual intakes of vitamin C (males: 0% vs. 47%; females: 0% vs. 43%; P<0.001) and magnesium (P<0.05) below the estimated average requirement (EAR) compared to non-consumers, and they were more likely to meet adequate intake levels for dietary fiber (P<0.05). Potassium and β-carotene intakes were significantly higher among grapefruit consumers (P<0.001). Diet quality as assessed by the Healthy Eating Index-2005 (HEI-2005) was higher in grapefruit consumers (males: 66.2 [95% CI: 61.0-71.5] vs. 55.4 [95% CI: 54.4-56.4]; females: 71.4 [95% CI: 65.1-77.6] vs. 61.2 [95% CI: 59.8-62.6]). Among women, grapefruit consumption was associated with lower body weight, waist circumference, body mass index (BMI), triglycerides, C-reactive protein (CRP), and higher high-density lipoprotein (HDL) cholesterol (P<0.05), However, risk of being overweight/obese was not associated with grapefruit consumption., Conclusion: Consumption of grapefruit was associated with higher intakes of vitamin C, magnesium, potassium, dietary fiber, and improved diet quality. Grapefruit may provide a healthful option for adults striving to meet fruit recommendations.

This article reviews the current landscape regarding food fortification in the United States; the content is based on a workshop sponsored by the North American Branch of the International Life Sciences Institute. Fortification of the food supply with vitamins and minerals is a public health strategy to enhance nutrient intakes of the population without increasing caloric intake. Many individuals in the United States would not achieve recommended micronutrient intakes without fortification of the food supply. The achievement and maintenance of a desirable level of nutritional quality in the nation's food supply is, thus, an important public health objective. While the addition of nutrients to foods can help maintain and improve the overall nutritional quality of diets, indiscriminate fortification of foods could result in overfortification or underfortification in the food supply and nutrient imbalances in the diets of individuals. Any changes in food fortification policy for micronutrients must be considered within the context of the impact they will have on all segments of the population and of food technology and safety applications and their limitations. This article discusses and evaluates the value of fortification, the success of current fortification efforts, and the future role of fortification in preventing or reversing nutrient inadequacies., (© 2014 International Life Sciences Institute.)

Being overweight and obese are significant health concerns for men and women, yet despite comparable needs for effective weight loss and maintenance strategies, little is known about the success of commercial weight loss programs in men. This study tests the hypothesis that men participating in a commercial weight loss program (Weight Watchers) had significantly greater weight loss than men receiving limited support from health professionals for weight loss (controls). A pooled analysis of weight loss and related physiologic parameter data from 2 randomized clinical trials was conducted. After 12 months, analysis of covariance tests showed that men in the commercial program group (n = 85) lost significantly more weight (P < .01) than men in the control group (n = 84); similar significant differences were observed for body mass index and waist circumference. These results suggest that participation in a commercial weight loss program may be a more effective means to lose weight and maintain weight loss., (Published by Elsevier Inc.)

The Nutrition Facts panel on food labels in the United States currently displays Daily Values (DVs) that are based on outdated RDAs. The FDA has indicated that it plans to update the DVs based on the newer Dietary Reference Intakes (DRIs), but there is controversy regarding the best method for calculating new DVs from the DRIs. To better understand the implications of DV revisions, assuming that manufacturers choose to maintain current label claims for micronutrients from voluntarily fortified foods, we modeled intake of 8 micronutrients using NHANES 2007-2008 data and 2 potential methods for calculating DVs: the population-weighted Estimated Average Requirement (EAR) and the population-coverage RDA. In each scenario, levels of fortified nutrients were adjusted to maintain the current %DV. Usual nutrient intakes and percentages with usual intakes less than the EAR were estimated for the U.S. population and subpopulations aged ≥ 4 y (n = 7976). For most nutrients, estimates of the percentage of the U.S. population with intakes below the EAR were similar regardless of whether the DV corresponded to the population-weighted EAR or the population-coverage RDA. Potential decreases were observed in adequacy of nutrients of concern for women of childbearing age, namely iron and folate (up to 9% and 3%, respectively), adequacy of calcium among children (up to 6%), and adequacy of vitamin A intakes in the total population (5%) assuming use of the population-weighted EAR compared with the population-coverage RDA for setting the DV. Results of this modeling exercise will help to inform decisions in revising the DVs.

Objective: The aim of this study was qualitatively to describe and examine the expectations and experiences of the midlife transition in Arab women living in Qatar., Method: Six focus groups were conducted with Arab women living in Qatar: three groups of local Qatari women, and three groups of non-Qatari Arab women originating from neighboring countries. A purposive sample of 41 pre-, peri-, and postmenopausal women aged 40-60 years participated. The semi-structured group format encouraged discussion around knowledge about menopause; physical, emotional and social experiences related to menopause; and cultural differences that may exist related to menopause., Results: The majority of women considered menopause as a maturing experience, although the term 'menopause' was considered to have negative connotations. Postmenopausal women described menopausal symptoms consistent with general knowledge, but many premenopausal women were unaware of symptoms, even if they knew someone who had experienced menopause. Postmenopausal women were more socially active than before and were able to participate in religious activities that they previously could not attend during menses. How a woman experienced menopause depended on the husband's level of support, and some women believed that Western women did not have the appropriate support from husbands and families that Arab women have; they felt this lack of support could lead to negative outcomes such as being at an increased risk for suicide caused by depression during menopause., Conclusion: Qatari and non-Qatari women had many similarities in how they perceived and experienced menopause, although they collectively believed that the experiences of Western women are different.

How does symbolic number knowledge performance help identify young children at risk for poor mathematics achievement outcomes? In research and practice, classification of mathematics learning disability (MLD, or dyscalculia) is typically based on composite scores from broad measures of mathematics achievement. These scores do predict later math achievement levels, but do not specify the nature of math difficulties likely to emerge among students at greatest risk for long-term mathematics failure. Here we report that gaps in 2nd and 3rd graders' number knowledge predict specific types of errors made on math assessments at Grade 8. Specifically, we show that early whole number misconceptions predict slower and less accurate performance, and atypical computational errors, on Grade 8 arithmetic tests. We demonstrate that basic number misconceptions can be detected by idiosyncratic responses to number knowledge items, and that when such misconceptions are evident during primary school they persist throughout the school age years, with variable manifestation throughout development. We conclude that including specific qualitative assessments of symbolic number knowledge in primary school may provide greater specificity of the types of difficulties likely to emerge among students at risk for poor mathematics outcomes.

The idea of scholarship within disciplines has long been discussed in the relevant literature. The concept of scholarship in teaching and learning has its foundations in Boyer's (1990) seminal work Scholarship Reconsidered. In this, Boyer made the case for teaching to be enhanced and made public and to be credited with equal weight as research activity within academic institutions. The activities of teaching and learning are truly academia's raison d'être however they get obscured in the mists of the importance placed on research activity. To this end it is vital that educators begin to critically examine their teaching to fully inform research and practice. One of the lenses through which this can be done is through the act of reflection. Reflection on action as a process first described by Schön in 1983 (Schön, 2005) necessitates not only the critical examination of what we do but also what are the underlying assumptions about why we do what we do. The paper outlines such reflective portfolio submitted as part requirement for Postgraduate Diploma in Teaching and Learning in Higher Education. It examines student midwives learning using the reflective lens of the benchmark course portfolio., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Accurate patient identification is a National Patient Safety Goal. Misidentification of surgical specimens is associated with increased morbidity, mortality, and costs of care. The authors developed 12 practical, process-based, standardized measures of surgical specimen identification defects during the preanalytic phase of pathology testing (from the operating room to the surgical pathology laboratory) that could be used to quantify the occurrence of these defects. The measures (6 container and 6 requisition identification defects) were developed by a panel of physicians, pathologists, nurses, and quality experts. A total of 69 hospitals prospectively collected data over 3 months. Overall, there were identification defects in 2.9% of cases (1780/60 501; 95% confidence interval [CI] = 2.0%-4.4%), 1.2% of containers (1018/81 656; 95% CI = 0.8%-2.0%), and 2.3% of requisitions (1417/61 245; 95% CI = 1.2%-4.6%). Future research is needed to evaluate if hospitals are able to use these measures to assess interventions meant to reduce the frequency of specimen identification defects and improve patient safety.

Fractions pose significant challenges for many children, but for some children those challenges persist into high school. Here we administered a fractions magnitude comparison test to 122 children, from Grades 4 to 8, to test whether their knowledge of fractions typically learned early in the sequence of formal math instruction (e.g., fractions equivalent to one-half, fraction pairs with common denominators) differentiates those with mathematics learning disability (MLD) versus low achievement (LA) or typical achievement (TA) in mathematics and whether long-term learning trajectories of this knowledge also differentiate these groups. We confirmed that although fourth graders with TA (n=93) were more accurate in evaluating "one-half" fractions than in evaluating "non-half" fractions (until they reached ceiling performance levels on both types of fractions), children with MLD (n=11) did not show a one-half advantage until Grade 7 and did not reach ceiling performance even by Grade 8. Both the MLD and LA groups had early difficulties with fractions, but by Grade 5 the LA group approached performance levels of the TA group and deviated from the MLD group. All groups showed a visual model advantage over Arabic number representation of fractions, but this advantage was short-lived for the TA group (because ceiling level was achieved across formats), whereas it was slightly more persistent for the LA group and persisted through Grade 8 for children with MLD. Thus, difficulties with fractions persist through Grade 8 for many students, but the nature and trajectories of those difficulties vary across children with math difficulties (MLD or LA)., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Folate, choline, and betaine participate in homocysteine metabolism. It is not known whether they interact during pregnancy., Objective: The objective was to investigate how folate status affects choline, betaine, and dimethylglycine during pregnancy., Design: Fasting plasma folate, cobalamin, free choline, betaine, dimethylglycine, and total homocysteine (tHcy) were measured longitudinally at <12, 15, 24-27, and 34 gestational weeks (GW); at labor (nonfasting); and in the cord in participants (n = 522) from the Reus-Tarragona Birth Cohort (NUTrició i Creixement Intrauterí Retardat phase). Timing, dose, and duration of folic acid supplement use were recorded. Folate status was classified as below (low) or above (high) median plasma folate at baseline (27.6 nmol/L) and at 24-27 GW (11.4 nmol/L). Associations between folate or betaine with tHcy were investigated by using multiple linear regression analysis., Results: Plasma betaine decreased by 34.8% (1.0%) throughout pregnancy, and dimethylglycine increased by 39.7% (2.7%) between 24-27 GW and labor (all P < 0.001). Compared with high folate status, low status was associated with a higher dimethylglycine/betaine ratio from 15 GW and with lower plasma betaine and higher dimethylglycine from 24 to 27 GW, for the rest of pregnancy. Regression analysis showed that by 24-27 GW, both plasma folate and betaine were inversely associated with tHcy when folate status was low and that the association between betaine and tHcy depended on folate status at 24-27 and 34 GW (interaction terms: P < 0.001 and P < 0.01). Betaine was inversely associated with tHcy at labor regardless of folate status., Conclusion: Low folate status enhances the reduction in betaine and the increase in dimethylglycine during pregnancy and strengthens the association between betaine and tHcy. This trial was registered at clinicaltrials.gov as NCT01778205.

Background: Limited information is available regarding the impact of candy consumption on health. The purpose of this study was to investigate associations between typical frequency of candy consumption and body weight status and select cardiovascular risk factors among adults in the United States., Methods: Using data collected in the 2003-2006 National Health and Nutrition Examination Surveys (NHANES), adults were categorized as infrequent (≤ 3 eating occasions [EO]/month), moderate (> 3 EO/month and ≤ 3.5 EO/week), or frequent (> 3.5 EO/week) candy consumers based on the combined frequency of chocolate and other candy consumption over the previous 12 months. Weight and adiposity status were analyzed using logistic regression models, and blood pressure, lipids, and insulin sensitivity were analyzed using linear regression models. Models were adjusted for age, sex and race/ethnicity, and also for additional covariates with potential associations with the outcomes. Appropriate statistical weights were used to yield results generalizable to the US population., Results: Frequency of candy consumption was not associated with the risk of obesity, overweight/obesity, elevated waist circumference, elevated skinfold thickness, blood pressure, low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol, triglycerides, or insulin resistance. Increased frequency of candy consumption was associated with higher energy intakes and higher energy adjusted intakes of carbohydrates, total sugars and added sugars, total fat, saturated fatty acids and monounsaturated fatty acids (p < 0.05), and lower adjusted intakes of protein and cholesterol (p < 0.001)., Conclusions: Increased frequency of candy consumption among adults in the United States was not associated with objective measures of adiposity or select cardiovascular risk factors, despite associated dietary differences. Given the cross-sectional study design, however, it cannot be concluded that candy consumption does not cause obesity or untoward levels of cardiovascular risk markers. The lack of an association between frequency of candy consumption and cardiovascular risk factors could be due to reduced intake of candy among the overweight due to dieting or a health professional's recommendations. Additionally, it is important to note that the analysis was based on frequency of candy consumption and not amount of candy consumed. Longitudinal studies are needed to confirm the lack of associations between frequency of candy consumption and cardiovascular risk factors.

Objectives: The study's purpose was to identify the antihyperglycemic affects of colesevelam-HCl (C-HCl) by characterizing the diurnal and postprandial glucose patterns in type 2 diabetic subjects treated concomitantly with metformin, sulfonylurea, or a combination of metformin/sulfonylurea. A secondary aim was to determine whether C-HCl significantly increased the risk of hypoglycemia., Methods: A prospective, randomized, double-blind, placebo-controlled, crossover study employing continuous glucose monitoring (CGM) with ambulatory glucose profile (AGP) analysis was undertaken. Fifteen males and 6 females, age 60 ± 8 years, treated with metformin (n = 8), sulfonylurea (n = 2), or combination (n = 11) participated., Results: Treatment with C-HCl led to reductions in glycated hemoglobin (HbA1c) (7.5 ± 0.3 to 7.0 ± 0.4% P<.0001), LDL (90.9 ± 18.6 to 68.9 ± 15.2 mg/dL, P<.0007) and total cholesterol (169.2 ± 24.4 to 147.8 ± 21.5 mg/dL, P<.001). Significantly lower normalized diurnal (21 mg/dL/hour, P = .0006), nocturnal (19 mg/dL/hour, P = .0005), and daytime (22 mg/dL/hour, P = .0008) glucose exposure was detected immediately upon C-HCl administration. Additionally, there was a significant (P<.004) decline in postprandial glucose excursions (averaging 15% or -36 mg/dL/hour) pronounced at dinner following C-HCl administration. There was a nonsignificant increase in the incidence of hypoglycemia (0.4-1%), with no difference due to antihyperglycemic medications., Conclusions: AGP analysis of CGM visually and quantitatively showed immediate and midterm impacts of C-HCl on basal and postprandial glucose patterns. This suggests a multifactorial glucose-lowering mechanism for C-HCl affecting both meal-related and basal glucose levels.

Employment status is related to treatment recovery and quality of life in breast cancer survivors, yet little is known about return to work in immigrant and minority survivors. We conducted an exploratory qualitative study using ethnically cohesive focus groups of urban breast cancer survivors who were African-American, African-Caribbean, Chinese, Filipina, Latina, or non-Latina white. We audio- and video-recorded, transcribed, and thematically coded the focus group discussions and we analyzed the coded transcripts within and across ethnic groups. Seven major themes emerged related to the participants' work experiences after diagnosis: normalcy, acceptance, identity, appearance, privacy, lack of flexibility at work, and employer support. Maintaining a sense of normalcy was cited as a benefit of working by survivors in each group. Acceptance of the cancer diagnosis was most common in the Chinese group and in participants who had a family history of breast cancer; those who described this attitude were likely to continue working throughout the treatment period. Appearance was important among all but the Chinese group and was related to privacy, which many thought was necessary to derive the benefit of normalcy at work. Employer support included schedule flexibility, medical confidentiality, and help maintaining a normal work environment, which was particularly important to our study sample. Overall, we found few differences between the different ethnic groups in our study. These results have important implications for the provision of support services to and clinical management of employed women with breast cancer, as well as for further large-scale research in disparities and employment outcomes.

Objective: To understand the association between parenting and children's dietary fat consumption, this study tested a comprehensive model of parenting that included parent household rules, parent modeling of rules, parent mediated behaviors, and parent support., Design: Cross-sectional., Setting: Baseline data from the MOVE/me Muevo project, a recreation site-based obesity prevention and control intervention trial., Participants: Five hundred forty-one parents of children between the ages of 5 and 8 years and living in San Diego County., Main Outcome Measure: Children's fat consumption based on parent report using a short food frequency questionnaire., Analysis: A hierarchical linear regression was conducted. In exploratory analyses, a stepwise backward elimination approach was used., Results: Children's fat consumption was positively associated with parent household rules (P < .01) and negatively associated with parent modeling of rules (P < .01)., Conclusions and Implications: Controlling parenting behaviors, such as rule setting, are associated with more frequent fat consumption, whereas role modeling healthful behaviors is associated with less frequent fat consumption. Changing parenting behaviors with regard to how they feed their children is a logical avenue for improving eating behaviors., (Copyright © 2012 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)

Background: DNA methylation is an epigenetic phenomenon that can modulate gene function by up or downregulation of gene expression. Vitamin B12 and folate pathways are involved in the production of S-Adenosylmethionine, the universal methyl donor., Findings: Brain vitamin B12 concentration and global DNA methylation was determined in transcobalamin receptor (TCblR/CD320) knock out (KO) (n = 4) and control mice (n = 4) at 20-24 weeks of age. Median [IQR] brain vitamin B12 concentrations (pg/mg) in TCblR/CD320 KO mice compared with control mice was 8.59 [0.52] vs 112.42 [33.12]; p < 0.05. Global DNA methylation levels in brain genomic DNA were lower in TCblR/CD320 KO compared with control mice (Median [IQR]: 0.31[0.16] % vs 0.55[0.15] %; p < 0.05.)., Conclusions: In TCblR/CD320 KO mice, brain vitamin B12 drops precipitously by as much as 90% during a 20 week period. This decrease is associated with a 40% decrease in global DNA methylation in the brain. Future research will reveal whether the disruption in gene expression profiles due to changes in DNA hypomethylation contribute to central nervous system pathologies that are frequently seen in vitamin B12 deficiency.

Background: Individuals consuming diets dense in fruits and vegetables consume an array of phytonutrients as well as recognized nutritional components, including vitamins, minerals, and fiber. There is a growing body of evidence that phytonutrients may play positive roles in health., Objective: The purpose of this research was to estimate usual intakes of nine individual phytonutrients by Americans consuming recommended levels of fruits and vegetables compared to intakes by adults not meeting these recommendations, and to identify contributions of food sources to total phytonutrient intakes. The phytonutrients examined in this study are found predominantly in fruits and vegetables., Design: Food consumption data from the National Health and Nutrition Examination Surveys 2003-2006 and phytonutrient concentration data from US Department of Agriculture databases and the published literature were used to estimate energy-adjusted usual intakes. Student's t tests were used to compare mean energy-adjusted phytonutrient intakes between subpopulations who consumed recommended amounts of fruits and vegetables vs those who did not. Percentage contributions of each phytonutrient by food source were estimated for all adults., Results: Energy-adjusted intakes of all phytonutrients other than ellagic acid were considerably higher among both men and women meeting dietary recommendations for fruit and vegetable intakes compared to those not meeting the recommendations; energy-adjusted intakes of ellagic acid were higher only among women meeting vs not meeting the recommendations. For five of the nine phytonutrients (α-carotene, β-cryptoxanthin, lycopene, hesperetin, and ellagic acid), a single food accounted for 64% or more of the total intake of the phytonutrient., Conclusions: Energy-adjusted intakes of carotenoids and flavonoids are higher among men and women whose diets conform to dietary guidance for fruits and vegetables. A limited number of foods provide the majority of these phytonutrients. Findings from this research provide important reference information on the phytonutrient contributions of a diet rich in fruits and vegetables.

Psychogenic nonepileptic seizures (PNES) remain poorly understood neurobiologically. Previously reported work suggests that adjunct ictal heart rates (HRs) may differentiate PNES from complex partial seizures (CPS). We retrospectively reviewed and compared preictal, ictal, and postictal HR differences in patients with PNES (n=42) and CPS controls (n=46) electively admitted for video/EEG monitoring to further characterize PNES autonomic patterns. Statistically significant preictal HR increases (P=0.006) and postictal (P=0.015) HR reductions normalized to baseline were identified in subjects with PNES compared with CPS controls. Ictal HRs were not found to differentiate between PNES and CPS events. This pattern of pre-event HR increases and postevent HR decreases in patients with PNES compared with those with CPS suggests frontolimbic neural circuit dysfunction and merits further exploration., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Many fresh pork products, in particular, fresh lean pork products, are nutrient-dense sources of protein and several other nutrients. The purpose of this study was to estimate nutritional contributions of fresh and fresh lean pork to adults' diets in the United States. Mean total nutrient intakes by fresh and fresh lean pork consumers on a day of recall were compared with intakes by nonconsumers to test the hypothesis that overall nutrient intakes by consumers were comparable with or better as compared with intakes by nonconsumers. Intakes were assessed using the National Health and Nutrition Examination Survey 2003 to 2006. Based on 1 day of dietary intake, 10% of adults consumed fresh pork, and 4% consumed fresh lean pork. Among consumers, fresh and fresh lean pork contributed 16% and 9%, respectively, of total fat and accounted for 23% to 31% of total protein, cholesterol, selenium, and thiamin intake. Fresh and fresh lean pork also accounted for 11% to 19% of total saturated fat, phosphorus, potassium, riboflavin, niacin, vitamin B(6), and vitamin B(12) in the diets of consumers and contributed 21% and 16%, respectively, of total zinc. Diets including fresh or fresh lean pork provided higher energy-adjusted amounts of protein, selenium, thiamin, and vitamin B(6) as compared with diets of adults not consuming fresh pork (P < .05) and provided comparable amounts of fat and saturated fat. Consumption of lean cuts of fresh pork is consistent with dietary guidance, and selection of fresh lean pork products by current nonconsumers could increase dietary variety without adversely affecting nutrient intake., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Muscle regeneration requires the coordinated interaction of multiple cell types. Satellite cells have been implicated as the primary stem cell responsible for regenerating muscle, yet the necessity of these cells for regeneration has not been tested. Connective tissue fibroblasts also are likely to play a role in regeneration, as connective tissue fibrosis is a hallmark of regenerating muscle. However, the lack of molecular markers for these fibroblasts has precluded an investigation of their role. Using Tcf4, a newly identified fibroblast marker, and Pax7, a satellite cell marker, we found that after injury satellite cells and fibroblasts rapidly proliferate in close proximity to one another. To test the role of satellite cells and fibroblasts in muscle regeneration in vivo, we created Pax7(CreERT2) and Tcf4(CreERT2) mice and crossed these to R26R(DTA) mice to genetically ablate satellite cells and fibroblasts. Ablation of satellite cells resulted in a complete loss of regenerated muscle, as well as misregulation of fibroblasts and a dramatic increase in connective tissue. Ablation of fibroblasts altered the dynamics of satellite cells, leading to premature satellite cell differentiation, depletion of the early pool of satellite cells, and smaller regenerated myofibers. Thus, we provide direct, genetic evidence that satellite cells are required for muscle regeneration and also identify resident fibroblasts as a novel and vital component of the niche regulating satellite cell expansion during regeneration. Furthermore, we demonstrate that reciprocal interactions between fibroblasts and satellite cells contribute significantly to efficient, effective muscle regeneration.

Postoperative cognitive dysfunction may be associated with the toxic products of lipid peroxidation, such as the α,β-unsaturated aldehyde acrolein, which accumulates in aging. We previously identified an acrolein-mediated, serotonin-derived melanoid product, or SDM. This study further characterizes this putative novel neuromelanin, which is not made from catecholamines. In addition to its strong protein-binding properties, we observed that SDM binds Fe(2+) readily and exhibits complex redox characteristics. SDM may exist as a two-dimensional network of polymers that coalesce into larger entities exhibiting electroactive properties. These observations suggest that SDM may contribute to the decline in cognition due to focal degeneration from SDM-mediated free-radical production. We know that inhalational anesthetics sequester acrolein, which is toxic to neurons, and we propose that the local increase in acrolein depletes serotonin levels and enhances neuronal vulnerability through the production of neuromelanin-like structures, such as SDM.

Muscle and its connective tissue are intimately linked in the embryo and in the adult, suggesting that interactions between these tissues are crucial for their development. However, the study of muscle connective tissue has been hindered by the lack of molecular markers and genetic reagents to label connective tissue fibroblasts. Here, we show that the transcription factor Tcf4 (transcription factor 7-like 2; Tcf7l2) is strongly expressed in connective tissue fibroblasts and that Tcf4(GFPCre) mice allow genetic manipulation of these fibroblasts. Using this new reagent, we find that connective tissue fibroblasts critically regulate two aspects of myogenesis: muscle fiber type development and maturation. Fibroblasts promote (via Tcf4-dependent signals) slow myogenesis by stimulating the expression of slow myosin heavy chain. Also, fibroblasts promote the switch from fetal to adult muscle by repressing (via Tcf4-dependent signals) the expression of developmental embryonic myosin and promoting (via a Tcf4-independent mechanism) the formation of large multinucleate myofibers. In addition, our analysis of Tcf4 function unexpectedly reveals a novel mechanism of intrinsic regulation of muscle fiber type development. Unlike other intrinsic regulators of fiber type, low levels of Tcf4 in myogenic cells promote both slow and fast myogenesis, thereby promoting overall maturation of muscle fiber type. Thus, we have identified novel extrinsic and intrinsic mechanisms regulating myogenesis. Most significantly, our data demonstrate for the first time that connective tissue is important not only for adult muscle structure and function, but is a vital component of the niche within which muscle progenitors reside and is a critical regulator of myogenesis.