Ethnic-Specific Differences in Vitamin D Status Is Associated with Adiposity

BackgroundLow circulating 25 hydroxyvitamin D [25(OH)D] concentrations are common in obesity (BMI ≥30 kg/m2) and a negative relationship with body fat distribution has recently been reported. Ethnic-specific differences in body fat distribution have been described with South Asians are reported to have greater visceral adipose tissue (VAT), which could influence circulating 25(OH)D concentrations. The objective of this study is to investigate the relationship between plasma 25(OH)D, adiposity, and body fat distribution in Europeans and South Asians.Methods/Principal Findings187 Europeans and 192 South Asians were assessed for demographics, anthropometrics, and plasma 25(OH)D concentrations. Subcutaneous adipose tissue (SAT) and VAT were quantified by CT scan, and percent body fat by DEXA. Data were assessed by general linear models. South Asians had lower (P<0.001) plasma 25(OH)D concentrations and higher VAT (P = 0.04) than Europeans. Plasma 25(OH)D concentrations were negatively (P<0.05) associated with BMI, waist circumference, percent body fat, total adipose tissue, VAT, and SAT in unadjusted models and negatively (P<0.05) associated with VAT, SAT, and percent body fat after adjusting for BMI, ethnicity, age, and season of blood collection in males and females. When percent body fat, VAT, and SAT were included in the same model, only VAT remained negatively (P<0.05) associated with plasma 25(OH)D concentrations. Ethnicity remained significant in all models (P<0.001).ConclusionCompared to other adipose tissue compartments, VAT may have a distinct role in determining plasma 25(OH)D concentrations, which may account for the lower levels in South Asians

L-5-methyltetrahydrofolate supplementation increases blood folate concentrations to a greater extent than folic acid supplementation in Malaysian women

Background: Folic acid fortification of grains is mandated in many countries to prevent neural tube defects. Concerns regarding excessive intakes of folic acid have been raised. A synthetic analog of the circulating form of folate, l-5-methyltetrahydrofolate (l-5-MTHF), may be a potential alternative. Objective: The objective of this study was to determine the effects of folic acid or l-5-MTHF supplementation on blood folate concentrations, methyl nutrient metabolites, and DNA methylation in women living in Malaysia, where there is no mandatory fortification policy. Methods: In a 12-wk, randomized, placebo-controlled intervention trial, healthy Malaysian women (n = 142, aged 20–45 y) were randomly assigned to receive 1 of the following supplements daily: 1 mg (2.27 μmol) folic acid, 1.13 mg (2.27 μmol) l-5-MTHF, or a placebo. The primary outcomes were plasma and RBC folate and vitamin B-12 concentrations. Secondary outcomes included plasma total homocysteine, total cysteine, methionine, betaine, and choline concentrations and monocyte long interspersed nuclear element-1 (LINE-1) methylation. Results: The folic acid and l-5-MTHF groups had higher (P < 0.001) RBC folate (mean ± SD: 1498 ± 580 and 1951 ± 496 nmol/L, respectively) and plasma folate [median (25th, 75th percentiles): 40.1 nmol/L (24.9, 52.7 nmol/L) and 52.0 nmol/L (42.7, 73.1 nmol/L), respectively] concentrations compared with RBC folate (958 ± 345 nmol/L) and plasma folate [12.6 nmol/L (8.80, 17.0 nmol/L)] concentrations in the placebo group at 12 wk. The l-5-MTHF group had higher RBC folate (1951 ± 496 nmol/L; P = 0.003) and plasma folate [52.0 nmol/L (42.7, 73.1 nmol/L); P = 0.023] at 12 wk than did the folic acid group [RBC folate, 1498 ± 580 nmol/L; plasma folate, 40.1 nmol/L (24.9, 52.7 nmol/L)]. The folic acid and l-5-MTHF groups had 17% and 15%, respectively, lower (P < 0.001) plasma total homocysteine concentrations than did the placebo group at 12 wk; there were no differences between the folic acid and l-5-MTHF groups. No differences in plasma vitamin B-12, total cysteine, methionine, betaine, and choline and monocyte LINE-1 methylation were observed. Conclusion: These findings suggest differential effects of l-5-MTHF compared with folic acid supplementation on blood folate concentrations but no differences on plasma total homocysteine lowering in Malaysian women. This trial was registered at clinicaltrials.gov as NCT01584050

The social value of a QALY : raising the bar or barring the raise?

Background: Since the inception of the National Institute for Health and Clinical Excellence (NICE) in England, there have been questions about the empirical basis for the cost-per-QALY threshold used by NICE and whether QALYs gained by different beneficiaries of health care should be weighted equally. The Social Value of a QALY (SVQ) project, reported in this paper, was commissioned to address these two questions. The results of SVQ were released during a time of considerable debate about the NICE threshold, and authors with differing perspectives have drawn on the SVQ results to support their cases. As these discussions continue, and given the selective use of results by those involved, it is important, therefore, not only to present a summary overview of SVQ, but also for those who conducted the research to contribute to the debate as to its implications for NICE. Discussion: The issue of the threshold was addressed in two ways: first, by combining, via a set of models, the current UK Value of a Prevented Fatality (used in transport policy) with data on fatality age, life expectancy and age-related quality of life; and, second, via a survey designed to test the feasibility of combining respondents’ answers to willingness to pay and health state utility questions to arrive at values of a QALY. Modelling resulted in values of £10,000-£70,000 per QALY. Via survey research, most methods of aggregating the data resulted in values of a QALY of £18,000-£40,000, although others resulted in implausibly high values. An additional survey, addressing the issue of weighting QALYs, used two methods, one indicating that QALYs should not be weighted and the other that greater weight could be given to QALYs gained by some groups. Summary: Although we conducted only a feasibility study and a modelling exercise, neither present compelling evidence for moving the NICE threshold up or down. Some preliminary evidence would indicate it could be moved up for some types of QALY and down for others. While many members of the public appear to be open to the possibility of using somewhat different QALY weights for different groups of beneficiaries, we do not yet have any secure evidence base for introducing such a system

Woman-Centered Design through Humanity, Activism, and Inclusion

Women account for over half of the global population, however, continue to be subject to systematic and systemic disadvantage, particularly in terms of access to health and education. At every intersection, where systemic inequality accounts for greater loss of life or limitations on full and healthy living, women are more greatly impacted by those inequalities. The design of technologies is no different, the very definition of technology is historically cast in terms of male activities, and advancements in the field are critical to improve women's quality of life. This article views HCI, a relatively new field, as well positioned to act critically in the ways that technology serve, refigure, and redefine women's bodies. Indeed, the female body remains a contested topic, a restriction to the development of women's health. On one hand, the field of women's health has attended to the medicalization of the body and therefore is to be understood through medical language and knowledge. On the other hand, the framing of issues associated with women's health and people's experiences of and within such system(s) remain problematic for many. This is visible today in, e.g., socio-cultural practices in disparate geographies or medical devices within a clinic or the home. Moreover, the biological body is part of a great unmentionable, i.e., the perils of essentialism. We contend that it is necessary, pragmatically and ethically, for HCI to turn its attention toward a woman-centered design approach. While previous research has argued for the dangers of gender-demarcated design work, we advance that designing for and with women should not be regarded as ghettoizing, but instead as critical to improving women's experiences in bodily transactions, choices, rights, and access to and in health and care. In this article, we consider how and why designing with and for woman matters. We use our design-led research as a way to speak to and illustrate alternatives to designing for and with women within HCI.QC 20200930</p

Determinants of fish consumption in older people: a community-based cohort study

Objectives: Habitual fish consumption and its determinants in older people have not been well investigated. We addressed these issues through a population-based cohort study. Methods: In 2001-2003 we interviewed a random sample of 3336 residents aged ≥60 years in China, documenting socioeconomic status (SES) and disease risk factors. In 2007-2009 we re-interviewed 1757 survivors, additionally surveying average self-reported intake of fish over the past two years. Results: Of 1757 participants, 1697 responded to the fish consumption questionnaire; 23.0% of whom had “never eat” fish, 43.4% “once a week”, 26.9% “more than twice a week”, and 6.7% “≥once a day”. There was an inverse association of fish consumption with older age (multivariate adjusted odds ratio 0.64 [95% CI 0.45-0.92] and 0.35 [0.24-0.52] at ages of 75-79, and ≥80 years), female gender (0.63, 0.47-0.84), smoking (0.65, 0.48-0.88), living in a rural area (0.10, 0.07-0.15), having educational level of ≤primary school (0.10, 0.05-0.19), occupation of peasant (0.08, 0.05-0.14), low income (0.11, 0.07-0.18), financial difficulties (0.25, 0.18-0.34), being never married/divorced (0.48, 0.28-0.81), having undetected hypertension (0.71, 0.55-0.91), depression (0.50, 0.29-0.84) and dementia (0.64, 0.41-0.98). However, participants with central obesity and heart disease at baseline had increased odds of fish consumption. Separate data analysis for different levels of fish consumption showed a dose-response trend for these associations. Conclusion: In older Chinese, there are large socioeconomic inequalities, and certain lifestyle, psychosocial factors and health-related conditions are strong determinants of fish consumption. Such information is important for future development or refinement of effective dietary interventions targeting older adults

Suboptimal biochemical riboflavin status is associated with lower hemoglobin and higher rates of anemia in a sample of Canadian and Malaysian women of reproductive age

Background: Riboflavin is required for several redox reactions. Clinical riboflavin deficiency occurs mainly in low-income countries, where it is associated with anemia. The functional significance of suboptimal riboflavin status in different populations and its role in anemia is not well understood. Objectives: We assessed the biomarker status of riboflavin and its association with hemoglobin concentration and anemia in women living in Vancouver, Canada, and Kuala Lumpur, Malaysia. Methods: Healthy nonpregnant, nonbreastfeeding women (19-45 y) were recruited from Canada ( n = 206) and Malaysia (n = 210) via convenience sampling. Fasting blood was collected to assess riboflavin status [erythrocyte glutathione reductase activity coefficient (EGRac)], hematological indicators, soluble transferrin receptor (sTfR), ferritin, vitamin A, folate, and vitamin B-12 concentrations. Linear and logistic regression models were used to assess the association of riboflavin status with hemoglobin concentration and anemia. Results: EGRac (mean ± SD) values were higher, indicating poorer riboflavin status, in Malaysian compared with Canadian women (1.49 ± 0.17 compared with 1.38 ± 0.11). Likewise, riboflavin biomarker deficiency (EGRac ≥1.40) was significantly more prevalent among Malaysians than Canadians (71% compared with 40%). More Malaysian than Canadian women were anemic (hemoglobin <120 g/L; 18% compared with 7%). With use of linear regression (pooled sample; n = 416), EGRac values were negatively associated with hemoglobin concentration (r = -0.18; P < 0.001). This relation remained significant (P = 0.029) after adjusting for age, parity, ethnicity, vitamin B-12, folate, sTfR, ferritin, and vitamin A. Women with riboflavin deficiency (EGRac ≥1.40) were twice as likely to present with anemia (adjusted OR: 2.38; 95% CI: 1.08, 5.27) compared with women with EGRac <1.40. Conclusions: Biochemical riboflavin deficiency was observed in Canadian and Malaysian women, with higher rates of deficiency among Malaysian women. Deficient biomarker status of riboflavin was a weak but significant predictor of hemoglobin and anemia, suggesting that the correction of riboflavin deficiency may potentially play a small protective role in anemia, but this requires further investigation

A model to prioritize access to elective surgery on the basis of clinical urgency and waiting time

<p>Abstract</p> <p>Background</p> <p>Prioritization of waiting lists for elective surgery represents a major issue in public systems in view of the fact that patients often suffer from consequences of long waiting times. In addition, administrative and standardized data on waiting lists are generally lacking in Italy, where no detailed national reports are available. This is true although since 2002 the National Government has defined implicit Urgency-Related Groups (URGs) associated with Maximum Time Before Treatment (MTBT), similar to the Australian classification. The aim of this paper is to propose a model to manage waiting lists and prioritize admissions to elective surgery.</p> <p>Methods</p> <p>In 2001, the Italian Ministry of Health funded the Surgical Waiting List Info System (SWALIS) project, with the aim of experimenting solutions for managing elective surgery waiting lists. The project was split into two phases. In the first project phase, ten surgical units in the largest hospital of the Liguria Region were involved in the design of a pre-admission process model. The model was embedded in a Web based software, adopting Italian URGs with minor modifications. The SWALIS pre-admission process was based on the following steps: 1) urgency assessment into URGs; 2) correspondent assignment of a pre-set MTBT; 3) real time prioritization of every referral on the list, according to urgency and waiting time. In the second project phase a prospective descriptive study was performed, when a single general surgery unit was selected as the deployment and test bed, managing all registrations from March 2004 to March 2007 (1809 ordinary and 597 day cases). From August 2005, once the SWALIS model had been modified, waiting lists were monitored and analyzed, measuring the impact of the model by a set of performance indexes (average waiting time, length of the waiting list) and Appropriate Performance Index (API).</p> <p>Results</p> <p>The SWALIS pre-admission model was used for all registrations in the test period, fully covering the case mix of the patients referred to surgery. The software produced real time data and advanced parameters, providing patients and users useful tools to manage waiting lists and to schedule hospital admissions with ease and efficiency. The model protected patients from horizontal and vertical inequities, while positive changes in API were observed in the latest period, meaning that more patients were treated within their MTBT.</p> <p>Conclusion</p> <p>The SWALIS model achieves the purpose of providing useful data to monitor waiting lists appropriately. It allows homogeneous and standardized prioritization, enhancing transparency, efficiency and equity. Due to its applicability, it might represent a pragmatic approach towards surgical waiting lists, useful in both clinical practice and strategic resource management.</p

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Similar or Different? The Role of the Ventrolateral Prefrontal Cortex in Similarity Detection

Patients with frontal lobe syndrome can exhibit two types of abnormal behaviour when asked to place a banana and an orange in a single category: some patients categorize them at a concrete level (e.g., “both have peel”), while others continue to look for differences between these objects (e.g., “one is yellow, the other is orange”). These observations raise the question of whether abstraction and similarity detection are distinct processes involved in abstract categorization, and that depend on separate areas of the prefrontal cortex (PFC). We designed an original experimental paradigm for a functional magnetic resonance imaging (fMRI) study involving healthy subjects, confirming the existence of two distinct processes relying on different prefrontal areas, and thus explaining the behavioural dissociation in frontal lesion patients. We showed that: 1) Similarity detection involves the anterior ventrolateral PFC bilaterally with a right-left asymmetry: the right anterior ventrolateral PFC is only engaged in detecting physical similarities; 2) Abstraction per se activates the left dorsolateral PFC

2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results. One possible avenue is the development of patient-derived models, e.g. by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), which can then be differentiated into any cell type for modelling. These systems contain key genetic information from the donors, and therefore have enormous potential as tools in the investigation of pathological mechanisms underlying disease phenotype, and progression, as well as in drug testing platforms. hiPSCs have been widely cultured in 2D systems, but in order to mimic human brain complexity, 3D models have been proposed as a more advanced alternative. This review will focus on the use of patient-derived hiPSCs to model AD, PD, HD and ALS. In brief, we will cover the available stem cells, types of 2D and 3D culture systems, existing models for neurodegenerative diseases, obstacles to model these diseases in vitro, and current perspectives in the field