Glycaemic control modifies the haptoglobin 2 allele-conferred susceptibility to coronary artery disease in Type 1 diabetes.

AIMS: We aimed to assess whether the association of the haptoglobin 2 allele with coronary artery disease is modified by glycaemic control in a prospective cohort study of individuals with childhood-onset Type 1 diabetes. METHODS: Coronary artery disease events (death from coronary artery disease, confirmed myocardial infarction, stenosis ≥50%, revascularization) were assessed between 1986 and 2013 among 480 individuals with Type 1 diabetes (baseline age 28 years; diabetes duration 19 years). Better glycaemic control was defined as an updated mean HbA1c during follow-up of <8% (64 mmol/mol). RESULTS: In crude models, the incidence of coronary artery disease increased with the number of haptoglobin 2 alleles (hazard ratio 1.34, 95% CI 1.05-1.71). This association was more pronounced in those with better than in those with worse glycaemic control (P interaction = 0.05) and remained essentially unaltered after multivariable adjustments (hazard ratio 2.65, 95% CI 1.30-5.41 in those with better glycaemic control and hazard ratio 1.20, 95% CI 0.93-1.56 in those with worse glycaemic control). CONCLUSIONS: These results suggest that, although better control may reduce the incidence of coronary artery disease in Type 1 diabetes, a residual risk related to the haptoglobin 2 allele remains.

Ectopic cardiovascular fat in middle-aged men: effects of race/ethnicity, overall and central adiposity. The ERA JUMP study.

BACKGROUND/OBJECTIVES: Higher volumes of ectopic cardiovascular fat (ECF) are associated with greater risk of coronary heart disease (CHD). Identifying factors that are associated with ECF volumes may lead to new preventive efforts to reduce risk of CHD. Significant racial/ethnic differences exist for overall and central adiposity measures, which are known to be associated with ECF volumes. Whether racial/ethnic differences also exist for ECF volumes and their associations with these adiposity measures remain unclear. SUBJECTS/METHODS: Body mass index (BMI), computerized tomography-measured ECF volumes (epicardial, pericardial and their summation) and visceral adipose tissue (VAT) were examined in a community-based sample of 1199 middle-aged men (24.2% Caucasians, 7.0% African-Americans, 23.6% Japanese-Americans, 22.0% Japanese, 23.2% Koreans). RESULTS: Significant racial/ethnic differences existed in ECF volumes and their relationships with BMI and VAT. ECF volumes were the highest among Japanese-Americans and the lowest among African-Americans. The associations of BMI and VAT with ECF differed by racial/ethnic groups. Compared with Caucasians, for each 1-unit increase in BMI, African-Americans had lower, whereas Koreans had higher increases in ECF volumes (P-values<0.05 for both). Meanwhile, compared with Caucasians, for each 1-unit increase in log-transformed VAT, African-Americans, Japanese-Americans and Japanese had similar increases, whereas Koreans had a lower increase in ECF volumes (P-value<0.05). CONCLUSIONS: Racial/ethnic groups differed in their propensity to accumulate ECF at increasing level of overall and central adiposity. Future studies should evaluate whether reducing central adiposity or overall weight will decrease ECF volumes more in certain racial/ethnic groups. Evaluating these questions might help in designing race-specific prevention strategy of CHD risk associated with higher ECF.

Small-for-gestational-age birth and maternal plasma antioxidant levels in mid-gestation: a nested case-control study.

OBJECTIVE: To assess whether maternal plasma antioxidant levels in mid-pregnancy are associated with small-for-gestational-age (SGA) birth. DESIGN: Case-control study nested within a population-based cohort study. SETTING: Four hospitals in Montreal, Canada. POPULATION: Pregnant women recruited before 24 weeks of gestation, whose pregnancies were not complicated by pre-eclampsia or preterm delivery. METHODS: Blood samples were obtained at 24-26 weeks and assayed for nutritionally derived antioxidant levels in SGA cases (n = 324) and randomly selected controls with birthweights between the 25th and 75th centiles (n = 672). We performed logistic regression analyses using the standardised z-score of each antioxidant as the main independent variable, after summing highly correlated antioxidants or combining via principle component analysis. We adjusted for risk factors for SGA that were associated with antioxidant levels. MAIN OUTCOME MEASURES: SGA, birthweight <10th centile for gestational age and sex. RESULTS: Retinol was positively associated with risk of SGA (adjusted odds ratio [OR] 1.41; 95% confidence interval [95% CI] 1.22-1.63, per SD increase). Carotenoids (log of the sum of ß-carotene, lutein/zeaxanthin, α- and ß-cryptoxanthin) were negatively associated with SGA (adjusted OR 0.64; 95% CI 0.54-0.78, per SD increase). We found no significant associations between SGA and lycopene or any of the forms of vitamin E assessed, including α-tocopherol, corrected α-tocopherol (per nmol/l of low-density lipoprotein articles), or γ-tocopherol. CONCLUSIONS: Elevated retinol may be associated with an increased risk of SGA, whereas elevated carotenoid levels may reduce the risk. A better understanding of the nature of these associations is required, however, before recommending specific nutritional interventions in an attempt to prevent SGA birth.

The effects of adiponectin and leptin on changes in bone mineral density.

UNLABELLED: We tested the hypothesis that low leptin and high adiponectin levels are associated with higher rates of bone mineral density (BMD) loss among 3,075 men and women, aged 70-79, from the Health Aging and Body Composition Study. Results suggest that adiponectin, but not leptin, is a risk factor for bone loss in women. INTRODUCTION: Adiponectin and leptin are hormones secreted by adipose cells that may impact BMD. Few studies have evaluated the longitudinal association of leptin and adiponectin levels with rates of BMD change. METHODS: Hip and whole-body areal BMD (aBMD) were measured five times using dual-energy X-ray absorptiometry over 10 years (average follow-up time, 7.95 ± 1.92 years). Trabecular lumbar spine volumetric BMD (vBMD) was measured using quantitative computed topography at baseline and year 6 in the Pittsburgh cohort only. Random slope and intercept models were used to account for within person correlation as a result of repeated measures of hip and whole-body aBMD. Linear regression was used to model changes in spine trabecular vBMD. RESULTS: Among women, the annualized rate of hip aBMD loss in the highest tertile of adiponectin was -0.67% (95% CI -0.77, -0.58) compared to [-0.43% (95% CI -0.51, -0.35)] in the lowest tertile (p trend = 0.019) after adjusting for age, race, BMI, diabetes, baseline hip aBMD, and weight change. In men, hip aBMD loss was greatest in the high adiponectin group (tertile 3), however this association was not significant (p trend = 0.148). After adjusting for weight change in women, the association between higher leptin and lower hip aBMD loss was attenuated and no longer significant (p trend = 0.134). Leptin and adiponectin levels were not associated with whole-body aBMD or trabecular lumbar spine vBMD loss. CONCLUSIONS: Adiponectin was associated with increased hip aBMD loss in women only, supporting evidence that adiponectin may have an important role in bone health.

Blood flow restriction training in South Africa - a panel discussion.

Background: Blood flow restriction (BFR) training uses a cuff to partially occlude venous blood flow and improve musculoskeletal training outcomes. Over the past 25 years, numerous studies have demonstrated its relative safety and efficacy. Objectives: Blood flow restriction training is under review by the Health Professions Council of South Africa due to safety and ethical concerns. The objective of this roundtable discussion is to gain better insight into the current use and perception of blood flow restriction training in South Africa. Formation of panel: The expert panel had experience with the use of BFR training and included one representative from each of the following professions, namely, sports medicine, physiotherapy and biokinetics. Discussion: The panellists provided their unique perspectives on BFR training, whilst reaching a relative consensus on its safety, screening, efficacy, and appropriate use. Agreement on appropriate loading and occlusion pressure protocols during different phases of rehabilitation was less clear. Conclusion: Although BFR is a safe and effective modality, the development of evidence-based protocols among different health professionals in South Africa is required to ensure good clinical practice.

Serum lipids and their associations with viral levels and liver disease severity in a treatment-naïve chronic hepatitis C type 1-infected cohort.

In patients with chronic hepatitis C virus (HCV) infection, steatosis and fibrosis have been shown to be inversely associated with total cholesterol (TC) and low-density lipoprotein cholesterol. Steatosis and fibrosis have also been found to be associated with triglyceride (TG) levels; though, the direction of the relationship is inconsistent across studies. The objective of this study was to assess whether viral level and histological factors are associated with the serum lipid profile in a treatment-naïve cohort with chronic HCV genotype 1 infection. Participants were from the prospective Study of Viral Resistance to Antiviral Therapy (Virahep-C). Fasting lipid profiles were analysed for 160 African Americans and 170 Caucasian Americans. Linear regression was used to evaluate associations of each lipid with viral load and liver disease. TG levels were significantly and directly associated with HCV levels (P = 0.0034) and steatosis (P < 0.0001). Other lipid parameters were significantly lower in those with fibrosis [HDLc (P = 0.001) and TC levels (P = 0.004)] than in those without fibrosis. In patients with HCV genotype 1 infection, more severe liver disease was associated with lower lipid levels, with the exception of TG levels that were directly related to steatosis. The direct relationship between viral load and TG levels is consistent with proposed the mechanisms of very low density lipoprotein/HCV particle secretion. In contrast, the direct relationship between TG level and steatosis is inconsistent with posited mechanisms of HCV-induced steatosis, a possible reflection of HCV genotype 1 infection and a metabolic aetiology of steatosis.

The association of serum 25-hydroxyvitamin D with indicators of bone quality in men of Caucasian and African ancestry.

UNLABELLED: We examined the association of serum 25-hydroxyvitamin D [25(OH)D] with indices of bone quality in older men. Positive associations for 25(OH)D and bone mineral density, content, cortical thickness, and axial and polar strength strain indices were observed among Caucasians; however, among men of African descent findings were either null or negative. INTRODUCTION: There are limited data on serum 25(OH)D and bone measures in men of African ancestry. To better understand racial differences in vitamin D status and bone health, a cross-sectional study among 446 Caucasian men in the US and 496 men of African ancestry in Tobago (age ≥ 65 years) was conducted. METHODS: Serum 25(OH)D (liquid chromatography and tandem mass spectrometry) was measured, and peripheral quantitative computed tomography scans were administered. Bone measures estimated included trabecular and cortical volumetric bone mineral density (vBMD), bone mineral content (BMC), bone geometry (cross-sectional area and cortical thickness), and polar and axial strength strain indices (SSIp and SSIx). RESULTS: Men of African ancestry had higher 25(OH)D than Caucasians (34.7 vs. 27.6 ng/ml, p < 0.01). Among Caucasians, 25(OH)D was positively (p trend < 0.05) associated with cortical vBMD, total BMC, cortical thickness, SSIp, and SSIx at the distal radius after adjustment for potential confounders. Similar patterns were observed at the distal tibia. In contrast, in men of African ancestry, there was an inverse association (p trend < 0.05) between 25(OH)D and the cross-sectional area, and SSIx. Race modified (p for interaction < 0.05) the association between 25(OH)D and total BMC, cross-sectional area, SSIp, SSIx, and trabecular vBMD of the radius. In men of African ancestry, there was evidence of a threshold effect (at approximately 18 ng/ml) for 25(OH)D on tibial total BMC and cortical thickness. CONCLUSIONS: More studies are needed to better comprehend these race differences for 25(OH)D and bone density, geometry, and indices of bone strength.

Association analysis of 33 lipoprotein candidate genes in multi-generational families of African ancestry.

African ancestry individuals have a more favorable lipoprotein profile than Caucasians, although the mechanisms for these differences remain unclear. We measured fasting serum lipoproteins and genotyped 768 tagging or potentially functional single nucleotide polymorphisms (SNPs) across 33 candidate gene regions in 401 Afro-Caribbeans older than 18 years belonging to 7 multi-generational pedigrees (mean family size 51, range 21-113, 3,426 relative pairs). All lipoproteins were significantly heritable (P<0.05). Gender-specific analysis showed that heritability for triglycerides was much higher (P<0.01) in women than in men (women, 0.62+/-0.18, P<0.01; men, 0.13+/-0.17, P>0.10), but the heritability for LDL cholesterol (LDL-C) was higher (P<0.05) in men than in women (men, 0.79+/-0.21, P<0.01; women, 0.39+/-0.12, P<0.01). The top 14 SNPs that passed the false discovery rate threshold in the families were then tested for replication in an independent population-based sample of 1,750 Afro-Caribbean men aged 40+ years. Our results revealed significant associations for three SNPs in two genes (rs5929 and rs6511720 in LDLR and rs7517090 in PCSK9) and LDL-C in both the family study and in the replication study. Our findings suggest that LDLR and PCSK9 variants may contribute to a variation in LDL-C among African ancestry individuals. Future sequencing and functional studies of these loci may advance our understanding of genetic factors contributing to LDL-C in African ancestry populations.

Temporal patterns in overweight and obesity in Type 1 diabetes.

AIMS: Time trends in overweight and obesity in the general population have been well documented; however, temporal patterns in Type 1 diabetes (T1DM) have not been thoroughly investigated. We therefore assessed temporal patterns in overweight and obesity and predictors of weight change in 589 individuals from the Pittsburgh Epidemiology of Diabetes Complications Study, a cohort of childhood-onset T1DM. METHODS: Participants were first seen in 1986-1988, when mean age and diabetes duration were 29 and 20 years, respectively, and biennially thereafter for 18 years. Overweight was defined as 25.0or=30.0 kg/m2. RESULTS: At baseline, the prevalence of overweight and obesity were 28.6% and 3.4%, respectively. After 18 years' follow-up, the prevalence of overweight increased by 47% while the prevalence of obesity increased sevenfold. Seven per cent were on intensive insulin therapy (>or=3 insulin injections per day or on insulin pump) at baseline; by 2004-2007, this was 82%. Predictors of weight change were a higher baseline HbA1c, symptomatic autonomic neuropathy (inversely), overt nephropathy (inversely), and going onto intensive insulin therapy during follow-up. CONCLUSIONS: These data demonstrate dramatic weight gain in T1DM and underscore the complexity of weight change in this disease.

A survey of family doctors on the likeability of migraine and other common diseases and their prevalence of migraine.

A survey of 148 family doctors attending a continuing medical education migraine update lecture was performed to assess whether family doctors like to treat migraine and other common disorders and the prevalence of migraine. Doctors were asked to respond to the following statement using a five-point Likert scale (from 1, strongly disagree to 5, strongly agree): 'I like to treat patients with this disease or symptom'. The response rate was 53% with a mean age of 51.5 years. Doctors reported liking to treat general medical conditions more (mean = 4.40) than migraine (mean = 3.38) and other neurological diseases (mean = 3.20). Doctors reported a personal history of migraine in the prior 1 year of 22.8% and 45.6% lifetime, with 17% becoming aware for the first time that they personally had migraine after attending the lecture. Respondents with a personal history of migraine liked to treat migraine more than those without a history.

Adiposity and mortality in type 1 diabetes.

BACKGROUND: In the general population, adiposity exhibits a J- or U-shaped relationship with mortality; however, in catabolic states this relationship is often inversely linear. We have recently documented an age-independent increase in overweight/obesity in the Pittsburgh Epidemiology of Diabetes Complications Study (EDC) of type 1 diabetes (T1D). As intensified insulin therapy (IIT) may promote weight gain, the impact of weight gain in T1D is of importance. We therefore assessed the association of adiposity with mortality in 655 EDC participants during 20 years of follow-up. METHODS: Individuals were categorized as underweight (body mass index (BMI)<20), normal (20< or = BMI <25), overweight (25< or = BMI <30), or obese (BMI > or =30). Cox models were constructed using BMI and covariates at baseline, updated means during follow-up, time variation (reflecting most recent status), and change during adulthood as predictors of mortality. RESULTS: The prevalence of IIT (3+ insulin shots daily and/or pump) increased from 7 to 82%. Overweight increased by 47% and obesity increased sevenfold. There were 146 deaths. In unadjusted models, BMI (modeled continuously) showed a quadratic relationship with mortality (P=0.002, <0.0001 <0.0001 for baseline, updated mean and time-varying models, respectively). However, only in the time-varying model were the obese significantly different from the normal weight, whereas the baseline model showed no differences by BMI category. In both the updated mean and time-varying models, the underweight were at greater risk than were the normal weight (P<0.0001 both models). The nonlinear relationship of adiposity with mortality remained after adjustment for diabetes complications and for biological or socioeconomic/lifestyle risk factors, with the exception of baseline socioeconomic/lifestyle risk factors, in which a linear association emerged. Adjustment for waist circumference eliminated risk in the obese. Finally, weight gain during follow-up was protective. CONCLUSION: The relationship of adiposity with mortality in T1D now seems to resemble that of the general population, albeit with a marked increased risk in those who are underweight.

Organ transplantation.

In the report "Pregnancy interception with a combination of prostaglandins: Studies in monkeys: by J. W. Wilks (30 Sept., p. 1407), figures 2 and 3 on page 1408 were interchanged.

Progesterone regulation of the occupied form of nuclear estrogen receptor.

Total concentrations of estrogen receptor in the uterine nuclear fraction are reduced rapidly after progesterone treatment of the proestrous hamster. Progesterone acts selectively on the occupied form of the nuclear estrogen receptor, with no effect on the concentration of an unoccupied form. This observation indicates that progesterone modulates the action of estrogen by controlling nuclear retention of the estrogen-receptor complex.

Molecular Origin of Io's Fast Sodium.

Neutral sodium emissions encircling Jupiter exhibit an intricate and variable structure that is well matched by a simple loss process from Io's atmosphere. These observations imply that fast neutral sodium is created locally in the Io plasma torus, both near Io and as much as 8 hours downstream. Sodium-bearing molecules may be present in Io's upper atmosphere, where they are ionized by the plasma torus and swept downstream. The molecular ions dissociate and dissociatively recombine on a short time scale, releasing neutral fragments into escape trajectories from Jupiter. This theory explains a diverse set of sodium observations, and it implies that molecular reactions (particularly electron impact ionization and dissociation) are important at the top of Io's atmosphere.

The Monitor Practice Program: implications for dentistry and dental education.

The restorative model of care, known colloquially as drilling and filling, has been challenged on the basis of its inappropriateness. The Caries Management System protocol was developed as an evidence-based strategy for non-surgical treatment of caries lesions and the Monitor Practice Program was designed to test the hypothesis that use of the protocol would reduce risk of dental caries experience. After 7 years, patients attending intervention practices, compared with those attending control practices, needed: 30%-50% fewer restorative interventions; 55% fewer first time restorative interventions; 32% fewer repeat restorative interventions; and were only 23% as likely to be classified as high risk. The outcome was cost-effective and patients attending intervention practices highly valued non-invasive care, and intervention dentists derived professional satisfaction from non-surgical caries management. The implications of the program are that the general public will likely embrace the benefits of non-invasive caries management, as will many current and future dental practitioners. This calls for dental practice reform including: the establishment of a clinical discipline in cariology; cariology curriculum development; revised accreditation regulations for cariology programs in dental schools; advanced training in clinical cariology leading to a specialty; support from the dental profession; and public health advocacy.

Ethnocentrism is an unacceptable rationale for health care policy: a critique of transplant tourism position statements.

Medical tourism has emerged as a global health care phenomenon, valued at $60 billion worldwide in 2006. Transplant tourism, unlike other more benign forms of medical tourism, has become a flashpoint within the transplant community, underscoring the uneasy relationships among science, religion, politics, ethics and international health care policies concerning the commercialization of transplantation. Numerous professional associations have drafted or issued position statements condemning transplant tourism. Often the criticism is misdirected. The real issue concerns both the source and circumstances surrounding the procurement of donor organs, including commercialization. Unfortunately, many of the position statements circulated to date represent an ethnocentric and decidedly western view of transplantation. As such, the merits of culturally insensitive policy statements issued by otherwise well-intended transplant professionals, and the organizations they represent, must be evaluated within the broader context of foreign relations and diplomacy, as well as cultural and ethical relativity. Having done so, many persons may find themselves reluctant to endorse statements that have produced a misleading social desirability bias, which, to a great extent, has impeded more thoughtful and inclusive deliberations on the issues. Therefore, instead of taking an official position on policy matters concerning the commercial aspects of transplantation, international professional associations should offer culturally respectful guidance.

Calibration of magnetic probes in the vicinity of a conducting well.

Measuring magnetic fields near the edge of a plasma device can be complicated by the geometric effects of the ports through which such measurements are made. The primary effect is an attenuation of the magnetic field at the probe coil due to the field expanding into the finite sized conducting well of the port. In addition, it is possible to determine the correspondence between the location of a field line as it intersects the probe coil inside the well, with its location far from the perturbation of the well. Here we explore several methods of experimentally characterizing the magnetic fields in the vicinity of the magnetic probe ports of a vacuum vessel, with the aim of improving the interpretation of magnetic measurements needed for experiments in plasma physics.

Caries risk reduction in patients attending a caries management clinic.

BACKGROUND: A Caries Management Clinic was established for patients at high risk of caries aiming to reduce caries incidence to close to zero. That is, to prevent new lesions on existing sound surfaces, along the susceptible restoration margins, and to remineralize existing cavitated and non-cavitated lesions. Twenty patients attended the clinic every two weeks from April to December 2005. METHODS: The Caries Management System is a ten-step non-invasive strategy to arrest and remineralize early lesions and includes consideration of the patient at risk, the status of each individual lesion, patient management, clinical management, and monitoring. RESULTS: After six months, there was a 42 per cent increase in gingival sites having Gingival Index scores of zero, and a 21 per cent decrease in sites having Gingival Index scores of 2 compared to baseline (chi(2 )=( )137.67, 4 df, p = 0.00001). Ready to change (RTC) patients had significantly fewer sites scored GI

The Monitor Practice Programme: is non-invasive management of dental caries in private practice effective?

BACKGROUND: This paper reviews the efficacy of an intensive, preventive-based, non-invasive approach to the management of dental caries within a randomized controlled trial. METHODS: The primary efficacy measure was the two-year DMFS increment. Changes in risk status, fluoride history, number of emergency visits and toothaches, along with demographic variables such as age, gender, health problems, and the location of the dental practice attended were measured. Regression analysis was undertaken to adjust for potential confounding variables. RESULTS: Nine hundred and two patients were recruited within 22 dental practices between May 2005 and March 2006. Baseline DMFS did not differ significantly between the control and study groups (p = 0.83). Age (p < 0.001), health status (p = 0.005), baseline risk (p < 0.001) and fluoride history (p < 0.001) were all independent significant predictors of two-year DMFS increment. Gender approached significance (p = 0.08). There were no statistically significant differences between the groups in the incidence of toothaches (p = 0.1) or number of treatment visits required (p = 0.35). There was a significant difference in the two-year incremental DMFS score in the study group compared to the control group (mean difference 2.2; p < 0.001). After adjusting for confounding variables the difference in the DMFS increment between the control and study groups remained significant (mean difference 1.7; p < 0.001). CONCLUSIONS: The results indicate efficacy of the preventive programme. Efficacy was independent of age, gender, medical concerns, fluoride history, or previous history of dental caries, in a population of patients attending for treatment in private dental practices, in a variety of locations, on a relatively short-term basis (two years). While encouraging, it will be essential that these results are followed over a longer period of time in order to determine whether the benefits are maintained.