Association of genetic vatiation within UBL5 with phenotypes of metabolic syndrome

The BEACON gene was initially identified using the differential display polymerase chain reaction on hypothalamic mRNA samples collected from lean and obese Psammomys obesus, a polygenic animal model of obesity. Hypothalamic BEACON gene expression was positively correlated with percentage of body fat, and intracerebroventricular infusion of the Beacon protein resulted in a dose-dependent increase in food intake and body weight. The human homolog of BEACON, UBL5, is located on chromosome 19p in a region previously linked to quantitative traits related to obesity. Our previous studies showed a statistically significant association between UBL5 sequence variation and several obesity- and diabetes-related quantitative physiological measures in Asian Indian and Micronesian cohorts. Here we undertake a replication study in a Mexican American cohort where the original linkage signal was first detected. We exhaustively resequenced the complete gene plus the putative promoter region for genetic variation in 55 individuals and identified five single nucleotide polymorphisms (SNPs), one of which was novel. These SNPs were genotyped in a Mexican American cohort of 900 individuals from 40 families. Using a quantitative trait linkage disequilibrium test, we found significant associations between UBL5 genetic variants and waist-to-hip ratio (p = 0.027), and the circulating concentrations of insulin (p = 0.018) and total cholesterol (p = 0.023) in fasted individuals. These data are consistent with our earlier published studies and further support a functional role for the UBL5 gene in influencing physiological traits that underpin the development of metabolic syndrome.

The limits of medicine and the social consequences for sufferers of chronic fatigue syndrome

Chronic fatigue syndrome (CFS) appears to be made up of several clusters of illness categories acting alone or in tandem to cause the decline of health through; fatigue/exhaustion, sensitivity/allergies, pain, general muscle and joint pains, cognitive impairment and gastrointestinal problems. This study investigated how patients interpret, evaluate and respond to the complex and varied symptoms of chronic fatigue syndrome. Data were collected from persons with CFS using a survey (n=90) and an interview (n=45). The researchers investigated how chronic fatigue syndrome is diagnosed by medical practitioners, how the label of CFS is determined and the social consequences for the patient. The results confirm the limited ability of the biomedical paradigm to diagnose adequately and treat effectively 'socially constructed' and medically ambiguous illnesses like CFS. In the absence of a legitimated regime of medical treatment for CFS, a range of often expensive treatments are employed by CFS sufferers, from formal use of pharmaceutical drugs through to 'alternative' therapies, including herbal, vitamin, homeopathic, esoteric meditative techniques, spiritual healing and general counselling are taken in no particular order.

Identifying depression in patients following admission for acute coronary syndrome

Chemerin is a novel adipokine associated with obesity and metabolic syndrome

Soluble protein hormones are key regulators of a number of metabolic processes, including food intake and insulin sensitivity. We have used a signal sequence trap to identify genes that encode secreted or membrane-bound proteins in Psammomys obesus, an animal model of obesity and type 2 diabetes (T2D). Using this signal sequence trap, we identified the chemokine chemerin as being a novel adipokine. Gene expression of chemerin and its receptor, chemokine-like receptor 1 (CMKLR1), was significantly higher in adipose tissue of obese and type 2 diabetic P. obesus compared with lean, normoglycemic P. obesus. Fractionation of P. obesus adipose tissue confirmed that chemerin was predominantly expressed in adipocytes, whereas CMKLR1 was expressed in both adipocytes and stromal-vascular cells of adipose tissue. In 3T3-L1 adipocytes, chemerin was markedly induced during differentiation, whereas CMKLR1 was down-regulated during differentiation. Serum chemerin levels were measured by ELISA in human plasma samples from 114 subjects with T2D and 142 normal glucose tolerant controls. Plasma chemerin levels were not significantly different between subjects with T2D and normal controls. However, in normal glucose tolerant subjects, plasma chemerin levels were significantly associated with body mass index, circulating triglycerides, and blood pressure. Here we report, for the first time, that chemerin is an adipokine, and circulating levels of chemerin are associated with several key aspects of metabolic syndrome.

Depression, anxiety and stress in women following acute coronary syndrome: implications for secondary prevention

Objective
To document incidence of depression, anxiety, and stress in women more than 6 months following an acute coronary syndrome.

Design
Participants were identified from a coronary care unit database. The Depression Anxiety Stress Scales 21 (DASS 21) was sent to potential participants via postal survey.

Setting
A metropolitan teaching hospital in Melbourne, Australia.

Participants
The cohort of women was aged between 55 and 70 years. They had been admitted to hospital with a diagnosis of acute coronary syndrome (ACS) between 6 and 14 months prior to participating in this study.

Main outcome measures
Scores on Depression, Anxiety, and Stress Scale (DASS 21).

Results
Of the 117 posted questionnaires, 39 women with a mean age of 63 (S.D. 4.97) responded to the survey, representing a response rate of 33.3%. Most participants scored within normal levels of depression (66.7%), anxiety (60.5%), and stress (70.3%), however, mild to extremely severe levels of each construct (33.4%, 39.6%, and 29.7%, respectively) were found.

Conclusions
The reporting of elevated levels of depression, anxiety and stress in a subset of women more than 6 months following an ACS event underscores the importance of ongoing screening for risk factors impacting on psychological well-being and the inclusion of this information in education and counseling strategies in both the inpatient and outpatient settings. Based on these pilot data, consideration of a screening system in the immediate post discharge period for women at risk and an education or support service are recommended.

Overweight, obesity and metabolic syndrome in rural southeastern Australia

OBJECTIVE: To measure the prevalence of overweight, obesity and the metabolic syndrome (MetS) in rural Australia.

DESIGN, SETTING AND PARTICIPANTS: Cross-sectional surveys were conducted in two rural areas in Victoria and South Australia in 2004-2005. A stratified random sample of men and women aged 25-74 years was selected from the electoral roll. Data were collected by a self-administered questionnaire, physical measurements and laboratory tests.

MAIN OUTCOME MEASURES: Prevalence of overweight and obesity, as defined by body mass index (BMI) and waist circumference; prevalence of MetS and its components.

RESULTS: Data on 806 participants (383 men and 423 women) were analysed. Based on BMI, the prevalence of overweight and obesity combined was 74.1% (95% CI, 69.7%-78.5%) in men and 64.1% (95% CI, 59.5%-68.7%) in women. Based on waist circumference, the prevalence of overweight and obesity was higher in women (72.4%; 95% CI, 68.1%-76.7%) than men (61.9%; 95% CI, 57.0%-66.8%). The overall prevalence of obesity was 30.0% (95% CI, 26.8%-33.2%) based on BMI (> or = 30.0 kg/m(2)) and 44.7% (95% CI, 41.2%-48.1%) based on waist circumference (> or = 102 cm [men] and > or= 88 cm [women]). The prevalence of MetS as defined by the US National Cholesterol Education Program Adult Treatment Panel III 2005 criteria was 27.1% (95% CI, 22.7%-31.6%) in men and 28.3% (95% CI, 24.0%-32.6%) in women; based on International Diabetes Federation criteria, prevalences for men and women were 33.7% (95% CI, 29.0%-38.5%) and 30.1% (95% CI, 25.7%-34.5%), respectively. Prevalences of MetS, central (abdominal) obesity, hyperglycaemia, hypertension and hypertriglyceridaemia increased with age.

CONCLUSIONS: In rural Australia, prevalences of MetS, overweight and obesity are very high. Urgent population-wide action is required to tackle the problem.

Genetic variation in BEACON influences quantitative variation in metabolic syndrome-related phenotypes

The BEACON gene (also known as UBL5) was identified as differentially expressed between lean and obese Psammomys obesus, a polygenic animal model of obesity, type 2 diabetes, and dyslipidemia. The human homologue of BEACON is located on chromosome 19p, a region likely to contain genes affecting metabolic syndrome–related quantitative traits as established by linkage studies. To assess whether the human BEACON gene may be involved in influencing these traits, we exhaustively analyzed the complete gene for genetic variation in 40 unrelated individuals and identified four variants (three novel). The two more common variants were tested for association with a number of quantitative metabolic syndrome–related traits in two large cohorts of unrelated individuals. Significant associations were found between these variants and fat mass (P = 0.026), percentage of fat (P = 0.001), and waist-to-hip ratio (P = 0.031). The same variants were also associated with total cholesterol (P = 0.024), LDL cholesterol (P = 0.019), triglycerides (P = 0.006), and postglucose load insulin levels (P = 0.018). Multivariate analysis of these correlated phenotypes also yielded a highly significant association (P = 0.0004), suggesting that BEACON may influence phenotypic variation in metabolic syndrome–related traits.

Associations of TV viewing and physical activity with the metabolic syndrome in Australian adults

Aims/hypothesis We analysed a sample of Australian adults to determine the strength of associations of TV viewing and participation in physical activity with the metabolic syndrome.

Methods This population-based cross-sectional study included 6,241 adults aged ge35 years who were free from diagnosed diabetes mellitus and self-reported ischaemic disease and were not taking lipid-lowering or antihypertensive drugs. The metabolic syndrome was defined according to the 1999 World Health Organization criteria. Participants self-reported TV viewing time and physical activity time for the previous week.

Results The adjusted odds ratio of having the metabolic syndrome was 2.07 (95% CI 1.49–2.88) in women and 1.48 (95% CI 0.95–2.31) in men who watched TV for >14 h per week compared with those who watched le7.0 h per week. Compared with those who were less active (<2.5 h per week), the odds ratio for the metabolic syndrome was 0.72 (95% CI 0.58–0.90) in men and 0.53 (95% CI 0.38–0.74) in women who were active (ge2.5 h per week). Longer TV viewing (>14 h per week) was associated with an increased risk of insulin resistance, obesity and dyslipidaemia in both men and women. A total physical activity time of ge2.5 h per week was associated with a reduced prevalence of both insulin resistance and dyslipidaemia in both sexes and reduced prevalence of both obesity and hypertension in women.

Conclusions/interpretation Increased TV viewing time was associated with an increased prevalence of the metabolic syndrome, while physical activity was associated with a reduced prevalence. Population strategies addressing the metabolic syndrome should focus on reducing sedentary behaviours such as TV viewing, as well as increasing physical activity.

The Pareto plus syndrome in top marketing journals: research and journal criteria

Purpose – Pareto’s Law often refers to the theory that a small percentage of a total is responsible for a large proportion of the total outcome. It is commonly known as the 80/20 law or principle. The objective is to review and debate whether there is a “Pareto syndrome” in the distribution of crucial research and journal criteria in top marketing journals.

Design/methodology/approach – The authors provide a review and a debate based upon previous research on top marketing journals. For this purpose, the Pareto syndrome concept is introduced, based upon a set of research and journal criteria. Their distribution is examined.

Findings – The review of research and journal criteria in top marketing journals generated an extremely skewed outcome. When it comes to the criteria, the top journals in marketing tend to be governed by narrow concerns of research rather than broad ones.

Research limitations/implications – The research and journal criteria that have a skewed outcome may reinforce the rigidity and the lack of innovativeness of the marketing discipline. The evolutionary speed of the discipline may at best be reduced or it may at worst grind to a halt. The authors argue that there are a number of serious concerns to be addressed in the future review and debate of top journals in marketing.

Practical implications – Editors and editorial boards need seriously to address the concerns reviewed and debated, namely the skewed distribution of criteria, such as affiliation, data and methodology.

Originality/value – The authors debate that there is evidence that confirms the existence of a Pareto plus syndrome in key research and journal criteria of top marketing journals.

Redistribution of glucose from skeletal muscle to adipose tissue during catch-up fat. A link between catch-up growth and later metabolic syndrome.

Catch-up growth, a risk factor for later obesity, type 2 diabetes, and cardiovascular diseases, is characterized by hyperinsulinemia and an accelerated rate for recovering fat mass, i.e., catch-up fat. To identify potential mechanisms in the link between hyperinsulinemia and catch-up fat during catch-up growth, we studied the in vivo action of insulin on glucose utilization in skeletal muscle and adipose tissue in a previously described rat model of weight recovery exhibiting catch-up fat caused by suppressed thermogenesis per se. To do this, we used euglycemic-hyperinsulinemic clamps associated with the labeled 2-deoxy-glucose technique. After 1 week of isocaloric refeeding, when body fat, circulating free fatty acids, or intramyocellular lipids in refed animals had not yet exceeded those of controls, insulin-stimulated glucose utilization in refed animals was lower in skeletal muscles (by 20–43%) but higher in white adipose tissues (by two- to threefold). Furthermore, fatty acid synthase activity was higher in adipose tissues from refed animals than from fed controls. These results suggest that suppressed thermogenesis for the purpose of sparing glucose for catch-up fat, via the coordinated induction of skeletal muscle insulin resistance and adipose tissue insulin hyperresponsiveness, might be a central event in the link between catch-up growth, hyperinsulinemia and risks for later metabolic syndrome.

Single vs. two steroid injections for carpal tunnel syndrome: a randomised clinical trial

We investigated the efficacy of a single vs. double steroid injections in the treatment of carpal tunnel syndrome (CTS) in a randomised double-blind controlled trial. Patients with idiopathic CTS were randomised into (i) one group receiving a baseline methylprednisolone acetate injection plus a saline injection 8 weeks later and (ii) a second group receiving methylprednisolone acetate injection at baseline and at 8 weeks. The primary outcome was the Global Symptom Score (GSS). Forty patients were recruited. By 40 weeks, the mean GSS improved from 25.6 to 14.1 in the single-injection group whereas from 26.7 to 12.6 in the reinjection group, but there was no significant difference in GSS between the two groups (p = 0.26). There were also no significant differences in terms of electrophysiological and functional outcomes. The results suggest that an additional steroid injection confers no added benefit to a single injection in terms of symptom relief.

Study of Proteinuria: Isolation of Proteins from the Nephrotic Syndrome

One of the most puzzling phenomena of abnormal renal physiology is the occurrence of the nephrotic syndrome. The syndrome has been defined by a collection of clinical and pathological symptoms, but there is no correlation between the clinical and pathological symptoms nor is the etiology of the syndrome known. Proteinuria is probably the most distinguishing feature in the nephrotic syndrome, and there are two possible explanations for its occurrence: (1) the excessive amounts of protein found in nephrotic urine could be due to an increased basement membrane permeability in the glomerulus of the kidney or (2) dysproteinemia. An attempt has been made to evaluate the theory of dysproteinemia in connection with the syndrome. The albumin fractions of nephrotic urine have been studied for their amino acid composition by separating them from the urine by paper electrophoresis, hydrolyzing them, and identifying the amino acids present by two-dimensional chromatography. There seem to be no variations in the qualitative makeup of nephrotic albumin from that of normal albumin, but the literature shows that there are some slight variations in the quantitative amino acid composition of nephrotic albumin compared with normal albumin. More extensive and highly developed experimentation along the lines of protein structure and composition must be done before it can conclusively be stated that dysproteinemia is of importance in the nephrotic syndrome.

Carpal tunnel syndrome: diagnostic usefulness of sonography

PURPOSE: To prospectively evaluate accuracy of sonography for diagnosis of carpal tunnel syndrome (CTS) in patients clinically suspected of having the disease in one or both hands.
MATERIALS AND METHODS: A prospective cohort of 133 patients suspected of having CTS were referred to a teaching hospital between October 2001 and June 2002 for electrodiagnostic study. One hundred twenty patients (98 women, 22 men; mean age, 49 years; range, 19–83 years) underwent sonography within 1 week after electrodiagnostic study. Radiologist was blinded to electrodiagnostic study results. Seventy-five patients had bilateral symptoms; 23 patients, right-hand symptoms; and 22 patients, left-hand symptoms (total, 195 symptomatic hands). Cross-sectional area of median nerve was measured at three levels: immediately proximal to carpal tunnel inlet, at carpal tunnel inlet, and at carpal tunnel outlet. Flexor retinaculum was used as a landmark to margins of carpal tunnel. Optimal threshold levels (determined with classification and regression tree analysis) for areas proximal to and at tunnel inlet and at tunnel outlet were used to discriminate between patients with and patients without disease. Sensitivity, specificity, and false-positive and false-negative rates were derived on the basis of final diagnosis, which was determined with clinical history and electrodiagnostic study results as reference standard.
RESULTS: For right hands, sonography had sensitivity of 94% (66 of 70); specificity, 65% (17 of 26); false-positive rate, 12% (nine of 75); and false-negative rate, 19% (four of 21) (cutoff, 0.09 cm2 proximal to tunnel inlet and 0.12 cm2 at tunnel outlet). For left hands, sensitivity was 83% (53 of 64); specificity, 73% (24 of 33); false-positive rate, 15% (nine of 62); and false-negative rate, 31% (11 of 35) (cutoff, 0.10 cm2 proximal to tunnel inlet).
CONCLUSION: Sonography is comparable to electrodiagnostic study in diagnosis of CTS and should be considered as initial test of choice for patients suspected of having CTS.

Profile of dyslipodemia in psammomys obesus, an animal model of the metabolic syndrome

Objective. To investigate lipid profiles in Psammomys obesus and relationships between lipid profile and other components of the Metabolic Syndrome.

Methods. A total number of 49 adults with a wide range of body weight and glucose tolerance were studied in a cross-sectional analysis. Plasma cholesterol distribution profiles were measured by size exclusion lipid chromatography. Blood glucose was measured using an enzymatic glucose analyser, and plasma insulin was determined by radioimmunossay.

Results. Obese diabetic Psammomys obesus had elevated plasma cholesterol (P=0.003) and triglyceride levels (p>0.001) compared to their lean littermates. The hypercholesterolemia was mainly due to increased circulating levels of VLDL-cholesterol (P=0.003) and LDL-cholesterol (P=0.003) in these animals. Multiple linear regression analyses revealed that body weight was independently associated with plasma cholesterol (P=0.011) and LDL concentration (P=0.009), while plasma insulin was associated with VLDL-cholesterol concentration (P=0.005). All of the variables measured exhibited continuous distributions across a wide range of phenotypes, from a normal rodent lipid profile to profound dyslipidemia.

Conclusions. These data suggest that the dyslipidemia in obese, diabetic Psammomys obesus is closely associated with other components of the Metabolic Syndrome, including obesity and insulin resistance.