A cross-sectional relation between short sleep and obesity has not been confirmed prospectively. We examined the relationship between sleep duration and changes in body mass index (BMI) and waist circumference using the Whitehall II study, a prospective cohort of 10,308 white-collar British civil servants aged 35–55 in 1985–88. Data were gathered in 1997–9 and 2003–4. Sleep duration and other covariates were assessed. Changes in BMI and waist circumference were assessed between the two phases. The incidence of obesity (BMI ≥30 kg/m2) was assessed among non-obese participants at baseline. In cross-sectional analyses (n=5,021), there were significant, inverse associations (p<0.001) between duration of sleep and both BMI and waist circumference. Compared to 7h sleep short duration of sleep (≤5h) was associated with higher BMI (β=+0.82 units; 95% CI 0.38 to 1.26) and waist circumference (β=+1.88 cm; 0.64 to 3.12), and with an increased risk of obesity (ORadj 1.65; 1.22 to 2.24). In prospective analyses, short duration of sleep was not associated with significant changes in BMI (β=−0.06; −0.26 to 0.14) or waist circumference (β=+0.44; −0.23 to 1.12), nor with the incidence of obesity (ORadj 1.05; 0.60 to 1.82). There is no temporal relationship between short duration of sleep and future changes in measures of body weight and central adiposity.

OBJECTIVE

To assess the relationship between habitual sleep disturbances and the incidence of type 2 diabetes and to obtain an estimate of the risk.

RESEARCH DESIGN AND METHODS

We conducted a systematic search of publications using MEDLINE (1955–April 2009), EMBASE, and the Cochrane Library and manual searches without language restrictions. We included studies if they were prospective with follow-up >3 years and had an assessment of sleep disturbances at baseline and incidence of type 2 diabetes. We recorded several characteristics for each study. We extracted quantity and quality of sleep, how they were assessed, and incident cases defined with different validated methods. We extracted relative risks (RRs) and 95% CI and pooled them using random-effects models. We performed sensitivity analysis and assessed heterogeneity and publication bias.

RESULTS

We included 10 studies (13 independent cohort samples; 107,756 male and female participants, follow-up range 4.2–32 years, and 3,586 incident cases of type 2 diabetes). In pooled analyses, quantity and quality of sleep predicted the risk of development of type 2 diabetes. For short duration of sleep (≤5–6 h/night), the RR was 1.28 (95% CI 1.03–1.60, P = 0.024, heterogeneity P = 0.015); for long duration of sleep (>8–9 h/night), the RR was 1.48 (1.13–1.96, P = 0.005); for difficulty in initiating sleep, the RR was 1.57 (1.25–1.97, P < 0.0001); and for difficulty in maintaining sleep, the RR was 1.84 (1.39–2.43, P < 0.0001).

CONCLUSIONS

Quantity and quality of sleep consistently and significantly predict the risk of the development of type 2 diabetes. The mechanisms underlying this relation may differ between short and long sleepers.

This exploratory study surveyed 418 parents attending a paediatric hospital in order to establish their smoking habits and preparedness to quit. We found that 27% were current smokers, of whom 81% were willing to try and quit in the near future. These and the parent's other responses to a questionnaire will be used to develop a programme of smoking cessation for parents attending a children's hospital.

Background

Proximal femoral fractures are associated with increased morbidity and mortality. Pre-existing malnutrition and weight loss amongst this patient group is of primary concern, with conventional nutrition support being largely ineffective. The inflammatory response post proximal femoral fracture surgery and the subsequent risk of cachexia may explain the inability of conventional high energy high protein management to produce an anabolic response amongst these patients. Omega-3 fatty acids derived from fish oils have been extensively studied for their anti-inflammatory benefits. Due to their anti-inflammatory properties, the benefit of fish oil combined with individualized nutrition support amongst proximal femoral fracture patients post surgery is an attractive potential therapeutic strategy. The aim of the ATLANTIC trial is to assess the potential benefits of an anti-inflammatory dose of fish oil within the context of a 12 week individualised nutrition program, commencing seven days post proximal femoral fracture surgery.

Methods/Design

This randomized controlled, double blinded trial, will recruit 150 community dwelling elderly patients aged ≥65 years, within seven days of surgery for proximal femoral fracture. Participants will be randomly allocated to receive either a 12 week individualized nutrition support program complemented with 20 ml/day anti-inflammatory dose fish oil (~3.6 g eicosapentaenoic acid, ~2.4 g docosahexanoic acid; intervention), or, a 12 week individualized nutrition support program complemented with 20 ml/day low dose fish oil (~0.36 g eicosapentaenoic acid, ~0.24 g docosahexanoic acid; control).

Discussion

The ATLANTIC trial is the first of its kind to provide fish oil combined with individualized nutrition therapy as an intervention to address the inflammatory response experienced post proximal femoral fracture surgery amongst elderly patients. The final outcomes of this trial will assist clinicians in the development of effective and alternative treatment methods post proximal femoral fracture surgery which may ultimately result in a reduction in systemic inflammation, loss of weight and lean muscle and improvements in nutritional status, mobility, independence and quality of life among elderly patients.

Trial Registration

ACTRN12609000241235

Background The human paraoxonase (PON1) protein detoxifies certain organophosphates, and the PON1 Q192R polymorphism (rs662) affects PON1 activity. Groups with higher dose exposure to organophosphate sheep dips or first Gulf War nerve toxins reported poorer health if they had 192R, and these associations have been used to exemplify Mendelian randomization analysis. However, a reported association of 192R with depression in a population-based study of older women recently cast doubt on the specificity of the higher dose findings. We aimed to examine associations between the PON1 Q192R polymorphism and self-reported poor health and depression in two independent population-based studies.

Methods We used logistic regression models to examine the associations in men and women aged 60–79 years from the English Longitudinal Study of Ageing (ELSA, n = 3158) and InCHIANTI (n = 761) population studies. Outcomes included the Center for Epidemiologic Studies Depression (CES-D) scale, self-rated general health status and (in ELSA only) diagnoses of depression.

Results The PON1 Q192R polymorphism was not associated with self-reported poor health {meta-analysis: odds ratio (OR) = 1.01 [confidence interval (CI) 0.91–1.13], P = 0.80} or depressive symptoms in either study or in meta-analyses [CES-D: OR = 1.01 (CI 0.87–1.17), P = 0.90]. There was also no association with histories of diagnosed depression in ELSA [OR = 1.03 (CI 0.82–1.30), P = 0.80].

Conclusions We found no evidence of an association between the PON1 Q192R polymorphism and poor general or mental health in two independent population-based studies. Neither the claimed Q192R association with depression in the general population nor its theoretical implications were supported.

Galectins are a sub-family of lectins, defined by their highly conserved β-sandwich structures and ability to bind to β-galactosides, like Gal β1-4 Glc (lactose). Here, we used 15N-1H HSQC and pulse field gradient (PFG) NMR spectroscopy to demonstrate that galectin-1 (gal-1) binds to the relatively large galactomannan Davanat, whose backbone is composed of β1-4-linked d-mannopyranosyl units to which single d-galactopyranosyl residues are periodically attached via α1-6 linkage (weight-average MW of 59 kDa). The Davanat binding domain covers a relatively large area on the surface of gal-1 that runs across the dimer interface primarily on that side of the protein opposite to the lactose binding site. Our data show that gal-1 binds Davanat with an apparent equilibrium dissociation constant (Kd) of 10 × 10−6 M, compared to 260 × 10−6 M for lactose, and a stiochiometry of about 3 to 6 gal-1 molecules per Davanat molecule. Mannan also interacts at the same galactomannan binding domain on gal-1, but with at least 10-fold lower avidity, supporting the role of galactose units in Davanat for relatively strong binding to gal-1. We also found that the β-galactoside binding domain remains accessible in the gal-1/Davanat complex, as lactose can still bind with no apparent loss in affinity. In addition, gal-1 binding to Davanat also modifies the supermolecular structure of the galactomannan and appears to reduce its hydrodynamic radius and disrupt inter-glycan interactions thereby reducing glycan-mediated solution viscosity. Overall, our findings contribute to understanding gal-1–carbohydrate interactions and provide insight into gal-1 function with potentially significant biological consequences.

Ensembles of widely distributed, heterogeneous resources, or Grids, have emerged as popular platforms for large-scale scientific applications. In this paper we present the Virtual Instrument project, which provides an integrated application execution environment that enables end-users to run and interact with running scientific simulations on Grids. This work is performed in the specific context of MCell, a computational biology application. While MCell provides the basis for running simulations, its capabilities are currently limited in terms of scale, ease-of-use, and interactivity. These limitations preclude usage scenarios that are critical for scientific advances. Our goal is to create a scientific “Virtual Instrument” from MCell by allowing its users to transparently access Grid resources while being able to steer running simulations. In this paper, we motivate the Virtual Instrument project and discuss a number of relevant issues and accomplishments in the area of Grid software development and application scheduling. We then describe our software design and report on the current implementation. We verify and evaluate our design via experiments with MCell on a real-world Grid testbed.

Building on previous findings that amiloride analogues inhibit HIV-1 replication in monocyte-derived macrophages (MDM), Biotron Limited has generated a library of over 300 small-molecule compounds with significant improvements in anti-HIV-1 activity. Our lead compound, BIT225, blocks Vpu ion channel activity and also shows anti-HIV-1 activity, with a 50% effective concentration of 2.25 ± 0.23 μM (mean ± the standard error) and minimal in vitro toxicity (50% toxic concentration, 284 μM) in infected MDM, resulting in a selectivity index of 126. In this study, we define the antiretroviral efficacy of BIT225 activity in macrophages, which are important drug targets because cells of the monocyte lineage are key reservoirs of HIV-1, disseminating virus to the peripheral tissues as they differentiate into macrophages. In assays with acutely and chronically HIV-1Ba-L-infected MDM, BIT225 resulted in significant reductions in viral integration and virus release as measured by real-time PCR and a reverse transcriptase (RT) activity assay at various stages of monocyte-to-macrophage differentiation. Further, the TZM-bl assay showed that the de novo virus produced at low levels in the presence of BIT225 was less infectious than virus produced in the absence of the compound. No antiviral activity was observed in MDM chronically infected with HIV-2, which lacks Vpu, confirming our initial targeting of and screening against this viral protein. The activity of BIT225 is post-virus integration, with no direct effects on the HIV-1 enzymes RT and protease. The findings of this study suggest that BIT225 is a late-phase inhibitor of the viral life cycle, targeting Vpu, and is a drug capable of significantly inhibiting HIV-1 release from both acute and chronically infected macrophages.

Objective. To assess the repeatability of the validated Flinders Calcium Food Frequency Questionnaire (FFQCA) for estimating dietary calcium intake in a sample of community dwelling older Australians. Methods. A test-retest repeatability study involving 100 subjects (≥65 years) living independently in metropolitan Adelaide, Australia. Estimates of daily calcium intake from the first (FFQCA1) and repeated administration (FFQCA2) were calculated from two versions (35-item and 15-item) of the FFQCA. The intraclass correlation coefficient (ICC) was used to assess the repeatability. Results. Moderate and comparable ICC values (r = 0.5, r = 0.6) were found across the two versions of the FFQCA. Conclusion. Both FFQCA versions demonstrated moderate repeatability, supporting the results of previous studies.

The interpretation and measurement of the architectural organization of mitochondria depend heavily upon the availability of good software tools for filtering, segmenting, extracting, measuring, and classifying the features of interest. Images of mitochondria contain many flow-like patterns and they are usually corrupted by large amounts of noise. Thus, it is necessary to enhance them by denoising and closing interrupted structures. We introduce a new approach based on anisotropic nonlinear diffusion and bilateral filtering for electron tomography of mitochondria. It allows noise removal and structure closure at certain scales, while preserving both the orientation and magnitude of discontinuities without the need for threshold switches. This technique facilitates image enhancement for subsequent segmentation, contour extraction, and improved visualization of the complex and intricate mitochondrial morphology. We perform the extraction of the structure-defining contours by employing a variational level set formulation. The propagating front for this approach is an approximate signed distance function which does not require expensive re-initialization. The behavior of the combined approach is tested for visualizing the structure of a HeLa cell mitochondrion and the results we obtain are very promising.

The authors examined sociodemographic, lifestyle, and comorbidity factors that could confound or mediate U-shaped associations between sleep duration and health in 6,472 United Kingdom adults from the Whitehall II Study (1997–1999) and 3,027 US adults from the Western New York Health Study (1996–2001). Cross-sectional associations between short (<6 hours) and long (>8 hours) durations of sleep across several correlates were calculated as multivariable odds ratios. For short sleep duration, there were significant, consistent associations in both samples for unmarried status (United Kingdom: adjusted odds ratio (AOR) = 1.49, 95% confidence interval (CI): 1.15, 1.94; United States: AOR = 1.49, 95% CI: 1.10, 2.02), body mass index (AORs were 1.04 (95% CI: 1.01, 1.07) and 1.02 (95% CI: 1.00, 1.05)), and Short Form-36 physical (AORs were 0.96 (95% CI: 0.95, 0.98) and 0.97 (95% CI: 0.96, 0.98)) and mental (AORs were 0.95 (95% CI: 0.94, 0.96) and 0.98 (95% CI: 0.96, 0.99)) scores. For long sleep duration, there were fewer significant associations: age among men (AORs were 1.08 (95% CI: 1.01, 1.14) and 1.05 (95% CI: 1.02, 1.08)), low physical activity (AORs were 1.75 (95% CI: 0.97, 3.14) and 1.60 (95% CI: 1.09, 2.34)), and Short Form-36 physical score (AORs were 0.96 (95% CI: 0.93, 0.99) and 0.97 (95% CI: 0.95, 0.99)). Being unmarried, being overweight, and having poor general health are associated with short sleep and may contribute to observed disease associations. Long sleep may represent an epiphenomenon of comorbidity.

gal-1 (galectin-1) mediates cell–cell and cell–extracellular matrix adhesion, essentially by interacting with β-galactoside-containing glycans of cell-surface glycoconjugates. Although most structural studies with gal-1 have investigated its binding to simple carbohydrates, in particular lactose and N-acetyl-lactosamine, this view is limited, because gal-1 functions at the cell surface by interacting with more complex glycans that are heterogeneous in size and composition. In the present study we used NMR spectroscopy to investigate the interaction of human gal-1 with a large (120 kDa) complex glycan, GRG (galactorhamnogalacturonate glycan), that contains non-randomly distributed mostly terminal β(1→4)-linked galactose side chains. We used 15N–1H-HSQC (heteronuclear single quantum coherence) NMR experiments with 15N-enriched gal-1 to identify the GRG-binding region on gal-1 and found that this region covers a large surface area on gal-1 that includes the quintessential lactose-binding site and runs from that site through a broad valley or cleft towards the dimer interface. HSQC and pulsed-field-gradient NMR diffusion experiments also show that gal-1 binds GRG with a gal-1:GRG stoichiometry of about 5:1 (or 6:1) and with average macroscopic and microscopic equilibrium dissociation constants (Kd) of 8×10−6 M and 40×10−6 M (or 48×10−6 M) respectively, indicating stronger binding than to lactose (Kd=520×10−6 M). Although gal-1 may bind GRG in various ways, the glycan can be competed for by lactose, suggesting that there is one major mode of interaction. Furthermore, even though terminal motifs on GRG are Gal-β(1→4)-Gal rather than the traditional Gal-β(1→4)-Glc/GlcNAc (where GlcNAc is N-acetylglucosamine), we show that the disaccharide Gal-β(1→4)-Gal can bind gal-1 at the lactose-binding domain. In addition, gal-1 binding to GRG disrupts inter-glycan interactions and decreases glycan-mediated solution viscosity, a glycan decongestion effect that may help explain why gal-1 promotes membrane fluidity and lateral diffusion of glycoconjugates within cell membranes. Overall, our results provide an insight into the function of galectin in situ and have potential significant biological consequences.

Background

Phase angle (PhA) is derived from the resistance and reactance measurements obtained from bioelectric impedance analysis (BIA) and is considered indicative of cellular health and membrane integrity. This study measured PhA values of rehabilitation patients and compared them to reference values, measures of functional ability and serum C-reactive protein (CRP) levels to explore their utility as a clinical tool to monitor disease progression and treatment efficacy.

Methods

This cross-sectional observational study was conducted on 215 ambulatory rehabilitation patients aged 20 – 94 years. All participants had been hospitalised for a stroke, orthopaedic or other condition resulting in a functional limitation. PhA was derived from BIA analysis and functional ability characterised using the Functional Independence Measure (FIM), timed up and go (TUG) and maximal quadriceps strength (MQS). Serum levels of CRP were also collected.

Results

Stroke patients had the highest PhA (5.3°) followed by elective orthopaedic surgery (5.0°) with the other group (4.3°) significantly lower than both previous categories (p < 0.001). Ambulatory rehabilitation patients' PhA values were dependent on age and sex (p < 0.001), lower than published age matched healthy reference values (p ≤ 0.05) and similar to other hospitalised or sick groups, but also higher than values reported in critically ill patients. Patients with CRP values less than 10 mg.L-1 had significantly (p = 0.005) higher mean PhA values. Furthermore, the highest functional status quartiles had significantly higher PhAs (p ≤ 0.04) for the FIM, MQS and TUG measures.

Conclusion

The results suggest that the phase angles of rehabilitation patients are between those of healthy individuals and seriously ill patients, thereby supporting claims that PhA is indicative of general health status. Phase angles are a potentially useful indicator of functional status in patients commencing an ambulatory rehabilitation program with a normal hydration status.