Energetics of rocked inhomogeneous ratchets

We study the efficiency of frictional thermal ratchets driven by finite frequency driving force and in contact with a heat bath. The efficiency exhibits varied behavior with driving frequency. Both nonmonotonic and monotonic behavior have been observed. In particular the magnitude of efficiency in finite frequency regime may be more than the efficiency in the adiabatic regime. This is our central result for rocked ratchets. We also show that for the simple potential we have chosen, the presence of only spatial asymmetry (homogeneous system) or only frictional ratchet (symmetric potential profile), the adiabatic efficiency is always more than in the nonadiabatic case.Comment: 5 figure

Effect of multivitamin and multimineral supplementation on cognitive function in men and women aged 65 years and over : a randomised controlled trial

Background: Observational studies have frequently reported an association between cognitive function and nutrition in later life but randomised trials of B vitamins and antioxidant supplements have mostly found no beneficial effect. We examined the effect of daily supplementation with 11 vitamins and 5 minerals on cognitive function in older adults to assess the possibility that this could help to prevent cognitive decline. Methods: The study was carried out as part of a randomised double blind placebo controlled trial of micronutrient supplementation based in six primary care health centres in North East Scotland. 910 men and women aged 65 years and over living in the community were recruited and randomised: 456 to active treatment and 454 to placebo. The active treatment consisted of a single tablet containing eleven vitamins and five minerals in amounts ranging from 50–210 % of the UK Reference Nutrient Intake or matching placebo tablet taken daily for 12 months. Digit span forward and verbal fluency tests, which assess immediate memory and executive functioning respectively, were conducted at the start and end of the intervention period. Risk of micronutrient deficiency at baseline was assessed by a simple risk questionnaire. Results: For digit span forward there was no evidence of an effect of supplements in all participants or in sub-groups defined by age or risk of deficiency. For verbal fluency there was no evidence of a beneficial effect in the whole study population but there was weak evidence for a beneficial effect of supplementation in the two pre-specified subgroups: in those aged 75 years and over (n 290; mean difference between supplemented and placebo groups 2.8 (95% CI -0.6, 6.2) units) and in those at increased risk of micronutrient deficiency assessed by the risk questionnaire (n 260; mean difference between supplemented and placebo groups 2.5 (95% CI -1.0, 6.1) units). Conclusion: The results provide no evidence for a beneficial effect of daily multivitamin and multimineral supplements on these domains of cognitive function in community-living people over 65 years. However, the possibility of beneficial effects in older people and those at greater risk of nutritional deficiency deserves further attention.Peer reviewedPublisher PD

Multiple current reversals in forced inhomogeneous ratchets

Transport properties of overdamped Brownian paricles in a rocked thermal ratchet with space dependent friction coefficient is studied. By tuning the parameters, the direction of current exhibit multiple reversals, both as a function of the thermal noise strength as well as the amplitude of rocking force. Current reversals also occur under deterministic conditions and exhibits intriguing structure. All these features arise due to mutual interplay between potential asymmetry,noise, driving frequency and inhomogeneous friction.Comment: 6 figure

Profiling of cardio-metabolic risk factors and medication utilisation among Type II diabetes patients in Ghana: a prospective cohort study

Background: Type II diabetes mellitus (T2DM) is complicated by multiple cardio-metabolic risk factors. Controlling these factors requires lifestyle modifications alongside utilisation of anti-diabetic medications. Different glucose lowering [(biguanides (BIGs), sulfonylureas (SUAs), thiazolidinediones (TNZ)], lipid lowering (statins), and anti-hypertensive medicines [angiotensin converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), angiotensin II receptor blockers (ARBs) and central acting drugs (CADs)] have been approved for controlling hyperglycaemia, dyslipidaemia and hypertension respectively. Here, we examined factors that characterise T2DM and explored the response to medication therapy among T2DM patients. Methods: This prospective cohort study recruited 241 T2DM patients reporting at a clinic in Ghana, from January through to August, 2016. Each patient’s demographic, medications and anthropometric data was obtained while information on medication adherence was captured using Morisky adherence scale-8 (MMAS-8). Fasting blood samples were collected for biochemical analysis. Results: The mean age of participants was 57.82 years for baseline and six-month follow-up. Physical activity differed at baseline and follow up (p \u3c 0.05) but not body mass index (BMI). BIG alone, or in combination with SUA and TNZ did not improve glycaemic status at follow up (p \u3e 0.05). Many participants using either ACEI or ARB were able to control their blood pressures. Among dyslipidaemia patients under statin treatment, there was an improved lipid profile at follow-up. Conclusions: Statin medications are effective for reducing dyslipidaemia in T2DM patients. However, control of modifiable risk factors, particularly blood glucose and to a lesser degree blood pressure is suboptimal. Addressing these will require concomitant interventions including education on medication adherence and correct dietary plans, lifestyle modifications and physical activity

Reduced clinical and postmortem measures of cardiac pathology in subjects with advanced Alzheimer's Disease

Background. Epidemiological studies indicate a statistical linkage between atherosclerotic vascular disease (ATH) and Alzheimer\u27s disease (AD). Autopsy studies of cardiac disease in AD have been few and inconclusive. In this report, clinical and gross anatomic measures of cardiac disease were compared in deceased human subjects with and without AD. Methods. Clinically documented cardiovascular conditions from AD (n = 35) and elderly non-demented control subjects (n = 22) were obtained by review of medical records. Coronary artery stenosis and other gross anatomical measures, including heart weight, ventricular wall thickness, valvular circumferences, valvular calcifications and myocardial infarct number and volume were determined at autopsy. Results. Compared to non-demented age-similar control subjects, those with AD had significantly fewer total diagnosed clinical conditions (2.91 vs 4.18), decreased coronary artery stenosis (70.8 vs 74.8%), heart weight (402 vs 489 g for males; 319 vs 412 g for females) and valvular circumferences. Carriage of the Apolipoprotein E-ε4 allele did not influence the degree of coronary stenosis. Group differences in heart weight remained significant after adjustment for age, gender, body mass index and apolipoprotein E genotype while differences in coronary artery stenosis were significantly associated with body mass index alone. Conclusions. The results are in agreement with an emerging understanding that, while midlife risk factors for ATH increase the risk for the later development of AD, once dementia begins, both risk factors and manifest disease diminish, possibly due to progressive weight loss with increasing dementia as well as disease involvement of the brain\u27s vasomotor centers. © 2011 Beach et al; licensee BioMed Central Ltd

A 4 year follow-up study of cognitive functioning in patients with type 2 diabetes mellitus

Contains fulltext : 90777.pdf (publisher's version ) (Open Access)AIMS/HYPOTHESIS: Type 2 diabetes mellitus is associated with moderate decrements in cognitive functioning, mainly in verbal memory, information-processing speed and executive functions. How this cognitive profile evolves over time is uncertain. The present study aims to provide detailed information on the evolution of cognitive decrements in type 2 diabetes over time. METHODS: Sixty-eight patients with type 2 diabetes and 38 controls matched for age, sex and estimated IQ performed an elaborate neuropsychological examination in 2002-2004 and again in 2006-2008, including 11 tasks covering five cognitive domains. Vascular and metabolic determinants were recorded. Data were analysed with repeated measures analysis of variance, including main effects for group, time and the group x time interaction. RESULTS: Patients with type 2 diabetes showed moderate decrements in information-processing speed (mean difference in z scores [95% CI] -0.37 [-0.69, -0.05]) and attention and executive functions (-0.25 [-0.49, -0.01]) compared with controls at both the baseline and the 4 year follow-up examination. After 4 years both groups showed a decline in abstract reasoning (-0.16 [-0.30, -0.02]) and attention and executive functioning (-0.29 [-0.40, -0.17]), but there was no evidence for accelerated cognitive decline in the patients with type 2 diabetes as compared with controls (all p > 0.05). CONCLUSIONS/INTERPRETATION: In non-demented patients with type 2 diabetes, cognitive decrements are moderate in size and cognitive decline over 4 years is largely within the range of what can be viewed in normal ageing. Apparently, diabetes-related cognitive changes develop slowly over a prolonged period of time.8 p

Simvastatin is associated with a reduced incidence of dementia and Parkinson's disease

<p>Abstract</p> <p>Background</p> <p>Statins are a class of medications that reduce cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Whether statins can benefit patients with dementia remains unclear because of conflicting results. We hypothesized that some of the confusion in the literature might arise from differences in efficacy of different statins. We used a large database to compare the action of several different statins to investigate whether some statins might be differentially associated with a reduction in the incidence of dementia and Parkinson's disease.</p> <p>Methods</p> <p>We analyzed data from the decision support system of the US Veterans Affairs database, which contains diagnostic, medication and demographic information on 4.5 million subjects. The association of lovastatin, simvastatin and atorvastatin with dementia was examined with Cox proportional hazard models for subjects taking statins compared with subjects taking cardiovascular medications other than statins, after adjusting for covariates associated with dementia or Parkinson's disease.</p> <p>Results</p> <p>We observed that simvastatin is associated with a significant reduction in the incidence of dementia in subjects ≥65 years, using any of three models. The first model incorporated adjustment for age, the second model included adjusted for three known risk factors for dementia, hypertension, cardiovascular disease or diabetes, and the third model incorporated adjustment for the Charlson index, which is an index that provides a broad assessment of chronic disease. Data were obtained for over 700000 subjects taking simvastatin and over 50000 subjects taking atorvastatin who were aged >64 years. Using model 3, the hazard ratio for incident dementia for simvastatin and atorvastatin are 0.46 (CI 0.44–0.48, <it>p </it>< 0.0001) and 0.91 (CI 0.80–1.02, <it>p </it>= 0.11), respectively. Lovastatin was not associated with a reduction in the incidence of dementia. Simvastatin also exhibited a reduced hazard ratio for newly acquired Parkinson's disease (HR 0.51, CI 0.4–0.55, <it>p </it>< 0.0001).</p> <p>Conclusion</p> <p>Simvastatin is associated with a strong reduction in the incidence of dementia and Parkinson's disease, whereas atorvastatin is associated with a modest reduction in incident dementia and Parkinson's disease, which shows only a trend towards significance.</p

The protocols for the 10/66 dementia research group population-based research programme

BACKGROUND: Latin America, China and India are experiencing unprecedentedly rapid demographic ageing with an increasing number of people with dementia. The 10/66 Dementia Research Group's title refers to the 66% of people with dementia that live in developing countries and the less than one tenth of population-based research carried out in those settings. This paper describes the protocols for the 10/66 population-based and intervention studies that aim to redress this imbalance. METHODS/DESIGN: Cross-sectional comprehensive one phase surveys have been conducted of all residents aged 65 and over of geographically defined catchment areas in ten low and middle income countries (India, China, Nigeria, Cuba, Dominican Republic, Brazil, Venezuela, Mexico, Peru and Argentina), with a sample size of between 1000 and 3000 (generally 2000). Each of the studies uses the same core minimum data set with cross-culturally validated assessments (dementia diagnosis and subtypes, mental disorders, physical health, anthropometry, demographics, extensive non communicable disease risk factor questionnaires, disability/functioning, health service utilisation, care arrangements and caregiver strain). Nested within the population based studies is a randomised controlled trial of a caregiver intervention for people with dementia and their families (ISRCTN41039907; ISRCTN41062011; ISRCTN95135433; ISRCTN66355402; ISRCTN93378627; ISRCTN94921815). A follow up of 2.5 to 3.5 years will be conducted in 7 countries (China, Cuba, Dominican Republic, Venezuela, Mexico, Peru and Argentina) to assess risk factors for incident dementia, stroke and all cause and cause-specific mortality; verbal autopsy will be used to identify causes of death. DISCUSSION: The 10/66 DRG baseline population-based studies are nearly complete. The incidence phase will be completed in 2009. All investigators are committed to establish an anonymised file sharing archive with monitored public access. Our aim is to create an evidence base to empower advocacy, raise awareness about dementia, and ensure that the health and social care needs of older people are anticipated and met

SerpinA3N is a novel hypothalamic gene upregulated by a high-fat diet and leptin in mice

Background: Energy homeostasis is regulated by the hypothalamus but fails when animals are fed a high-fat diet (HFD), and leptin insensitivity and obesity develops. To elucidate the possible mechanisms underlying these effects, a microarray-based transcriptomics approach was used to identify novel genes regulated by HFD and leptin in the mouse hypothalamus. Results: Mouse global array data identified serpinA3N as a novel gene highly upregulated by both a HFD and leptin challenge. In situ hybridisation showed serpinA3N expression upregulation by HFD and leptin in all major hypothalamic nuclei in agreement with transcriptomic gene expression data. Immunohistochemistry and studies in the hypothalamic clonal neuronal cell line, mHypoE-N42 (N42), confirmed that alpha 1-antichymotrypsin (α1AC), the protein encoded by serpinA3, is localised to neurons and revealed that it is secreted into the media. SerpinA3N expression in N42 neurons is upregulated by palmitic acid and by leptin, together with IL-6 and TNFα, and all three genes are downregulated by the anti-inflammatory monounsaturated fat, oleic acid. Additionally, palmitate upregulation of serpinA3 in N42 neurons is blocked by the NFκB inhibitor, BAY11, and the upregulation of serpinA3N expression in the hypothalamus by HFD is blunted in IL-1 receptor 1 knockout (IL-1R1−/−) mice. Conclusions: These data demonstrate that serpinA3 expression is implicated in nutritionally mediated hypothalamic inflammation