Glycaemic behaviour during breastfeeding in women with Type 1 diabetes

Aim To describe glycaemia in both breastfeeding women and artificially feeding women with Type 1 diabetes, and the changes in glycaemia induced by suckling. Methods A blinded continuous glucose monitor was applied for up to 6 days in eight breastfeeding and eight artificially feeding women with Type 1 diabetes 2–4 months postpartum. Women recorded glucose levels, insulin dosages, oral intake and breastfeeding episodes. A standardized breakfast was consumed on 2 days. A third group (clinic controls) were identified from a historical database. Results Carbohydrate intake tended to be higher in breastfeeding than artificially feeding women (P = 0.09) despite similar insulin requirements. Compared with breastfeeding women, the high blood glucose index and standard deviation of glucose were higher in artificially feeding women (P = 0.02 and 0.06, respectively) and in the clinical control group (P = 0.02 and 0.05, respectively). The low blood glucose index and hypoglycaemia were similar. After suckling, the low blood glucose index increased compared with before (P < 0.01) and during (P < 0.01) suckling. Hypoglycaemia (blood glucose < 4.0 mmol/l) occurred within 3 h of suckling in 14% of suckling episodes, and was associated with time from last oral intake (P = 0.04) and last rapid-acting insulin (P = 0.03). After a standardized breakfast, the area under the glucose curve was positive. In breastfeeding women the area under the glucose curve was positive if suckling was avoided for 1 h after eating and negative if suckling occurred within 30 min of eating. Conclusions Breastfeeding women with Type 1 diabetes had similar hypoglycaemia but lower glucose variability than artificially feeding women. Suckling reduced maternal glucose levels but did not cause hypoglycaemia in most episodes.

Dynamics and control of buckling type devices using SMA wire integrated beam

An analysis and design study using Shape Memory Alloy (SMA) wire integrated beam and its buckling shape control are reported. The dynamical system performance is analyzed with a mathematical set-up involving nonlocal and rate sensitive kinetics of phase transformation in the SMA wire. A standard phenomenological constitutive model reported by Brinson (1993) is modified by considering certain consistency conditions in the material property tensors and by eliminating spurious singularity. Considering the inhomogeneity effects, a finite element model of the SMA wire is developed. Simulations are carried out to study the buckling shape control of a beam integrated with SMA wire.

The impact of the metabolic syndrome and parental risk factors in patients with type 1 diabetes

Background: One-third of patients with type 1 diabetes develop diabetic complications, such as diabetic nephropathy. The diabetic complications are related to a high mortality from cardiovascular disease, impose a great burden on the health care system, and reduce the health-related quality of life of patients. Aims: This thesis assessed, whether parental risk factors identify subjects at a greater risk of developing diabetic complications. Another aim was to evaluate the impact of a parental history of type 2 diabetes on patients with type 1 diabetes. A third aim was to assess the role of the metabolic syndrome in patients with type 1 diabetes, both its presence and its predictive value with respect to complications. Subjects and methods: This study is part of the ongoing nationwide Finnish Diabetic Nephropathy (FinnDiane) Study. The study was initiated in 1997, and, thus far, 4,800 adult patients with type 1 diabetes have been recruited. Since 2004, follow-up data have also been collected in parallel to the recruitment of new patients. Studies I to III have a cross-sectional design, whereas Study IV has a prospective design. Information on parents was obtained from the patients with type 1 diabetes by a questionnaire. Results: Clustering of parental hypertension, cardiovascular disease, and diabetes (type 1 and type 2) was associated with diabetic nephropathy in patients with type 1 diabetes, as was paternal mortality. A parental history of type 2 diabetes was associated with a later onset of type 1 diabetes, a higher prevalence of the metabolic syndrome, and a metabolic profile related to insulin resistance, despite no difference in the distribution of human leukocyte antigen genotypes or the presence of diabetic complications. A maternal history of type 2 diabetes, seemed to contribute to a worse metabolic profile in the patients with type 1 diabetes than a paternal history. The metabolic syndrome was a frequent finding in patients with type 1 diabetes, observed in 38% of males and 40% of females. The prevalence increased with worsening of the glycemic control and more severe renal disease. The metabolic syndrome was associated with a 3.75-fold odds ratio for diabetic nephropathy, and all of the components of the syndrome were independently associated with diabetic nephropathy. The metabolic syndrome, independent of diabetic nephropathy, increased the risk of cardiovascular events and cardiovascular and diabetes-related mortality over a 5.5-year follow-up. With respect to progression of diabetic nephropathy, the role of the metabolic syndrome was less clear, playing a strong role only in the progression from macroalbuminuria to end-stage renal disease. Conclusions: Familial factors and the metabolic syndrome play an important role in patients with type 1 diabetes. Assessment of these factors is an easily applicable tool in clinical practice to identify patients at a greater risk of developing diabetic complications.

Long-term effects of fenofibrate on lipoproteins and surrogate markers of macrovascular and microvascular disease in people with type 2 diabetes

Background and aims. Diabetic dyslipidemia is a highly atherogenic triad of increased triglycerides, decreased HDL cholesterol, and small dense LDL. Fibrates have a beneficial effect on diabetic dyslipidemia, and they have reduced cardiovascular events in randomized trials. Fenofibrate has reduced albuminuria and markers of low-grade inflammation and endothelial dysfunction. The present studies were undertaken to characterize the alterations of VLDL and LDL subclasses and to investigate the binding of LDL to arterial wall in type 2 diabetes. Further purpose was to elucidate the effects of fenofibrate on several lipoprotein subclasses, augmentation index (AIx), carotid intima-media thickness (IMT), and renal function. Subjects. 239 type 2 diabetic subjects were recruited among participants of the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study at the Helsinki centre. The patients were randomized to fenofibrate (200mg/d) or placebo for 5 years. Additionally, a healthy control group (N = 93) was recruited. Results. VLDL1 triglycerides increased in similar proportion to total triglycerides in type 2 diabetic patients and control subjects. Despite the increase in total apoCIII levels, VLDL apoCIII was decreased in diabetic patients. Enrichment of LDL with apoCIII induced a small increase in binding of LDL to arterial wall proteoglycan. Intrinsic characteristics of diabetic LDL, rather than levels of apoCIII, were responsible for increased proteoglycan binding of diabetic LDL with high apoCIII. Fenofibrate reduced triglycerides, increased LDL size, and shifted HDL subclasses towards smaller particles with no change in levels of HDL cholesterol. High levels of homocysteine were associated with lower increase of HDL cholesterol and apoA-I during fenofibrate treatment. Long-term fenofibrate treatment did not improve IMT, AIx, inflammation, or endothelial function. Fenofibrate decreased creatinine clearance and estimated glomerular filtration rate. No effect on albuminuria was seen with fenofibrate. Instead, Cystatin C was increased during fenofibrate treatment. Conclusions. 1) Elevation of VLDL 1 triglycerides was the major determinant of plasma triglyceride concentration in control subjects and type 2 diabetic patients. 2) LDL with high apoCIII showed multiple atherogenic properties, that were only partially mediated by apoCIII per se in type 2 diabetes 3) Fenofibrate demonstrated no effect on surrogate markers of atherosclerosis. 4) Fenofibrate had no effect on albuminuria and the observed decrease in markers of renal function could complicate the clinical surveillance of the patients. 5) Fenofibrate can be used to treat severe hypertriglyceridemia or in combination therapy with statins, but not to increase HDL levels.

New algorithms of the Q-learning type

We propose two algorithms for Q-learning that use the two-timescale stochastic approximation methodology. The first of these updates Q-values of all feasible state–action pairs at each instant while the second updates Q-values of states with actions chosen according to the ‘current’ randomized policy updates. A proof of convergence of the algorithms is shown. Finally, numerical experiments using the proposed algorithms on an application of routing in communication networks are presented on a few different settings.

Tuning the beta-turn segment in designed peptide beta-hairpins: Construction of a stable type I ' beta-turn nucleus and hairpin-helix transition promoting segments

Designed octapeptides Boc-Leu-Val-Val-Aib-(D)Xxx-Leu- Val-Val-OMe ((D)Xxx = (D)Ala, 3a; (D)Val, 3c and (D)Pro, 5a) and Boc-Leu-Phe-Val-Aib-DAla-Leu-Phe-Val-OMe (3b) have been investigated to construct models of a stable type I' beta-turn nucleated hairpin and to generate systems for investigating helix-hairpin conformational transitions. Peptide 5a, which contains a central Aib-(D)Pro segment, is shown to adopt a stable type I' beta-turn nucleated hairpin structure, stabilized by four cross-strand hydrogen bonds. The stability of the structure in diverse solvents is established by the observation of all diagnostic NOEs expected in a beta-hairpin conformation. Replacement of (D)Pro5 by (D)Ala/(D)Val (3a-c) results in sequences that form beta-hairpins in hydrogen bonding solvents like CD3OH and DMSO-d(6). However, in CDCl3 evidence for population of helical conformations is obtained. Peptide 6b (Boc-Leu-Phe-Val-Aib-Aib-Leu-Phe-Val-OMe), which contains a centrally positioned Aib-Aib segment, provides a clear example of a system, which exhibits a helical conformation in CDCl3 and a significant population of both helices and hairpins in CD3OH and DMSO-d(6). The coexistence of multiple conformations is established by the simultaneous observation of diagnostic NOEs. Control over stereochemistry of the central beta-turn permits generation of models for robust beta-hairpins and also for the construction of systems that may be used to probe helix-hairpin conformational transitions. (c) 2006 Wiley Periodicals, Inc.

Evidence for an association with type 2 diabetes mellitus at the PPARG locus in a South Indian population

Peroxisome proliferator activated receptor-gamma 2 (PPARG2) is a nuclear hormone receptor of ligand-dependent ranscription factor involved in adipogenesis and a molecular target of the insulin sensitizers thiazolidinediones. We addressed the question of whether the 3 variants (-1279G/A, Pro12Ala, and His478His) in the PPARG2 gene are associated with type 2 diabetes mellitus and its related traits in a South Indian population. The study subjects (1000 type 2 diabetes mellitus and 1000 normal glucose-tolerant subjects) were chosen randomly from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in southern India. The variants were screened by single-stranded conformational variant, direct sequencing, and restriction fragment length polymorphism. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies. The -1279G/A, Pro12Ala, and His478His variants of the PPARG2 gene were not associated with type 2 diabetes mellitus. However, the 2-loci analyses showed that, in the presence of Pro/Pro genotype of the Pro12Ala variant, the -1279G/A promoter variant showed increased susceptibility to type 2 diabetes mellitus (odds ratio, 2.092; 95% confidence interval, 1.22-3.59; P = .008), whereas in the presence of 12Ala allele, the -1279G/A showed a protective effect against type 2 diabetes mellitus (odds ratio, 0.270; 95% confidence interval, 0.15-0.49; P < .0001). The 3-loci haplotype analysis showed that the A-Ala-T (-1279G/A-Pro12Ala-His478His) haplotype was associated with a reduced risk of type 2 diabetes mellitus (P < .0001). Although our data indicate that the PPARG2 gene variants, independently, have no association with type 2 diabetes mellitus, the 2-loci genotype analysis involving -1279G/A and Pro12Ala variants and the 3-loci haplotype analysis have shown a significant association with type 2 diabetes mellitus in this South Indian population. (C) 2010 Elsevier Inc. All rights reserved.

Energetics of carbohydrate binding by a 14 kDa S-type mammalian lectin

The thermodynamics of the binding of derivatives of galactose and lactose to a 14 kDa beta-galactoside-binding lectin (L-14) from sheep spleen has been studied in 10 nM phosphate/150 mM NaCl/10 mM beta-mercaptoethanol buffer, pH 7.4, and in the temperature range 285-300 K using titration calorimetry. The single-site binding constants of various sugars for the lectin were in the following order: N-acetyl-lactosamine thiodigalactoside > 4-methylumbelliferyl lactoside > lactose > 4-methylumbelliferyl alpha-D-galactoside > methyl-alpha-galactose > methyl-beta-galactose. Reactions were essentially enthalpically driven with the binding enthalpies ranging from -53.8 kJ/mol for thiodigalactoside at 301 K to -2.2 kJ/mol for galactose at 300 K, indicating that hydrogen-bonding and van der Waals interactions provide the major stabilization for these reactions. However, the binding of 4-methylumbelliferyl-alpha-D-galactose displays relatively favourable entropic contributions, indicating the existence of a non-polar site adjacent to the galactose-binding subsite. From the increments in the enthalpies for the binding of lactose, N-acetyl-lactosamine and thiodigalactoside relative to methyl-beta-galactose, the contribution of glucose binding in the subsite adjacent to that for galactose shows that glucose makes a major contribution to the stability of L-14 disaccharide complexes. Observation of enthalpy-entropy compensation for the recognition of saccharides such as lactose by L-14 and the absence of it for monosaccharides such as galactose, together with the lack of appreciable changes in the heat capacity (delta Cp), indicate that reorganization of water plays an important role in these reactions.

Psychosocial processes of health behaviour change in a lifestyle intervention : Influences of gender, socioeconomic status and personality

Background: The onset of many chronic diseases such as type 2 diabetes can be delayed or prevented by changes in diet, physical activity and obesity. Known predictors of successful behaviour change include psychosocial factors such as selfefficacy, action and coping planning, and social support. However, gender and socioeconomic differences in these psychosocial mechanisms underlying health behaviour change have not been examined, despite well-documented sociodemographic differences in lifestyle-related mortality and morbidity. Additionally, although stable personality traits (such as dispositional optimism or pessimism and gender-role orientation: agency and communion) are related to health and health behaviour, to date they have rarely been studied in the context of health behaviour interventions. These personality traits might contribute to health behaviour change independently of the more modifiable domain-specific psychosocial factors, or indirectly through them, or moderated by them. The aims were to examine in an intervention setting: (1) whether changes (during the three-month intervention) in psychological determinants (self-efficacy beliefs, action planning and coping planning) predict changes in exercise and diet behaviours over three months and 12 months, (2) the universality assumption of behaviour change theories, i.e. whether preintervention levels and changes in psychosocial determinants are similar among genders and socioeconomic groups, and whether they predict changes in behaviour in a similar way in these groups, (3) whether the personality traits optimism, pessimism, agency and communion predict changes in abdominal obesity, and the nature of their interplay with modifiable and domain-specific psychosocial factors (self-efficacy and social support). Methods: Finnish men and women (N = 385) aged 50 65 years who were at an increased risk for type 2 diabetes were recruited from health care centres to participate in the GOod Ageing in Lahti Region (GOAL) Lifestyle Implementation Trial. The programme aimed to improve participants lifestyle (physical activity, eating) and decrease their overweight. The measurements of self-efficacy, planning, social support and dispositional optimism/pessimism were conducted pre-intervention at baseline (T1) and after the intensive phase of the intervention at three months (T2), and the measurements of exercise at T1, T2 and 12 months (T3) and healthy eating at T1 and T3. Waist circumference, an indicator of abdominal obesity, was measured at T1 and at oneyear (T3) and three-year (T4) follow-ups. Agency and communion were measured at T4 with the Personal Attributes Questionnaire (PAQ). Results: (1) Increases in self-efficacy and planning were associated with three-month increases in exercise (Study I). Moreover, both the post-intervention level and three-month increases (during the intervention) in self-efficacy in dealing with barriers predicted the 12-month increase in exercise, and a high postintervention level of coping plans predicted the 12-month decrease in dietary fat (Study II). One- and three-year waist circumference reductions were predicted by the initial three-month increase in self-efficacy (Studies III, IV). (2) Post-intervention at three months, women had formed more action plans for changing their exercise routines and received less social support for behaviour change than men had. The effects of adoption self-efficacy were similar but change in planning played a less significant role among men (Study I). Examining the effects of socioeconomic status (SES), psychosocial determinants at baseline and their changes during the intervention yielded largely similar results. Exercise barriers self-efficacy was enhanced slightly less among those with low SES. Psychosocial determinants predicted behaviour similarly across all SES groups (Study II). (3) Dispositional optimism and pessimism were unrelated to waist circumference change, directly or indirectly, and they did not influence changes in self-efficacy (Study III). Agency predicted 12-month waist circumference reduction among women. High communion coupled with high social support was associated with waist circumference reduction. However, the only significant predictor of three-year waist circumference reduction was an increase in health-related self-efficacy during the intervention (Study IV). Conclusions: Interventions should focus on improving participants self-efficacy early on in the intervention as well as prompting action and coping planning for health behaviour change. Such changes are likely to be similarly effective among intervention participants regardless of gender and educational level. Agentic orientation may operate via helping women to be less affected by the demands of the self-sacrificing female role and enabling them to assertively focus on their own goals. The earlier mixed results regarding the role of social support in behaviour change may be in part explained by personality traits such as communion.

Genetic characterization of Indian type O FMD virus 3A region in context with host cell preference

The 3A region of foot-and-mouth disease virus has been implicated in host range and virulence. For example, amino acid deletions in the porcinophilic strain (O/TAW/97) at 93-102 aa of the 153 codons long 3A protein have been recognized as the determinant of species specificity. In the present study, 18 type 0 FMDV isolates from India were adapted in different cell culture systems and the 3A sequence was analyzed. These isolates had complete 3A coding sequence (153 aa) and did not exhibit growth restriction in cells based on species of origin. The 3A region was found to be highly conserved at N-terminal half (1-75 aa) but exhibited variability or substitutions towards C-terminal region (80-153). Moreover the amino acid substitutions were more frequent in recent Indian buffalo isolates but none of the Indian isolates showed deletion in 3A protein, which may be the reason for the absence of host specificity in vitro. Further inclusive analysis of 3A region will reveal interesting facts about the variability of FMD virus 3A region in an endemic environment. (C) 2010 Elsevier B.V. All rights reserved.

Type I seesaw mechanism for quasi-degenerate neutrinos

We discuss symmetries and scenarios leading to quasi-degenerate neutrinos in type I seesaw models. The existence of degeneracy in the present approach is not linked to any specific structure for the Dirac neutrino Yukawa coupling matrix y(D) and holds in general. Basic input is the application of the minimal flavour violation principle to the leptonic sector. Generalizing this principle, we assume that the structure of the right-handed neutrino mass matrix is determined by y(D) and the charged lepton Yukawa coupling matrix y(l) in an effective theory invariant under specific groups G(F) contained in the full symmetry group of the kinetic energy terms. G(F) invariance also leads to specific structure for the departure from degeneracy. The neutrino mass matrix (with degenerate mass m(0)) resulting after seesaw mechanism has a simple form Mv approximate to m(0)(I - py(l)y(l)(T)) in one particular scenario based on supersymmetry. This form is shown tolead to correct description of neutrino masses and mixing angles. The thermal leptogenesis after inclusion of flavour effects can account for the observed baryon asymmetry of the universe within the present scenario. Rates for lepton flavour violating processes can occur at observable levels in the supersymmetric version of the scenario. (c) 2010 Elsevier B.V. All rights reserved.

X-ray studies on crystalline complexes involving amino acids and peptides. XV. Crystal structures of L-lysine D-glutamate and L-lysine D-aspartate monohydrate and the effect of chirality on molecular aggregation

L-Lysine D-glutamate crystallizes in the monoclinic space group P2(1) with a = 4.902, b = 30.719, c = 9.679 A, beta = 90 degrees and Z = 4. The crystals of L-lysine D-aspartate monohydrate belong to the orthorhombic space group P2(1)2(1)2(1) with a = 5.458, b = 7.152, c = 36.022 A and Z = 4. The structures were solved by the direct methods and refined to R values of 0.125 and 0.040 respectively for 1412 and 1503 observed reflections. The glutamate complex is highly pseudosymmetric. The lysine molecules in it assume a conformation with the side chain staggered between the alpha-amino and the alpha-carboxylate groups. The interactions of the side chain amino groups of lysine in the two complexes are such that they form infinite sequences containing alternating amino and carboxylate groups. The molecular aggregation in the glutamate complex is very similar to that observed in L-arginine D-aspartate and L-arginine D-glutamate trihydrate, with the formation of double layers consisting of both types of molecules. In contrast to the situation in the other three LD complexes, the unlike molecules in L-lysine D-aspartate monohydrate aggregate into alternating layers as in the case of most LL complexes. The arrangement of molecules in the lysine layer is nearly the same as in L-lysine L-aspartate, with head-to-tail sequences as the central feature. The arrangement of aspartate ions in the layers containing them is, however, somewhat unusual. Thus the comparison between the LL and the LD complexes analyzed so far indicates that the reversal of chirality of one of the components in a complex leads to profound changes in molecular aggregation, but these changes could be of more than one type.

Modelling studies on neurodegenerative disease causing triplet repeat sequences d(CGG/GCC) and d(CAG/CTG): Duplexes vs Quadruplexes

Model building and molecular mechanics studies have been carried out to examine the potential structures for d(GGC/GCC)5 and d(CAG/CTG)5 that might relate to their biological function and association with triplet repeat expansion diseases. Model building studies suggested that hairpin and quadruplex structures could be formed with these repeat sequences. Molecular mechanics studies have demonstrated that the hairpin and hairpin dimmer structures of triplet repeat sequences formed by looping out of the two strands are as favourable as the corresponding B-DNA type hetero duplex structures. Further, at high salt condition, Greek key type quadruplex structures are energetically comparable with hairpin dimer and B-DNA type duplex structures. All tetrads in the quadruplex structures are well stacked and provide favourable stacking energy values. Interestingly, in the energy minimized hairpin dimer and Greek key type quadruplex structures, all the bases even in the non-G tetrads are cyclically hydrogen bonded, even though the A, C and T-tetrads were not hydrogen bonded in the starting structures.

Uncoupling Protein 2 and 3 Gene Polymorphisms and Their Association with Type 2 Diabetes in Asian Indians

Background: This study examined the association of -866G/A, Ala55Val, 45bpI/D, and -55C/T polymorphisms at the uncoupling protein (UCP) 3-2 loci with type 2 diabetes in Asian Indians. Methods: A case-control study was performed among 1,406 unrelated subjects (487 with type 2 diabetes and 919 normal glucose-tolerant NGT]), chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in Southern India. The polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Haplotype frequencies were estimated using an expectation-maximization algorithm. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies. Results: The genotype (P = 0.00006) and the allele (P = 0.00007) frequencies of Ala55Val of the UCP2 gene showed a significant protective effect against the development of type 2 diabetes. The odds ratios (adjusted for age, sex, and body mass index) for diabetes for individuals carrying Ala/Val was 0.72, and that for individuals carrying Val/Val was 0.37. Homeostasis insulin resistance model assessment and 2-h plasma glucose were significantly lower among Val-allele carriers compared to the Ala/Ala genotype within the NGT group. The genotype (P = 0.02) and the allele (P = 0.002) frequencies of -55C/T of the UCP3 gene showed a significant protective effect against the development of diabetes. The odds ratio for diabetes for individuals carrying CT was 0.79, and that for individuals carrying TT was 0.61. The haplotype analyses further confirmed the association of Ala55Val with diabetes, where the haplotypes carrying the Ala allele were significantly higher in the cases compared to controls. Conclusions: Ala55Val and -55C/T polymorphisms at the UCP3-2 loci are associated with a significantly reduced risk of developing type 2 diabetes in Asian Indians.

Diaphragm-type sputtered platinum thin film strain gauge pressure transducer

A diaphragm-type pressure transducer with a sputtered platinum film strain gauge (sensing film) has been designed and fabricated. The various steps followed to prepare thin film strain gauges on the diaphragm are described. M-bond 450 adhesive (Measurements Group, USA) has been employed as the insulating layer. A detailed procedure to cure this layer is given. A d.c. sputtering method is employed to prepare the platinum films. This paper also includes details of the strain gauge pattern and its location on the diaphragm. A description of the output characteristics and overall behaviour of the platinum thin film pressure transducer is reported.