Effect of alogliptin on hypertensive chronic kidney disease patients with type 2 diabetes mellitus

BackgroundDiabetes mellitus (DM) is a leading cause of chronic kidney disease (CKD). The antihyperglycemic treatment options for patients with Type 2 DM are limited because of safety and tolerability concerns.AimsTo retrospectively assess the effect of using Alogliptin; a dipeptidyl peptidase-4 inhibitor (DPP-4i) along with conventional gliclazide: a sulphonylurea (SU) on renal outcomes and glycaemic control in T2DM patients with mild CKD and hypertension.MethodsA total of 76 patient records (38 males and 38 females) of patient ages 40–60 were analysed from the kidney unit at Punjab Care hospital, Lahore, Pakistan. All patients had a confirmed history of T2DM with mild CKD and established hypertension.Eligible patients were divided into two groups of 38 individuals each. Group SU received gliclazide monotherapy (SU) or Alogliptin (DPP-4i)+gliclazide (SU) add on therapy. All patients were followed up for 12 months.ResultsThe alogliptin (DPP-4i) plus gliclazide (SU) add on therapy group, in comparison to the group only receiving gliclazide (SU), showed a significant difference in eGFR values. The mean±SD GFR values post 12 months were 74.8±0.31 (95%CI:74.8±0.09;74.7–74.9) and 76.1±0.25 (95%CI: 76.1±0.08;76.0-76.2) for SU vs. SU+DPP-4i, respectively, with mean calculated effect size of 1.6,. HbA1c, 1,5 AG and ipid profile values have significantly changed (

Fuzzy uncertainty analysis in the flutter boundary of an aircraft wing subjected to a thrust force

In this study, flutter uncertainty analysis of an aircraft wing subjected to a thrust force is investigated using fuzzy method. The linear wing model contains bending and torsional flexibility and the engine is considered as a rigid external mass with thrust force. Peters’ unsteady thin airfoil theory is used to model the aerodynamic loading. The aeroelastic governing equations are derived based on Hamilton’s principle and converted to a set of ordinary differential equations using Galerkin method. In the flutter analysis, it is assumed that the wing static deflections do not have influence on the results. The wing bending and torsional rigidity, aerodynamic lift curve slope and air density are considered as uncertain parameters and modelled as triangle and trapezium membership functions. The eigenvalue problem with fuzzy input parameters is solved using fuzzy Taylor expansion method and a sensitivity analysis is performed. Also, the upper and lower bounds of flutter region at different α-cuts are extracted. Results show that this method is a low-cost method with reasonable accuracy to estimate the flutter speed and frequency in the presence of uncertainties

A pilot randomised controlled trial of personalised care for depressed patients with symptomatic coronary heart disease in South London general practices: the UPBEAT-UK RCT protocol and recruitment.

ABSTRACT: Background: Community studies reveal people with coronary heart disease (CHD) are twice as likely to be depressed as the general population and that this co-morbidity negatively affects the course and outcome of both conditions. There is evidence for the efficacy of collaborative care and case management for depression treatment, and whilst NICE guidelines recommend these approaches only where depression has not responded to psychological, pharmacological, or combined treatments, these care approaches may be particularly relevant to the needs of people with CHD and depression in the earlier stages of stepped care in primary care settings. Methods: This pilot randomised controlled trial will evaluate whether a simple intervention involving a personalised care plan, elements of case management and regular telephone review is a feasible and acceptable intervention that leads to better mental and physical health outcomes for these patients. The comparator group will be usual general practitioner (GP) care. 81 participants have been recruited from CHD registers of 15 South London general practices. Eligible participants have probable major depression identified by a score of ≥8 on the Hospital Anxiety and Depression Scale depression subscale (HADS-D) together with symptomatic CHD identified using the Modified Rose Angina Questionnaire. Consenting participants are randomly allocated to usual care or the personalised care intervention which involves a comprehensive assessment of each participant’s physical and mental health needs which are documented in a care plan, followed by regular telephone reviews by the case manager over a 6-month period. At each review, the intervention participant’s mood, function and identified problems are reviewed and the case manager uses evidence based behaviour change techniques to facilitate achievement of goals specified by the patient with the aim of increasing the patient’s self efficacy to solve their problems. Depressive symptoms measured by HADS score will be collected at baseline and 1, 6- and 12 months post randomisation. Other outcomes include CHD symptoms, quality of life, wellbeing and health service utilisation. Discussion: This practical and patient-focused intervention is potentially an effective and accessible approach to the health and social care needs of people with depression and CHD in primary care. Trial registration: ISRCTN21615909

Woody lianas increase in dominance and maintain compositional integrity across an Amazonian dam-induced fragmented landscape

Tropical forest fragmentation creates insular biological communities that undergo species loss and changes in community composition over time, due to area- and edge-effects. Woody lianas thrive in degraded and secondary forests, due to their competitive advantage over trees in these habitats. Lianas compete both directly and indirectly with trees, increasing tree mortality and turnover. Despite our growing understanding of liana-tree dynamics, we lack detailed knowledge of the assemblage-level responses of lianas themselves to fragmentation, particularly in evergreen tropical forests. We examine the responses of both sapling and mature liana communities to landscape-scale forest insularization induced by a mega hydroelectric dam in the Brazilian Amazon. Detailed field inventories were conducted on islands created during reservoir filling, and in nearby mainland continuous forest. We assess the relative importance of variables associated with habitat fragmentation such as area, isolation, surrounding forest cover, fire and wind disturbance, on liana community attributes including abundance, basal area, diversity, and composition. We also explore patterns of liana dominance relative to tree saplings and adults ≥10 cm diameter at breast height. We find that 1) liana community composition remains remarkably similar across mainland continuous forest and islands, regardless of extreme area- and edge- effects and the loss of vertebrate dispersers in the latter; and 2) lianas are increasing in dominance relative to trees in the sapling layer in the most degraded islands, with both the amount of forest cover surrounding islands and fire disturbance history predicting liana dominance. Our data suggest that liana communities persist intact in isolated forests, regardless of extreme area- and edge-effects; while in contrast, tree communities simultaneously show evidence of increased turnover and supressed recruitment. These processes may lead to lianas becoming a dominant component of this dam-induced fragmented landscape in the future, due to their competitive advantage over trees in degraded forest habitats. Additional loss of tree biomass and diversity brought about through competition with lianas, and the concurrent loss of carbon storage, should be accounted for in impact assessments of future dam development

Distinct Mechanisms Underlying Tolerance to Intermittent and Constant Hypoxia in Drosophila melanogaster

BACKGROUND: Constant hypoxia (CH) and intermittent hypoxia (IH) occur during several pathological conditions such as asthma and obstructive sleep apnea. Our research is focused on understanding the molecular mechanisms that lead to injury or adaptation to hypoxic stress using Drosophila as a model system. Our current genome-wide study is designed to investigate gene expression changes and identify protective mechanism(s) in D. melanogaster after exposure to severe (1% O(2)) intermittent or constant hypoxia. METHODOLOGY/PRINCIPAL FINDINGS: Our microarray analysis has identified multiple gene families that are up- or down-regulated in response to acute CH or IH. We observed distinct responses to IH and CH in gene expression that varied in the number of genes and type of gene families. We then studied the role of candidate genes (up-or down-regulated) in hypoxia tolerance (adult survival) for longer periods (CH-7 days, IH-10 days) under severe CH or IH. Heat shock proteins up-regulation (specifically Hsp23 and Hsp70) led to a significant increase in adult survival (as compared to controls) of P-element lines during CH. In contrast, during IH treatment the up-regulation of Mdr49 and l(2)08717 genes (P-element lines) provided survival advantage over controls. This suggests that the increased transcript levels following treatment with either paradigm play an important role in tolerance to severe hypoxia. Furthermore, by over-expressing Hsp70 in specific tissues, we found that up-regulation of Hsp70 in heart and brain play critical role in tolerance to CH in flies. CONCLUSIONS/SIGNIFICANCE: We observed that the gene expression response to IH or CH is specific and paradigm-dependent. We have identified several genes Hsp23, Hsp70, CG1600, l(2)08717 and Mdr49 that play an important role in hypoxia tolerance whether it is in CH or IH. These data provide further clues about the mechanisms by which IH or CH lead to cell injury and morbidity or adaptation and survival

Molecular complexity determines the number of olfactory notes and the pleasantness of smells

One major unresolved problem in olfaction research is to relate the percept to the molecular structure of stimuli. The present study examined this issue and showed for the first time a quantitative structure-odor relationship in which the more structurally complex a monomolecular odorant, the more numerous the olfactory notes it evokes. Low-complexity odorants were also rated as more aversive, reflecting the fact that low molecular complexity may serve as a warning cue for the olfactory system. Taken together, these findings suggest that molecular complexity provides a framework to explain the subjective experience of smells

The Effect of Map Boundary on Estimates of Landscape Resistance to Animal Movement

BACKGROUND: Artificial boundaries on a map occur when the map extent does not cover the entire area of study; edges on the map do not exist on the ground. These artificial boundaries might bias the results of animal dispersal models by creating artificial barriers to movement for model organisms where there are no barriers for real organisms. Here, we characterize the effects of artificial boundaries on calculations of landscape resistance to movement using circuit theory. We then propose and test a solution to artificially inflated resistance values whereby we place a buffer around the artificial boundary as a substitute for the true, but unknown, habitat. METHODOLOGY/PRINCIPAL FINDINGS: We randomly assigned landscape resistance values to map cells in the buffer in proportion to their occurrence in the known map area. We used circuit theory to estimate landscape resistance to organism movement and gene flow, and compared the output across several scenarios: a habitat-quality map with artificial boundaries and no buffer, a map with a buffer composed of randomized habitat quality data, and a map with a buffer composed of the true habitat quality data. We tested the sensitivity of the randomized buffer to the possibility that the composition of the real but unknown buffer is biased toward high or low quality. We found that artificial boundaries result in an overestimate of landscape resistance. CONCLUSIONS/SIGNIFICANCE: Artificial map boundaries overestimate resistance values. We recommend the use of a buffer composed of randomized habitat data as a solution to this problem. We found that resistance estimated using the randomized buffer did not differ from estimates using the real data, even when the composition of the real data was varied. Our results may be relevant to those interested in employing Circuitscape software in landscape connectivity and landscape genetics studies

Association of CAPN10 SNPs and Haplotypes with Polycystic Ovary Syndrome among South Indian Women

Polycystic Ovary Syndrome (PCOS) is known to be characterized by metabolic disorder in which hyperinsulinemia and peripheral insulin resistance are central features. Given the physiological overlap between PCOS and type-2 diabetes (T2DM), and calpain 10 gene (CAPN10) being a strong candidate for T2DM, a number of studies have analyzed CAPN10 SNPs among PCOS women yielding contradictory results. Our study is first of its kind to investigate the association pattern of CAPN10 polymorphisms (UCSNP-44, 43, 56, 19 and 63) with PCOS among Indian women. 250 PCOS cases and 299 controls from Southern India were recruited for this study. Allele and genotype frequencies of the SNPs were determined and compared between the cases and controls. Results show significant association of UCSNP-44 genotype CC with PCOS (p = 0.007) with highly significant odds ratio when compared to TC (OR = 2.51, p = 0.003, 95% CI = 1.37–4.61) as well as TT (OR = 1.94, p = 0.016, 95% CI = 1.13–3.34). While the haplotype carrying the SNP-44 and SNP-19 variants (21121) exhibited a 2 fold increase in the risk for PCOS (OR = 2.37, p = 0.03), the haplotype containing SNP-56 and SNP-19 variants (11221) seems to have a protective role against PCOS (OR = 0.20, p = 0.004). Our results support the earlier evidence for a possible role of UCSNP-44 of the CAPN10 gene in the manifestation of PCOS