A metabolomics approach to uncover effects of different exercise modalities in type 1 diabetes

Introduction

Exercise-associated metabolism in type 1 diabetes (T1D) remains under-studied due to the complex interplay between exogenous insulin, counter-regulatory hormones and insulin-sensitivity.

Objective

To identify the metabolic differences induced by two exercise modalities in T1D using ultra high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC–HRMS) based metabolomics.

Methods

Twelve T1D adults performed intermittent high-intensity (IHE) and continuous-moderate-intensity (CONT) exercise. Serum samples were analysed by UHPLC–HRMS.

Results

Metabolic profiling of IHE and CONT highlighted exercise-induced changes in purine and acylcarnitine metabolism.

Conclusion

IHE may increase beta-oxidation through higher ATP-turnover. UHPLC–HRMS based metabolomics as a data-driven approach without an a priori hypothesis may help uncover distinctive metabolic effects during exercise in T1D.Clinical trial registration number is www.clinicaltrials.gov: NCT02068638.

     

Optimal Designs for Estimating the Percentiles of the Risk in Multistage Models of Carcinogenesis

The multistage carcinogenesis models describe a process by which a normal cell becomes malignant and gives rise to a tumor. This paper aims at evaluating the percentiles of the risk function derived as dose-response relationship in a multi-stage model. These percentiles have been known as “virtual safe dose” levels or risk specific dose levels. The optimal design theory is applied to estimate the appropriate percentile and the sequential approach of design is adopted through a stochastic approximation scheme. If the initial design is D-optimal the limit design is D-optimal as well and it is the one with the minimum entropy.     

How can ontologies help vector biology?

The reach of genomics has now extended to vector biology, with three mosquito genomes already sequenced and more arthropod vector genomes in the pipeline. The availability of these genomes has paved the way for high-throughput investigations on genome-wide gene expression and proteomics in vector biology. Such investigations would not have been possible without parallel progress in bioinformatics. It is now necessary to construct specific ontologies that will enable vector biologists to achieve computer-comprehensible annotation of genes and genomes, but also of various experimental, clinical and surveillance data. This will inevitably lead to the enhanced usage of such controlled vocabularies, and to an effort to develop novel ontologies, particularly in the context of disease control.     

Application of chiral cyclic nitrones to the diastereoselective synthesis of bicyclic isoxazolidine nucleoside analogues

New bicyclic isoxazolidine nucleoside analogues are synthesized through 1,3-dipolar cycloaddition of enantiopure cyclic nitrones to appropriate vinyl nucleobases. The reactions are diastereoselective, giving as the main or the sole product the exo-Re cycloadducts. The diastereoselectivity depends on both the kind of the base and the substitution pattern of the nitrone.     

Reporting distress and quality of life of patients with diabetes mellitus in primary and secondary care in Greece

Background and aim This study constitutes an initial attempt at elucidating the relationship between quality of life (QoL), health status and psychological distress in patients with diabetes mellitus (DM) in Greece, by comparing patients with DM registered at a rural primary healthcare centre (PHCC) and those attending a diabetes outpatient clinic (DOC) at an urban hospital.Methods Cross-sectional study. Participants were consecutive, consenting patients with a known history of type 2DM(T2 DM), currently registered at either of the two centres. All patients were administered the Short Form-36 version 2 (SF-36 v2) and the Problem Areas In Diabetes (PAID) questionnaire, and information in relation to socio-demographic data and clinical characteristics were also obtained.Results Patients with DM had a lower QoL over all domains when compared with general population normative data. In addition, mean scores for the SF-36 v2 Physical Component Summary (PCS) and Mental Component Summary (MCS) and six subscales of the SF-36 v2 demonstrated significant differences between the two participating centres (P < 0.0001). The mean PAID score was 19.18 (±15.58) for patients from the PHCC, versus 40.19 (±17.36) for the DOC (P < 0.0001). Lower scores on the MCS of the SF-36 v2, and higher scores on PAID in patients with T2 DM were related to major co-morbidities, insulin use and duration of DM.Conclusions Patients with T2 DM from the urban DOC had significantly higher levels of distress and consequently lower levels of QoL compared with patients from the rural PHCC. The findings from this study may have important implications with regard to the individualisation of patient care in Greece, and encouragement of patient participation in the treatment process.     

Vaccination targeting a surface sialidase of P. acnes: implication for new treatment of acne vulgaris

Background

Acne vulgaris afflicts more than fifty million people in the United State and the severity of this disorder is associated with the immune response to Propionibacterium acnes (P. acnes). Systemic therapies for acne target P. acnes using antibiotics, or target the follicle with retinoids such as isotretinoin. The latter systemic treatment is highly effective but also carries a risk of side effects including immune imbalance, hyperlipidemia, and teratogenicity. Despite substantial research into potential new therapies for this common disease, vaccines against acne vulgaris are not yet available.

Methods and Findings

Here we create an acne vaccine targeting a cell wall-anchored sialidase of P. acnes. The importance of sialidase to disease pathogenesis is shown by treatment of a human sebocyte cell line with recombinant sialidase that increased susceptibility to P. acnes cytotoxicity and adhesion. Mice immunized with sialidase elicit a detectable antibody; the anti-sialidase serum effectively neutralized the cytotoxicity of P. acnes in vitro and P. acnes-induced interleukin-8 (IL-8) production in human sebocytes. Furthermore, the sialidase-immunized mice provided protective immunity against P. acnes in vivo as this treatment blocked an increase in ear thickness and release of pro-inflammatory macrophage inflammatory protein (MIP-2) cytokine.

Conclusions

Results indicated that acne vaccines open novel therapeutic avenues for acne vulgaris and other P. acnes-associated diseases.     

Differentiation and gene flow among European populations of Leishmania infantum MON-1

Background

Leishmania infantum is the causative agent of visceral and cutaneous leishmaniasis in the Mediterranean region, South America, and China. MON-1 L. infantum is the predominating zymodeme in all endemic regions, both in humans and dogs, the reservoir host. In order to answer important epidemiological questions it is essential to discriminate strains of MON-1.

Methodology/Principal Findings

We have used a set of 14 microsatellite markers to analyse 141 strains of L. infantum mainly from Spain, Portugal, and Greece of which 107 strains were typed by MLEE as MON-1. The highly variable microsatellites have the potential to discriminate MON-1 strains from other L. infantum zymodemes and even within MON-1 strains. Model- and distance-based analysis detected a considerable amount of structure within European L. infantum. Two major monophyletic groups—MON-1 and non-MON-1—could be distinguished, with non-MON-1 being more polymorphic. Strains of MON-98, 77, and 108 were always part of the MON-1 group. Among MON-1, three geographically determined and genetically differentiated populations could be identified: (1) Greece; (2) Spain islands–Majorca/Ibiza; (3) mainland Portugal/Spain. All four populations showed a predominantly clonal structure; however, there are indications of occasional recombination events and gene flow even between MON-1 and non-MON-1. Sand fly vectors seem to play an important role in sustaining genetic diversity. No correlation was observed between Leishmania genotypes, host specificity, and clinical manifestation. In the case of relapse/re-infection, only re-infections by a strain with a different MLMT profile can be unequivocally identified, since not all strains have individual MLMT profiles.

Conclusion

In the present study for the first time several key epidemiological questions could be addressed for the MON-1 zymodeme, because of the high discriminatory power of microsatellite markers, thus creating a basis for further epidemiological investigations.