Comment on “minimal and maximal models to quantitate glucose metabolism : tools to measure, to simulate and to run in silico clinical trials"

Comment on “Minimal and Maximal Models to Quantitate Glucose Metabolism: Tools to Measure, to Simulate and to Run in Silico Clinical Trials

Comparison between breathing and aerobic exercise on clinical control in patients with moderate-to-severe asthma: protocol of a randomized trial

Abstract\ud \ud Background\ud Asthma is a chronic inflammatory airway disease characterized by reversible obstruction, inflammation and hyperresponsiveness to different stimulus. Aerobic and breathing exercises have been demonstrated to benefit asthmatic patients; however, there is no evidence comparing the effectiveness of these treatments.\ud \ud \ud Methods/design\ud This is a prospective, comparative, blinded, and randomized clinical trial with 2 groups that will receive distinct interventions. Forty-eight asthmatic adults with optimized medical treatment will be randomly divided into either aerobic (AG) or breathing exercises (BG). Patients will perform breathing or aerobic exercise twice a week for 3 months, totalizing 24 sessions of 40 minutes each. Before intervention, both groups will complete an educational program consisting of 2 educational classes. Before and after interventions, the following parameters will be quantified: clinical control (main outcome), health related quality of life, levels of anxiety and depression, daily living physical activity and maximal exercise capacity (secondary outcome). Hyperventilation syndrome symptoms, autonomic nervous imbalance, thoracoabdominal kinematics, inflammatory cells in the sputum, fraction of exhaled nitric oxide (FENO) and systemic inflammatory cytokines will also be evaluated as possible mechanisms to explain the benefits of both interventions.\ud \ud \ud Discussion\ud Although the benefits of breathing and aerobic exercises have been extensively studied, the comparison between both has never been investigated. Furthermore, the findings of our results will allow us to understand its application and suitability to patients that will have more benefits for every intervention optimizing its effect.\ud \ud \ud Trial registration\ud Clinicaltrials.gov; Identifier: \ud NCT02065258\ud \ud .This work was supported by São Paulo Research Foundation - FAPESP (grants\ud 2009/53904-9 and 2011/50071-6)

CACNA1E Variants Affect Beta Cell Function in Patients with Newly Diagnosed Type 2 Diabetes. The Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 3

Background: Genetic variability of the major subunit (CACNA1E) of the voltage-dependent Ca 2+ channel Ca V2.3 is associated to risk of type 2 diabetes, insulin resistance and impaired insulin secretion in nondiabetic subjects. The aim of the study was to test whether CACNA1E common variability affects beta cell function and/or insulin sensitivity in patients with newly diagnosed type 2 diabetes. Methodology/Principal Findings: In 595 GAD-negative, drug naïve patients (mean6SD; age: 58.5610.2 yrs; BMI: 29.965 kg/m 2, HbA1c: 7.061.3) with newly diagnosed type 2 diabetes we: 1. genotyped 10 tag SNPs in CACNA1E region reportedly covering,93 % of CACNA1E common variability: rs558994, rs679931, rs2184945, rs10797728, rs3905011, rs12071300, rs175338, rs3753737, rs2253388 and rs4652679; 2. assessed clinical phenotypes, insulin sensitivity by the euglycemic insulin clamp and beta cell function by state-of-art modelling of glucose/C-peptide curves during OGTT. Five CACNA1E tag SNPs (rs10797728, rs175338, rs2184945, rs3905011 and rs4652679) were associated with specific aspects of beta cell function (p,0.0520.01). Both major alleles of rs2184945 and rs3905011 were each (p,0.01 and p,0.005, respectively) associated to reduced proportional control with a demonstrable additive effect (p,0.005). In contrast, only the major allele of rs2253388 was related weakly to more severe insulin resistance (p,0.05). Conclusions/Significance: In patients with newly diagnosed type 2 diabetes CACNA1E common variability is strongl

Structural identifiability of dynamic systems biology models

22 páginas, 5 figuras, 2 tablas.-- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.A powerful way of gaining insight into biological systems is by creating a nonlinear differential equation model, which usually contains many unknown parameters. Such a model is called structurally identifiable if it is possible to determine the values of its parameters from measurements of the model outputs. Structural identifiability is a prerequisite for parameter estimation, and should be assessed before exploiting a model. However, this analysis is seldom performed due to the high computational cost involved in the necessary symbolic calculations, which quickly becomes prohibitive as the problem size increases. In this paper we show how to analyse the structural identifiability of a very general class of nonlinear models by extending methods originally developed for studying observability. We present results about models whose identifiability had not been previously determined, report unidentifiabilities that had not been found before, and show how to modify those unidentifiable models to make them identifiable. This method helps prevent problems caused by lack of identifiability analysis, which can compromise the success of tasks such as experiment design, parameter estimation, and model-based optimization. The procedure is called STRIKE-GOLDD (STRuctural Identifiability taKen as Extended-Generalized Observability with Lie Derivatives and Decomposition), and it is implemented in a MATLAB toolbox which is available as open source software. The broad applicability of this approach facilitates the analysis of the increasingly complex models used in systems biology and other areasAFV acknowledges funding from the Galician government (Xunta de Galiza, Consellería de Cultura, Educación e Ordenación Universitaria http://www.edu.xunta.es/portal/taxonomy/term/206) through the I2C postdoctoral program, fellowship ED481B2014/133-0. AB and AFV were partially supported by grant DPI2013-47100-C2-2-P from the Spanish Ministry of Economy and Competitiveness (MINECO). AFV acknowledges additional funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 686282 (CanPathPro). AP was partially supported through EPSRC projects EP/M002454/1 and EP/J012041/1.Peer reviewe

Brace related stress in scoliosis patients – Comparison of different concepts of bracing

<p>Abstract</p> <p>Background</p> <p>The BSSQbrace questionnaire has been shown to be reliable with good internal consistency and reproducibility estimating the stress scoliosis patients have whilst wearing their brace. Eight questions are provided focussing on this topic. A max. score of 24 can be achieved (from 0 for most stress to 24 for no stress). The subdivision of the score values is: 0–8 (strong stress), 9–16 (medium stress) and 17–24 (little stress).</p> <p>Study design</p> <p>Two BSSQbrace questionnaires have been posted to 65 patients under brace treatment from our Cheneau light data base. All patients had another kind of brace prior to the Cheneau light. The patients have been asked to rate their stress level using one questionnaire for the current brace and the other for the previous one.</p> <p>Results</p> <p>63 Patients (59 girls and 4 boys) returned their fully completed questionnaires (average age 13,6 years, average Cobb angle 43,7 degrees). Stress level in the previous brace was 11,04 and in the Cheneau light(r) 13,87. The differences were highly significant in the t-test; t = -4,67; p < 0,001.</p> <p>Conclusion</p> <p>The use of the Cheneau light^®brace leads to reduced stress and/or impairment for the patients under treatment compared to heavier brace models used so far.</p

Development and preliminary validation of Brace Questionnaire (BrQ): a new instrument for measuring quality of life of brace treated scoliotics

BACKGROUND: The quality of life among children with idiopathic scoliosis during their adolescence has been reported to be affected by the brace itself. However, a controversy exists whether brace treated scoliotics experience a poor quality of life, thus there is a need for the development of a brace-oriented instrument, as the now-existing questionnaires that are commonly used, such as the SRS -22, take into consideration the effects of both the conservative and the surgical treatment on quality of life of scoliotic children. The aim of the present study is to assess the validity and reliability of Brace Questionnaire (BrQ), a new instrument for measuring quality of life of scoliotic adolescents who are treated conservatively with a brace. MATERIAL-METHOD: Methodology of development involved literature review, patient and health care professionals' in-depth interviews and content validity analysis on patients. A validation study was performed on 28 brace treated scoliotic children aged between 9 and 18 years old. BrQ was assessed for the following psychometric properties: item convergent validity, floor and ceiling effects, internal consistency reliability, clinical validity and responsiveness to change. RESULTS: BrQ is self administrated and developmentally appropriate for ages 9 to 18 years old and is consisted of 34 Likert-scale items associated with eight domains: general health perception, physical functioning, emotional functioning, self esteem and aesthetics, vitality, school activity, bodily pain and social functioning of scoliotic children treated conservatively with a brace. The subscales of these eight dimensions can be combined to produce a total score. Higher scores mean a better quality of life. An item convergent validity ≥ 0.40 was satisfied by all items in the present study. A satisfactory internal consistency reliability for the BrQ was recorded (Cronbach's alpha coefficient was 0.82). There were no floor or ceiling effects. The correlation between BrQ overall scores and mild and moderate scoliosis was statistically significant (p < 0.001), revealing high clinical validity. An increase in effect sizes for the patient with improved scoliotic curves indicates that the BrQ is responsive to change in health status. CONCLUSION: BrQ is reliable, valid and responsive to change in adolescents with IS who are treated conservatively with a brace

Characterisation of sugar beet (Beta vulgaris L. ssp. vulgaris) varieties using microsatellite markers

<p>Abstract</p> <p>Background</p> <p>Sugar beet is an obligate outcrossing species. Varieties consist of mixtures of plants from various parental combinations. As the number of informative morphological characteristics is limited, this leads to some problems in variety registration research.</p> <p>Results</p> <p>We have developed 25 new microsatellite markers for sugar beet. A selection of 12 markers with high quality patterns was used to characterise 40 diploid and triploid varieties. For each variety 30 individual plants were genotyped. The markers amplified 3-21 different alleles. Varieties had up to 7 different alleles at one marker locus. All varieties could be distinguished. For the diploid varieties, the expected heterozygosity ranged from 0.458 to 0.744. The average inbreeding coefficient F_iswas 0.282 ± 0.124, but it varied widely among marker loci, from F_is= +0.876 (heterozygote deficiency) to F_is= -0.350 (excess of heterozygotes). The genetic differentiation among diploid varieties was relatively constant among markers (F_st= 0.232 ± 0.027). Among triploid varieties the genetic differentiation was much lower (F_st= 0.100 ± 0.010). The overall genetic differentiation between diploid and triploid varieties was F_st= 0.133 across all loci. Part of this differentiation may coincide with the differentiation among breeders' gene pools, which was F_st= 0.063.</p> <p>Conclusions</p> <p>Based on a combination of scores for individual plants all varieties can be distinguished using the 12 markers developed here. The markers may also be used for mapping and in molecular breeding. In addition, they may be employed in studying gene flow from crop to wild populations.</p

The experience of brace treatment in children/adolescents with scoliosis

BACKGROUND: Idiopathic scoliosis is a chronic illness with several different braces used for its treatment. Brace treatment during childhood/adolescence can produce stress. There are studies supporting that it can decrease body-image perception while other studies support that it has no such effect. The purpose of this study was to explore the experience of brace treatment in children/adolescents with scoliosis. The aim was to investigate which feelings are created by the bracing experience in children/adolescents with scoliosis and what are the children/adolescents' with scoliosis opinions of the support provided to them by health-care professionals and by their families. METHODS: We conducted interviews with the help of a semi-structured interview guide in order to address the topic of the experience of brace treatment. A convenient sample of twelve children and adolescents with scoliosis was selected from patients attending follow-up appointments at the Outpatient Scoliosis Clinics of two Greek hospitals. The data was analysed using the method of content analysis. RESULTS: Patients in the sample were 10–16 years old and they were mainly females (71%). Almost all of the participants reported having to deal with stress, denial, fear, anger, and shame. They were satisfied with the information they received regarding their condition and therapy. However, the information was not accompanied by support from the health care professionals. They reported that they were receiving support mainly from their families, friends, and classmates. CONCLUSION: The present study is contributing to the development of a better understanding of significant issues related to the experience of bracing therapy. It is clear that scoliosis children/adolescents have to be provided with support during the long period of bracing. It is apparent that those children/adolescents have unmet needs for care and health professionals and policy makers should try to find a way to address those needs