Mesenchymal stem cells and their use as cell replacement therapy and disease modelling tool.

Mesenchymal stem cells (MSCs) from adult somatic tissues may differentiate in vitro and in vivo into multiple mesodermal tissues including bone, cartilage, adipose tissue, tendon, ligament or even muscle. MSCs preferentially home to damaged tissues where they exert their therapeutic potential. A striking feature of the MSCs is their low inherent immunogenicity as they induce little, if any, proliferation of allogeneic lymphocytes and antigen-presenting cells. Instead, MSCs appear to be immunosuppressive in vitro. Their multilineage differentiation potential coupled to their immuno-privileged properties is being exploited worldwide for both autologous and allogeneic cell replacement strategies. Here, we introduce the readers to the biology of MSCs and the mechanisms underlying immune tolerance. We then outline potential cell replacement strategies and clinical applications based on the MSCs immunological properties. Ongoing clinical trials for graft-versus-host-disease, haematopoietic recovery after co-transplantation of MSCs along with haematopoietic stem cells and tissue repair are discussed. Finally, we review the emerging area based on the use of MSCs as a target cell subset for either spontaneous or induced neoplastic transformation and, for modelling non-haematological mesenchymal cancers such as sarcomas

Investigating the association between obesity and asthma in 6- to 8-year-old Saudi children:a matched case-control study

Background: Previous studies have demonstrated an association between obesity and asthma, but there remains considerable uncertainty about whether this reflects an underlying causal relationship. Aims: To investigate the association between obesity and asthma in pre-pubertal children and to investigate the roles of airway obstruction and atopy as possible causal mechanisms. Methods: We conducted an age- and sex-matched case–control study of 1,264 6- to 8-year-old schoolchildren with and without asthma recruited from 37 randomly selected schools in Madinah, Saudi Arabia. The body mass index (BMI), waist circumference and skin fold thickness of the 632 children with asthma were compared with those of the 632 control children without asthma. Associations between obesity and asthma, adjusted for other potential risk factors, were assessed separately in boys and girls using conditional logistic regression analysis. The possible mediating roles of atopy and airway obstruction were studied by investigating the impact of incorporating data on sensitisation to common aeroallergens and measurements of lung function. Results: BMI was associated with asthma in boys (odds ratio (OR)=1.14, 95% confidence interval (CI), 1.08–1.20; adjusted OR=1.11, 95% CI, 1.03–1.19) and girls (OR=1.37, 95% CI, 1.26–1.50; adjusted OR=1.38, 95% CI, 1.23–1.56). Adjusting for forced expiratory volume in 1 s had a negligible impact on these associations, but these were attenuated following adjustment for allergic sensitisation, particularly in girls (girls: OR=1.25; 95% CI, 0.96–1.60; boys: OR=1.09, 95% CI, 0.99–1.19). Conclusions: BMI is associated with asthma in pre-pubertal Saudi boys and girls; this effect does not appear to be mediated through respiratory obstruction, but in girls this may at least partially be mediated through increased risk of allergic sensitisation

Bow shocks, nova shells, disc winds and tilted discs: the nova-like V341 Ara has it all

V341 Ara was recently recognized as one of the closest (d ≃ 150 pc) and brightest (V ≃ 10) nova-like cataclysmic variables. This unique system is surrounded by a bright emission nebula, likely to be the remnant of a recent nova eruption. Embedded within this nebula is a prominent bow shock, where the system’s accretion disc wind runs into its own nova shell. In order to establish its fundamental properties, we present the first comprehensive multiwavelength study of the system. Long-term photometry reveals quasi-periodic, super-orbital variations with a characteristic time-scale of 10–16 d and typical amplitude of ≃1 mag. High-cadence photometry from theTransiting Exoplanet Survey Satellite (TESS) reveals for the first time both the orbital period and a ‘negative superhump’ period. The latter is usually interpreted as the signature of a tilted accretion disc. We propose a recently developed disc instability model as a plausible explanation for the photometric behaviour. In our spectroscopic data, we clearly detect antiphased absorption and emission-line components. Their radial velocities suggest a high mass ratio, which in turn implies an unusually low white-dwarf mass. We also constrain the wind mass-loss rate of the system from the spatially resolved [O III] emission produced in the bow shock; this can be used to test and calibrate accretion disc wind models. We suggest a possible association between V341 Ara and a ‘guest star’ mentioned in Chinese historical records in AD 1240. If this marks the date of the system’s nova eruption, V341 Ara would be the oldest recovered nova of its class and an excellent laboratory for testing nova theory

Comparative effectiveness of asthma interventions within a practice based research network

<p>Abstract</p> <p>Background</p> <p>Asthma is a chronic lung disease that affects more than 23 million people in the United States, including 7 million children. Asthma is a difficult to manage chronic condition associated with disparities in health outcomes, poor medical compliance, and high healthcare costs. The research network coordinating this project includes hospitals, urgent care centers, and outpatient clinics within Carolinas Healthcare System that share a common electronic medical record and billing system allowing for rapid collection of clinical and demographic data. This study investigates the impact of three interventions on clinical outcomes for patients with asthma. Interventions are: an integrated approach to care that incorporates asthma management based on the chronic care model; a shared decision making intervention for asthma patients in underserved or disadvantaged populations; and a school based care approach that examines the efficacy of school-based programs to impact asthma outcomes including effectiveness of linkages between schools and the healthcare providers.</p> <p>Methods/Design</p> <p>This study will include 95 Practices, 171 schools, and over 30,000 asthmatic patients. Five groups (A-E) will be evaluated to determine the effectiveness of three interventions. Group A is the usual care control group without electronic medical record (EMR). Group B practices are a second control group that has an EMR with decision support, asthma action plans, and population reports at baseline. A time delay design during year one converts practices in Group B to group C after receiving the integrated approach to care intervention. Four practices within Group C will receive the shared decision making intervention (and become group D). Group E will receive a school based care intervention through case management within the schools. A centralized database will be created with the goal of facilitating comparative effectiveness research on asthma outcomes specifically for this study. Patient and community level analysis will include results from patient surveys, focus groups, and asthma patient density mapping. Community variables such as income and housing density will be mapped for comparison. Outcomes to be measured are reduced hospitalizations and emergency department visits; improved adherence to medication; improved quality of life; reduced school absenteeism; improved self-efficacy and improved school performance.</p> <p>Discussion</p> <p>Identifying new mechanisms that improve the delivery of asthma care is an important step towards advancing patient outcomes, avoiding preventable Emergency Department visits and hospitalizations, while simultaneously reducing overall healthcare costs.</p

Increasing body mass index from age 5 to 14 years predicts asthma among adolescents: evidence from a birth cohort study

Background:Obesity and asthma are common disorders, and the prevalence of both has increased in recent decades. It has been suggested that increases in the prevalence of obesity might in part explain the increase in asthma prevalence. This study aims to examine the prospective association between change in body mass index (BMI) z-score between ages 5 and 14 years and asthma symptoms at 14 years. Methods:Data was taken from the Mater University Study of Pregnancy and its outcomes (MUSP), a birth cohort of 7223 mothers and children started in Brisbane (Australia) in 1981. BMI was measured at age 5 and 14 years. Asthma was assessed from maternal reports of symptoms at age 5 and 14 years. In this study analyses were conducted on 2911 participants who had information on BMI and asthma at both ages. Results: BMI z-score at age 14 and the change in BMI z-score from age 5 to 14–years were positively associated with asthma symptoms at age 14 years, whereas BMI z-score at age 5 was not associated with asthma at age 14. Adjustment for a range of early-life exposures did not substantially alter these findings. The association between change in BMI z-score with asthma symptoms at 14 years appeared stronger for male subjects compared with female subjects but there was no statistical evidence for a sex difference (P=0.36). Conclusions: Increase in BMI z-score between age 5 and 14 years is associated with increased risk of asthma symptoms in adolescence

Early intestinal Bacteroides fragilis colonisation and development of asthma

<p>Abstract</p> <p>Background</p> <p>The 'hygiene hypothesis' suggests that early exposure to microbes can be protective against atopic disease. The intestinal microbial flora could operate as an important postnatal regulator of the Th1/Th2 balance. The aim of the study was to investigate the association between early intestinal colonisation and the development of asthma in the first 3 years of life.</p> <p>Methods</p> <p>In a prospective birth cohort, 117 children were classified according to the Asthma Predictive Index. A positive index included wheezing during the first three years of life combined with eczema in the child in the first years of life or with a parental history of asthma. A faecal sample was taken at the age of 3 weeks and cultured on selective media.</p> <p>Results</p> <p>Asthma Predictive Index was positive in 26/117 (22%) of the children. The prevalence of colonisation with <it>Bacteroides fragilis </it>was higher at 3 weeks in index+ compared to index- children (64% vs. 34% p < 0,05). <it>Bacteroides fragilis </it>and <it>Total Anaerobes </it>counts at 3 weeks were significantly higher in children with a positive index as compared with those without. After adjusting for confounders a positive association was found between <it>Bacteroides fragilis </it>colonisation and Asthma Predictive Index (odds ratio: 4,4; confidence interval: 1,7 – 11,8).</p> <p>Conclusion</p> <p><it>Bacteroides fragilis </it>colonisation at age 3 weeks is an early indicator of possible asthma later in life. This study could provide the means for more accurate targeting of treatment and prevention and thus more effective and better controlled modulation of the microbial milieu.</p

First-Principles Study of the Electronic and Magnetic Properties of Defects in Carbon Nanostructures

Understanding the magnetic properties of graphenic nanostructures is instrumental in future spintronics applications. These magnetic properties are known to depend crucially on the presence of defects. Here we review our recent theoretical studies using density functional calculations on two types of defects in carbon nanostructures: Substitutional doping with transition metals, and sp$^3$-type defects created by covalent functionalization with organic and inorganic molecules. We focus on such defects because they can be used to create and control magnetism in graphene-based materials. Our main results are summarized as follows: i)Substitutional metal impurities are fully understood using a model based on the hybridization between the $d$ states of the metal atom and the defect levels associated with an unreconstructed D$_{3h}$ carbon vacancy. We identify three different regimes, associated with the occupation of distinct hybridization levels, which determine the magnetic properties obtained with this type of doping; ii) A spin moment of 1.0 $\mu_B$ is always induced by chemical functionalization when a molecule chemisorbs on a graphene layer via a single C-C (or other weakly polar) covalent bond. The magnetic coupling between adsorbates shows a key dependence on the sublattice adsorption site. This effect is similar to that of H adsorption, however, with universal character; iii) The spin moment of substitutional metal impurities can be controlled using strain. In particular, we show that although Ni substitutionals are non-magnetic in flat and unstrained graphene, the magnetism of these defects can be activated by applying either uniaxial strain or curvature to the graphene layer. All these results provide key information about formation and control of defect-induced magnetism in graphene and related materials.Comment: 40 pages, 17 Figures, 62 References; Chapter 2 in Topological Modelling of Nanostructures and Extended Systems (2013) - Springer, edited by A. R. Ashrafi, F. Cataldo, A. Iranmanesh, and O. Or

Determinants in early life for asthma development

A reliable screening test in newborns for the subsequent development of bronchial asthma (BA) has not been found yet. This is mainly due to the complexity of BA, being made up by different types and underlying mechanisms. In different studies, a number of risk factors for BA have been identified. These include a positive family history of BA, passive smoking (also during pregnancy), prematurity (including pulmonary infections, RDS and BPD), early viral respiratory infections (such as RSV-bronchiolitis), male gender, early lung function abnormalities and atopic constitution. The major risk factor for persistent BA is an underlying allergic constitution. Therefore, early symptoms and markers of allergy (i.e. The Allergic March) and a positive family history for allergy should be considered as important risk factors for the development of BA