Ferumoxytol-enhanced MRI in patients with prior cardiac transplantation.

Objectives: Ultra-small superparamagnetic particles of iron oxide (USPIO)-enhanced MRI can detect cellular inflammation within tissues and may help non-invasively identify cardiac transplant rejection. Here, we aimed to determine the normal reference values for USPIO-enhanced MRI in patients with a prior cardiac transplant and examine whether USPIO-enhanced MRI could detect myocardial inflammation in patients with transplant rejection. Methods: Ten volunteers and 11 patients with cardiac transplant underwent T2, T2* and late gadolinium enhancement 1.5T MRI, with further T2* imaging at 24 hours after USPIO (ferumoxytol, 4 mg/kg) infusion, at baseline and 3 months. Results: Ten patients with clinically stable cardiac transplantation were retained for analysis. Myocardial T2 values were higher in patients with cardiac transplant versus healthy volunteers (53.8±5.2 vs 48.6±1.9 ms, respectively; p=0.003). There were no differences in the magnitude of USPIO-induced change in R2* in patients with transplantation (change in R2*, 26.6±7.3 vs 22.0±10.4 s-1 in healthy volunteers; p=0.28). After 3 months, patients with transplantation (n=5) had unaltered T2 values (52.7±2.8 vs 52.12±3.4 ms; p=0.80) and changes in R2* following USPIO (29.42±8.14 vs 25.8±7.8 s-1; p=0.43). Conclusion: Stable patients with cardiac transplantation have increased myocardial T2 values, consistent with resting myocardial oedema or fibrosis. In contrast, USPIO-enhanced MRI is normal and stable over time suggesting the absence of chronic macrophage-driven cellular inflammation. It remains to be determined whether USPIO-enhanced MRI may be able to identify acute cardiac transplant rejection. Trial registration number: NCT02319278349 (https://clinicaltrials.gov/ct2/show/NCT02319278) Registered 03.12.2014 EUDraCT 2013-002336-24

Using honey to heal diabetic foot ulcers

Diabetic ulcers seem to be arrested in the inflammatory/proliferative stage of the healing process, allowing infection and inflammation to preclude healing. Antibiotic-resistant bacteria have become a major cause of infections, including diabetic foot infections. It is proposed here that the modern developments of an ancient and traditional treatment for wounds, dressing them with honey, provide the solution to the problem of getting diabetic ulcers to move on from the arrested state of healing. Honeys selected to have a high level of antibacterial activity have been shown to be very effective against antibiotic-resistant strains of bacteria in laboratory and clinical studies. The potent anti-inflammatory action of honey is also likely to play an important part in overcoming the impediment to healing that inflammation causes in diabetic ulcers, as is the antioxidant activity of honey. The action of honey in promotion of tissue regeneration through stimulation of angiogenesis and the growth of fibroblasts and epithelial cells, and its insulin-mimetic effect, would also be of benefit in stimulating the healing of diabetic ulcers. The availability of honey-impregnated dressings which conveniently hold honey in place on ulcers has provided a means of rapidly debriding ulcers and removing the bacterial burden so that good healing rates can be achieved with neuropathic ulcers. With ischemic ulcers, where healing cannot occur because of lack of tissue viability, these honey dressings keep the ulcers clean and prevent infection occurring

Early-Life Determinants of Total and HDL Cholesterol Concentrations in 8-Year-Old Children; The PIAMA Birth Cohort Study

BACKGROUND: Adult cholesterol concentrations might be influenced by early-life factors, such as breastfeeding and birth weight, referred to as "early programming". How such early factors exert their influence over the life course is still poorly understood. Evidence from studies in children and adolescents is scarce and conflicting. We investigated the influence of 6 different perinatal risk factors on childhood total and HDL cholesterol concentrations and total-to-HDL cholesterol ratio measured at 8 years of age, and additionally we studied the role of the child's current Body Mass Index (BMI). METHODS: Anthropometric measures and blood plasma samples were collected during a medical examination in 751 8-year-old children participating in the prospective Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study. Linear and logistic regression were performed to estimate associations of total and HDL cholesterol concentrations with breastfeeding, birth weight, infant weight gain, maternal overweight before pregnancy, gestational diabetes and maternal smoking during pregnancy, taking into account the child's current BMI. RESULTS: Linear regressions showed an association between total-to-HDL cholesterol ratio and maternal pre-pregnancy overweight (β = 0.15, Confidence Interval 95% (CI): 0.02, 0.28), rapid infant weight gain (β = 0.13, 95%CI: 0.01, 0.26), and maternal smoking during pregnancy (β = 0.14, 95%CI: 0.00, 0.29). These associations were partly mediated by the child's BMI. CONCLUSION: Total-to-HDL cholesterol ratio in 8-year-old children was positively associated with maternal pre-pregnancy overweight, maternal smoking during pregnancy and rapid infant weight gain

Constructing majority-rule supertrees

<p>Abstract</p> <p>Background</p> <p>Supertree methods combine the phylogenetic information from multiple partially-overlapping trees into a larger phylogenetic tree called a supertree. Several supertree construction methods have been proposed to date, but most of these are not designed with any specific properties in mind. Recently, Cotton and Wilkinson proposed extensions of the majority-rule consensus tree method to the supertree setting that inherit many of the appealing properties of the former.</p> <p>Results</p> <p>We study a variant of one of Cotton and Wilkinson's methods, called majority-rule (+) supertrees. After proving that a key underlying problem for constructing majority-rule (+) supertrees is NP-hard, we develop a polynomial-size exact integer linear programming formulation of the problem. We then present a data reduction heuristic that identifies smaller subproblems that can be solved independently. While this technique is not guaranteed to produce optimal solutions, it can achieve substantial problem-size reduction. Finally, we report on a computational study of our approach on various real data sets, including the 121-taxon, 7-tree Seabirds data set of Kennedy and Page.</p> <p>Conclusions</p> <p>The results indicate that our exact method is computationally feasible for moderately large inputs. For larger inputs, our data reduction heuristic makes it feasible to tackle problems that are well beyond the range of the basic integer programming approach. Comparisons between the results obtained by our heuristic and exact solutions indicate that the heuristic produces good answers. Our results also suggest that the majority-rule (+) approach, in both its basic form and with data reduction, yields biologically meaningful phylogenies.</p

Acute bronchiolitis in infancy as risk factor for wheezing and reduced pulmonary function by seven years in Akershus County, Norway

BACKGROUND: Acute viral bronchiolitis is one of the most common causes of hospitalisation during infancy in our region with respiratory syncytial virus (RSV) historically being the major causative agent. Many infants with early-life RSV bronchiolitis have sustained bronchial hyperreactivity for many years after hospitalisation and the reasons for this are probably multifactorial. The principal aim of the present study was to investigate if children hospitalised for any acute viral bronchiolitis during infancy in our region, and not only those due to RSV, had more episodes of subsequent wheezing up to age seven years and reduced lung function at that age compared to children not hospitalised for acute bronchiolitis during infancy. A secondary aim was to compare the hospitalised infants with proven RSV bronchiolitis (RS+) to the hospitalised infants with non-RSV bronchiolitis (RS-) according to the same endpoints. METHODS: 57 infants hospitalised at least once with acute viral bronchiolitis during two consecutive winter seasons in 1993–1994 were examined at age seven years. An age-matched control group of 64 children, who had not been hospitalised for acute viral bronchiolitis during infancy, were recruited from a local primary school. Epidemiological and clinical data were collected retrospectively from hospital discharge records and through structured clinical interviews and physical examinations at the follow-up visit. RESULTS: The children hospitalised for bronchiolitis during infancy had decreased lung function, more often wheezing episodes, current medication and follow-up for asthma at age seven years than did the age matched controls. They also had lower average birth weight and more often first order family members with asthma. We did not find significant differences between the RSV+ and RSV- groups. CONCLUSION: Children hospitalised for early-life bronchiolitis are susceptible to recurrent wheezing and reduced pulmonary function by seven years compared to age-matched children not hospitalised for early-life bronchiolitis. We propose that prolonged bronchial hyperreactivity could follow early-life RSV negative as well as RSV positive bronchiolitis

A genome-wide screen in human embryonic stem cells reveals novel sites of allele-specific histone modification associated with known disease loci

<p>Abstract</p> <p>Background</p> <p>Chromatin structure at a given site can differ between chromosome copies in a cell, and such imbalances in chromatin structure have been shown to be important in understanding the molecular mechanisms controlling several disease loci. Human genetic variation, DNA methylation, and disease have been intensely studied, uncovering many sites of allele-specific DNA methylation (ASM). However, little is known about the genome-wide occurrence of sites of allele-specific histone modification (ASHM) and their relationship to human disease. The aim of this study was to investigate the extent and characteristics of sites of ASHM in human embryonic stem cells (hESCs).</p> <p>Results</p> <p>Using a statistically rigorous protocol, we investigated the genomic distribution of ASHM in hESCs, and their relationship to sites of allele-specific expression (ASE) and DNA methylation. We found that, although they were rare, sites of ASHM were substantially enriched at loci displaying ASE. Many were also found at known imprinted regions, hence sites of ASHM are likely to be better markers of imprinted regions than sites of ASM. We also found that sites of ASHM and ASE in hESCs colocalize at risk loci for developmental syndromes mediated by deletions, providing insights into the etiology of these disorders.</p> <p>Conclusion</p> <p>These results demonstrate the potential importance of ASHM patterns in the interpretation of disease loci, and the protocol described provides a basis for similar studies of ASHM in other cell types to further our understanding of human disease susceptibility.</p

Birth weight and blood lipid levels in Spanish adolescents: Influence of selected APOE, APOC3 and PPARgamma2 gene polymorphisms. The AVENA Study

Background There is increasing evidence indicating that genes involved in certain metabolic processes of cardiovascular diseases may be of particular influence in people with low body weight at birth. We examined whether the apolipoprotein (APO) E, APOC3 and the peroxisome proliferator-activated receptor-γ-2 (PPARγ2) polymorphisms influence the association between low birth weight and blood lipid levels in healthy adolescents aged 13–18.5 years. Methods A cross-sectional study of 502 Spanish adolescents born at term was conducted. Total (TC) and high density lipoprotein cholesterol (HDLc), triglycerides (TG), apolipoprotein (apo) A and B, and lipoprotein(a) [Lp(a)] were measured. Low density lipoprotein cholesterol (LDLc), TC-HDLc, TC/HDLc and apoB/apoA were calculated. Results Low birth weight was associated with higher levels of TC, LDLc, apoB, Lp(a), TC-HDLc, TC/HDLc and apoB/apoA in males with the APOE ε3ε4 genotype, whereas in females, it was associated with lower HDLc and higher TG levels. In males with the APOC3 S1/S2 genotype, low birth weight was associated with lower apoA and higher Lp(a), yet this association was not observed in females. There were no associations between low birth weight and blood lipids in any of the PPARγ2 genotypes. Conclusion The results indicate that low birth weight has a deleterious influence on lipid profile particularly in adolescents with the APOE ε3/ε4 genotype. These findings suggest that intrauterine environment interact with the genetic background affecting the lipid profile in later life.The AVENA study was supported by the Spanish Ministry of Health Instituto de Salud Carlos III (FIS PI021830), the Spanish Ministry of Health, FEDER-FSE funds FIS n° 00/0015, CSD grants 05/UPB32/0, 109/UPB31/03 and 13/UPB20/04, the Spanish Ministry of Education (AP-2004-2745; EX-2007-1124), scholarships from Panrico S.A., Madaus S.A. and Procter and Gamble S.A

Impact of the Spanish Smoking Law on Exposure to Second-Hand Smoke and Respiratory Health in Hospitality Workers: A Cohort Study

A smoke-free law came into effect in Spain on 1st January 2006, affecting all enclosed workplaces except hospitality venues, whose proprietors can choose among totally a smoke-free policy, a partial restriction with designated smoking areas, or no restriction on smoking on the premises. We aimed to evaluate the impact of the law among hospitality workers by assessing second-hand smoke (SHS) exposure and the frequency of respiratory symptoms before and one year after the ban

The role of inflammation in epilepsy.

Epilepsy is the third most common chronic brain disorder, and is characterized by an enduring predisposition to generate seizures. Despite progress in pharmacological and surgical treatments of epilepsy, relatively little is known about the processes leading to the generation of individual seizures, and about the mechanisms whereby a healthy brain is rendered epileptic. These gaps in our knowledge hamper the development of better preventive treatments and cures for the approximately 30% of epilepsy cases that prove resistant to current therapies. Here, we focus on the rapidly growing body of evidence that supports the involvement of inflammatory mediators-released by brain cells and peripheral immune cells-in both the origin of individual seizures and the epileptogenic process. We first describe aspects of brain inflammation and immunity, before exploring the evidence from clinical and experimental studies for a relationship between inflammation and epilepsy. Subsequently, we discuss how seizures cause inflammation, and whether such inflammation, in turn, influences the occurrence and severity of seizures, and seizure-related neuronal death. Further insight into the complex role of inflammation in the generation and exacerbation of epilepsy should yield new molecular targets for the design of antiepileptic drugs, which might not only inhibit the symptoms of this disorder, but also prevent or abrogate disease pathogenesis