Increased Birth Weight is Associated with Altered Gene Expression in Neonatal Foreskin

Elevated birth weight is linked to glucose intolerance and obesity health-related complications later in life. No studies have examined if infant birth weight is associated with gene expression markers of obesity and inflammation in a tissue that comes directly from the infant following birth. We evaluated the association between birth weight and gene expression on fetal programming of obesity. Foreskin samples were collected following circumcision, and gene expression analyzed comparing the 15% greatest birth weight infants (n = 7) v. the remainder of the cohort (n = 40). Multivariate linear regression models were fit to relate expression levels on differentially expressed genes to birth weight group with adjustment for variables selected from a list of maternal and infant characteristics. Glucose transporter type 4 (GLUT4), insulin receptor substrate 2 (IRS2), leptin receptor (LEPR), lipoprotein lipase (LPL), low-density lipoprotein receptor-related protein 1 (LRP1), matrix metalloproteinase 2 (MMP2), plasminogen activator inhibitor-1 (PAI-1) and transcription factor 7-like 2 (TCF7L2) were significantly upregulated and histone deacetylase 1 (HDAC1) and thioredoxin (TXN) downregulated in the larger birth weight neonates v. controls. Multivariate modeling revealed that the estimated adjusted birth weight group difference exceeded one standard deviation of the expression level for eight of the 10 genes. Between 25 and 50% of variation in expression level was explained by multivariate modeling for eight of the 10 genes. Gene expression related to glycemic control, appetite/energy balance, obesity and inflammation were altered in tissue from babies with elevated birth weight, and these genes may provide important information regarding fetal programming in macrosomic babies

Polymer-coated bioactive glass S53P4 increases VEGF and TNF expression in an induced membrane model in vivo

The two-stage induced-membrane technique for treatment of large bone defects has become popular among orthopedic surgeons. In the first operation, the bone defect is filled with poly(methyl methacrylate) (PMMA), which is intended to produce a membrane around the implant. In the second operation, PMMA is replaced with autograft or allograft bone. Bioactive glasses (BAGs) are bone substitutes with bone-stimulating and angiogenetic properties. The aim of our study was to evaluate the inductive vascular capacity of BAG-S53P4 and poly(lactide-co-glycolide) (PLGA)-coated BAG-S53P4 for potential use as bone substitutes in a single-stage induced-membrane technique. Sintered porous rods of BAG-S53P4, PLGA-coated BAG-S53P4 and PMMA were implanted in the femur of 36 rabbits for 2, 4 and 8 weeks. The expression of vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha (TNF) in the induced membranes of implanted materials was analyzed with real-time quantitative polymerase chain reaction and compared with histology. Both uncoated BAG-S53P4 and PLGA-coated BAG-S53P4 increase expression of VEGF and TNF, resulting in higher amounts of capillary beds, compared with the lower expression of VEGF and less capillary beads observed for negative control and PMMA samples. A significantly higher expression of VEGF was observed for PLGA-coated BAG-S53P4 than for PMMA at 8 weeks (p <0.036). VEGF and TNF expression in the induced membrane of BAG-S53P4 and PLGA-coated BAG-S53P4 is equal or superior to PMMA, the "gold standard" material used in the induced-membrane technique. Furthermore, the VEGF and TNF expression for PLGA-coated BAG-S53P4 increased during follow-up.Peer reviewe

Geographical patterns in blood lead in relation to industrial emissions and traffic in Swedish children, 1978–2007

<p>Abstract</p> <p>Background</p> <p>Blood lead concentrations (B-Pb) were measured in 3 879 Swedish school children during the period 1978–2007. The objective was to study the effect of the proximity to lead sources based on the children's home and school location.</p> <p>Methods</p> <p>The children's home address and school location were geocoded and their proximity to a lead smelter and major roads was calculated using geographical information system (GIS) software. All the statistical analyses were carried out using means of generalized log-linear modelling, with natural-logarithm-transformed B-Pb, adjusted for sex, school year, lead-exposing hobby, country of birth and, in the periods 1988–1994 and 1995–2007, parents' smoking habits.</p> <p>Results</p> <p>The GIS analysis revealed that although the emission from the smelter and children's B-Pb levels had decreased considerably since 1978, proximity to the lead smelter continued to affect levels of B-Pb, even in recent years (geometric mean: near smelter: 22.90 μg/l; far from smelter 19.75 μg/l; p = 0.001). The analysis also revealed that proximity to major roads noticeably affected the children's B-Pb levels during the period 1978–1987 (geometric mean near major roads: 44.26 μg/l; far from roads: 38.32 μg/l; p = 0.056), due to the considerable amount of lead in petrol. This effect was, however, not visible after 1987 due to prohibition of lead in petrol.</p> <p>Conclusion</p> <p>The results show that proximity to the lead smelter still has an impact on the children's B-Pb levels. This is alarming since it could imply that living or working in the vicinity of a former lead source could pose a threat years after reduction of the emission. The analysis also revealed that urban children exposed to lead from traffic were only affected during the early period, when there were considerable amounts of lead in petrol, and that the prohibition of lead in petrol in later years led to reduced levels of lead in the blood of urban children.</p

Characteristics of self-care interventions for patients with a chronic condition: A scoping review

Background: Self-care is a fundamental element of treatment for patients with a chronic condition and a major focus of many interventions. A large body of research exists describing different types of self-care interventions, but these studies have never been compared across conditions. Examination of heterogeneous interventions could provide insights into effective approaches that should be used in diverse patient populations. Objectives: To provide a comprehensive and standardized cross-condition overview of interventions to enhance self-care in patients with a chronic condition. Specific aims were to: 1) identify what self-care concepts and behaviors are evaluated in self-care interventions; 2) classify and quantify heterogeneity in mode and type of delivery; 3) quantify the behavior change techniques used to enhance self-care behavior; and 4) assess the dose of self-care interventions delivered. Design: Scoping review DATA SOURCES: Four electronic databases - PubMed, EMBASE, PsychINFO and CINAHL - were searched from January 2008 through January 2019. Eligibility criteria for study selection: Randomized controlled trials (RCTs) with concealed allocation to the intervention were included if they compared a behavioral or educational self- care intervention to usual care or another self-care intervention and were conducted in adults. Nine common chronic conditions were included: hypertension, coronary artery disease, arthritis, chronic kidney disease, heart failure, stroke, asthma, chronic obstructive lung disease, and type 2 diabetes mellitus. Diagnoses that are psychiatric (e.g. schizophrenia), acute rather than chronic, or benefitting little from self-care (e.g. dementia) were excluded. Studies had to be reported in English with full-text available. Results: 9309 citations were considered and 233 studies were included in the final review. Most studies addressed type 2 diabetes mellitus (n = 85; 36%), hypertension (n = 32; 14%) or heart failure (n = 27; 12%). The majority (97%) focused on healthy behaviors like physical activity (70%), dietary intake (59%), and medication management (52%). Major deficits found in self-care interventions included a lack of attention to the psychological consequences of chronic illness, technology and behavior change techniques were rarely used, few studies focused on helping patients manage signs and symptoms, and the interventions were rarely innovative. Research reporting was generally poor. Conclusions: Major gaps in targeted areas of self-care were identified. Opportunities exist to improve the quality and reporting of future self-care intervention research. Registration: The study was registered in the PROSPERO database (#123,719)

Factors associated with lack of improvement in submaximal exercise capacity of patients with heart failure

Aims Improvement in exercise capacity is the primary goal of physical activity programmes for patients with heart failure (HF). Although activity programmes are effective for some patients, others do not benefit. Identifying factors related to a lack of improvement in submaximal exercise capacity may help us interpret findings and design new interventions. The aim of this study is to identify factors contributing to a lack of improvement in submaximal exercise capacity 3 months after physical activity advice or an exergame intervention in patients with HF. Additionally, we aimed to assess differences in lack of improvement in submaximal exercise capacity of patients whose baseline exercise capacity predicted a worse compared with better prognosis of HF.Methods and results This secondary analysis of the HF-Wii study analysed baseline and 3 month data of the 6 min walk test (6MWT) from 480 patients (mean age 67 years, 72% male). Data were analysed separately in patients with a pre-defined 6 min walking distance at baseline of &lt;300 m (n = 79) and &gt;= 300 m (n = 401). Among patients with a baseline 6MWT of &gt;= 300 m, 18% had deteriorated submaximal exercise capacity. In the multiple logistic regression analysis, lower baseline levels of self-reported physical activity [odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.60-0.97], lower baseline levels of cognitive function (OR = 0.87, 95%CI = 0.79-0.96) were significantly associated with lack of improvement in exercise capacity at 3 months. Not randomized to exergaming (OR = 0.63, 95%CI = 0.37-1.09) was likely (P = 0.097) to be associated with lack of improvement in exercise capacity at 3 months. Among the 79 patients with baseline 6MWT of &lt;300 m, 41% (n = 32) did not improve 6MWT distance at 3 months. Independent predictors for the lack of improvement for 6MWT were New York Heart Association class III/IV (OR = 4.68, 95%CI = 1.08-20.35), higher levels of serum creatinine (OR = 1.02, 95%CI = 1.003-1.03), lower cognitive function (OR = 0.86, 95%CI = 0.75-0.99), and fewer anxiety symptoms (OR = 0.84, 95%CI = 0.72-0.98).Conclusions Lower self-reported physical activity and cognitive impairment predict lack of improvement in submaximal exercise capacity in HF patients. Patients who have a worse prognosis (score &lt;300 m at the 6MWT) are often frail and gain less in exercise capacity. These patients may need a more comprehensive approach to have an effect on exercise capacity, including an individually tailored exercise programme with aerobic exercise (if tolerated) and strength exercises

Effects of exergaming on exercise capacity in patients with heart failure: results of an international multicentre randomized controlled trial

Aims Exergaming is a new tool to increase physical activity. This study aimed to determine the effects of access to a home-based exergame (Nintendo Wii) in patients with heart failure (HF) on exercise capacity, self-reported physical activity and patient-reported outcome measures.Methods and results We enrolled 605 HF patients in New York Heart Association functional class I-IV, independent of ejection fraction, in an international multicentre randomized controlled trial. Patients were randomized to exergame (intervention) or motivational support (control). The primary endpoint was change in submaximal aerobic exercise capacity as measured by the distance walked in 6 min (6MWT) between baseline and 3 months. Secondary endpoints included long-term submaximal aerobic exercise capacity, muscle function, self-reported physical activity, exercise motivation, exercise self-efficacy at 3, 6 and 12months. At baseline, patients on average walked 403142m on the 6MWT. Patients in the exergame group walked further compared to controls at 3 months (454123 vs. 420 +/- 127m, P = 0.005), at 6 months (452 +/- 123 vs. 426 +/- 133m, P = 0.015) and 12months (456 +/- 122 vs. 420 +/- 135m, P = 0.004). However, correcting for baseline 6MWT values by means of a linear mixed-effects model revealed no main effect for the intervention on 6MWT. Small significant effects on muscle function were found. Statistically significant treatment effects were found for muscle function but after correction for baseline and confounders, only the treatment effect for the heel-rise left at 6 months was significant (P&lt;0.05). No treatment effect was found for exercise motivation, exercise self-efficacy, or self-reported physical activity.ConclusionExergaming was safe and feasible in patients with HF with different profiles in different health care systems, cultures and climates. However, it was not effective in improving outcomes on submaximal aerobic exercise capacity. Subgroup analysis did not identify specific subgroups benefiting from the intervention.Clinical Trial Registration: Identifier: NCT01785121

An effective serum- and xeno-free chemically defined freezing procedure for human embryonic and induced pluripotent stem cells

Both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) bear a great potential in regenerative medicine. In addition to optimized clinical grade culture conditions, efficient clinical grade cryopreservation methods for these cells are needed. Obtaining good survival after thawing has been problematic

Mutation and deletion analysis of GFRα-1, encoding the co-receptor for the GDNF/RET complex, in human brain tumours

Glial cell line-derived neurotrophic factor (GDNF) plays a key role in the control of vertebrate neuron survival and differentiation in both the central and peripheral nervous systems. GDNF preferentially binds to GFRα-1 which then interacts with the receptor tyrosine kinase RET. We investigated a panel of 36 independent cases of mainly advanced sporadic brain tumours for the presence of mutations in GDNF and GFRα-1. No mutations were found in the coding region of GDNF. We identified six previously described GFRα-1 polymorphisms, two of which lead to an amino acid change. In 15 of 36 brain tumours, all polymorphic variants appeared to be homozygous. Of these 15 tumours, one also had a rare, apparently homozygous, sequence variant at codon 361. Because of the rarity of the combination of homozygous sequence variants, analysis for hemizygous deletion was pursued in the 15 samples and loss of heterozygosity was found in 11 tumours. Our data suggest that intragenic point mutations of GDNF or GFRα-1 are not a common aetiologic event in brain tumours. However, either deletion of GFRα-1 and/or nearby genes may contribute to the pathogenesis of these tumours