Doppler detection of valvular regurgitation after radiofrequency ablation of accessory connections

Radiofrequency current was used recently to ablate accessory connections in patients with supraventricular tachycardia.1-5 After locating the accessory connection by electrophysiologic mapping, ablation is achieved by positioning a 7Fr catheter (with 4 mm electrode at distal tip) within the ipsilateral cardiac chamber and adjacent to the accessory connection. Radiofrequency current is then delivered at the point of earliest electrical activation along the atrioventricular valve annulus. For a left-sided accessory connection, the catheter is usually passed retrograde across the aortic valve into the left ventricle and under the posterior mitral valve leaflet. For a right-sided accessory connection, the catheter is passed anterograde into the right atrium or ventricle.1-5 Systematic evaluation of the effects of this technique on the function of all cardiac valves has not been reported. This study evaluates the effects of catheter manipulation and radiofrequency current delivery on valve competence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29958/1/0000320.pd

Tachycardia Related Cardiomyopathy: Response to Control of the Arrhythmia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75609/1/j.1540-8183.1989.tb00780.x.pd

'She's like a daughter to me': insights into care, work and kinship from rural Russia

This article draws on ethnographic research into a state-funded homecare service in rural Russia. The article discusses intersections between care, work and kinship in the relationships between homecare workers and their elderly wards and explores the ways in which references to kinship, as a means of authenticating paid care and explaining its emotional content, reinforce public and private oppositions while doing little to relieve the tensions and conflicts of care work. The discussion brings together detailed empirical insights into local ideologies and practices as a way of generating new theoretical perspectives, which will be of relevance beyond the particular context of study

Stabilization of the Cysteine-Rich Conotoxin MrIA by Using a 1,2,3-Triazole as a Disulfide Bond Mimetic

The design of disulfide bond mimetics is an important strategy for optimising cysteine-rich peptides in drug development. Mimetics of the drug lead conotoxin MrIA, in which one disulfide bond is selectively replaced of by a 1,4-disubstituted-1,2,3-triazole bridge, are described. Sequential copper-catalyzed azide–alkyne cycloaddition (CuAAC; click reaction) followed by disulfide formation resulted in the regioselective syntheses of triazole–disulfide hybrid MrIA analogues. Mimetics with a triazole replacing the Cys4–Cys13 disulfide bond retained tertiary structure and full in vitro and in vivo activity as norepinephrine reuptake inhibitors. Importantly, these mimetics are resistant to reduction in the presence of glutathione, thus resulting in improved plasma stability and increased suitability for drug development.NHMRC 1045964 & 107211

Congenital aortic arch thrombosis diagnosed by echocardiography

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26803/1/0000359.pd

The emerging role of NG2 in pediatric diffuse intrinsic pontine glioma.

Diffuse intrinsic pontine gliomas (DIPGs) have a dismal prognosis and are poorly understood brain cancers. Receptor tyrosine kinases stabilized by neuron-glial antigen 2 (NG2) protein are known to induce gliomagenesis. Here, we investigated NG2 expression in a cohort of DIPG specimens (n= 50). We demonstrate NG2 expression in the majority of DIPG specimens tested and determine that tumors harboring histone 3.3 mutation express the highest NG2 levels. We further demonstrate that microRNA 129-2 (miR129-2) is downregulated and hypermethylated in human DIPGs, resulting in the increased expression of NG2. Treatment with 5-Azacytidine, a methyltransferase inhibitor, results in NG2 downregulation in DIPG primary tumor cells in vitro. NG2 expression is altered (symmetric segregation) in mitotic human DIPG and mouse tumor cells. These mitotic cells co-express oligodendrocyte (Olig2) and astrocyte (glial fibrillary acidic protein, GFAP) markers, indicating lack of terminal differentiation. NG2 knockdown retards cellular migration in vitro, while NG2 expressing neurospheres are highly tumorigenic in vivo, resulting in rapid growth of pontine tumors. NG2 expression is targetable in vivo using miR129-2 indicating a potential avenue for therapeutic interventions. This data implicates NG2 as a molecule of interest in DIPGs especially those with H3.3 mutation

Relationship between mediation analysis and the structured life course approach

© The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association. Many questions in life course epidemiology involve mediation and/or interaction because of the long latency period between exposures and outcomes. In this paper, we explore how mediation analysis (based on counterfactual theory and implemented using conventional regression approaches) links with a structured approach to selecting life course hypotheses. Using theory and simulated data, we show how the alternative life course hypotheses assessed in the structured life course approach correspond to different combinations of mediation and interaction parameters. For example, an early life critical period model corresponds to a direct effect of the early life exposure, but no indirect effect via the mediator and no interaction between the early life exposure and the mediator. We also compare these methods using an illustrative real-data example using data on parental occupational social class (early life exposure), own adult occupational social class (mediator) and physical capability (outcome)

The Effect of Various Doses of Phenylalanine Supplementation on Blood Phenylalanine and Tyrosine Concentrations in Tyrosinemia Type 1 Patients

Tyrosinemia type 1 (TT1) treatment with 2-(2-nitro-4-trifluormethyl-benzyl)-1,3-cyclohexanedione (NTBC) and a phenylalanine-tyrosine restricted diet is associated with low phenylalanine concentrations. Phenylalanine supplementation is prescribed without comprehensive consideration about its effect on metabolic control. We investigated the effect of phenylalanine supplementation on bloodspot phenylalanine, tyrosine, NTBC and succinylacetone. Eleven TT1 patients received 0, 20 and 40 mg/kg/day phenylalanine supplementation with the phenylalanine-tyrosine free L-amino acid supplements. Bloodspots were collected before breakfast, midday and evening meal. Differences between study periods, sample times and days within a study period were studied using (generalized) linear mixed model analyses. Twenty and 40 mg/kg/day phenylalanine supplementation prevented daytime phenylalanine decreases (p = 0.05) and most low phenylalanine concentrations, while tyrosine concentrations increased (p <0.001). Furthermore, NTBC and succinylacetone concentrations did not differ between study periods. To conclude, 20 mg/kg/day phenylalanine supplementation can prevent most low phenylalanine concentrations without increasing tyrosine to concentrations above the target range or influencing NTBC and succinylacetone concentrations, while 40 mg/kg/day increased tyrosine concentrations to values above the targeted range. Additionally, this study showed that the effect of phenylalanine supplementation, and a possible phenylalanine deficiency, should be assessed using pre-midday meal blood samples that could be combined with an overnight fasted sample when in doubt

The effect of cigarette smoke exposure on the development of inflammation in lungs, gut and joints of TNFΔARE mice

The inflammatory cytokine TNF-alpha is a central mediator in many immune-mediated diseases, such as Crohn's disease (CD), spondyloarthritis (SpA) and chronic obstructive pulmonary disease (COPD). Epidemiologic studies have shown that cigarette smoking (CS) is a prominent common risk factor in these TNF-dependent diseases. We exposed TNF Delta ARE mice; in which a systemic TNF-alpha overexpression leads to the development of inflammation; to 2 or 4 weeks of air or CS. We investigated the effect of deregulated TNF expression on CS-induced pulmonary inflammation and the effect of CS exposure on the initiation and progression of gut and joint inflammation. Upon 2 weeks of CS exposure, inflammation in lungs of TNF Delta ARE mice was significantly aggravated. However, upon 4 weeks of CS-exposure, this aggravation was no longer observed. TNF Delta ARE mice have no increases in CD4+ and CD8+ T cells and a diminished neutrophil response in the lungs after 4 weeks of CS exposure. In the gut and joints of TNF Delta ARE mice, 2 or 4 weeks of CS exposure did not modulate the development of inflammation. In conclusion, CS exposure does not modulate gut and joint inflammation in TNF Delta ARE mice. The lung responses towards CS in TNF Delta ARE mice however depend on the duration of CS exposure

Psychological interventions for vaccine injections in children and adolescents: Systematic review of randomized and quasi-randomized controlled trials

Background: This systematic review evaluated the effectiveness of psychological interventions for reducing vaccination pain and related outcomes in children and adolescents. Design/Methods: Database searches identified relevant randomized and quasi-randomized controlled trials. Data were extracted and pooled using established methods. Pain, fear, and distress were considered critically important outcomes. Results: Twenty-two studies were included; 2 included adolescents. Findings showed no benefit of false suggestion (n=240) for pain (standardized mean difference [SMD] -0.21 [-0.47, 0.05]) or distress (SMD -0.28 [-0.59, 0.11]), or for use of repeated reassurance (n=82) for pain (SMD -0.18 [-0.92, 0.56]), fear (SMD -0.18 [-0.71, 0.36]), or distress (SMD 0.10 [-0.33, 0.54]). Verbal distraction (n=46) showed reduced distress (SMD -1.22 [-1.87, -0.58]), but not reduced pain (SMD -0.27 [-1.02, 0.47]). Similarly, video distraction (n=328) showed reduced distress (SMD -0.58 [-0.82, -0.34]), but not reduced pain (SMD -0.88 [-1.78, 0.02]) or fear (SMD 0.08 [-0.25, 0.41]). Music distraction demonstrated reduced pain when used with children (n=417) (SMD -0.45 [-0.71, -0.18]), but not with adolescents (n=118) (SMD -0.04 [-0.42, 0.34]). Breathing with a toy (n=368) showed benefit for pain (SMD -0.49 [-0.85, -0.13]), but not fear (SMD -0.60 [-1.22, 0.02]); whereas breathing without a toy (n=136) showed no benefit for pain (SMD -0.27 [-0.61, 0.07]) or fear (SMD -0.36 [-0.86, 0.15]). There was no benefit for a breathing intervention (cough) in children and adolescents (n=136) for pain (SMD -0.17 [-0.41, 0.07]). Conclusions: Psychological interventions with some evidence of benefit in children include: verbal distraction, video distraction, music distraction, and breathing with a toy