Influence of receptor activator of nuclear factor kappa B on human aortic valve myofibroblasts

Calcific aortic valve stenosis, the main heart valve disease in the elderly, is based on progressive calcification and fibrous thickening of the valve. Several reports addressed the pathogenesis of tissue calcification in this disorder, but few data exist on the molecular mechanisms of the fibrosis and remodeling of the extracellular matrix. The cytokine "receptor activator of nuclear factor kappa B ligand" (RANKL), is expressed in stenotic aortic valves and involved in valvular calcification during calcific aortic valve stenosis. The present study aimed to assess the influence of RANKL on the molecular mechanisms of connective tissue remodeling. In an established cell culture model of primary human aortic valve myofibroblasts, stimulation with RANKL increased cell proliferation as compared to medium alone. Matrix metalloproteinase (MMP)-1 was detectable time-dependently in conditioned media from RANKL-stimulated cells, but absent in media from control cells. MMP-1 activity was increased by RANKL, as measured by collagenase activity assay. Zymography showed an increase in active MMP-2 in RANKL-stimulated cells. These results support the concept that MMPs are involved in the connective tissue remodeling during calcific aortic valve stenosis. RANKL might regulate this process by promoting cell proliferation and MMP expression and activation.     

Flexible bronchoscopy as a valuable tool in the evaluation of persistent wheezing in children

Background

Persistent wheezing is a common problem in early childhood and leads to a diagnostic dilemma, excessive investigations, drug administration and additional cost.

Objective

To determine the efficacy and the safety of FOB in children with persistent wheezing despite bronchodilator and inhaled steroid therapy.

Methods

Patients with persistent wheezing that lasted at least 6 weeks and did not respond to bronchodilator and inhaled steroid therapy and to whom flexible bronchoscopy was performed were included to the study.

Results

Between 1997 and 2009; 113 patients were enrolled to the study. Sixty-three percent of the children were male. Median age was 14 months at presentation and median duration of symptoms was 5 months. Bronchoscopy revealed pathological findings in 48% of the patients. Thirty-eight patients had malacia disorders, 14 had foreign body aspiration and two had external compression of airways which were later diagnosed as vascular ring. Major and minor complications were not seen in 92% of the patients while transient hypoxia was seen in 6%, stridor in 1% and tachycardia in 1% of the patients.

Conclusion

Flexible bronchoscopy provided rapid and definitive diagnosis for our patients with persistent wheezing without any major complications. This study is one of the largest studies concerning persistent wheezing. Early bronchoscopic evaluation can reduce cost by providing rapid and accurate diagnosis and preventing unnecessary investigations and drug administration. Flexible bronchoscopy is a safe procedure and should be considered in the evaluation of children with persistent wheezing.     

Prevalence of sleep-disordered breathing and associated risk factors in primary school children in urban and rural environments

Sleep and Breathing - Sleep-disordered breathing (SDB) in primary school children is a significant problem, yet its prevalence is not well known outside large urban settings. Information on the...     

Predictors of oligoamenorrhea at 1-year follow-up in premenopausal women using a levonorgestrel-releasing intrauterine system

OBJECTIVE: The study was conducted to identify predictors of oligoamenorrhea at 12 months in levonorgestrel-releasing intrauterine system (LNG-IUS) users. DESIGN: A 12-month observational study. SETTING: Gynecologic outpatient clinic in a large regional hospital in Flanders, Belgium. POPULATION OR SAMPLE: A total of 150 women who had made an informed decision to use a LNG-IUS either as a method of contraception or to manage menorrhagia. METHODS: All women were premenopausal and first-time users. The variables recorded prior to insertion on Days 1 to 5 of the menstrual cycle were age, parity, body mass index, indication for LNG-IUS use, prior contraceptive use, menstrual bleeding history, length of the uterine cavity, endometrial thickness, number of antral follicles, serum follicle-stimulating hormone, inhibin B and anti-Müllerian hormone. Menstrual bleeding pattern, patient satisfaction or wish to discontinue the method was noted at 3, 6 and 12 months of follow-up visits. MAIN OUTCOME MEASURES: Menstrual bleeding pattern (amenorrhea, oligomenorrhea, menorrhagia) at 12 months was taken as the primary outcome measurement. Patient satisfaction was followed as a secondary outcome. RESULTS: Oligoamenorrhea was associated with a high patient satisfaction. A bleeding period less than 5 days, absence of severe uterine bleeding at baseline, LNG-IUS use for contraception and oligoamenorrhea at 3 months were predictors of a favorable outcome at 12 months in a univariate analysis. The absence of severe bleeding prior to LNG-IUS insertion was the only clinically useful predictor of favorable outcome in the multivariate analysis (odds ratio 0.13, 95% confidence interval 0.02-0.66). CONCLUSIONS: Patient profiling as described is not helpful in counselling women for intentional LNG-IUS use, especially not if it is planned as a method of managing menorrhagia.     

Biodegradable polymersomes loaded with both paclitaxel and doxorubicin permeate and shrink tumors, inducing apoptosis in proportion to accumulated drug.

Cytotoxicity can in principle be maximized if drugs with different activities can be delivered simultaneously to the same cell. However, combination therapy with drugs having distinct properties such as solubility generally requires use of multiple carriers or solvents, limiting the likelihood of simultaneous delivery. In this brief report, we describe the in vivo use of biodegradable polymersomes for systemic delivery of an anticancer cocktail. These polymer-based shells exploit a thick hydrophobic membrane and an aqueous lumen to efficiently carry both hydrophobic and hydrophilic drugs, respectively paclitaxel and doxorubicin. Polymersomes are long-circulating in vivo but also degrade and release their drugs on a time scale of about 1 day, by which time the tumors treated here will otherwise have almost doubled in volume. A single systemic injection of the dual drug combination shows a higher maximum tolerated dose than the free drug cocktail and shrinks tumors more effectively and more sustainably than free drug: 50% smaller tumors are seen at 5 days with polymersomes. The polymersomes cause two-fold higher cell death in tumors than free drug and show quantitatively similar increases in maximum tolerated dose and drug accumulation within the tumors-suggesting promise for multi-drug delivery.     

Portfolio assessment: does it really give the benefits that it purports to offer? Views of early childhood and first-grade teachers

Early childhood (n?=?10) and first-grade teachers’ (n?=?10) views concerning portfolio usage were investigated in the current research. After collecting the data, six themes were constituted regarding the teachers’ opinions about portfolio use concerning ‘portfolio conception’, ‘advantages, disadvantages and challenges of portfolios’, ‘the content of early childhood portfolio’, ‘teacher's role in the portfolio process’, ‘sharing the portfolio with parents’, and ‘transfer of portfolios from early childhood to first grade’. The findings indicated that participants had similar ideas regarding the conception and content of portfolios. According to the teachers, as well as advantages, there are also disadvantages and challenges in the portfolio process. Moreover, most of the participants described similar roles for children, parents, and teachers in the portfolio process. Although the teachers stated that in principle they knew how to communicate with parents concerning the use of portfolios, most of them mentioned that they employed different ways of communicating in practice due to different reasons. Additionally, both groups of teachers confirmed that early childhood portfolios are not sent to the first-grade teachers, but both groups stated that this would be beneficial if it were to be possible.