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Progresses in multimodal treatments have significantly improved the outcomes for childhood cancer. Nonetheless, for about one-third of patients with Ewing sarcoma, rhabdomyosarcoma, or osteosarcoma steady remission has remained intangible. Thus, new biomarkers to improve early diagnosis and the development of precision-targeted medicine remain imperative. Over the last decade, remarkable progress has been made in the basic understanding of miRNAs function and in interpreting the contribution of their dysregulation to cancer development and progression. On this basis, this review focuses on what has been learned about the pivotal roles of miRNAs in the regulation of key genes implicated in childhood sarcomas. [ABSTRACT FROM AUTHOR]

We present a Raman spectroscopy investigation of the vibrational properties of l-histidine crystals at low temperatures. The temperature dependence of the spectra show discontinuities at 165 K, which we identify with modifications in the bonds associated to both the NH and CO motifs indicative of a conformational phase transition that changes the intermolecular bonds. Additional evidence of such a phase transition is provided by differential scanning calorimetry measurements, which identified an enthalpic anomaly at ∼165 K. [ABSTRACT FROM AUTHOR]

Education and diagnostic tests capable of early detection represent our most effective means of preventing transmission of human immunodeficiency virus (HIV). The importance of early detection is underlined by studies demonstrating increased life expectancy following early initiation of antiviral treatment. The Elecsys HIV combi PT assay is a fourth-generation antigen-antibody combination assay developed to allow earlier detection of seroconversion, and to have increased sensitivity and improved specificity. We aimed to determine how early the assay could detect infection compared with existing assays; whether all HIV variants could be detected; and the assay's specificity using samples from blood donors, routine specimens, and patients with potential cross-reacting factors. Samples were identified as positive by the Elecsys assay 4.9 days after a positive polymerase chain reaction result (as determined by the panel supplier), which was earlier than the 5.3-7.1 days observed with comparators. The analytical sensitivity of the Elecsys HIV combi PT assay for the HIV-1 p24 antigen was 1.05 IU/mL, which compares favorably with the comparator assays. In addition, the Elecsys assay identified all screened HIV subtypes and displayed greater sensitivity to HIV-2 homologous antigen and antibodies to HIV-1 E and O and HIV-2 than the other assays. Overall, the specificity of the Elecsys assay was 99.88 % using samples from blood donors and 99.81 % when analyzing unselected samples. Potential cross-reacting factors did not interfere with assay performance. The Elecsys HIV combi PT assay is a sensitive and specific assay that has been granted the CE mark according to Directive 2009/886/EC. [ABSTRACT FROM AUTHOR]

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In order to evaluate the incidence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in Portugal, we analyzed a collection of 38 S. aureus isolates recovered from 30 children attending the pediatric emergency department of a central hospital in Lisbon due to skin and soft tissue infections. Molecular characterization identified seven clonal lineages among the 35 methicillin-susceptible S. aureus (MSSA) isolates, of which the major lineage PFGE A/t159/ST121 included 63% of the isolates. The three MRSA isolates belonged to the Pediatric clone PFGE D/t535/ST5-IV ( n = 2) and to the European CA-MRSA clone PFGE G/t044/ST80-IVc ( n = 1). All isolates harbored several virulence factors, namely, leukocidins. Panton-Valentine leukocidin (PVL) was produced by isolates from five MSSA lineages and by the ST80 MRSA. Of interest, this is the first reported isolation of CA-MRSA ST80 in Portugal. [ABSTRACT FROM AUTHOR]

Background:Since obesity affects children's health and social integration, treatment concepts with long-term efficiency are necessary.Methods:We analyzed changes of standard deviation score of body mass index (SDS-BMI) quarterly in the first year and once a year during the next 3 years in all obese children participating in the 1-year outpatient intervention program ‘Obeldicks’, which was based on physical exercise, nutrition education and behavior therapy. All analyses were performed on the intention-to-treat approach.Results:One hundred and thirty-one children (77%) of the 170 children (mean age 10.5 years, 51% female, mean BMI 26.9 kg/m2, mean SDS-BMI 2.54) attending the ‘Obeldicks’ intervention program reduced their overweight at the end of intervention (mean SDS-BMI reduction 0.41) and 122 (66%) 3 years after end of intervention (mean SDS-BMI reduction 0.48). The reduction of overweight was independent of the child's gender, age and parental age and BMI. Reduction of 0.33 SDS-BMI in the first 3 months was the best predictor for long-term success (95% predictive value).Conclusions:Participating in the 1-year outpatient obesity intervention program ‘Obeldicks’ was associated with a decrease of overweight, which was sustained 3 years after the end of intervention. Reduction of overweight in the first 3 months of the intervention was highly predictive for long-term success.International Journal of Obesity (2007) 31, 1074–1077; doi:10.1038/sj.ijo.0803637; published online 1 May 2007 [ABSTRACT FROM AUTHOR]

To elucidate the biochemical pathways leading to spontaneous apoptosis in primary cultures of human and rat hepatocytes, we examined the activation of the caspase cascade, the expression of Bcl-2-related-proteins and heat shock proteins. Comparisons were made before and after dexamethasone (DEX) treatment. We show that DEX inhibited spontaneous apoptosis in a dose-dependent manner. DEX increases the expression of anti-apoptotic Bcl-2 and Bcl-X[sub L] proteins, decreases the expression of pro-apoptotic Bax and inhibits Bad translocation thereby preventing the release of cytochrome c, the activation of caspases, and cell death. Although, the expression of Hsp27 and Hsp70 proteins remained unchanged, the oncogenic protein c-Myc is upregulated upon DEX-treatment. These results indicate that DEX mediates its survival effect against spontaneous apoptosis by acting upstream of the mitochondrial changes. Thus, the mitochondrial apoptotic pathway plays a major role in regulating spontaneous apoptosis in these cells. Blocking this pathway therefore may assist with organ preservation for transplant, drug screening, and other purposes. [ABSTRACT FROM AUTHOR]

We examined the effects of dexamethasone (DEX) on the apoptotic process in primary cultures of human and rat hepatocytes. DEX prolonged cell viability, inhibited the development of an apoptotic morphology, and stabilised the expression of procaspase-3 in both human and rat hepatocytes. In addition, the inhibition of apoptosis by DEX was strongly correlated with a decrease of caspase-3-like protease activity. Moreover, DEX treatment increased the expression of anti-apoptotic Bcl-2 and Bcl-xL proteins in human and rat hepatocytes, respectively, whereas the expression of pro-apoptotic proteins Bcl-xS or Bad was not detected or remained unchanged. The bcl-xL transcript is regulated at the transcriptional level and its expression paralleled that of Bcl-xL protein in DEX-treated rat hepatocytes. Taken together, these results indicate that this glucocorticoid exerts a protective role on cell survival and it delays apoptosis of human and rat hepatocytes by modulating caspase-3-like protease activity and bcl-2 and bcl-x gene expression. [ABSTRACT FROM AUTHOR]

Bicuspic aortic valve is the most common congenital cardiac anomaly (Fedak et al. 106:900–904, 2002), and it is associated with other structural anomalies of the aorta, such as coarctation, suggesting a common embryologic developmental mechanism (Mergan et al. 104:118–119, 2004). In more than a half of patients, it is associated with progressive dilation and aneurysm formation of the aorta (Warnes 89:965–966, 2003) despite normally functioning bicuspid aortic valves. In this context, aneurysms of the right subclavian artery are extremely rare, and even more so when associated with a right-sided aortic arch that has a left aberrant subclavian artery with a Kommerell diverticulum, as found in the reported case. These aneurysms represent a significant risk for thromboembolism and rupture, and elective surgical management should be advised, even for asymptomatic cases. [ABSTRACT FROM AUTHOR]