Growth in ataxia telangiectasia

BACKGROUND: Ataxia telangiectasia (A-T) is a DNA repair disorder that affects multiple body systems. Neurological problems and immunodeficiency are two important features of this disease. At this time, two main severity groups are defined in A-T: classic (the more severe form) and mild. Poor growth is a common problem in classic A-T. An objective of this study was to develop growth references for classic A-T. Another objective was to compare growth patterns in classic A-T and mild A-T with each other and with the general population, using the CDC growth references. A final objective was to examine the effects of chronic infection on height. RESULTS: We found that classic A-T patients were smaller overall, and suffered from height and weight faltering that continued throughout childhood and adolescence. When compared to the CDC growth references, the median heights and weights for both male and female patients eventually fell to or below the 3rd centile on the CDC charts. Height faltering was more pronounced in females. Birthweight was lower in the classic A-T group compared to mild A-T and the general population, whereas birth length was not. Finally, we investigated height and BMI faltering in relation to number of infections and found no association. CONCLUSIONS: Classic A-T appears to affect growth in utero. Although children appear to grow well in very early life, faltering begins early, and is unrelenting

Apoptosis and the activity of ceramide, Bax and Bcl-2 in the lungs of neonatal rats exposed to limited and prolonged hyperoxia

BACKGROUND: The aim of the study is to examine the effect of limited and prolonged hyperoxia on neonatal rat lung. This is done by examining the morphologic changes of apoptosis, the expression of ceramide, an important mediator of apoptosis, the expression of inflammatory mediators represented by IL-1β and the expression of 2 proto-oncogenes that appear to modulate apoptosis (Bax and Bcl-2). METHODS: Newborn rats were placed in chambers containing room air or oxygen above 90% for 7 days. The rats were sacrificed at 3, 7 or 14 days and their lungs removed. Sections were fixed, subjected to TUNEL, Hoechst, and E-Cadherin Staining. Sections were also incubated with anti-Bcl-2 and anti-Bax antisera. Bcl-2 and Bax were quantitated by immunohistochemistry. Lipids were extracted, and ceramide measured through a modified diacylglycerol kinase assay. RT-PCR was utilized to assess IL-1β expression. RESULTS: TUNEL staining showed significant apoptosis in the hyperoxia-exposed lungs at 3 days only. Co-staining of the apoptotic cells with Hoechst, and E-Cadherin indicated that apoptotic cells were mainly epithelial cells. The expression of Bax and ceramide was significantly higher in the hyperoxia-exposed lungs at 3 and 14 days of age, but not at 7 days. Bcl-2 was significantly elevated in the hyperoxia-exposed lungs at 3 and 14 days. IL-1β expression was significantly increased at 14 days. CONCLUSION: Exposure of neonatal rat lung to hyperoxia results in early apoptosis documented by TUNEL assay. The early rise in Bax and ceramide appears to overcome the anti-apoptotic activity of Bcl-2. Further exposure did not result in late apoptotic changes. This suggests that apoptotic response to hyperoxia is time sensitive. Prolonged hyperoxia results in acute lung injury and the shifting balance of ceramide, Bax and Bcl-2 may be related to the evolution of the inflammatory process

Participation of the PI-3K/Akt-NF-κB signaling pathways in hypoxia-induced mitogenic factor-stimulated Flk-1 expression in endothelial cells

BACKGROUND: Hypoxia-induced mitogenic factor (HIMF), a lung-specific growth factor, promotes vascular tubule formation in a matrigel plug model. We initially found that HIMF enhances vascular endothelial growth factor (VEGF) expression in lung epithelial cells. In present work, we tested whether HIMF modulates expression of fetal liver kinase-1 (Flk-1) in endothelial cells, and dissected the possible signaling pathways that link HIMF to Flk-1 upregulation. METHODS: Recombinant HIMF protein was intratracheally instilled into adult mouse lungs, Flk-1 expression was examined by immunohistochemistry and Western blot. The promoter-luciferase reporter assay and real-time RT-PCR were performed to examine the effects of HIMF on Flk-1 expression in mouse endothelial cell line SVEC 4–10. The activation of NF-kappa B (NF-κB) and phosphorylation of Akt, IKK, and IκBα were examined by luciferase assay and Western blot, respectively. RESULTS: Intratracheal instillation of HIMF protein resulted in a significant increase of Flk-1 production in lung tissues. Stimulation of SVEC 4–10 cells by HIMF resulted in increased phosphorylation of IKK and IκBα, leading to activation of NF-κB. Blocking NF-κB signaling pathway by dominant-negative mutants of IKK and IκBα suppressed HIMF-induced Flk-1 upregulation. Mutation or deletion of NF-κB binding site within Flk-1 promoter also abolished HIMF-induced Flk-1 expression in SVEC 4–10 cells. Furthermore, HIMF strongly induced phosphorylation of Akt. A dominant-negative mutant of PI-3K, Δp85, as well as PI-3K inhibitor LY294002, blocked HIMF-induced NF-κB activation and attenuated Flk-1 production. CONCLUSION: These results suggest that HIMF upregulates Flk-1 expression in endothelial cells in a PI-3K/Akt-NF-κB signaling pathway-dependent manner, and may play critical roles in pulmonary angiogenesis

International entrepreneurship in SMEs: a study of influencing factors in the textile industry

The final publication is available at Springer via http://dx.doi.org/10.1007/s11365-012-0242-3International entrepreneurship is an incipient research area with a rapidly increasing body of knowledge and contributions. An important part of this literature has focused on the analysis of the contributing factors to IE development. From these studies, this work attempts to analyse and validate through an integrative model the effect on this construct in SME of some of the main factors proposed by the literature such as Skills and Competences, Attitude and Proactiveness, Creativity and Innovation, Networking, Employees and Activity. To proceed with this aim, we conducted an empirical research focused on 174 textile SME in Spain. The results obtained confirm a positive relationship between the studied factors and the IE development. 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The Peter Pan paradigm

Genetic and environmental agents that disrupt organogenesis are numerous and well described. Less well established, however, is the role of delay in the developmental processes that yield functionally immature tissues at birth. Evidence is mounting that organs do not continue to develop postnatally in the context of these organogenesis insults, condemning the patient to utilize under-developed tissues for adult processes. These poorly differentiated organs may appear histologically normal at birth but with age may deteriorate revealing progressive or adult-onset pathology. The genetic and molecular underpinning of the proposed paradigm reveals the need for a comprehensive systems biology approach to evaluate the role of maternal-fetal environment on organogenesis

Application of medical and analytical methods in Lyme borreliosis monitoring

Lyme borreliosis (LB) is one of the most common tick-borne diseases in the northern hemisphere. It is a chronic inflammatory disease caused by the spirochaete Borrelia burgdorferi. In its early stages, pathological skin lesions, namely erythema chronicum migrans, appear. The lesions, usually localised at the site of the bite, may become visible from a few weeks up to 3 months after the infection. Predominant clinical symptoms of the disease also involve joint malfunctions and neurological or cardiac disorders. Lyme disease, in all its stages, may be successfully treated with antibiotics. The best results, however, are obtained in its early stages. In order to diagnose the disease, numerous medical or laboratory techniques have been developed. They are applied to confirm the presence of intact spirochaetes or spirochaete components such as DNA or proteins in tick vectors, reservoir hosts or patients. The methods used for the determination of LB biomarkers have also been reviewed. These biomarkers are formed during the lipid peroxidation process. The formation of peroxidation products generated by human organisms is directly associated with oxidative stress. Apart from aldehydes (malondialdehyde and 4-hydroxy-2-nonenal), many other unsaturated components such as isoprostenes and neuroprostane are obtained. The fast determination of these compounds in encephalic fluid, urine or plasma, especially in early stages of the disease, enables its treatment. Various analytical techniques which allow the determination of the aforementioned biomarkers have been reported. These include spectrophotometry as well as liquid and gas chromatography. The analytical procedure also requires the application of a derivatization step by the use of selected reagents

A systematic review of the psychometric properties of self-report research utilization measures used in healthcare

<p>Abstract</p> <p>Background</p> <p>In healthcare, a gap exists between what is known from research and what is practiced. Understanding this gap depends upon our ability to robustly measure research utilization.</p> <p>Objectives</p> <p>The objectives of this systematic review were: to identify self-report measures of research utilization used in healthcare, and to assess the psychometric properties (acceptability, reliability, and validity) of these measures.</p> <p>Methods</p> <p>We conducted a systematic review of literature reporting use or development of self-report research utilization measures. Our search included: multiple databases, ancestry searches, and a hand search. Acceptability was assessed by examining time to complete the measure and missing data rates. Our approach to reliability and validity assessment followed that outlined in the <it>Standards for Educational and Psychological Testing</it>.</p> <p>Results</p> <p>Of 42,770 titles screened, 97 original studies (108 articles) were included in this review. The 97 studies reported on the use or development of 60 unique self-report research utilization measures. Seven of the measures were assessed in more than one study. Study samples consisted of healthcare providers (92 studies) and healthcare decision makers (5 studies). No studies reported data on acceptability of the measures. Reliability was reported in 32 (33%) of the studies, representing 13 of the 60 measures. Internal consistency (Cronbach's Alpha) reliability was reported in 31 studies; values exceeded 0.70 in 29 studies. Test-retest reliability was reported in 3 studies with Pearson's <it>r </it>coefficients > 0.80. No validity information was reported for 12 of the 60 measures. The remaining 48 measures were classified into a three-level validity hierarchy according to the number of validity sources reported in 50% or more of the studies using the measure. Level one measures (n = 6) reported evidence from any three (out of four possible) <it>Standards </it>validity sources (which, in the case of single item measures, was all applicable validity sources). Level two measures (n = 16) had evidence from any two validity sources, and level three measures (n = 26) from only one validity source.</p> <p>Conclusions</p> <p>This review reveals significant underdevelopment in the measurement of research utilization. Substantial methodological advances with respect to construct clarity, use of research utilization and related theory, use of measurement theory, and psychometric assessment are required. Also needed are improved reporting practices and the adoption of a more contemporary view of validity (<it>i.e.</it>, the <it>Standards</it>) in future research utilization measurement studies.</p