Increased Matrix Metalloproteinase (MMPs) Levels Do Not Predict Disease Severity or Progression in Emphysema

Rationale: Though matrix metalloproteinases (MMPs) are critical in the pathogenesis of COPD, their utility as a disease biomarker remains uncertain. This study aimed to determine whether bronchoalveolar lavage (BALF) or plasma MMP measurements correlated with disease severity or functional decline in emphysema. Methods: Enzyme-linked immunosorbent assay and luminex assays measured MMP-1, -9, -12 and tissue inhibitor of matrix metalloproteinase-1 in the BALF and plasma of non-smokers, smokers with normal lung function and moderate-to-severe emphysema subjects. In the cohort of 101 emphysema subjects correlative analyses were done to determine if MMP or TIMP-1 levels were associated with key disease parameters or change in lung function over an 18-month time period. Main Results: Compared to non-smoking controls, MMP and TIMP-1 BALF levels were significantly elevated in the emphysema cohort. Though MMP-1 was elevated in both the normal smoker and emphysema groups, collagenase activity was only increased in the emphysema subjects. In contrast to BALF, plasma MMP-9 and TIMP-1 levels were actually decreased in the emphysema cohort compared to the control groups. Both in the BALF and plasma, MMP and TIMP-1 measurements in the emphysema subjects did not correlate with important disease parameters and were not predictive of subsequent functional decline. Conclusions: MMPs are altered in the BALF and plasma of emphysema; however, the changes in MMPs correlate poorly with parameters of disease intensity or progression. Though MMPs are pivotal in the pathogenesis of COPD, these findings suggest that measuring MMPs will have limited utility as a prognostic marker in this disease. © 2013 D'Armiento et al

Oral rehydration versus intravenous therapy for treating dehydration due to gastroenteritis in children: a meta-analysis of randomised controlled trials

BACKGROUND: Despite treatment recommendations from various organizations, oral rehydration therapy (ORT) continues to be underused, particularly by physicians in high-income countries. We conducted a systematic review of randomised controlled trials (RCTs) to compare ORT and intravenous therapy (IVT) for the treatment of dehydration secondary to acute gastroenteritis in children. METHODS: RCTs were identified through MEDLINE, EMBASE, CENTRAL, authors and references of included trials, pharmaceutical companies, and relevant organizations. Screening and inclusion were performed independently by two reviewers in order to identify randomised or quasi-randomised controlled trials comparing ORT and IVT in children with acute diarrhea and dehydration. Two reviewers independently assessed study quality using the Jadad scale and allocation concealment. Data were extracted by one reviewer and checked by a second. The primary outcome measure was failure of rehydration. We analyzed data using standard meta-analytic techniques. RESULTS: The quality of the 14 included trials ranged from 0 to 3 (Jadad score); allocation concealment was unclear in all but one study. Using a random effects model, there was no significant difference in treatment failures (risk difference [RD] 3%; 95% confidence intervals [CI]: 0, 6). The Mantel-Haenzsel fixed effects model gave a significant difference between treatment groups (RD 4%; 95% CI: 2, 5) favoring IVT. Based on the four studies that reported deaths, there were six in the IVT groups and two in ORT. There were no significant differences in total fluid intake at six and 24 hours, weight gain, duration of diarrhea, or hypo/hypernatremia. Length of stay was significantly shorter for the ORT group (weighted mean difference [WMD] -1.2 days; 95% CI: -2.4,-0.02). Phlebitis occurred significantly more often with IVT (number needed to treat [NNT] 33; 95% CI: 25,100); paralytic ileus occurred more often with ORT (NNT 33; 95% CI: 20,100). These results may not be generalizable to children with persistent vomiting. CONCLUSION: There were no clinically important differences between ORT and IVT in terms of efficacy and safety. For every 25 children (95% CI: 20, 50) treated with ORT, one would fail and require IVT. The results support existing practice guidelines recommending ORT as the first course of treatment in appropriate children with dehydration secondary to gastroenteritis

Vascular responses of the extremities to transdermal application of vasoactive agents in Caucasian and African descent individuals

This is an accepted manuscript of an article published by Springer in European Journal of Applied Physiology on 04/04/2015, available online: https://doi.org/10.1007/s00421-015-3164-2 The accepted version of the publication may differ from the final published version.© 2015, Springer-Verlag Berlin Heidelberg. Purpose: Individuals of African descent (AFD) are more susceptible to non-freezing cold injury than Caucasians (CAU) which may be due, in part, to differences in the control of skin blood flow. We investigated the skin blood flow responses to transdermal application of vasoactive agents. Methods: Twenty-four young males (12 CAU and 12 AFD) undertook three tests in which iontophoresis was used to apply acetylcholine (ACh 1 w/v %), sodium nitroprusside (SNP 0.01 w/v %) and noradrenaline (NA 0.5 mM) to the skin. The skin sites tested were: volar forearm, non-glabrous finger and toe, and glabrous finger (pad) and toe (pad). Results: In response to SNP on the forearm, AFD had less vasodilatation for a given current application than CAU (P = 0.027–0.004). ACh evoked less vasodilatation in AFD for a given application current in the non-glabrous finger and toe compared with CAU (P = 0.043–0.014) with a lower maximum vasodilatation in the non-glabrous finger (median [interquartile], AFD n = 11, 41[234] %, CAU n = 12, 351[451] %, P = 0.011) and non-glabrous toe (median [interquartile], AFD n = 9, 116[318] %, CAU n = 12, 484[720] %, P = 0.018). ACh and SNP did not elicit vasodilatation in the glabrous skin sites of either group. There were no ethnic differences in response to NA. Conclusion: AFD have an attenuated endothelium-dependent vasodilatation in non-glabrous sites of the fingers and toes compared with CAU. This may contribute to lower skin temperature following cold exposure and the increased risk of cold injuries experienced by AFD.Published versio

Satisfaction with web-based training in an integrated healthcare delivery network: do age, education, computer skills and attitudes matter?

<p>Abstract</p> <p>Background</p> <p>Healthcare institutions spend enormous time and effort to train their workforce. Web-based training can potentially streamline this process. However the deployment of web-based training in a large-scale setting with a diverse healthcare workforce has not been evaluated. The aim of this study was to evaluate the satisfaction of healthcare professionals with web-based training and to determine the predictors of such satisfaction including age, education status and computer proficiency.</p> <p>Methods</p> <p>Observational, cross-sectional survey of healthcare professionals from six hospital systems in an integrated delivery network. We measured overall satisfaction to web-based training and response to survey items measuring Website Usability, Course Usefulness, Instructional Design Effectiveness, Computer Proficiency and Self-learning Attitude.</p> <p>Results</p> <p>A total of 17,891 healthcare professionals completed the web-based training on HIPAA Privacy Rule; and of these, 13,537 completed the survey (response rate 75.6%). Overall course satisfaction was good (median, 4; scale, 1 to 5) with more than 75% of the respondents satisfied with the training (rating 4 or 5) and 65% preferring web-based training over traditional instructor-led training (rating 4 or 5). Multivariable ordinal regression revealed 3 key predictors of satisfaction with web-based training: Instructional Design Effectiveness, Website Usability and Course Usefulness. Demographic predictors such as gender, age and education did not have an effect on satisfaction.</p> <p>Conclusion</p> <p>The study shows that web-based training when tailored to learners' background, is perceived as a satisfactory mode of learning by an interdisciplinary group of healthcare professionals, irrespective of age, education level or prior computer experience. Future studies should aim to measure the long-term outcomes of web-based training.</p

Stability of Strong Species Interactions Resist the Synergistic Effects of Local and Global Pollution in Kelp Forests

Foundation species, such as kelp, exert disproportionately strong community effects and persist, in part, by dominating taxa that inhibit their regeneration. Human activities which benefit their competitors, however, may reduce stability of communities, increasing the probability of phase-shifts. We tested whether a foundation species (kelp) would continue to inhibit a key competitor (turf-forming algae) under moderately increased local (nutrient) and near-future forecasted global pollution (CO2). Our results reveal that in the absence of kelp, local and global pollutants combined to cause the greatest cover and mass of turfs, a synergistic response whereby turfs increased more than would be predicted by adding the independent effects of treatments (kelp absence, elevated nutrients, forecasted CO2). The positive effects of nutrient and CO2 enrichment on turfs were, however, inhibited by the presence of kelp, indicating the competitive effect of kelp was stronger than synergistic effects of moderate enrichment of local and global pollutants. Quantification of physicochemical parameters within experimental mesocosms suggests turf inhibition was likely due to an effect of kelp on physical (i.e. shading) rather than chemical conditions. Such results indicate that while forecasted climates may increase the probability of phase-shifts, maintenance of intact populations of foundation species could enable the continued strength of interactions and persistence of communities

Polarimetry of binary systems: polars, magnetic CVs, XRBs

Polarimetry provides key physical information on the properties of interacting binary systems, sometimes difficult to obtain by any other type of observation. Indeed, radiation processes such as scattering by free electrons in the hot plasma above accretion discs, cyclotron emission by mildly relativistic electrons in the accretion shocks on the surface of highly magnetic white dwarfs and the optically thin synchrotron emission from jets can be observed. In this review, I will illustrate how optical/near-infrared polarimetry allows one to estimate magnetic field strengths and map the accretion zones in magnetic Cataclysmic Variables as well as determine the location and nature of jets and ejection events in X-ray binaries.Comment: 26 pages, 16 figures; to be published in Astrophysics and Space Science Library 460, Astronomical Polarisation from the Infrared to Gamma Rays, Editors: Mignani, R., Shearer, A., S{\l}owikowska, A., Zane,

Induction of the interleukin 6/ signal transducer and activator of transcription pathway in the lungs of mice sub-chronically exposed to mainstream tobacco smoke

<p>Abstract</p> <p>Background</p> <p>Tobacco smoking is associated with lung cancer and other respiratory diseases. However, little is known about the global molecular changes that precede the appearance of clinically detectable symptoms. In this study, the effects of mainstream tobacco smoke (MTS) on global transcription in the mouse lung were investigated.</p> <p>Methods</p> <p>Male C57B1/CBA mice were exposed to MTS from two cigarettes daily, 5 days/week for 6 or 12 weeks. Mice were sacrificed immediately, or 6 weeks following the last cigarette. High density DNA microarrays were used to characterize global gene expression changes in whole lung. Microarray results were validated by Quantitative real-time RT-PCR. Further analysis of protein synthesis and function was carried out for a select set of genes by ELISA and Western blotting.</p> <p>Results</p> <p>Globally, seventy nine genes were significantly differentially expressed following the exposure to MTS. These genes were associated with a number of biological processes including xenobiotic metabolism, redox balance, oxidative stress and inflammation. There was no differential gene expression in mice exposed to smoke and sampled 6 weeks following the last cigarette. Moreover, cluster analysis demonstrated that these samples clustered alongside their respective controls. We observed simultaneous up-regulation of <it>interleukin 6 </it>(<it>IL-6</it>) and its antagonist, <it>suppressor of cytokine signalling </it>(<it>SOCS3</it>) mRNA following 12 weeks of MTS exposure. Analysis by ELISA and Western blotting revealed a concomitant increase in total IL-6 antigen levels and its downstream targets, including phosphorylated signal transducer and activator of transcription 3 (Stat3), basal cell-lymphoma extra large (BCL-XL) and myeloid cell leukemia 1 (MCL-1) protein, in total lung tissue extracts. However, in contrast to gene expression, a subtle decrease in total SOCS3 protein was observed after 12 weeks of MTS exposure.</p> <p>Conclusion</p> <p>Global transcriptional analysis identified a set of genes responding to MTS exposure in mouse lung. These genes returned to basal levels following smoking cessation, providing evidence to support the benefits of smoking cessation. Detailed analyses were undertaken for IL-6 and its associated pathways. Our results provide further insight into the role of these pathways in lung injury and inflammation induced by MTS.</p

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Motif Minang Kaluak Paku Kacang Balimbiang pada Busana Kasual

Minangkabau sebagai salah satu suku bangsa yang mengisi kekhasan budaya Indonesia memiliki warisan budaya yang terpencar dalam berbagai aspek kehidupannya. Salah satu warisan budaya adalah seni ukir. Seni ukir yang dikembangkan dengan mengambil ide dari alam memiliki makna-makna filosofi bagi kehidupan masyarakat Minangkabau. Semua jenis ukiran yang dipahatkan di Rumah Gadang menunjukkan unsur penting pembentuk budaya Minangkabau bercerminkan kepada apa yang ada di alam. Salah satu ukiran pada rumah gadang yaitu kaluak paku. Kaluak paku adalah nama salah satu motif ukiran dalam adat Minangkabau. Berasal dari motif gulungan (kelukan/kaluak) pada ujung tanaman pakis (paku) yang masih muda. Ukiran kaluak paku rumah gadang melambangkan tanggung jawab seorang lelaki dalam adat Minangkabau kepada generasi penerus, sebagai ayah dari anak-anaknya dan sebagai mamak dari kemenakan (keponakan). Ukiran rumah gadang kaluak paku minangkabau inilah yang menjadi sumber ide penciptaan busana pada tugas akhir ini. Pada Penciptaan karya ini menggunakan beberapa metode, yaitu metode pendekatan estetis dan ergonomis, metode pengumpulan data dengan studi pustaka, dan motode penciptaan dengan teori Gustami Sp 3 tahap 6 Langkah. Dalam proses pembuatan karya dibutuhkan beberapa data, cara pengumpulan data acuan berdasarkan pengumpulan data pustaka yaitu berupa buku, jurnal pada media sosial, serta aplikasi pada smartphone seperti pinterest. Data yang dikumpulkan yang paling utama adalah gambar bentuk visual dari ukiran tanaman kaluak paku minangkabau dan busana kasual. Penciptaan karya yang dihasilkan yaitu berupa 8 busana kasual. Siluet pada kesuluruhan hasil karya yaitu memiliki siluet A yang mengembang pada bagian bawah. Pada penciptaan karya ini menggunakan bahan utama primisima. Perpaduan warna yang diterapkan menggunakan warna khas minangkabau yang diambil dari warna bendera adatnya “marawa” yaitu merah, hitam, dan kuning. Karya- karya yang dihasilkan dengan penggunaan warna tersebut sangat sesuai dengan tema yang mengangkat ukiran rumah gadang kaluak paku minangkabau. Kata Kunci : Minang, Kaluak Paku Kacang Balimbiang, Kasua