4,266 research outputs found
TGFβ1 orchestrates renal fibrosis following Escherichia coli pyelonephritis
Renal scarring after pyelonephritis is linked to long-term health risks for hypertension and chronic kidney disease. Androgen exposure increases susceptibility to, and severity of, uropathogenic Escherichia coli (UPEC) pyelonephritis and resultant scarring in both male and female mice, while anti-androgen therapy is protective against severe urinary tract infection (UTI) in these models. This work employed androgenized female C57BL/6 mice to elucidate the molecular mechanisms of post-infectious renal fibrosis and to determine how these pathways are altered by the presence of androgens. We found that elevated circulating testosterone levels primed the kidney for fibrosis by increasing local production of TGFβ1 before the initiation of UTI, altering the ratio of transcription factors Smad2 and Smad3 and increasing the presence of mesenchymal stem cell (MSC)-like cells and Gli1 + activated myofibroblasts, the cells primarily responsible for deposition of scar components. Increased production of TGFβ1 and aberrations in Smad2:Smad3 were maintained throughout the course of infection in the presence of androgen, correlating with renal scarring that was not observed in non-androgenized female mice. Pharmacologic inhibition of TGFβ1 signaling blunted myofibroblast activation. We conclude that renal fibrosis after pyelonephritis is exacerbated by the presence of androgens and involves activation of the TGFβ1 signaling cascade, leading to increases in cortical populations of MSC-like cells and the Gli1 + activated myofibroblasts that are responsible for scarring
A preliminary longitudinal study of white matter alteration in cocaine use disorder subjects
Background Previous diffusion tensor imaging (DTI) studies have consistently shown that subjects with cocaine use disorder (CocUD) had altered white matter microstructure in the corpus callosum. It is believed that these alterations are due to preexisting factors, chronic cocaine use, or both. However, there is no published longitudinal DTI study on human cocaine users yet which could shed light on the relationship between cocaine use and DTI findings. Methods This study used a longitudinal design and DTI to test if the white matter microstructure shows quicker alteration in CocUD subjects than controls. DTI data were acquired from eleven CocUD subjects who participated a treatment study and eleven non-drug-using controls at baseline (Scan 1) and after ten weeks (Scan 2). The baseline fractional anisotropy (FA), a general measure of white matter microstucture, and the change in FA (ΔFA, equals Scan 1 FA minus Scan 2 FA) were both compared between groups. Results The two groups did not show a difference in FA at baseline. The CocUD subjects had significantly greater ΔFA than the controls in the left splenium of the corpus callosum. In CocUD subjects, greater ΔFA in this region was associated with shorter lifetime cocaine use and greater number of positive cocaine urine samples collected during the treatment. Conclusion The finding in the left splenium is consistent with previous animal studies and provide indirect evidence about the effects of chronic cocaine use on white matter alterations. The subject sample size is small, therefore the results should be treated as preliminary
Multi-Terabyte EIDE Disk Arrays running Linux RAID5
High-energy physics experiments are currently recording large amounts of data
and in a few years will be recording prodigious quantities of data. New methods
must be developed to handle this data and make analysis at universities
possible. Grid Computing is one method; however, the data must be cached at the
various Grid nodes. We examine some storage techniques that exploit recent
developments in commodity hardware. Disk arrays using RAID level 5 (RAID-5)
include both parity and striping. The striping improves access speed. The
parity protects data in the event of a single disk failure, but not in the case
of multiple disk failures.
We report on tests of dual-processor Linux Software RAID-5 arrays and
Hardware RAID-5 arrays using a 12-disk 3ware controller, in conjunction with
250 and 300 GB disks, for use in offline high-energy physics data analysis. The
price of IDE disks is now less than $1/GB. These RAID-5 disk arrays can be
scaled to sizes affordable to small institutions and used when fast random
access at low cost is important.Comment: Talk from the 2004 Computing in High Energy and Nuclear Physics
(CHEP04), Interlaken, Switzerland, 27th September - 1st October 2004, 4
pages, LaTeX, uses CHEP2004.cls. ID 47, Poster Session 2, Track
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School-Based Telemedicine Interventions for Asthma: A Systematic Review.
BackgroundSchool health systems are increasingly investing in telemedicine platforms to address acute and chronic illnesses. Asthma, the most common chronic illness in childhood, is of particular interest given its high burden on school absenteeism.ObjectiveConduct a systematic review evaluating impact of school-based telemedicine programs on improving asthma-related outcomes.Data sourcesPubMed, Cochrane CENTRAL, CINAHL, ERIC, PsycINFO, Embase, and Google Scholar.Study eligibility criteriaOriginal research, including quasi-experimental studies, without restriction on the type of telemedicine.ParticipantsSchool-aged pediatric patients with asthma and their families.InterventionsSchool-based telemedicine.Study appraisal and synthesis methodsTwo authors independently screened each abstract, conducted full-text review, assessed study quality, and extracted information. A third author resolved disagreements.ResultsOf 371 articles identified, 7 were included for the review. Outcomes of interest were asthma symptom-free days, asthma symptom frequency, quality of life, health care utilization, school absences, and spirometry. Four of 7 studies reported significant increases in symptom-free days and/or decrease in symptom frequency. Five of 6 reported increases in at least one quality-of-life metric, 2 of 7 reported a decrease in at least 1 health care utilization metric, 1 of 3 showed reductions in school absences, and 1 of 2 reported improvements in spirometry measures.LimitationsVariability in intervention designs and outcome measures make comparisons and quantitative analyses across studies difficult. Only 2 of 7 studies were randomized controlled trials.Conclusions and implications of key findingsHigh-quality evidence supporting the use of school-based telemedicine programs to improve patient outcomes is limited. While available evidence suggests benefit, only 2 comparative trials were identified, and the contribution of telemedicine to these studies' results is unclear
Parenting Stress as a Mediator of Exposure to Potentially Traumatic Events and Behavioral Health Outcomes in Children and Youth
The research team has been examining parenting stress, defined as stress that parents feel in their parenting role, as a mediator of behavioral health outcomes for children exposed to potentially traumatic events. The results of our studies demonstrate the interplay between a child’s exposure to potentially traumatic events and their parent/caregiver’s report of stress related to parenting their child
Corporate Governance and Equity Prices
Corporate-governance provisions related to takeover defenses and shareholder rights vary substantially across firms. In this paper, we use the incidence of 24 different provisions to build a 'Governance Index' for about 1,500 firms per year, and then we study the relationship between this index and several forward-looking performance measures during the 1990s. We find a striking relationship between corporate governance and stock returns. An investment strategy that bought the firms in the lowest decile of the index (strongest shareholder rights) and sold the firms in the highest decile of the index (weakest shareholder rights) would have earned abnormal returns of 8.5 percent per year during the sample period. Furthermore, the Governance Index is highly correlated with firm value. In 1990, a one-point increase in the index is associated with a 2.4 percentage-point lower value for Tobin's Q. By 1999, this difference had increased significantly, with a one-point increase in the index associated with an 8.9 percentage-point lower value for Tobin's Q. Finally, we find that weaker shareholder rights are associated with lower profits, lower sales growth, higher capital expenditures, and a higher amount of corporate acquisitions. We conclude with a discussion of several causal interpretations.
Pharmacokinetic and Biodistribution Assessment of a Near Infrared-Labeled PSMA-Specific Small Molecule in Tumor-Bearing Mice
Prostate cancer is themost frequently diagnosed cancer in men and often requires surgery. Use of near infrared (NIR) technologies to perform image-guided surgery may improve accurate delineation of tumor margins. To facilitate preclinical testing of such outcomes, here we developed and characterized a PSMA-targeted small molecule, YC-27. IRDye 800CW was conjugated to YC-27 or an anti-PSMA antibody used for reference. Human 22Rv1, PC3M-LN4, and/or LNCaP prostate tumor cells were exposed to the labeled compounds. In vivo targeting and clearance properties were determined in tumor-bearing mice. Organs and tumors were excised and imaged to assess probe localization. YC-27 exhibited a dose dependent increase in signal upon binding. Binding specificity and internalization were visualized by microscopy. In vitro and in vivo blocking studies confirmed YC-27 specificity. In vivo, YC-27 showed good tumor delineation and tissue contrast at doses as low as 0.25 nmole. YC-27 was cleared via the kidneys but bound the proximal tubules of the renal cortex and epididymis. Since PSMA is also broadly expressed on the neovasculature of most tumors, we expect YC-27 will have clinical utility for image-guided surgery and tumor resections
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