168 research outputs found
Robotank biathlon
In this article the competition of “biathlon of “robotanks” considers as formation of engineering-technical staff for high-tech economy of Russia. What is more, it develops children's engineering and algorithmic intellectionВ статье рассматривается соревнование «Роботанковый биатлон» как формирование инженерно-технических кадров для высокотехнологичной экономики России, а так же развитие у детей инженерного и алгоритмического мышлени
Aggregation kinetics of human mesenchymal stem cells under wave motion
Human mesenchymal stem cells (hMSCs) are a primary candidate in cell therapy and regenerative medicine to treat a wide range of diseases in clinical trials. Recent studies showed that hMSC have innate ability to self-assemble into three-dimensional (3D) aggregates that enhances their therapeutic functions with augmented multi-lineage differentiation potential, migration ability, secretion of anti-inflammatory and angiogenic factors, and resistance to ischemic conditions post-transplantation. To date, many laboratory methods have been developed for hMSC aggregation, including hanging drops, centrifugation with microfabricated surface, cell suspension on a low attachment surface, thermal lifting, and microfluidic technologies. However, these methods have limited scalability and/or poor control in aggregate size, and cannot meet the required production in clinical trials.
The objective of current study is to investigate the conditions for the scalable production of hMSC aggregates in non-adherent plates under wave motion. The repeated back and forth wave motion induced by rocking provides mixing of bulk medium under low shear stress that facilitates cell-cell collisions and subsequent aggregation. Our results showed that aggregate size can be controlled by adjusting the combination of rocking angle (3˚, 6˚, and 9˚) and rocking speed (10, 15, and 20 rpm). To quantify the impact of fluid shear stress on aggregation kinetics, simulation of shear stress distribution by COMSOL Multiphysics® showed a time-dependent oscillatory function under different rocking condition. In addition, an inverse correlation between aggregate size and maximum shear stress was observed and that both can be regressed by a two-variable linear regression of rocking angle and rocking speed. In the regression, the coefficient of rocking angle is much higher than that of rocking speed, revealing that rocking angle has a more significant effect than rocking speed on both aggregate size and shear stress. In addition to fluid shear stress, the effects of cell binding molecules, the frequency of cell-cell collision, and the extension of cultivation time on aggregate size distribution were also investigated. Analysis of the therapeutic functional supported that hMSCs derived from engineered aggregates in the wave motion system have enhanced their therapeutic properties compared to those from monolayer culture
Antilymphoid antibody preconditioning and tacrolimus monotherapy for pediatric kidney transplantation
Objective: Heavy post-transplant immunosuppression may contribute to long-term immunosuppression dependence by subverting tolerogenic mechanisms; thus, we sought to determine if this undesirable consequence could be mitigated by pretransplant lymphoid depletion and minimalistic post-transplant monotherapy. Study design: Lymphoid depletion in 17 unselected pediatric recipients of live (n = 14) or deceased donor kidneys (n = 3) was accomplished with antithymocyte globulin (ATG) (n = 8) or alemtuzumab (n = 9). Tacrolimus was begun post-transplantation with subsequent lengthening of intervals between doses (spaced weaning). Maintenance immunosuppression, morbidity, graft function, and patient/graft survival were collated. Results: Steroids were added temporarily to treat rejection in two patients (both ATG subgroup) or to treat hemolytic anemia in two others. After 16 to 31 months (mean 22), patient and graft survival was 100% and 94%, respectively. The only graft loss was in a nonweaned noncompliant recipient. In the other 16, serum creatinine was 0.85 ± 0.35 mg/dL and creatinine clearance was 90.8 ± 22.1 mL/1.73 m2. All 16 patients are on monotherapy (15 tacrolimus, one sirolimus), and 14 receive every other day or 3 times per week doses. There were no wound or other infections. Two patients developed insulin-dependent diabetes. Conclusion: The strategy of lymphoid depletion and minimum post-transplant immunosuppression appears safe and effective for pediatric kidney recipients. © 2006 Elsevier Inc. All rights reserved
Reliability and technical diagnostics of electronic equipment failures, having a random character
Anti-inflammatory recombinant TSG-6 stabilizes the progression of focal retinal degeneration in a murine model
<p>Abstract</p> <p>Background</p> <p>Inflammatory responses are detected in the retina of patients with age-related macular degeneration and <it>Ccl2<sup>-/-</sup>/Cx3cr1<sup>-/- </sup></it>mice on rd8 background,(<it>Ccl2<sup>-/-</sup>/Cx3cr1<sup>-/- </sup></it>mice) a model that develops progressive age-related macular degeneration-like retinal lesions including focal photoreceptor degeneration, abnormal retinal pigment epithelium and A2E accumulation. Tumor necrosis factor-inducible gene 6 protein is an anti-inflammatory protein and has been shown to improve myocardial infarction outcome and chemically injured cornea in mice by suppressing inflammation. In this study, we evaluated the effect of an intravitreous injection of recombinant TSG-6 on the retinal lesions of <it>Ccl2<sup>-/-</sup>/Cx3cr1<sup>-/- </sup></it>mice.</p> <p>Methods</p> <p>Recombinant TSG-6 (400 ng) was administered by intravitreous injection into the right eye of six-week-old C<it>cl2<sup>-/-</sup>/Cx3cr1<sup>-/- </sup></it>mice. Their left eye was injected with phosphate-buffered saline as a control. Funduscopic pictures were taken before injection and sequentially once a month after injection. The mice were killed two months after injection and the ocular histology examined. Retinal A2E, a major component of lipofuscin, was measured by high performance liquid chromatography. The microarray of ocular mRNA of 92 immunological genes was performed. The genes showing differentiated expression in microarray were further compared between the injected right eye and the contralateral (control) eye by [real-time quantitative reverse transcription polymerase chain reaction] qRT-PCR.</p> <p>Results</p> <p>The continuous monitoring of the fundus for two months showed a slower progression or alleviation of retinal lesions in the treated right eyes as compared with the untreated left eyes. Among 23 pairs of eyes, the lesion levels improved in 78.3%, stayed the same in 8.7% and progressed in 13.0%. Histology confirmed the clinical observation. Even though there was no difference in the level of A2E between the treated and the untreated eyes, microarray analysis of 92 immune genes showed that <it>IL-17a </it>was substantially decreased after the treatment. Expression of <it>TNF-α </it>showed a similar pattern to <it>IL-17a</it>. The results were consistent in duplicated arrays and confirmed by qRT-PCR.</p> <p>Conclusions</p> <p>We concluded that intravitreous administration of recombinant TSG-6 might stabilize retinal lesions in <it>Ccl2<sup>-/-</sup>/Cx3cr1<sup>-/- </sup></it>mice on rd8 background. Modulation of ocular immunological gene expressions, especially IL-17a, could be one of the mechanisms.</p
Adult Cardiac Progenitor Cell Aggregates Exhibit Survival Benefit Both In Vitro and In Vivo
Background: A major hurdle in the use of exogenous stems cells for therapeutic regeneration of injured myocardium remains the poor survival of implanted cells. To date, the delivery of stem cells into myocardium has largely focused on implantation of cell suspensions. Methodology and Principal Findings: We hypothesize that delivering progenitor cells in an aggregate form would serve to mimic the endogenous state with proper cell-cell contact, and may aid the survival of implanted cells. Microwell methodologies allow for the culture of homogenous 3D cell aggregates, thereby allowing cell-cell contact. In this study, we find that the culture of cardiac progenitor cells in a 3D cell aggregate augments cell survival and protects against cellular toxins and stressors, including hydrogen peroxide and anoxia/reoxygenation induced cell death. Moreover, using a murine model of cardiac ischemia-reperfusion injury, we find that delivery of cardiac progenitor cells in the form of 3D aggregates improved in vivo survival of implanted cells. Conclusion: Collectively, our data support the notion that growth in 3D cellular systems and maintenance of cell-cell contact improves exogenous cell survival following delivery into myocardium. These approaches may serve as a strategy to improve cardiovascular cell-based therapies
CKD-MBD after kidney transplantation
Successful kidney transplantation corrects many of the metabolic abnormalities associated with chronic kidney disease (CKD); however, skeletal and cardiovascular morbidity remain prevalent in pediatric kidney transplant recipients and current recommendations from the Kidney Disease Improving Global Outcomes (KDIGO) working group suggest that bone disease—including turnover, mineralization, volume, linear growth, and strength—as well as cardiovascular disease be evaluated in all patients with CKD. Although few studies have examined bone histology after renal transplantation, current data suggest that bone turnover and mineralization are altered in the majority of patients and that biochemical parameters are poor predictors of bone histology in this population. Dual energy X-ray absorptiometry (DXA) scanning, although widely performed, has significant limitations in the pediatric transplant population and values have not been shown to correlate with fracture risk; thus, DXA is not recommended as a tool for the assessment of bone density. Newer imaging techniques, including computed tomography (quantitative CT (QCT), peripheral QCT (pQCT), high resolution pQCT (HR-pQCT) and magnetic resonance imaging (MRI)), which provide volumetric assessments of bone density and are able to discriminate bone microarchitecture, show promise in the assessment of bone strength; however, future studies are needed to define the value of these techniques in the diagnosis and treatment of renal osteodystrophy in pediatric renal transplant recipients
History, epidemiology and regional diversities of urolithiasis
Archeological findings give profound evidence that humans have suffered from kidney and bladder stones for centuries. Bladder stones were more prevalent during older ages, but kidney stones became more prevalent during the past 100 years, at least in the more developed countries. Also, treatment options and conservative measures, as well as ‘surgical’ interventions have also been known for a long time. Our current preventive measures are definitively comparable to those of our predecessors. Stone removal, first lithotomy for bladder stones, followed by transurethral methods, was definitively painful and had severe side effects. Then, as now, the incidence of urolithiasis in a given population was dependent on the geographic area, racial distribution, socio-economic status and dietary habits. Changes in the latter factors during the past decades have affected the incidence and also the site and chemical composition of calculi, with calcium oxalate stones being now the most prevalent. Major differences in frequency of other constituents, particularly uric acid and struvite, reflect eating habits and infection risk factors specific to certain populations. Extensive epidemiological observations have emphasized the importance of nutritional factors in the pathogenesis of urolithiasis, and specific dietary advice is, nowadays, often the most appropriate for prevention and treatment of urolithiasis
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.
Defining Priorities for Future Research:Results of the UK Kidney Transplant Priority Setting Partnership
It has been suggested that the research priorities of those funding and performing research in transplantation may differ from those of end service users such as patients, carers and healthcare professionals involved in day-to-day care. The Kidney Transplant Priority Setting Partnership (PSP) was established with the aim of involving all stakeholders in prioritising future research in the field.The PSP methodology is as outlined by the James Lind Alliance. An initial survey collected unanswered research questions from patients, carers and clinicians. Duplicate and out-of-scope topics were excluded and the existing literature searched to identify topics answered by current evidence. An interim prioritisation survey asked patients and professionals to score the importance of the remaining questions to create a ranked long-list. These were considered at a final consensus workshop using a modified nominal group technique to agree a final top ten.The initial survey identified 497 questions from 183 respondents, covering all aspects of transplantation from assessment through to long-term follow-up. These were grouped into 90 unanswered "indicative" questions. The interim prioritisation survey received 256 responses (34.8% patients/carers, 10.9% donors and 54.3% professionals), resulting in a ranked list of 25 questions that were considered during the final workshop. Participants agreed a top ten priorities for future research that included optimisation of immunosuppression (improved monitoring, choice of regimen, personalisation), prevention of sensitisation and transplanting the sensitised patient, management of antibody-mediated rejection, long-term risks to live donors, methods of organ preservation, induction of tolerance and bioengineering of organs. There was evidence that patient and carer involvement had a significant impact on shaping the final priorities.The final list of priorities relates to all stages of the transplant process, including access to transplantation, living donation, organ preservation, post-transplant care and management of the failing transplant. This list of priorities will provide an invaluable resource for researchers and funders to direct future activity
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