Proliferating or interleukin 1-activated human vascular smooth muscle cells secrete copious interleukin 6

The cells that make up blood vessel walls appear to participate actively in local immune and inflammatory responses, as well as in certain vascular diseases. We tested here whether smooth muscle cells (SMC) can produce the important inflammatory mediator IL6. Unstimulated SMC in vitro elaborated 5 X 10(3) pg recIL6/24h (i.e., biological activity equivalent to 5 X 10(3) pg recombinant IL6 (recIL6), as determined in B9-assay with a recIL6 standard). Several pathophysiologically relevant factors augmented IL6 release from SMC including 10 micrograms LPS/ml (10(4) pg recIL6), 10 ng tumor necrosis factor/ml (4 X 10(4) pg recIL6), and most notably 10 ng IL1/ml (greater than or equal to 3.2 X 10(5) pg recIL6). Production of IL6 activity corresponded to IL6 mRNA accumulation and de novo synthesis. SMC released newly synthesized IL6 rapidly, as little metabolically labeled material remained cell-associated. In supernatants of IL1-stimulated SMC, IL6 accounted for as much as 4% of the secreted proteins. In normal vessels SMC seldom divide, but SMC proliferation can occur in hypertension or during atherogenesis. We therefore tested the relationship between IL6 production and SMC proliferation in response to platelet-derived growth factor (PDGF) in vitro. Quiescent SMC released scant IL6 activity, whereas PDGF (1-100 ng/ml) produced concentration-dependent and coordinate enhancement of SMC proliferation and IL6 release (linear regression of growth vs. IL6 release yielded r greater than 0.9). IL6 itself neither stimulated nor inhibited SMC growth or IL6 production. Intact medial strips studied in short-term organoid culture produced large quantities of IL6, similar to the results obtained with cultured SMC. These findings illustrate a new function of vascular SMC by which these cells might participate in local immunoregulation and in the pathogenesis of various important vascular diseases as well as in inflammatory responses generally

Numerical simulation of the electron beam distribution in tissueequivalent materials using GEANT4

The numerical model of the electron beam dose distribution in ABS and HIPS plastics was developed. The calculation results were compared with experimental data of depth dose distribution of electron beam in water phantom for applicability estimation of these polymer materials for the imitation of biological tissues

Patient intrathecal pain pump safety

Background: A large tertiary care hospital in the Midwest manages care for approximately 200 patients with implanted intrathecal pain pumps. Nurses perform the high-risk task of refilling these pumps with highly concentrated medications. An inherent risk, with the potential for adverse events, of this process is a “pocket fill” where medication inadvertently leaks into the surrounding tissue. A pocket fill can cause overdose symptoms including death if not treated promptly. Local problem: In 2020, there were 752 intrathecal pump refills with 3 reported pocket fills. Two patients required hospital stays. This was an increase from 2019 when there were 834 intrathecal pump refills and 1 reported pocket fill. Method: Pain management nurses and leadership conducted an apparent cause analysis of the intrathecal pump refill process and post-procedure care, with input from quality, patient safety, pharmacy, pain management providers, and clinical informatics. The team collected data, reviewed existing research and medical device literature, and surveyed other organizations. Based upon the review, a group of interventions were put into an action plan. Interventions implemented including written informed consent prior to each pump refill, reinforcing patient education about pocket fills, prescribing and educating on the use of Narcan, observing patients post-procedure for 30 minutes, performing pre- and post- assessments of level of consciousness and gait/ambulation, and recommending that all patients be discharged with a responsible adult for transportation and continued observation for 3 hours post refill. Results/Conclusions: Intrathecal pump complications improved in 2021, during which there was 1 pocket fill and 675 intrathecal pump refills. The increased post-procedure monitoring allowed the clinic to identify and treat the complication during the clinical episode of care. Implications for practice: Nurses will continue to educate patients and require 30-minute post-procedure observation with expanded clinical assessments and risk mitigation interventions for all intrathecal pump refills

Current industry perceptions of the role of the contractor in the LEED certification process

2011 Spring.Includes bibliographical references.LEED certification has been rapidly adopted on the Front Range of Colorado as the primary green building rating system. LEED has required project teams and contractors to adopt new tasks and management activities in order to meet LEED requirements and owner expectations. It is understood that contractors are critical to successful implementation of the LEED process and ultimately meeting the LEED goals of a project. This research was designed to help determine what opportunities exist for contractors to better add value to the LEED process on future projects, and to identify differences among architects and designers, green building consultants and contractors in their perception of the contractor's role in LEED. A survey was distributed to building professionals with LEED experience on the Front Range of Colorado asking for feedback about the contractor's role, opportunities to add value and factors that may limit contractor success in LEED. Findings confirm that contractors have significant impact on the LEED process, and that there is opportunity for contractors to further add value to the process in the future. Also, that difference in perception of the contractor's role and contractor opportunity to add value does vary among the three main research groups: architects and designers, green building consultants and contractors. Key opportunities for contractors to better add value to the LEED process include: engagement in an integrated design process, taking on leadership in the LEED process, better LEED related cost estimating and management, better or expanded use of technology, better tracking tools and LEED management processes, and continuing education and LEED credentialing. Contractors and green building consultants often have closely aligned perception of the contractor's role in LEED, however each group showed variation in their perception of the contractor's role that was specific to their area of professional practice

Adhesion Molecule Regulation of Regulatory T Cell Migration

Regulatory T (Treg) cells mediate tumor immune evasion by suppressing anti-tumor effector T cell responses in peripheral lymphoid tissues and within the tumor. While elevated Treg cell numbers have been shown to correlate with increased tumor growth, mechanisms that regulate their distribution within secondary lymphoid tissue and tumor tissue are not well understood. L-selectin, an adhesion molecule constitutively expressed on all classes of leukocytes, functions early in the adhesion cascade and regulates the migration of lymphocytes to lymph nodes through high endothelial venules. In addition, L-selectin can mediate migration of lymphocytes to sites of inflammation by binding to ligands present on inflamed endothelium. Treg cells express high levels of L-selectin and require L-selectin for entry into resting lymph nodes. However, the role of L-selectin in regulating Treg cell distribution and migration into tumors and lymph nodes during chronic inflammation, such as cancer, has not been examined. Therefore, we investigated the role of L-selectin in regulating Treg cell rolling and adhesion to an endothelial cell monolayer in vitro as well as the distribution and migratory patterns of Treg cells using the murine 4T1 breast cancer model. Importantly, ɑ4ɑ7 integrin/VCAM-1 interactions were found to significantly contribute to Treg cell adhesion to endothelial cell monolayers under shear stress only in the presence of L-selectin function. In vivo, Treg cell populations preferentially accumulated in tumors and tumor-draining lymph nodes during progression of disease, and increased at higher rates than conventional CD4+ T cell populations as tumors progressed. Furthermore, Treg cells preferentially migrated to tumors and tumor-draining lymph nodes in a L-selectin-dependent manner, thereby promoting immune suppressive environments. These studies provide further insight into the mechanisms of L-selectin function in regulating Treg cell distribution during chronic inflammation such as cancer, and may lead to a better understanding of tumor immune evasion and provide new targets for immunotherapeutic strategies

Inflammation and prolonged QT time: Results from the Cardiovascular Disease, Living and Ageing in Halle (CARLA) study

Background: Previous research found an association of CRP with QT time in population based samples. Even more, there is evidence of a substantial involvement of the tumor necrosis factor-alpha system in the pathophysiology of cardiac arrhythmia, while the role of Interleukin 6 remains inconclusive. Objective: To determine the association between inflammation with an abnormally prolonged QT-time (APQT) in men and women of the elderly general population. Methods: Data descend from the baseline examination of the prospective, population-based Cardiovascular Disease, Living and Ageing in Halle (CARLA) Study. After exclusion of subjects with atrial fibrillation and missing ECG recording the final study cohort consisted of 919 men and 797 women. Blood parameters of inflammation were the soluble TNF-Receptor 1 (sTNF-R1), the high-sensitive C-reactive protein (hsCRP), and Interleukin 6 (IL-6). In accordance with major cardiologic societies we defined an APQT above a QT time of 460 ms in women and 450 ms in men. Effect sizes and the corresponding 95% confidence intervals (CI) were estimated by performing multiple linear and logistic regression analyses including the analysis of sex differences by interaction terms. Results: After covariate adjustment we found an odds ratio (OR) of 1.89 (95% CI: 1.13, 3.17) per 1000 pg/mL increase of sTNF-R1 in women, and 0.74 (95% CI: 0.48, 1.15) in men. In the covariate adjusted linear regression sTNF-R1 was again positively associated with QT time in women (5.75 ms per 1000 pg/mL, 95% CI: 1.32, 10.18), but not in men. Taking possible confounders into account IL-6 and hsCRP were not significantly related to APQT in both sexes. Conclusion: Our findings from cross-sectional analyses give evidence for an involvement of TNF-alpha in the pathology of APQT in women

Romariáh: blog de viagem

TCC (graduação) - Universidade Federal de Santa Catarina, Centro Sócio Econômico, Curso de Administração.Os blogs de viagens são modelos virtuais recentes de negócios em construção e desenvolvimento. O Romariáh, blog de viagem criado inicialmente em 2014, trouxe como oportunidade a realização deste trabalho. Mesmo com o antigo blog desativado, a procura de leitores sobre informações de viagens e documentos necessários continuou até o momento. Esta procura tornou-se motivação e oportunidade para o desenvolvimento deste trabalho a fim de construir e validar um modelo de negócio ideal para blog de viagem, por meio de uma pesquisa envolvendo leitores e parceiros ao blog. Desta forma, criou-se um novo blog de viagem como MVP para este trabalho, delimitando para teste as primeiras publicações do blog na cidade de Florianópolis, SC. O modelo de negócio utilizado para o desenvolvimento do blog foi por meio da metodologia Canvas BMG. Além disso, as ações de melhoria propostas pelas pesquisas ocorreram paralelamente durante a construção do MVP