Softening and elution of monomers in ethanol

ObjectivesThe purpose of this study was to investigate the effect of light-curing protocol on softening and elution of monomers in ethanol as measured on a model polymer. It was a further aim to correlate the measured values with previously reported data on degree of conversion and glass transition temperature for the same polymer and curing protocols.MethodsDifferent light-curing protocols were used in order to investigate the influence of energy density, power density, and mode of cure on the properties of a model polymer. The modes of cure were continuous, pulse-delay, and stepped irradiation of the specimens. Wallace hardness was used to determine the softening of the polymer after storage in ethanol for 24 h. Elution of monomers from the polymer was assessed after 7 days in ethanol by means of high-pressure liquid chromatography (HPLC). Data were submitted to two- and three-way analysis of variance (ANOVA), Newman–Keuls’ multiple comparison test, and linear regression analysis.ResultsEnergy density, power density, and mode of cure of the polymer influenced the softening and elution of monomers in ethanol. As energy density increased, softening and elution in ethanol decreased. At same energy density, the influence of power density varied with the mode of cure. When compared to the continuous mode of cure, and at same energy density, pulse-delay irradiation resulted in polymers that in general were more susceptible to softening, but eluted monomers to a lower extent. Less elution was also found with step-cured polymers. Significant, negative correlations were detected between softening and elution in ethanol, respectively, and degree of conversion and between softening and elution in ethanol, respectively, and glass transition temperature.SignificanceA complex relationship exists between curing protocol and the properties selected for investigation. The effect of different combinations of exposure periods and power densities are important to understanding how the curing protocol affects the properties of polymer-based materials.     

Improved tissue repair in articular cartilage defects in vivo by rAAV-mediated overexpression of human fibroblast growth factor 2.

Therapeutic gene transfer into articular cartilage is a potential means to stimulate reparative activities in tissue lesions. We previously demonstrated that direct application of recombinant adeno-associated virus (rAAV) vectors to articular chondrocytes in their native matrix in situ as well as sites of tissue damage allowed for efficient and sustained reporter gene expression. Here we test the hypothesis that rAAV-mediated overexpression of fibroblast growth factor 2 (FGF-2), one candidate for enhancing the repair of cartilage lesions, would lead to the production of a biologically active factor that would facilitate the healing of articular cartilage defects. In vitro, FGF-2 production from an rAAV-delivered transgene was sufficient to stimulate chondrocyte proliferation over a prolonged period of time. In vivo, application of the therapeutic vector significantly improved the overall repair, filling, architecture, and cell morphology of osteochondral defects in rabbit knee joints. Differences in matrix synthesis were also observed, although not to the point of statistical significance. This process may further benefit from cosupplementation with other factors. These results provide a basis for rAAV application to sites of articular cartilage damage to deliver agents that promote tissue repair.     

Treatment with soluble interleukin-15Ralpha exacerbates intracellular parasitic infection by blocking the development of memory CD8+ T cell response

Interferon (IFN)-gamma-producing CD8+ T cells are important for the successful resolution of the obligate intracellular parasite Toxoplasma gondii by preventing the reactivation or controlling a repeat infection. Previous reports from our laboratory have shown that exogenous interleukin (IL)-15 treatment augments the CD8+ T cell response against the parasite. However, the role of endogenous IL-15 in the proliferation of activated/memory CD8+ T cells during toxoplasma or any other infection is unknown. In this study, we treated T. gondii immune mice with soluble IL-15 receptor alpha (sIL-15Ralpha) to block the host endogenous IL-15. The treatment markedly reduced the ability of the immune animals to control a lethal infection. CD8+ T cell activities in the sIL-15Ralpha-administered mice were severely reduced as determined by IFN-gamma release and target cell lysis assays. The loss of CD8+ T cell immunity due to sIL-15Ralpha treatment was further demonstrated by adoptive transfer experiments. Naive recipients transferred with CD44(hi) activated/memory CD8+ T cells and treated with sIL-15Ralpha failed to resist a lethal T. gondii infection. Moreover, sIL-15Ralpha treatment of the recipients blocked the ability of donor CD44(hi) activated/memory CD8+ T cells to replicate in response to T. gondii challenge. To our knowledge, this is the first demonstration of the important role of host IL-15 in the development of antigen-specific memory CD8+ T cells against an intracellular infection.     

In- and out-hospital mortality rate in surgical patients

Background: Death rates after surgery are increasingly analysed for clinical audit and quality assessment. Many studies commonly provide information only on deaths that occur during hospital stay, known as in-hospital death rates. By using hospital data set linked to death certificate registry, we recorded in- and out-hospital deaths within 30 and 60 post-operative days.

Methods: The study included all consecutive surgical procedures (denominator) under general or locoregional anaesthesia in adult patients admitted for elective or non-elective inpatient surgery. Patients undergoing planned day-case surgery or obstetrical procedures were excluded. The primary outcome was 30- and 60-day post-operative mortality rate (numerator) whether before or after discharge.

Results: The study material consisted of a sample of 36,494 surgical procedures corresponding to 28,202 patients. At 30-day, 384 (crude mortality rate of 1.1%) patients died, 314 (82%) during their hospitalisation and 70 (18%) after discharge. Factors that were associated with in-hospital mortality are ASA scores, emergency, duration of surgery and rate of admission to critical care unit. Within the 30–60 days interval, we recorded 231 supplemental deaths, 103 (45%) after discharge.

Conclusion: In-hospital mortality alone is an incomplete measure of mortality even within 30 days of care. To identify the missing deaths, hospital records need to be linked to data from death certificate. This connection with the national death registry will allow obtaining the rate of in-hospital and out-hospital death.     

Trends and challenges in diabetes for middle-income countries: Evidence from Mexico

The epidemiological and economic burden of diabetes poses one of the main challenges for health systems worldwide. This is particularly relevant in middle-income countries because of the constant growing trends that have been observed in recent years. In order to identify trends and challenges on epidemiological and economic burden from diabetes in a middle-income country we developed a longitudinal analysis on costs and trends in the number of cases of diabetes in Mexico. The study population included total annual cases of diabetes at national level. Regarding the annual cumulative incidence for 2016 versus 2018, depending on the institution there is an increase of 9–13% (p?p?相似文献   

Novel mode of action of c-kit tyrosine kinase inhibitors leading to NK cell-dependent antitumor effects

Mutant isoforms of the KIT or PDGF receptors expressed by gastrointestinal stromal tumors (GISTs) are considered the therapeutic targets for STI571 (imatinib mesylate; Gleevec), a specific inhibitor of these tyrosine kinase receptors. Case reports of clinical efficacy of Gleevec in GISTs lacking the typical receptor mutations prompted a search for an alternate mode of action. Here we show that Gleevec can act on host DCs to promote NK cell activation. DC-mediated NK cell activation was triggered in vitro and in vivo by treatment of DCs with Gleevec as well as by a loss-of-function mutation of KIT. Therefore, tumors that are refractory to the antiproliferative effects of Gleevec in vitro responded to Gleevec in vivo in an NK cell-dependent manner. Longitudinal studies of Gleevec-treated GIST patients revealed a therapy-induced increase in IFN-gamma production by NK cells, correlating with an enhanced antitumor response. These data point to a novel mode of antitumor action for Gleevec.     

Human leukocyte antigen class II alleles may contribute to the severity of hepatitis C virus-related liver disease

To investigate whether genetic differences in cytokine promoter polymorphisms effect various outcomes after exposure to Epstein-Barr virus (EBV) infection, 30 patients with EBV-positive gastric carcinoma (GC), 120 patients with EBV-negative GC, and 220 control subjects were enrolled. Promoter polymorphisms of tumor necrosis factor (TNF)-alpha at positions -238 and -308 and of interleukin (IL)-10 at position -1082 were determined. The frequency of the high-producer allele (-308A) in the TNF-alpha gene was significantly higher among EBV-positive GC patients compared with control subjects (23.3% vs. 12.0%, P<.05), whereas the frequency of the high-producer allele (-1082G) in the IL-10 gene was significantly higher among EBV-negative GC patients compared with control subjects (6.3% vs. 3.0%, P<.05). These data support the notion that genetic factors may modify the outcomes of infectious diseases through different TNF-alpha- or IL-10-producing capabilities.     

Evidence of species-specific detoxification processes for trace elements in shorebirds

This study investigated sub-lethal effects and detoxification processes activated in free-ranging Red Knots (RKs) (Calidris canutus) from the Pertuis Charentais on the Atlantic coast of France, and compared the results with previous data obtained on another shorebird species, the Black-tailed Godwit (Limosa limosa). The concentrations of 13 trace elements (Ag, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se, Zn) were assessed in the liver, kidneys, muscle and feathers. Stable isotope analyses of carbon and nitrogen were carried out to determine whether differences in diet explained variations in elemental uptake. The mRNA expression of relevant genes (cytochrome c oxidase 1, acetyl-CoA carboxylase, Cu/Zn and Mn superoxide dismutase, catalase, metallothionein, malic enzyme), antioxidant enzyme activities (catalase, glutathione peroxidase (GPx), superoxide dismutase), and metallothionein (MT) levels were investigated to shed light on trace element detoxification and toxic effects. Although Red Knots were characterized by elevated As and Se concentrations which were potentially toxic, most elements were usually below toxicity threshold levels. The results strongly suggested a dietary specialization of Red Knots, with individuals feeding on higher trophic status prey experiencing higher As, Hg and Se burdens. Red Knots and Godwits also showed discrepancies in elemental accumulation and detoxification processes. Higher As and Se concentrations in Red Knots enhanced catalase gene expression and enzyme activity, while Godwits had higher Ag, Cu, Fe and Zn levels and showed higher MT production and GPx activity. The results strongly suggest that detoxification pathways are essentially trace element- and species-specific.