Ciprofloxacin-resistant Salmonella enterica Typhimurium and Choleraesuis from Pigs to Humans, Taiwan

We evaluated the disk susceptibility data of 671 nontyphoid Salmonella isolates collected from different parts of Taiwan from March 2001 to August 2001 and 1,261 nontyphoid Salmonella isolates from the National Taiwan University Hospital from 1996 to 2001. Overall, ciprofloxacn resistance was found in 2.7% (18/671) of all nontyphoid Salmonella isolates, in 1.4% (5/347) of Salmonella enterica serotype Typhimurium and in 7.5% (8/107) in S. enterica serotype Choleraesuis nationwide. MICs of six newer fluoroquinolones were determined for the following isolates: 37 isolates of ciprofloxacin-resistant (human) S. enterica Typhimurium (N = 26) and Choleraesuis (N = 11), 10 isolates of ciprofloxacin-susceptible (MIC <1 μg/mL) (human) isolates of these two serotypes, and 15 swine isolates from S. enterica Choleraesuis (N = 13) and Typhmurium (N = 2) with reduced susceptibility to ciprofloxacin (MIC >0.12 μg/mL). Sequence analysis of the gryA, gyrB, parC, parE, and acrR genes, ciprofloxacin accumulation; and genotypes generated by pulsed-field gel electrophoresis with three restriction enzymes (SpeI, XbaI, and BlnI) were performed. All 26 S. enterica Typhimurium isolates from humans and pigs belonged to genotype I. For S. enterica Choleraesuis isolates, 91% (10/11) of human isolates and 54% (7/13) of swine isolates belonged to genotype B. These two genotypes isolates from humans all exhibited a high-level of resistance to ciprofloxacin (MIC 16–64 μg/mL). They had two-base substitutions in the gyrA gene at codons 83 (Ser83Phe) and 87 (Asp87Gly or Asp87Asn) and in the parC gene at codon 80 (Ser80Arg, Ser80Ile, or Ser84Lys). Our investigation documented that not only did these two S. enterica isolates have a high prevalence of ciprofloxacin resistance nationwide but also that some closely related ciprofloxacin-resistant strains are disseminated from pigs to humans

Metabolic syndrome is associated with change in subclinical arterial stiffness - A community-based Taichung Community Health Study

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to evaluate the effect of MetS on arterial stiffness in a longitudinal study.</p> <p>Methods</p> <p>Brachial-ankle pulse wave velocity (baPWV), a measurement interpreted as arterial stiffness, was measured in 1518 community-dwelling persons at baseline and re-examined within a mean follow-up period of 3 years. Multivariate linear regression with generalized estimating equations (GEE) were used to examine the longitudinal relationship between MetS and its individual components and baPWV, while multivariate logistic regression with GEE was used to examine the longitudinal relationship between MetS and its individual components and the high risk group with arterial stiffness.</p> <p>Results</p> <p>Subjects with MetS showed significantly greater baPWV at the end point than those without MetS, after adjusting for age, gender, education, hypertension medication and mean arterial pressure (MAP). MetS was associated with the top quartile of baPWV (the high-risk group of arterial stiffness, adjusted odds ratio [95% confidence interval] 1.52 [1.21-1.90]), and a significant linear trend of risk for the number of components of MetS was found (p for trend < 0.05). In further considering the individual MetS component, elevated blood pressure and fasting glucose significantly predicted a high risk of arterial stiffness (adjusted OR [95% CI] 3.72 [2.81-4.93] and 1.35 [1.08-1.68], respectively).</p> <p>Conclusions</p> <p>MetS affects the subject's progression to arterial stiffness. Arterial stiffness increased as the number of MetS components increased. Management of MetS is important for preventing the progression to advanced arterial stiffness.</p

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Caractérisation du rôle des CD8 pro-inflammatoire au cours de la réponse immunitaire

La réaction inflammatoire est décrite comme une réponse induits par les pathogènes ou les tissus endommagés impliquant des cellules innées. Mon étude est basée sur deux modèles: d'une part des cellules HY répondant à l'antigène mâle en l'absence de signaux de danger, d'autre part des cellules OT-1 répondant à l'infection par L/ster/a-OVA. Dans les deux cas, nous avons identifié une forte expression de cytokines et chimiokines pro-inflammatoires immédiatement après l'activation des cellules T CD8. Une injection locale de ces cellules T au niveau de l'oreille induit l'hypertrophie du ganglion drainant et le recrutement préférentiel de monocytes inflammatoires, PMN, cellules dendritiques et cellules NK. Ces résultats démontrent que la réponse T CD8 induit deux phases effectrices distinctes, inflammatoire puis cytotoxique. Nous avons ainsi mis en évidence un nouvel aspect de l'inflammation qui pourra conduire aux nouvelles thérapies anti-inflammatoires ou un rejet de transplantation.The inflammatory reaction is believed to be induced by pathogens or tissue damage and mediated by innate cells. In this PhD work I used two immune response models, the response of anti-HY cells to male cells (no danger signals) or the response of OT1 cells to infection with L/ster/a-OVA. In both cases we found that immediately after activation CDS T cells expressed high levels of pro-inflammatory cytokines and chemokines. A local injection of these pro-inflammatory effectors in the ear induced the hypertrophy of the draining lymph node and the preferential recruitment of inflammatory monocytes, PMNs, cDCs and NK cells. These results demonstrated that CDS responses involved two distinct effector phases (inflammatory to cytotoxic) and that antigen recognition by CDS T cells is sufficient to initiate inflammatory reactions, even when danger signals are absent. We expect our results to give new important perspectives on anti-inflammatory therapy during infection and transplant rejection.PARIS5-BU Méd.Cochin (751142101) / SudocSudocFranceF

Increased risk of thrombosis in FcγRIIA 131RR patients with HIT due to defective control of platelet activation by plasma IgG2

International audienceThrombosis results in heparin-induced thrombocytopenia (HIT) from cellular activation involving Fc receptors. In this study, the FcγRIIA 131RR genotype was found to increase the risk of thrombosis in HIT patients (odds ratio: 5.9; 95% confidence interval: 1.7-20). When platelet aggregation tests (PATs) were performed with platelet-rich plasma (PRP), a shorter lag time was measured in 131RR donors compared to individuals with the HR and HH genotypes in response to HIT plasma or 5B9, a recently developed humanized monoclonal antibody to PF4/heparin. Importantly, this difference was no longer detectable when PATs were performed with washed platelets or immunoglobulin (Ig)G-depleted PRP. Moreover, polyclonal IgG or monoclonal IgG1 added to IgG-depleted PRP increased the lag time in response to 5B9. HH platelets were also sensitive to IgG2, which in contrast, failed to inhibit the response of 131RR platelets to 5B9. Finally, higher tissue factor messenger RNA levels were measured in the whole blood of 131RR donors after activation by HIT antibodies, with increased phospholipid procoagulant activity. These results demonstrate that HIT patients homozygous for the FcγRIIA 131R allele have a higher risk of thrombosis, probably due to increased cell activation by antibodies to PF4/heparin, with a lower inhibitory effect of endogenous IgG, especially from the IgG2 subclass

Exopolysaccharides of Bacillus amyloliquefaciens Amy-1 Mitigate Inflammation by Inhibiting ERK1/2 and NF-&kappa;B Pathways and Activating p38/Nrf2 Pathway

Bacillus amyloliquefaciens is a probiotic for animals. Evidence suggests that diets supplemented with B. amyloliquefaciens can reduce inflammation; however, the underlying mechanism is unclear and requires further exploration. The exopolysaccharides of B. amyloliquefaciens amy-1 displayed hypoglycemic activity previously, suggesting that they are bioactive molecules. In addition, they counteracted the effect of lipopolysaccharide (LPS) on inducing cellular insulin resistance in exploratory tests. Therefore, this study aimed to explore the anti-inflammatory effect and molecular mechanisms of the exopolysaccharide preparation of amy-1 (EPS). Consequently, EPS reduced the expression of proinflammatory factors, the phagocytic activity and oxidative stress of LPS-stimulated THP-1 cells. In animal tests, EPS effectively ameliorated ear inflammation of mice. These data suggested that EPS possess anti-inflammatory activity. A mechanism study revealed that EPS inhibited the nuclear factor-&kappa;B pathway, activated the mitogen-activated protein kinase (MAPK) p38, and prohibited the extracellular signal-regulated kinase 1/2, but had no effect on the c-Jun-N-terminal kinase 2 (JNK). EPS also activated the anti-oxidative nuclear factor erythroid 2&ndash;related factor 2 (Nrf2) pathway. Evidence suggested that p38, but not JNK, was involved in activating the Nrf2 pathway. Together, these mechanisms reduced the severity of inflammation. These findings support the proposal that exopolysaccharides may play important roles in the anti-inflammatory functions of probiotics

Long-term outcome of patients with very small coronary artery disease: A comparison of drug-eluting and bare metal stents

Background: Among patients with very small vessel disease and chronic kidney disease (CKD), the comparative efficacy of bare metal stents (BMSs) versus drug-eluting stents (DESs) is not frequently addressed. This study aimed to evaluate the long-term outcomes of patients with very small vessel disease managed with percutaneous coronary intervention. Methods: Our study included 158 consecutive patients undergoing percutaneous coronary intervention from January 2003 to December 2013. The primary end points were cardiovascular death and target vessel failure, which consisted of cardiovascular death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization. Results: BMSs were used in 37 patients, while DESs were utilized in 121 patients. During the mean follow-up period of 2.7 ± 2.2 years (median 2.1 years; interquartile range, 1.3−4.2 years), the target vessel failure rate was 48.6% versus 28.1% (BMS vs. DES, p = 0.020) and the cardiovascular death rate was 27% versus 18.2% (BMS vs. DES, p = 0.241). The use of a DES (hazard ratio: 0.44, 95% confidence interval: 0.24–0.79, p = 0.006) remained the most significant predictor of target vessel failure after multivariate analysis. In CKD subgroup analysis, the benefit of a 2.25 mm DES was evident only in the subgroup with CKD, but such a benefit disappeared in those without CKD. Conclusion: Compared with BMSs, implantation of DESs in a patient population with very small vessel disease effectively reduced target vessel failure. However, the beneficial effects of DESs appeared to be evident only in the subgroup with CKD

Novel, genetically induced mouse model that recapitulates the histological morphology and immunosuppressive tumor microenvironment of metastatic peritoneal carcinomatosis

BackgroundPeritoneal carcinomatosis is a hallmark of advanced peritoneal tumor progression, particularly for tubal/ovarian high-grade serous carcinomas (HGSCs). Patients with peritoneal carcinomatosis have poor survival rates and are difficult to treat clinically due to widespread tumor dissemination in the peritoneal cavity.MethodsWe developed a clinically relevant, genetically induced, peritoneal carcinomatosis model that recapitulates the histological morphology and immunosuppressive state of the tumor microenvironment of metastatic peritoneal HGSCs by intraperitoneally injecting shp53, AKT, c-Myc, luciferase and sleeping beauty transposase, followed by electroporation (EP) in the peritoneal cavity of immunocompetent mice (intraperitoneal (IP)/EP mice).ResultsSimilar to the spread of human ovarian cancers, IP/EP mice displayed multiple tumor nodules attached to the surface of the abdomen. Histopathological analysis indicated that these tumors were epithelial in origin. These IP/EP mice also displayed a loss of CD3+ T cell infiltration in tumors, highly expressed inhibitory checkpoint molecules in tumor-infiltrating and global CD4+ and CD8+ T cells, and increased levels of transforming growth factor-β in the ascites, all of which contribute to the promotion of tumor growth.ConclusionsOverall, our tumor model recapitulates clinical peritoneal HGSC metastasis, which makes it ideal for preclinical drug screening, testing of immunotherapy-based therapeutics and studying of the tumor biology of peritoneal carcinomatosis