Etiology analysis of an acute gastroenteritis outbreak caused by co-infection with Vibrio parahaemolyticus and non-O1/O139 Vibrio cholerae

ObjectiveTo analyze an acute gastroenteritis outbreak caused by co-infection with Vibrio parahaemolyticus （V. parahaemolyticus） and non-O1/O139 Vibrio cholerae （V. cholerae）.MethodsFour anal swabs， 12 food samples， and 8 environmental samples enriched in liquid culture media were subjected to pathogen screening with real-time PCR. V. parahaemolyticus and V. cholerae strains isolated were subjected to whole genome sequencing， and virulence and antibiotic resistance genes were screened. Cladograms were constructed based on core genome single nucleotide polymorphisms.ResultsV. parahaemolyticus strains were detected in anal swab samples with real-time PCR that were toxRVP+/tdh+/trh-， and two of them were positive for V. cholerae. The positive rate of V. parahaemolyticus in the anal swab samples was 100% （4/4）， the isolates were toxRVP+/tdh+/trh-， and their serotype was O4：KUT. The positive rate of V. cholerae culture in the anal swabs of patients was 50% （2/4）. The serogroup of the isolates was non-O1/O139， and one of them was toxRVC+/ctx/t3ss+. The positive rate of V. parahaemolyticus in the food samples was 66.67% （8/12）， and that in the environment samples was 12.50% （1/8）. The strains isolated from food and environmental samples were toxRVP+/tdh-/trh-. The positive rate of V. cholerae culture in the food samples was 25.00% （3/12） and the isolated strains were toxRVC+/ctx/t3ss-. The V. parahaemolyticus strains isolated from patient， food， and environment samples formed 10 distinct lineages. The four patient isolates were highly clonal. The V. cholerae strains isolated from two patients and three food samples formed five distinct lineages.ConclusionThe outbreak was caused by co-infection with V. parahaemolyticus and non-O1/O139 V. cholerae. Real-time PCR and whole-genome sequence analysis of strains should be performed in the detection and analysis of outbreaks caused by vibrio co-infection. Additionally， optimization of vibrio culture pathways is recommended

Central IKKβ inhibition prevents air pollution mediated peripheral inflammation and exaggeration of type II diabetes

Abstract Background Prior experimental and epidemiologic data support a link between exposure to fine ambient particulate matter (<2.5 μm in aerodynamic diameter, PM2.5) and development of insulin resistance/Type II diabetes mellitus (Type II DM). We investigated the role of hypothalamic inflammation in PM2.5-mediated diabetes development. Methods KKay mice, a genetically susceptible model of Type II DM, were assigned to either concentrated PM2.5 or filtered air (FA) for 4–8 weeks via a versatile aerosol concentrator and exposure system, or administered intra-cerebroventricular with either IKKβ inhibitor (IMD-0354) or TNFα antibody (infliximab) for 4–5 weeks simultaneously with PM2.5 exposure. Glucose tolerance, insulin sensitivity, oxygen consumption and heat production were evaluated. At euthanasia, blood, spleen, visceral adipose tissue and hypothalamus were collected to measure inflammatory cells using flow cytometry. Standard immunohistochemical methods and quantitative PCR were used to assess targets of interest. Results PM2.5 exposure led to hyperglycemia and insulin resistance, which was accompanied by increased hypothalamic IL-6, TNFα, and IKKβ mRNA expression and microglial/astrocyte reactivity. Targeting the NFκB pathway with intra-cerebroventricular administration of an IKKβ inhibitor [IMD-0354, n = 8 for each group)], but not TNFα blockade with infliximab [(n = 6 for each group], improved glucose tolerance, insulin sensitivity, rectified energy homeostasis (O2 consumption, CO2 production, respiratory exchange ratio and heat generation) and reduced peripheral inflammation in response to PM2.5. Conclusions Central inhibition of IKKβ prevents PM2.5 mediated peripheral inflammation and exaggeration of type II diabetes. These results provide novel insights into how air pollution may mediate susceptibility to insulin resistance and Type II DM.http://deepblue.lib.umich.edu/bitstream/2027.42/109486/1/12989_2014_Article_53.pd

Research Progress on Graphitic Carbon Nitride/Metal Oxide Composites: Synthesis and Photocatalytic Applications

Although graphitic carbon nitride (g-C3N4) has been reported for several decades, it is still an active material at the present time owing to its amazing properties exhibited in many applications, including photocatalysis. With the rapid development of characterization techniques, in-depth exploration has been conducted to reveal and utilize the natural properties of g-C3N4 through modifications. Among these, the assembly of g-C3N4 with metal oxides is an effective strategy which can not only improve electron–hole separation efficiency by forming a polymer–inorganic heterojunction, but also compensate for the redox capabilities of g-C3N4 owing to the varied oxidation states of metal ions, enhancing its photocatalytic performance. Herein, we summarized the research progress on the synthesis of g-C3N4 and its coupling with single- or multiple-metal oxides, and its photocatalytic applications in energy production and environmental protection, including the splitting of water to hydrogen, the reduction of CO2 to valuable fuels, the degradation of organic pollutants and the disinfection of bacteria. At the end, challenges and prospects in the synthesis and photocatalytic application of g-C3N4-based composites are proposed and an outlook is given

Exaggerated effects of particulate matter air pollution in genetic type II diabetes mellitus

Abstract Background Prior experimental and epidemiologic data support a link between exposure to fine ambient particulate matter (<2.5 μm in aerodynamic diameter, PM2.5) and development of insulin resistance/Type II diabetes mellitus. This study was designed to investigate whether inhalational exposure of concentrated PM2.5 in a genetically susceptible animal model would result in abnormalities in energy metabolism and exacerbation of peripheral glycemic control. Methods KKay mice, which are susceptible to Type II DM, were assigned to either concentrated ambient PM2.5 or filtered air (FA) for 5–8 weeks via a whole body exposure system. Glucose tolerance, insulin sensitivity, oxygen consumption and heat production were evaluated. At euthanasia, blood, spleen and visceral adipose tissue were collected to measure inflammatory cells using flow cytometry. Standard immnunohistochemical methods, western blotting and quantitative PCR were used to assess targets of interest. Results PM2.5 exposure influenced energy metabolism including O2 consumption, CO2 production, respiratory exchange ratio and thermogenesis. These changes were accompanied by worsened insulin resistance, visceral adiposity and inflammation in spleen and visceral adipose depots. Plasma adiponectin were decreased in response to PM2.5 exposure while leptin levels increased. PM2.5 exposure resulted in a significant increase in expression of inflammatory genes and decreased UCP1 expression in brown adipose tissue and activated p38 and ERK pathways in the liver of the KKay mice. Conclusions Concentrated ambient PM2.5 exposure impairs energy metabolism, concomitant with abnormalities in glucose homeostasis, increased inflammation in insulin responsive organs, brown adipose inflammation and results in imbalance in circulating leptin/adiponectin levels in a genetically susceptible diabetic model. These results provide additional insights into the mechanisms surrounding air pollution mediated susceptibility to Type II DM.http://deepblue.lib.umich.edu/bitstream/2027.42/109523/1/12989_2013_Article_305.pd

Photoreceptor Degeneration is Correlated With the Deterioration of Macular Retinal Sensitivity in High Myopia

To investigate structural changes in the retinal outer layers and choroid using adaptive optics (AO) and optical coherence tomography (OCT) in eyes with myopia, and to correlate the changes with decreased macular light sensitivity (MLS). This prospective study included 27 subjects with emmetropia and low myopia (EM/LM), 25 with moderate myopia (MM), and 25 with high myopia (HM). Microperimetry was used to quantify MLS in each subject, while AO and OCT images of fundus were analyzed to quantify cone density and regularity and thickness of outer retinal sublayers and choroid. Differences of MLS, cone distribution, and chorioretinal thicknesses were compared among the three groups, and the associations among photoreceptor morphological alterations, MLS, and other parameters were analyzed. In HM, the MLS, cone density and regularity, and thicknesses of the myoid and ellipsoid zone (MEZ), Henle fiber layer and outer nuclear layer, interdigitation zone and RPE/Bruch complex, and choroid were lower than in EM/LM. Decreased MLS was correlated with lower cone density and regularity, and thinner MEZ and choroid in the inner region, and with lower cone density, thinner MEZ and choroid, and longer axial length in the outer region. Multivariate regression showed that better MLS was correlated with thicker MEZ in the inner region and with higher cone density in the outer region. Altered cone distribution and outer retinal thickness, especially cone density and MEZ thickness, were significantly correlated with decline of MLS in HM, which may help to evaluate and monitor visual impairment in HM

Inflammatory response to fine particulate air pollution exposure: neutrophil versus monocyte.

Studies have shown that chronic exposure to ambient fine particulate matter (less than 2.5 µm in aerodynamic diameter, PM₂.₅) pollution induces insulin resistance through alterations in inflammatory pathways. It is critical to study how the immune system responds to this stimulant, which has been linked to cardiovascular and autoimmune diseases, but few studies have been focused on such involvement of both neutrophils and monocytes in a timely manner. We hypothesized that the neutrophil was involved in the inflammatory response to air pollution.C57BL/6 mice were exposed to PM₂.₅ or filtered air (6 hours/day, 5 days/week) for 5, 14, and 21 days, respectively, in Columbus, OH. At the end of each of the exposure periods, we investigated the inflammatory response through flow cytometry, histology, intravital microscopy, and real-time PCR. PM₂.₅-exposed mice demonstrated a significant inflammatory response after 5 days of exposure. In the lung tissue and bronchoalveolar lavage fluid, monocytes/macrophages showed a transient response, while neutrophils showed a cumulative response. In addition, exposure to PM₂.₅ resulted in elevation of the monocyte chemoattractant protein 1 (MCP-1) cytokine, a monocyte/macrophage attractant in blood, at an early stage of exposure.These findings suggest that PM₂.₅ exposure induces the inflammatory responses from both macrophages and neutrophils involvement

Regulatory domain phosphorylation to distinguish the mechanistic basis underlying acute CFTR modulators

Modulator compounds intended to overcome disease-causing mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) show significant promise in clinical testing for cystic fibrosis. However, the mechanism(s) of action underlying these compounds are not fully understood. Activation of CFTR ion transport requires PKA-regulated phosphorylation of the regulatory domain (R-D) and dimerization of the nucleotide binding domains. Using a newly developed assay, we evaluated nine compounds including both CFTR potentatiators and activators discovered via various high-throughput screening strategies to acutely augment CFTR activity. We found considerable differences in the effects on R-D phosphorylation. Some (including UC CF-152) stimulated robust phosphorylation, and others had little effect (e.g., VRT-532 and VX-770). We then compared CFTR activation by UC CF-152 and VRT-532 in Ussing chamber studies using two epithelial models, CFBE41o - and Fischer rat thyroid cells, expressing various CFTR forms. UC CF-152 activated wild-type-, G551D-, and rescued F508del-CFTR currents but did not potentiate cAMP-mediated CFTR activation. In contrast, VRT-532 moderately activated CFTR short-circuit current and strongly potentiated forskolin-mediated current. Combined with the result that UC CF-152, but not VRT-532 or VX-770, acts by increasing CFTR R-D phosphorylation, these findings indicate that potentiation of endogenous cAMP-mediated activation of mutant CFTR is not due to a pathway involving augmented R-D phosphorylation. This study presents an assay useful to distinguish preclinical compounds by a crucial mechanism underlying CFTR activation, delineates two types of compound able to acutely augment CFTR activity (e.g., activators and potentiators), and demonstrates that a number of different mechanisms can be successfully employed to activate mutant CFTR. © the American Physiological Society

Open Access Exaggerated effects of particulate matter air pollution in genetic type II diabetes mellitus

Background: Prior experimental and epidemiologic data support a link between exposure to fine ambient particulate matter (&lt;2.5 μm in aerodynamic diameter, PM2.5) and development of insulin resistance/Type II diabetes mellitus. This study was designed to investigate whether inhalational exposure of concentrated PM2.5 in a genetically susceptible animal model would result in abnormalities in energy metabolism and exacerbation of peripheral glycemic control. Methods: KKay mice, which are susceptible to Type II DM, were assigned to either concentrated ambient PM2.5 or filtered air (FA) for 5–8 weeks via a whole body exposure system. Glucose tolerance, insulin sensitivity, oxygen consumption and heat production were evaluated. At euthanasia, blood, spleen and visceral adipose tissue were collected to measure inflammatory cells using flow cytometry. Standard immnunohistochemical methods, western blotting and quantitative PCR were used to assess targets of interest. Results: PM2.5 exposure influenced energy metabolism including O2 consumption, CO2 production, respiratory exchange ratio and thermogenesis. These changes were accompanied by worsened insulin resistance, visceral adiposity and inflammation in spleen and visceral adipose depots. Plasma adiponectin were decreased in response to PM2.5 exposure while leptin levels increased. PM2.5 exposure resulted in a significant increase in expression o