Persistent Hepatic Structural Alterations Following Nanoceria Vascular Infusion in the Rat

Understanding the long-term effects and possible toxicity of nanoceria, a widely utilized commercial metal oxide, is of particular importance as it is poised for development as a therapeutic agent based on its autocatalytic redox behavior. We show here evidence of acute and subacute adverse hepatic responses, after a single infusion of an aqueous dispersion of 85 mg/kg, 30 nm nanoceria into Sprague Dawley rats. Light and electron microscopic evidence of avid uptake of nanoceria by Kupffer cells was detected as early as 1 hr after infusion. Biopersistent nanoceria stimulated cluster of differentiation 3+ lymphocyte proliferation that intermingled with nanoceria-containing Kupffer cells to form granulomata that were observed between days 30 and 90. Ultrastructural tracking of ceria nanoparticles revealed aggregated nanoceria in phagolysosomes. An increased formation of small nanoceria over time observed in the latter suggests possible dissolution and precipitation of nanoceria. However, the pathway for nanoceria metabolism/secretion remains unclear. Although frank hepatic necrosis was not observed, the retention of nanoceria increased hepatic apoptosis acutely, this persisted to day 90. These findings, together with our earlier reports of 5-nm ceria-induced liver toxicity, provide additional guidance for nanoceria development as a therapeutic agent and for its risk assessment

PECTIN METHYLESTERASE INHIBITOR6 Promotes <i>Arabidopsis</i> Mucilage Release by Limiting Methylesterification of Homogalacturonan in Seed Coat Epidermal Cells

Abstract Imbibed seeds of the Arabidopsis thaliana accession Djarly are affected in mucilage release from seed coat epidermal cells. The impaired locus was identified as a pectin methylesterase inhibitor gene, PECTIN METHYLESTERASE INHIBITOR6 (PMEI6), specifically expressed in seed coat epidermal cells at the time when mucilage polysaccharides are accumulated. This spatio-temporal regulation appears to be modulated by GLABRA2 and LEUNIG HOMOLOG/MUCILAGE MODIFIED1, as expression of PMEI6 is reduced in mutants of these transcription regulators. In pmei6, mucilage release was delayed and outer cell walls of epidermal cells did not fragment. Pectin methylesterases (PMEs) demethylate homogalacturonan (HG), and the majority of HG found in wild-type mucilage was in fact derived from outer cell wall fragments. This correlated with the absence of methylesterified HG labeling in pmei6, whereas transgenic plants expressing the PMEI6 coding sequence under the control of the 35S promoter had increased labeling of cell wall fragments. Activity tests on seeds from pmei6 and 35S:PMEI6 transgenic plants showed that PMEI6 inhibits endogenous PME activities, in agreement with reduced overall methylesterification of mucilage fractions and demucilaged seeds. Another regulator of PME activity in seed coat epidermal cells, the subtilisin-like Ser protease SBT1.7, acts on different PMEs, as a pmei6 sbt1.7 mutant showed an additive phenotype.</jats:p

Serum and exhaled breath condensate inflammatory cytokines in community-acquired pneumonia: a prospective cohort study

Background The role and relationship between pro- and anti-inflammatory cytokines represents one of the least studied aspects of the pathogenesis of community-acquired pneumonia (CAP). The aim of the present study was to evaluate pro- and anti-inflammatory cytokines at both local (lung) and systemic (blood) levels and their relationship with the severity of the disease on admission and time for a patient to reach clinical stability during hospitalisation. Methods This was an observational, prospective, cohort study of hospitalised patients with a diagnosis of CAP at the IRCCS Policlinico Hospital, Milan, Italy, between April 2010 and January 2012. Ten pro-inflammatory cytokines (interleukin [IL]-1, IL-1\u3b1, IL-1\u3b2, IL-2, IL-6, IL-8, tumor necrosis factor [TNF]\u3b1 and interferon [IFN]\u3b3) and anti-inflammatory cytokines (IL-4 and IL-10) were measured in both serum and exhaled breath condensate within 24 h after hospital admission. Results A total of 74 patients (median age: 76 years; gender: 61 % male) were enrolled. The anti- to pro-inflammatory cytokine ratio was reduced in patients with severe disease on admission and prolonged time to reach clinical stability. This was due to lower levels of anti-inflammatory cytokines in the exhaled breath condensate and higher levels of pro-inflammatory cytokines in serum. Conclusions Dis-regulation between pro- and anti-inflammatory pathways might be a part of the pathogenic mechanisms that lead to severe infection and worse early clinical outcomes in CAP patients

Alexithymia and interleukin variations in somatoform disorder

Objective: The aim of the present study was to investigate if somatoform disorders (SFD) are associated with changes in the normal serum levels of important interleukins, and further, to establish if these changes are related to the presence and severity of alexithymia in patients with SFD. Methods: Twenty-four unmedicated patients who met the International Classification of Diseases (ICD-10) diagnostic criteria for SFD completed the psychological questionnaire to assess alexithymia (Toronto Alexithymia Scale), symptom reporting (SCL-90-R) and diagnostic criteria for SFD (Screening for Somatoform Symptoms scale). Serum concentrations of soluble interleukin 2 receptor α (sIL-2 Rα), IL-4, IL-6, IL-10 and IL-12 were determined in patients with SFD and in 9 healthy subjects. Results: In patients with SFD, serum levels of IL-6 (p < 0.001), IL-10 (p = 0.047) and immunoglobulin E (p = 0.045) were significantly increased in comparison with healthy controls. Additionally, a negative correlation was observed between the level of alexithymia ('total' Toronto Alexithymia Scale score) and the serum levels of sIL-2 Rα (r = -0.538) in SFD. Conclusions: Taken together, these results suggest that SFD, with clinically significant alexithymia, are associated with a reduction in Th1-mediated immune function and an increase in the activation of the Th2 immune function, indicated by the augmented serum levels of IL-6 and IL-10 and elevated immunoglobulin E. Copyright © 2007 S. Karger AG

Characteristics and Outcomes of Adults Hospitalized with SARS-CoV-2 Community-Acquired Pneumonia in Louisville, Kentucky

Background: Patients infected with the novel coronavirus SARS-CoV-2 are frequently hospitalized with community-acquired pneumonia (CAP). The objective of this study was to define the clinical characteristics and outcomes of hospitalized patients with SARS-CoV-2 CAP in the city of Louisville, KY. Methods: This was a retrospective observational study of 700 patients with SARS-CoV-2 infection hospitalized to eight of the adult hospitals in the city of Louisville. Patients with 1) a positive RT-PCR for SARS-CoV-2, 2) fever, cough, or shortness of breath, and 3) an infiltrate at chest imaging were defined as having SARS-CoV-2 CAP. Demographic characteristics of the study population were compared with census data from the city of Louisville. For each patient more than 500 variables were abstracted from electronic medical records and recorded using Research Electronic Data Capture software. Data was analyzed by descriptive and inferential statistics using R version 3.4.0. Results: SARS-CoV-2 CAP was identified in 632 (90%) patients hospitalized with COVID-19. The median age of the patients was 63 years, 53% were females, 31% were black and 12% Hispanic. The most frequent comorbidities were hypertension (56%), obesity (50%), and diabetes (33%). Mortality was 17% for the total population and 34% for the 249 patients admitted to ICU. For each category of race, ethnicity and comorbidities, the proportion of hospitalized patients with SARS-CoV-2 CAP was significantly different when compared to the Louisville population (p \u3c 0.001). Conclusion: Patients of black race, Hispanic ethnicity, and patients with history of hypertension, obesity or diabetes are overrepresented among hospitalized patients with SARS-CoV-2 CAP when compared to the Louisville population. Hospitalized patients with SARS-CoV-2 CAP are likely to require ICU care, with death occurring in approximately one of six hospitalizations

INDIGO-DataCloud: a Platform to Facilitate Seamless Access to E-Infrastructures

[EN] This paper describes the achievements of the H2020 project INDIGO-DataCloud. The project has provided e-infrastructures with tools, applications and cloud framework enhancements to manage the demanding requirements of scientific communities, either locally or through enhanced interfaces. The middleware developed allows to federate hybrid resources, to easily write, port and run scientific applications to the cloud. In particular, we have extended existing PaaS (Platform as a Service) solutions, allowing public and private e-infrastructures, including those provided by EGI, EUDAT, and Helix Nebula, to integrate their existing services and make them available through AAI services compliant with GEANT interfederation policies, thus guaranteeing transparency and trust in the provisioning of such services. Our middleware facilitates the execution of applications using containers on Cloud and Grid based infrastructures, as well as on HPC clusters. 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