Perfluorooctanoic acid exposure triggers oxidative stress in the mouse pancreas

• PFOA triggers focal ductal hyperplasia following 7 day exposure. • PFOA exposure increases 8-iso-PGF2α levels in the pancreas. • Antioxidant gene expression is upregulated in the pancreas following PFOA exposure. , Perfluorooctanoic acid (PFOA) is used in the manufacture of many industrial and commercial products. PFOA does not readily decompose in the environment, and is biologically persistent. Human epidemiologic and animal studies suggest that PFOA exposure elicits adverse effects on the pancreas. While multiple animal studies have examined PFOA-mediated toxicity in the liver, little is known about the potential adverse effects of PFOA on the pancreas. To address this, we treated C57Bl/6 mice with vehicle, or PFOA at doses of 0.5, 2.5 or 5.0 mg/kg BW/day for 7 days. Significant accumulation of PFOA was found in the serum, liver and pancreas of PFOA-treated animals. Histopathologic examination of the pancreas revealed focal ductal hyperplasia in mice treated with 2.5 and 5.0 mg/kg BW/day PFOA, while inflammation was observed only in the high dose group. Elevated serum levels of amylase and lipase were observed in the 2.5 mg/kg BW/day PFOA treatment group. In addition, PFOA exposure resulted in a dose-dependent increase in the level of the lipid peroxidation product 8-iso-PGF2α and induction of the antioxidant response genes Sod1, Sod2, Gpx2 and Nqo1. Our findings provide additional evidence that the pancreas is a target organ for PFOA-mediated toxicity and suggest that oxidative stress may be a mechanism through which PFOA induces histopathological changes in the pancreas

I Keep my Problems to Myself: Negative Social Network Orientation, Social Resources, and Health-Related Quality of Life in Cancer Survivors

Cancer survivors treated with hematopoietic stem cell transplant rely on their social network for successful recovery. However, some survivors have negative attitudes about using social resources (negative social network orientation) that are critical for their recovery

An Exploratory Study of Lecturers' Views of Out-of-class Academic Collaboration Among Students

This article reports an exploratory study of lecturers' perceptions of out-of-class academic collaboration (OCAC) among students at a large Singapore university. Two types of OCAC were investigated: collaboration initiated by students, e.g., groups decide on their own to meet to prepare for exams, and collaboration required by teachers, e.g., teachers assign students to do projects in groups. Data were collected via one-on-one interviews with 18 faculty members from four faculties at the university. Findings suggest that OCAC, especially of a teacher-required kind, is fairly common at the university. Faculty members' views on factors affecting the success of OCAC are discussed for the light they might shed on practices to enhance the effectiveness of OCAC

Meningococcal Disease in Patients With Human Immunodeficiency Virus Infection: A Review of Cases Reported Through Active Surveillance in the United States, 2000-2008.

BackgroundAlthough human immunodeficiency virus (HIV) infection is an established risk factor for several bacterial infections, the association between HIV infection and meningococcal disease remains unclear.MethodsExpanded chart reviews were completed on persons with meningococcal disease and HIV infection reported from 2000 through 2008 from 9 US sites participating in an active population-based surveillance system for meningococcal disease. The incidence of meningococcal disease among patients meeting Centers for Disease Control and Prevention acquired immune deficiency syndrome (AIDS) surveillance criteria was estimated using data from the National HIV Surveillance System for the participating sites.ResultsThirty-three cases of meningococcal disease in individuals with HIV infection were reported from participating sites, representing 2.0% of all reported meningococcal disease cases. Most (75.8%) persons with HIV infection were adult males aged 25 to 64 years old. Among all meningococcal disease cases aged 25 to 64 years old, case fatality ratios were similar among HIV-infected and HIV-uninfected persons (13.3% vs 10.6%; P = .6). The cumulative, mean incidence of meningococcal disease among patients aged 25 to 64 years old with HIV infection ever classified as AIDS was 3.5 cases per 100000 person years (95% confidence interval [CI], 2.1-5.6), compared with 0.3 cases per 100000 person years (95% CI, 0.3-0.3) for persons of the same age group not reported to have AIDS (relative risk = 12.9; 95% CI, 7.9-20.9).ConclusionsIndividuals with HIV infection meeting the AIDS surveillance case definition have a higher incidence of meningococcal disease compared with the general adult population

A common and unstable copy number variant is associated with differences in Glo1 expression and anxiety-like behavior

Glyoxalase 1 (Glo1) has been implicated in anxiety-like behavior in mice and in multiple psychiatric diseases in humans. We used mouse Affymetrix exon arrays to detect copy number variants (CNV) among inbred mouse strains and thereby identified a approximately 475 kb tandem duplication on chromosome 17 that includes Glo1 (30,174,390-30,651,226 Mb; mouse genome build 36). We developed a PCR-based strategy and used it to detect this duplication in 23 of 71 inbred strains tested, and in various outbred and wild-caught mice. Presence of the duplication is associated with a cis-acting expression QTL for Glo1 (LOD>30) in BXD recombinant inbred strains. However, evidence for an eQTL for Glo1 was not obtained when we analyzed single SNPs or 3-SNP haplotypes in a panel of 27 inbred strains. We conclude that association analysis in the inbred strain panel failed to detect an eQTL because the duplication was present on multiple highly divergent haplotypes. Furthermore, we suggest that non-allelic homologous recombination has led to multiple reversions to the non-duplicated state among inbred strains. We show associations between multiple duplication-containing haplotypes, Glo1 expression and anxiety-like behavior in both inbred strain panels and outbred CD-1 mice. Our findings provide a molecular basis for differential expression of Glo1 and further implicate Glo1 in anxiety-like behavior. More broadly, these results identify problems with commonly employed tests for association in inbred strains when CNVs are present. Finally, these data provide an example of biologically significant phenotypic variability in model organisms that can be attributed to CNVs.These studies were funded by MH070933, MH79103 and MH020065

The effects of sildenafil on ciliary beat frequency in patients with pulmonary non-tuberculous mycobacteria disease: phase I/II trial.

RATIONALE:Pulmonary non-tuberculous mycobacterial (PNTM) disease has increased over the past several decades, especially in older women. Abnormal mucociliary clearance and abnormal nasal nitric oxide (nNO) have been associated with PNTM disease in other patient cohorts. Mucociliary clearance can be affected by NO-cyclic guanosine monophosphate signalling and, therefore, modulation of the pathway may be possible with phosphodiesterase inhibitors such as sildenafil as a novel therapeutic approach. OBJECTIVE:To define ex vivo characteristics of PNTM disease affected by sildenafil. METHODS:Subjects with PNTM infections were recruited into an open-label dose-escalation trial of sildenafil. Laboratory measurements and mucociliary measurements-ciliary beat frequency, nNO and 24-hour sputum production-were collected throughout the study period. Patients received sildenafil daily during the study period, with escalation from 20 to 40 mg three times per day. MEASUREMENTS AND MAIN RESULTS:Increased ciliary beat frequency occurred after a single dose of 40 mg sildenafil and after extended dosing of 40 mg sildenafil. The increase ciliary beat frequency was not seen with 20 mg sildenafil dosing. There were no changes in sputum production, nNO production, Quality of Life-Bronchiectasis-NTM module (QOL-B-NTM) questionnaire or the St George's Respiratory Questionnaire during the study period. CONCLUSION:Sildenafil, 40 mg, increased ciliary beat frequency acutely as well as with extended administration

Differential control of Zap1-regulated genes in response to zinc deficiency in Saccharomyces cerevisiae

<p>Abstract</p> <p>Background</p> <p>The Zap1 transcription factor is a central player in the response of yeast to changes in zinc status. We previously used transcriptome profiling with DNA microarrays to identify 46 potential Zap1 target genes in the yeast genome. In this new study, we used complementary methods to identify additional Zap1 target genes.</p> <p>Results</p> <p>With alternative growth conditions for the microarray experiments and a more sensitive motif identification algorithm, we identified 31 new potential targets of Zap1 activation. Moreover, an analysis of the response of Zap1 target genes to a range of zinc concentrations and to zinc withdrawal over time demonstrated that these genes respond differently to zinc deficiency. Some genes are induced under mild zinc deficiency and act as a first line of defense against this stress. First-line defense genes serve to maintain zinc homeostasis by increasing zinc uptake, and by mobilizing and conserving intracellular zinc pools. Other genes respond only to severe zinc limitation and act as a second line of defense. These second-line defense genes allow cells to adapt to conditions of zinc deficiency and include genes involved in maintaining secretory pathway and cell wall function, and stress responses.</p> <p>Conclusion</p> <p>We have identified several new targets of Zap1-mediated regulation. Furthermore, our results indicate that through the differential regulation of its target genes, Zap1 prioritizes mechanisms of zinc homeostasis and adaptive responses to zinc deficiency.</p

Understanding the Role of Government and Buyers in Supplier Energy Efficiency Initiatives

In environmental management, companies must respond to myriad needs and pressures from stakeholders such as buyers, regulators, communities and NGOs. While researchers recognize that these stakeholder entities have different saliency and influences over a focal firm, the influences from multiple stakeholders are often aggregated as a single factor, overlooking differences among them. Stakeholders may have competing demands: A buyer may consider only potential environment-cost trade-offs while the government balances the environment, increased cost-competitive manufacturing and job creation. Such demands compete for the same resources within the supplier’s organization, forcing suppliers to satisfice and compromise. This paper qualitatively examines Chinese suppliers’ responses to requests to adopt energy efficiency initiatives in their production plants by two of their most critical stakeholders: buyers and the government. We identify three categories of energy efficiency (EE) initiatives implemented by the suppliers and find that their implementations are contingent on their ownership characteristics and value alignment with these two stakeholders. Further, we find that suppliers interpret buyers’ motives regarding EE in the context of buyer-supplier relationships and environmental positioning of the buyers’ products. These findings are articulated in a set of propositions that are introduced based on our analysis of these case study data.KEYWORDS: Environmental decision-making, Supply management, Energy efficiency, China, Buyer-supplier relationship, Sustainability, case study, Stakeholder theory, Government influenceThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The article is copyrighted by the Institute for Supply Management, Inc. and published by John Wiley & Sons Ltd. It can be found at: http://onlinelibrary.wiley.com/journal/10.1111/%28ISSN%291745-493X

Statistical Evaluations of the Reproducibility and Reliability of 3-Tesla High Resolution Magnetization Transfer Brain Images: A Pilot Study on Healthy Subjects

Magnetization transfer imaging (MT) may have considerable promise for early detection and monitoring of subtle brain changes before they are apparent on conventional magnetic resonance images. At 3 Tesla (T), MT affords higher resolution and increased tissue contrast associated with macromolecules. The reliability and reproducibility of a new high-resolution MT strategy were assessed in brain images acquired from 9 healthy subjects. Repeated measures were taken for 12 brain regions of interest (ROIs): genu, splenium, and the left and right hemispheres of the hippocampus, caudate, putamen, thalamus, and cerebral white matter. Spearman's correlation coefficient, coefficient of variation, and intraclass correlation coefficient (ICC) were computed. Multivariate mixed-effects regression models were used to fit the mean ROI values and to test the significance of the effects due to region, subject, observer, time, and manual repetition. A sensitivity analysis of various model specifications and the corresponding ICCs was conducted. Our statistical methods may be generalized to many similar evaluative studies of the reliability and reproducibility of various imaging modalities