Modulation of the host immune response as a result of Chlamydia psittaci infection.

After intraperitoneal injection of mice with infectious, inactivated, or envelope preparations of the elementary body of Chlamydia psittaci, lymphocyte transformation of spleen cells to the mitogens concanavalin A, phytohemagglutinin, and lipopolysaccharide was significantly reduced 1 and 2 weeks postinjection. Lymphocyte response returned to the control values by 4 weeks. Similarly, transformation of cells by chlamydial antigen was not detected until 4 weeks postinjection. Injection of the noninfectious intracellular reticulate body, in contrast, had little effect on transformation of cells to concanavalin A. When control spleen cells were incubated with infectious or inactivated elementary bodies in vitro, response to all three mitogens was also reduced. The sooner the organisms were added after the addition of mitogen, the greater the reduction in transformation. Incubation with elementary body envelopes and reticulate bodies had no effect on lymphocyte transformation of the spleen cells to concanavalin A. The relationship between the observed ability to reduce the response in the in vitro assay of lymphocyte transformation and the actual in vivo establishment of infection is discussed

Process Improvement for Simethicone use During Endoscopic Procedures

https://digitalcommons.psjhealth.org/summit_all/1056/thumbnail.jp

Does case management improve diabetes outcomes?

Patients with type 2 diabetes benefit from case management, as evidenced by decreased glycated hemoglobin (HbA1c). The improvement in HbA1c appeared larger when case managers could make changes in medications independently and multidisciplinary teams were used (strength of recommendation [SOR]: C, 2 meta-analyses of randomized controlled trials [RCTs] with consistent disease-oriented findings). Patients with type 1 diabetes who have case management and "intense control" experience fewer cardiovascular events and decreased retinopathy and clinical neuropathy (SOR: B, 1 large, good-quality RCT)

Genome-wide maps of alkylation damage, repair, and mutagenesis in yeast reveal mechanisms of mutational heterogeneity

DNA base damage is an important contributor to genome instability, but how the formation and repair of these lesions is affected by the genomic landscape and contributes to mutagenesis is unknown. Here, we describe genome-wide maps of DNA base damage, repair, and mutagenesis at single nucleotide resolution in yeast treated with the alkylating agent methyl methanesulfonate (MMS). Analysis of these maps revealed that base excision repair (BER) of alkylation damage is significantly modulated by chromatin, with faster repair in nucleosome-depleted regions, and slower repair and higher mutation density within strongly positioned nucleosomes. Both the translational and rotational settings of lesions within nucleosomes significantly influence BER efficiency; moreover, this effect is asymmetric relative to the nucleosome dyad axis and is regulated by histone modifications. Our data also indicate that MMS-induced mutations at adenine nucleotides are significantly enriched on the nontranscribed strand (NTS) of yeast genes, particularly in BER-deficient strains, due to higher damage formation on the NTS and transcription-coupled repair of the transcribed strand (TS). These findings reveal the influence of chromatin on repair and mutagenesis of base lesions on a genome-wide scale and suggest a novel mechanism for transcription-associated mutation asymmetry, which is frequently observed in human cancers

Protein Disulfide Isomerase, a Component of the Estrogen Receptor Complex, Is Associated with Chlamydia trachomatis Serovar E Attached to Human Endometrial Epithelial Cells

Chlamydia trachomatis serovar E, the leading bacterial agent responsible for sexually transmitted diseases, is required to invade genital epithelial cells for its growth and survival, yet little is known about the adhesin-receptor interactions promoting its entry. In contrast, much has been published on the heparan sulfate receptor for binding C. trachomatis L2 elementary bodies (EBs) prior to entry into HeLa cells. Using a different experimental approach in which a biotinylated apical membrane protein receptor(s) attached to EB at 4°C was stripped off the surface of polarized HEC-1B cells and immunoprecipitated with polyclonal anti-EB antibodies, an ∼55-kDa protein was reproducibly detected by enhanced chemiluminescence and two-dimensional gel electrophoresis. Matrix-assisted laser desorption ionization mass-spectrometry sequence analysis revealed the 55-kDa protein to be protein disulfide isomerase (PDI), a member of the estrogen receptor complex which carries out thiol-disulfide exchange reactions at infected host cell surfaces. Exposure of HEC-1B cells during EB attachment (1.5 to 2 h) to three different inhibitors of PDI reductive reactions—(i) the thiol-alkylating reagent DTNB (5,5′-dithiobis[2-nitrobenzoic acid]), (ii) bacitracin, and (iii) anti-PDI antibodies—resulted in reduced chlamydial infectivity. Since (i) C. trachomatis serovar E attachment to estrogen-dominant primary human endometrial epithelial cells is dramatically enhanced and (ii) productive entry into and infectivity of EB in host cells is dependent on reduction of EB cross-linked outer membrane proteins at the host cell surface, these data provide some preliminary evidence for an intriguing new potential receptor candidate for further analysis of luminal C. trachomatis serovar E entry

Molecular characterization and outer membrane association of a Chlamydia trachomatis protein related to the hsp70 family of proteins.

One route by which Chlamydia trachomatis is internalized into host endometrial epithelial cells is receptor-mediated endocytosis. Although this implies an adhesin-receptor interaction exists, specific chlamydial surface molecules have not been identified. We are investigating potential adhesin molecules using an in vitro functional assay to select for chlamydial recombinant Escherichia coli expressing an adherent phenotype. We have previously shown that E. coli JM109(pPBW58) attaches to epithelial cells by a specific process paralleling C. trachomatis and expresses at least three plasmid-encoded proteins (18, 28, and 82 kDa; Schmiel, D. H., Knight, B. T., Raulston, J. E., Choong, J., Davis, C. H., and Wyrick, P. B. (1991) Infect. Immun. 59, 4001-4012).One route by which Chlamydia trachomatis is internalized into host endometrial epithelial cells is receptor-mediated endocytosis. Although this implies an adhesin-receptor interaction exists, specific chlamydial surface molecules have not been identified. We are investigating potential adhesin molecules using an in vitro functional assay to select for chlamydial recombinant Escherichia coli expressing an adherent phenotype. We have previously shown that E. coli JM109(pPBW58) attaches to epithelial cells by a specific process paralleling C. trachomatis and expresses at least three plasmid-encoded proteins (18, 28, and 82 kDa; Schmiel, D. H., Knight, B. T., Raulston, J. E., Choong, J., Davis, C. H., and Wyrick, P. B. (1991) Infect. Immun. 59, 4001-4012)

The Effects of a Web-Based Alcohol Prevention Program on Social Norms, Expectancies, and Intentions to Prevent Harm among College Student-Athletes

College athletes are at risk for heavy alcohol use, which jeopardizes their general health, academic standing, and athletic performance. Effective prevention programming reduces these risks by targeting theory-based intermediate factors that predict alcohol use while tailoring content to student-athletes. The purpose of this study was to examine the impact of the myPlaybook online prevention program on student-athletes’ social norms, negative alcohol expectancies, and intentions to use alcohol-related harm prevention strategies. NCAA Division II student-athletes were recruited from 60 institutions across the United States to complete myPlaybook and pretest/posttest surveys measuring demographics and targeted outcome variables. Participants were randomly assigned to the treatment group (pretest-program-posttest; final n=647) or the delayed treatment “control” group (pretest-posttest-program; final n=709). Results revealed significant program effects on social norms (pp=.14). Implications for future research and practice are discussed

Better Pumps: Promoting Reliable Water Infrastructure for Everyone

Approximately 90 million people in Africa lack access to safe drinking water, despite having water infrastructure installed in their community. The India Mark II and the Afridev handpumps are among the most widely used handpumps in the world. Sadly, studies show that approximately 30% of these handpumps are non-operational due to failures of the bearings, seals, head flange, and other common components. The Better Pumps team of the Collaboratory provides engineering support for partners who are working to improve handpump sustainability. We have partnered with Tony Beers and AlignedWorks to validate a bearing test methodology for the India Mark II handpump. By modifying the loading conditions in our handpump test machine, we were able to replicate failures observed by AlignedWorks in a field trial of their bearing design. However, these modifications caused our test machine tabletop to noticeably deflect, so we made modifications to stiffen the tabletop. We partnered with Matt Schwiebert and Living Water International to test new seal designs for the India Mark II and Afridev handpumps. Seal performance data collected by the team was used to validate a new design in advance of field trials by Living Water International. We developed and performed clear cylinder testing on the seals to visualize the leak paths. A new Afridev testing apparatus is being designed to test the longevity of the Afridev bearings and seals. Test methodologies and results are reported. Funding for this work provided by The Collaboratory for Strategic Partnerships and Applied Research.https://mosaic.messiah.edu/engr2022/1000/thumbnail.jp

Investigating Risk Factors Predictive of Problem Outcomes Experienced by First Year Drinking and Non-Drinking Collegiate Student-Athletes

This study examined risk factors for problem outcomes experienced by drinking and non-drinking first year collegiate student-athletes. Freshman and transfer student-athletes (N=2956) reported their alcohol use, problems experienced and demographic/sport-related data via an online survey. We hypothesized extreme drinking, male, out-of-season, team sport and Division III would significantly predict experiencing more alcohol, sport and other-related problem outcomes. Results suggest that out-of-season, team sport and light, heavy or extreme drinking (versus non-drinking) student-athletes were more likely to report alcohol-related problems. Female and in-season student-athletes were more likely to experience sport-related problems. Other problem outcomes were more likely to be experienced by heavy and extreme drinkers but not light drinkers. Findings should guide prevention programming that targets high-risk student-athlete groups