Effects of Pregnancy and Bacterial Vaginosis on Proinflammatory Cytokine and Secretory Leukocyte Protease Inhibitor Concentrations in Vaginal Secretions

We compared vaginal proinflammatory cytokine and secretory leukocyte protease inhibitor (SLPI) concentrations among pregnant and nonpregnant women according to bacterial vaginosis (BV) status. One-hundred and twenty-two women at 12–20 weeks' gestation and 133 nonpregnant controls had vaginal concentrations of interleukin (IL)-1β, IL-6, IL-8, and SLPI measured by enzyme immunoassay. Multivariable linear regression was used to evaluate factors independently associated with vaginal cytokine and SLPI response. Pregnancy and BV were both independently associated with increased vaginal concentrations of IL-1β and IL-8; pregnant women had increased concentrations of SLPI, while women with BV had decreased SLPI concentrations

Changes in DOM and alum doses for two rivers of contrasting catchments after intense wildfires

The dynamics of dissolved organic matter (DOM) in two river waters were investigated after their catchments had been severely burnt in the 2019/20 Australian wildfires. Shortly after these wildfires, dissolved organic carbon (DOC) concentrations were recorded at high levels (∼ 19 mg/L & 30 mg/L) and these became much lower (up to ∼80% less) in the following winter when river flows had increased. Satellite imagery-based data indicated up to 95% of catchment areas burnt and up to ∼50% subsequent vegetation recoveries after two years. Shifts in burn index values for the burnt areas coincided with DOC concentration variations. Specific colour of waters increased up to 40% as daily river flows increased, indicating higher input of humic content from the burnt catchments. Chlorophyll-a was detected at highest levels in waters soon after the fires when river flows were lowest. Enhanced alum doses were predicted using two feed-forward models; one based on DOC and turbidity data and the other based on UV@254nm, colour and turbidity. Doses predicted using the two models showed high correlations (r > 0.9) and were highest for waters directly after the fires. These models were developed for diverse source waters including those impacted by extreme climate events

Perceptions and Practices of Key Worker Stakeholder Groups in Hospital Animal- Assisted Intervention Programs on Occupational Benefits and Perceived Risks

Background: Animal-assisted intervention (AAI) programs, used widely for patient benefit, have increasingly been used for healthcare workers (HCW) to reduce occupational stress. However, there are barriers to these programs which limit their utilization, for both patients and HCW, specifically infectious disease concerns. The aim of the research project is to identify barriers and facilitators to AAI program use for healthcare worker benefit, and determine knowledge, beliefs, and practices regarding infectious disease risk and control policies, in order to understand the contextual parameters of program implementation. Methods: We collected perceptions of key stakeholders involved with hospital AAI programs (HCW and AAI workers) through semi-structured in-depth interviews. We used framework analysis to guide thematic coding, completed independently by three researchers. Results: We interviewed 37 participants in this study. We divided our themes into two topic areas: program use for HCW and perceived infectious disease risk. Use for healthcare workers included perspectives on the benefits for HCW and program barriers and facilitators (specifically collaboration and leadership). Perceived risk included opinions on infection concerns with AAI, thoughts on control measures to reduce this risk, and responsibility for safety during these programs. Conclusions: While significant benefits were reported for HCW, they were limited by administrative barriers and hazard concerns. Facilitators to surmount these barriers are best implemented with collaboration across the hospital and appropriate leadership roles to direct safe program implementation. By addressing these barriers through targeted facilitators in the form of evidence-backed guidelines, AAI programs can be used to benefit both patients and HCW

Temporal Variability of Human Vaginal Bacteria and Relationship with Bacterial Vaginosis

Little is known about short-term bacterial fluctuations in the human vagina. This study used PCR to assess the variability in concentrations of key vaginal bacteria in healthy women and the immediate response to antibiotic treatment in women with bacterial vaginosis (BV).Twenty-two women assessed for BV using Amsel's criteria were evaluated daily for 7 or 14 days, then at 2, 3 and 4 weeks, using a panel of 11 bacterium-specific quantitative PCR assays. Participants with BV were treated with 5 days of intravaginal metronidazole. Participants without BV had vaginal biotas dominated by lactobacilli, whose levels fluctuated with menses. With onset of menstruation, quantities of Lactobacillus jensenii and Lactobacillus crispatus decreased and were found to be inversely related to Gardnerella vaginalis concentrations (p<0.001). Women with BV had a variety of fastidious bacteria whose concentrations dropped below detection thresholds 1-5 days after starting metronidazole. Recurrent BV was characterized by initial profound decreases of BV-associated bacteria after treatment followed by subsequent increases at relapse.The microbiota of the human vagina can be highly dynamic. Healthy women are colonized with Lactobacillus species, but levels can change dramatically over a month. Marked increases in G. vaginalis were observed during menses. Participants with BV have diverse communities of fastidious bacteria that are depleted by vaginal metronidazole therapy. Women with recurrent BV initially respond to antibiotic treatment with steep declines in bacterial concentrations, but these bacteria later reemerge, suggesting that antibiotic resistance in these bacteria is not an important factor mediating BV recurrence

Microbial sharing between pediatric patients and therapy dogs during hospital animal-assisted intervention programs

Microbial sharing between humans and animals has been demonstrated in a variety of settings. However, the extent of microbial sharing that occurs within the healthcare setting during animal-assisted intervention programs is unknown. Understanding microbial transmission between patients and therapy dogs can provide important insights into potential health benefits for patients, in addition to addressing concerns regarding potential pathogen transmission that limits program utilization. This study evaluated for potential microbial sharing between pediatric patients and therapy dogs and tested whether patient-dog contact level and a dog decolonization protocol modified this sharing. Patients, therapy dogs, and the hospital environment were sampled before and after every group therapy session and samples underwent 16S rRNA sequencing to characterize microbial communities. Both patients and dogs experienced changes in the relative abundance and overall diversity of their nasal microbiome, suggesting that the exchange of microorganisms had occurred. Increased contact was associated with greater sharing between patients and therapy dogs, as well as between patients. A topical chlorhexidine-based dog decolonization was associated with decreased microbial sharing between therapy dogs and patients but did not significantly affect sharing between patients. These data suggest that the therapy dog is both a potential source of and a vehicle for the transfer of microorganisms to patients but not necessarily the only source. The relative contribution of other potential sources (e.g., other patients, the hospital environment) should be further explored to determine their relative importance

Comparison of oral and vaginal metronidazole for treatment of bacterial vaginosis in pregnancy: impact on fastidious bacteria

<p>Abstract</p> <p>Background</p> <p>Bacterial vaginosis (BV) is a common condition that is associated with preterm birth and acquisition of complex communities of vaginal bacteria that include several fastidious species. Treatment of BV in pregnancy has mixed effects on the risk of preterm delivery, which some hypothesize is due to variable antibiotic efficacy for the fastidious bacteria. Both oral and intravaginal metronidazole can be used to treat bacterial vaginosis in pregnancy, but little is known about the impact of different routes of antibiotic administration on concentrations of fastidious vaginal bacteria.</p> <p>Methods</p> <p>This was a sub-study of a larger randomized trial of oral versus vaginal metronidazole for treatment of BV in pregnancy. Fifty-three women were evaluated, including 30 women who received oral metronidazole and 23 who received intravaginal metronidazole. Bacterial taxon-specific quantitative PCR assays were used to measure concentrations of bacterial vaginosis associated bacterium (BVAB) 1, 2, and 3, <it>Gardnerella vaginalis, Atopobium </it>species, <it>Leptotrichia/Sneathia </it>species, <it>Megasphaera </it>species, and <it>Lactobacillus crispatus </it>before and after antibiotic treatment.</p> <p>Results</p> <p>Concentrations of <it>Leptotrichia </it>and <it>Sneathia </it>spp. and the fastidious Clostridia-like bacterium designated BVAB1 decreased significantly with oral (p = .002, p = .02) but not vaginal therapy (p = .141, p = .126). The fastidious bacterium BVAB3 did not significantly decrease with either treatment. Concentrations of <it>Atopobium </it>spp., reportedly resistant to metronidazole <it>in vitro</it>, dropped significantly with oral (p = .002) and vaginal (p = .001) treatment. There was no significant difference in the magnitude of change in bacterial concentrations between oral and vaginal treatment arms for any of the bacterial species. <it>Lactobacillus crispatus </it>concentrations did not change.</p> <p>Conclusion</p> <p>Both oral and vaginal metronidazole therapy in pregnant women result in a significant decrease in concentrations of most BV-associated anaerobic bacteria, with the exception that <it>Leptotrichia, Sneathia </it>and BVAB1 do not significantly decrease with vaginal metronidazole therapy. These data suggest that the route of antibiotic administration has a minor impact on bacterial eradication in pregnant women with BV.</p> <p>Trail Registration</p> <p>This trial is registered with ClinicalTrials.gov, number NCT00153517</p

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN