Background Urinary tract infections (UTI) affect approximately 250 million people annually worldwide. Patients often experience a cycle of antimicrobial treatment and recurrent UTI (rUTI) that is thought to be facilitated by a gut reservoir of uropathogenic Escherichia coli (UPEC). Methods 125 patients with UTI caused by an antibiotic-resistant organism (ARO) were enrolled from July 2016 to May 2019 in a longitudinal, multi -center cohort study. Multivariate statistical models were used to assess the relationship between uropathogen colonization and recurrent UTI (rUTI), controlling for clinical characteristics. 644 stool samples and 895 UPEC isolates were interrogated for taxonomic composition, antimicrobial resistance genes, and phenotypic resistance. Cohort UTI gut microbiome pro fi les were compared against published healthy and UTI reference microbiomes, as well as assessed within-cohort for timepoint- and recurrence-speci fi c differences. Findings Risk of rUTI was not independently associated with clinical characteristics. The UTI gut microbiome was distinct from healthy reference microbiomes in both taxonomic composition and antimicrobial resistance gene (ARG) burden, with 11 differentially abundant taxa at the genus level. rUTI and non-rUTI gut microbiomes in the cohort did not generally differ, but gut microbiomes from urinary tract colonized patients were elevated in E. coli abundance 7 - 14 days post-antimicrobial treatment. Corresponding UPEC gut isolates from urinary tract colonizing lineages showed elevated phenotypic resistance against 11 of 23 tested drugs compared to noncolonizing lineages. Interpretation The gut microbiome is implicated in UPEC urinary tract colonization during rUTI, serving as an ARGenriched reservoir for UPEC. UPEC can asymptomatically colonize the gut and urinary tract, and post-antimicrobial blooms of gut E. coli among urinary tract colonized patients suggest that cross -habitat migration of UPEC is an important mechanism of rUTI. Thus, treatment duration and UPEC populations in both the urinary and gastrointestinal tract should be considered in treating rUTI and developing novel therapeutics. Copyright (c) 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Copyright (c) 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Active management of fire-dependent ecosystems for specific species leads to complex tradeoffs, which affect conservation outcomes to other species. Therefore a multi-species evaluation of management actions is required. Habitat Suitability Models (HSMs) can help in predicting the likelihood of species occurrence using corresponding environmental variables and empirical relationships that link occurrence with specific environmental conditions. Incorporating multiple species into HSMs and relating them to habitat dynamics is crucial for ecosystems that require active management with prescribed fire. To address this issue, we developed multi-species HSM driven within an existing population model of the longleaf pine-hardwood ecosystem to assess the suitability of an ecosystem given different fire management strategies and environmental conditions. The population model used in this study provides spatial and temporal changes of longleaf pine-hardwood habitat structure in response to fire. These habitat values are used by the HSM to calculate habitat suitability for three threatened and endangered faunal species of this ecosystem, which all thrive with frequent fire, but have unique habitat requirements. Transient habitat conditions are traced to predict longleaf pine ecosystem trajectories under various management strategies, thereby evaluating current land management actions, such as thinning or prescribed fire frequencies. We tested a suite of environmental conditions to emphasize the sensitivity of the species to different fire management actions. The results of our modeling suggest that maximum suitable habitat for all three species can be achieved with fire frequency occurring at approximately once every three years. The modeling results support current management actions and provide a new habitat assessment tool that incorporates ecological factors for multiple species, thus providing for habitat optimization.

Abstract Background A5350, a phase II, randomized, double-blind study, evaluated the safety and tolerability of the probiotic Visbiome Extra Strength (ES) over 24 weeks and measured effects on inflammation and intestinal barrier function. Methods The primary outcome was change in soluble CD14 (sCD14) levels; secondary outcomes included safety and tolerability, markers of inflammation and cellular activation, and microbiome. In a substudy, gut permeability was assessed by paired colonic biopsies measuring the area of lamina propria occupied by CD4+ cells, interleukin (IL)-17+ cells, and myeloperoxidase (MPO). Changes between arms were compared with the 2-sample t test with equal variance or the Wilcoxon rank-sum test. For safety, the highest graded adverse events (AEs) were compared between arms using the Fisher exact test. Results Overall, 93 participants enrolled: 86% male, median age 51 years, median CD4 count 712 cells/mm3. Visbiome ES was safe and well tolerated. There was no difference in mean change in sCD14 from baseline to week 25/26 between placebo (mean change, 92.3 µg/L; 95% CI, –48.5 to 233 µg/L) and Visbiome ES (mean change, 41.0 µg/L; 95% CI, –94.1 to 176.2 µg/L; P=.60). Similarly, no statistically significant differences between arms in inflammatory marker changes were identified. In substudy participants, no statistical differences between arms for change in cellular marker expression or gut permeability were observed (P>.05 for all). The microbiome demonstrated increased probiotic species and a significant decrease in Gammaproteobacteria (P=.044) in the Visbiome ES arm. Conclusions Visbiome ES was safe and altered the microbiome but demonstrated no effect on systemic inflammatory markers, pathology, or gut permeability in antiretroviral therapy–treated people with HIV.

Coupled fire-atmosphere models are increasingly being used to study low-intensity fires, such as those that are used in prescribed fire applications. Thus, the need arises to evaluate these models for their ability to accurately represent fire spread in marginal burning conditions. In this study, wind and fuel data collected during the Prescribed Fire Combustion and Atmospheric Dynamics Research Experiments (RxCADRE) fire campaign were used to generate initial and boundary conditions for coupled fire-atmosphere simulations. We present a novel method to obtain fuels representation at the model grid scale using a combination of imagery, machine learning, and field sampling. Several methods to generate wind input conditions for the model from eight different anemometer measurements are explored. We find a strong sensitivity of fire outcomes to wind inputs. This result highlights the critical need to include variable wind fields as inputs in modeling marginal fire conditions. This work highlights the complexities of comparing physics-based model results against observations, which are more acute in marginal burning conditions, where stronger sensitivities to local variability in wind and fuels drive fire outcomes.

Each year, a growing international collection of researchers meets at the NIH to share and discuss developments in the microbiome HIV story. This past year has seen continued progress toward a detailed understanding of host-microbe interactions both within and outside the field of HIV. Commensal microbes are being linked to an ever-growing list of maladies and physiologic states, including major depressive disorder, chronic kidney disease, and Parkinson disease. PubMed citations for "microbiome" are growing at an exponential rate with over 11,000 in 2018. Various microbial taxa have been associated with HIV infection, and some of these taxa associated with HIV infection have also been associated with systemic markers of inflammation in HIV infected individuals. Causality remains unclear however as environmental and behavioral factors may drive HIV risk, inflammation, and gut enterotype. Much of the work currently being done addresses potential mechanisms by which gut microbes influence immune and inflammatory pathways. No portion of the microbiome landscape has grown as rapidly as study of the interplay between gut microbes and response to cancer immunotherapy. As Dr. Wargo discussed in her keynote address, this area has opened the door to better understanding on how commensal microbes interact with the human immune system.

AIDS Research and Human RetrovirusesVol. 36, No. 8 Letter to the EditorSleep Health Should be Included as a Therapeutic Target in the Treatment of HIVHelen J. Burgess, Brett Williams, Alan Landay, Phillip Engen, Shohreh Raeisi, Ankur Naqib, Louis L. Fogg, Ali Keshavarzian, Heather E. Rasmussen, Xiaowei Zhang, Bruce Hamaker, and Stefan J. GreenHelen J. BurgessAddress correspondence to: Helen J. Burgess, PhD, Department of Psychiatry, Sleep and Circadian Rhythms Research Laboratory, University of Michigan, Rachel Upjohn Building, 4250 Plymouth Road, Ann Arbor, MI 48109, USA E-mail Address: bhelen@med.umich.eduDepartment of Psychiatry, University of Michigan, Ann Arbor, Michigan, USA.Search for more papers by this author, Brett WilliamsDepartment of Immunology, Rush University Medical Center, Chicago, Illinois, USA.Search for more papers by this author, Alan LandayDepartment of Immunology, Rush University Medical Center, Chicago, Illinois, USA.Search for more papers by this author, Phillip EngenDepartment of Immunology, Rush University Medical Center, Chicago, Illinois, USA.Search for more papers by this author, Shohreh RaeisiDepartment of Immunology, Rush University Medical Center, Chicago, Illinois, USA.Search for more papers by this author, Ankur NaqibDepartment of Immunology, Rush University Medical Center, Chicago, Illinois, USA.Search for more papers by this author, Louis L. FoggDepartment of Immunology, Rush University Medical Center, Chicago, Illinois, USA.Search for more papers by this author, Ali KeshavarzianDepartment of Immunology, Rush University Medical Center, Chicago, Illinois, USA.Search for more papers by this author, Heather E. RasmussenDepartment of Nutrition and Health Sciences, University of Nebraska, Lincoln, Nebraska, USA.Search for more papers by this author, Xiaowei ZhangDepartment of Food Science, Purdue University, West Lafayette, Indiana, USA.Search for more papers by this author, Bruce HamakerDepartment of Food Science, Purdue University, West Lafayette, Indiana, USA.Search for more papers by this author, and Stefan J. GreenSequencing Core, Research Resources Center, University of Illinois at Chicago, Chicago, Illinois, USA.Search for more papers by this authorPublished Online:31 Jul 2020https://doi.org/10.1089/aid.2020.0094AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Sleep Health Should be Included as a Therapeutic Target in the Treatment of HIV." AIDS Research and Human Retroviruses, 36(8), p. 631FiguresReferencesRelatedDetailsCited byThe IDOze Study: The Link Between Sleep Disruption and Tryptophan-Kynurenine Pathway Activation in Women With Human Immunodeficiency Virus8 July 2022 | The Journal of Infectious Diseases, Vol. 226, No. 8Sleep Disturbance in the Context of HIV: A Concept Analysis20 April 2022 | SAGE Open Nursing, Vol. 8 Volume 36Issue 8Aug 2020 InformationCopyright 2020, Mary Ann Liebert, Inc., publishersTo cite this article:Helen J. Burgess, Brett Williams, Alan Landay, Phillip Engen, Shohreh Raeisi, Ankur Naqib, Louis L. Fogg, Ali Keshavarzian, Heather E. Rasmussen, Xiaowei Zhang, Bruce Hamaker, and Stefan J. Green.Sleep Health Should be Included as a Therapeutic Target in the Treatment of HIV.AIDS Research and Human Retroviruses.Aug 2020.631-631.http://doi.org/10.1089/aid.2020.0094Published in Volume: 36 Issue 8: July 31, 2020Online Ahead of Print:June 16, 2020Online Ahead of Editing: May 15, 2020PDF download

It remains unclear whether differences in gut microbiota noted between HIV-infected and uninfected individuals are driven by HIV or sexual behavior. We evaluated rectal swab microbiota of HIV-infected and uninfected women with similar demographic, neighborhood, and diet characteristics enrolled in the Chicago Women's Interagency HIV Study (WIHS). DNA was amplified for sequencing of fragments of bacterial small subunit (SSU or 16S) ribosomal RNA (rRNA) genes. HIV-infected and uninfected women did not differ by Shannon diversity index (p = .14), non-metric multidimensional scaling (NMDS) plot of Bray-Curtis indices (p = .488, r = 0.0027), or copy number of individual taxa. Both groups demonstrated marked microbiome stability over time (p = .889).

Introduction: HIV-infected individuals have evidence of intestinal microbial translocation which is associated with immune activation and unfavorable clinical outcomes. Rifaximin, a non-absorbable antibiotic which reduces microbial translocation in other disease states, was shown to have a marginal beneficial effect on microbial translocation, T-cell activation, and inflammation in a multisite randomized trial (ACTG A5286; NCT01466595) of HIV-infected persons with poor immunologic recovery receiving ART. Here, we report analysis of the rectal microbiome changes associated with that trial.Methods: HIV-1-infected individuals receiving ART with CD4-T cell count <350cells/mm3 and viral suppression were randomized 2:1 to rifaximin or no therapy for 4 weeks. Rectal swabs were collected at baseline (pre-treatment) and at week 4 of rifaximin therapy. Genomic DNA extracted from rectal swab samples was analyzed using high throughput sequencing and quantitative PCR of bacterial 16S ribosomal RNA (rRNA) genes.Results: Forty-eight HIV-infected participants (31 received rifaximin, 17 no treatment) were included. There was broad variability in the recovery of bacterial rRNA from the specimens at baseline. No major significant (FDR P<0.05) effects of rifaximin treatment on alpha- or beta- diversity or individual taxa were observed between or within the treatment arms, with analyses conducted at taxonomic levels from phylum to genus.Conclusions: Rifaximin did not meaningfully alter the diversity or composition of the rectal microbiome of HIV-infected individuals after 4 weeks of therapy, although rectal swab specimens varied widely in their microbial load.

BACKGROUND:Dipeptidyl peptidase-4 (DPP-4) inhibitors have pleotropic anti-inflammatory and immune regulatory effects in addition to glucoregulation. We evaluated inflammation and immune markers in suppressed human immunodeficiency virus (HIV) infection during treatment with the DPP-4 inhibitor sitagliptin. METHODS:Virologically suppressed adults with HIV without diabetes on stable antiretroviral therapy (ART) with ≥100/μL CD4 cells were randomized to 16 weeks of sitagliptin 100 mg/day vs placebo in a multicenter trial. The primary endpoint was the change in plasma soluble CD14 (sCD14) from baseline to week 15-16. RESULTS:Ninety participants were randomized, and 42 from each arm were included in per-protocol analyses. Participants were 45% non-Hispanic white, 38% non-Hispanic black, and 15% Hispanic, with a median age of 51 years; 83% were male; and the median CD4 count was 602 cells/μL. At week 15-16, there was no difference in sCD14 change between the 2 arms (P = .69). Relative to placebo, the sitagliptin arm had 47% greater decline in CXCL10 (95% confidence interval, -57% to -35%) at week 15 (P < .001). There were no significant between-arm differences in other soluble biomarkers, total CD4 and CD8 counts, or markers of lymphocyte or monocyte activation. Sitagliptin was well tolerated. CONCLUSIONS:Sixteen weeks of sitagliptin had no effect on sCD14 levels in virologically suppressed participants with HIV. CXCL10, a chemokine involved in atherogenesis that predicts non-AIDS events during ART, declined markedly with sitagliptin. This suggests that DPP-4 inhibition has the potential to reduce cardiovascular morbidity in treated HIV infection. CLINICAL TRIALS REGISTRATION:NCT01426438.

Monitoring understory plant diversity is important, allowing managers to track current diversity status and trends both spatially and temporally at a landscape-scale. Improving precision in quantifying patterns in understory plant diversity improves efficiency in monitoring design and more accurate measures of success of management intervention over time. Patterns of species diversity are dependent upon the scale in which they are examined an increase in small-scale diversity across a gradient can convert to a decrease in large-scale diversity across that same gradient. Using two extensive datasets including both mined historical data and supplemental experimental data, we performed an additive partitioning of plant diversity to elucidate the hierarchical spatial patterns of understory plant species richness, and independent measures of alpha and beta diversity in the species-rich longleaf pine ecosystem at Eglin Air Force Base in northwestern FL, USA. This analysis allowed us to identify the spatial scale that most effectively captures plant diversity to inform monitoring efforts by using measures of species turnover, specifically beta diversity. We found that while species richness and alpha diversity increased with spatial scale, beta diversity began to reach an asymptote at smaller (1 m(2)) scales. Furthermore, we found the sampling effort at this 1 m(2) scale required as few as 60 plots to effectively estimate plant diversity within management blocks. While our results are attributable to Eglin AFB specifically, these scaling analyses can help to streamline monitoring efforts in other ecosystems that seek to elucidate the individual contributions of diversity components.

Background: Since 2006, Centers for Disease Control and Prevention guidelines recommend routine opt-out human immunodeficiency virus (HIV) testing among sexually active 13- to 64-year-olds. Earlier diagnosis and treatment of HIV infection reduces morbidity and mortality and can limit transmission to others. Objective: Our aim was to increase HIV testing, diagnosis, and linkage to care in the emergency department (ED). Methods: Beginning May 4, 2015, we utilized our electronic health record (EHR) to enhance HIV testing in patients seen in the Rush University Medical Center emergency department in Chicago, IL, who were 13-64 years of age, did not have HIVlisted on their problem list, and did not have an HIV antigen/antibody (Ag/Ab) test in the EHR within the past rolling 12-month period. Strategies included use of a "Best Practice Advisory" and later auto-order screening linked to a complete blood count order. Results: Our baseline HIV test rate was 2.5% of the target population by age (average of 93 tests per month). From May 4, 2015 to January 31, 2019, 137,749 patients of 240,091 ED visits met our test criteria and 23,588 (17.1% of the target population) HIVAg/Ab tests were performed, resulting in 164 positive tests. We identified 18 acute seroconverters, 51 new chronically infected persons, and 95 known infected, many of who had not disclosed their status. Our positive test rate was 0.70%, which dropped to 0.29% if only newly diagnosed individuals were counted. Conclusions: EHR enhancements in a large urban ED identifies both newly diagnosed acute and chronically HIV-infected persons. Identification of previously diagnosed patients offers an opportunity to relink them to care. (C) 2019 Elsevier Inc. All rights reserved.

Our microbial cotravelers have increasingly apparent roles in both maintaining health and causing disease in several organ systems. Investigators gather annually at the National Institutes of Health to present new discoveries regarding the role of the microbiome in human health and a special focus on persons living with HIV. Here, we summarize the discussions from the third annual Virology Education workshop on the microbiome in HIV, which took place in October of 2017.

The annual rate of placement of cardiovascular implantable electronic devices (CIEDs), which includes pacemakers and implantable cardiac defibrillators, has steadily increased over the last several decades. With an increasing number of implantations has been an increasing incidence of CIED infections. It is generally recommended that patients with infections of CIEDs complete a course of antibiotics and have the device removed if possible. However, gram-negative organisms are uncommon in CIED infection, and it has been suggested that cases of suspected gram-negative CIED infection may not necessitate the same management approach. Here, we report a case of presumed Pasteurella multocida CIED infection and share our experience with its several management challenges.

The components of the human gut microbiome have been found to influence a broad array of pathologic conditions ranging from heart disease to diabetes and even to cancer. HIV infection upsets the delicate balance in the normal host-microbe interaction both through alterations in the taxonomic composition of gut microbial communities as well as through disruption of the normal host response mechanisms. In this article we review the current methods of gut microbiome analysis and the resulting data regarding how HIV infection might change the balance of commensal bacteria in the gut. Additionally, we cover the various effects gut microbes have on host immune homeostasis and the preliminary but intriguing data on how HIV disrupts those mechanisms. Finally, we briefly describe some of the important biomolecules produced by gut microbiota and the role that they may play in maintaining host immune homeostasis with and without HIV infection.

Commensal organisms appear to play significant roles in normal homeostasis as well as in the pathogenesis of HIV infection in a number of different organ systems. On November 17th and 18th, 2016, leading researchers from around the world met to discuss their insights on advances in our understanding of HIV and the microbiome at the National Institutes of Health (NIH) in Bethesda. Dr. Elhanan Borenstein of the University of Washington gave a keynote address where he discussed new developments in systems biology which hold the promise of illuminating the pathways by which these organisms interact with human physiology. He suggested that we need to get past correlations in microbiome research by using models and informatics which incorporate metagenomics to predict functional changes in the microbiome.

Frequently burned low-latitude coniferous forests maintain a high-diversity understory. Longleaf pine (Pinus palustris Mill.) forests and woodlands have exceptionally high diversity at fine scales and very frequent fire return intervals (1-3 yr). Furthermore, the positive association between high-frequency, low-intensity surface fires and high species richness in longleaf pine ecosystems is well documented but poorly understood. Recent studies have demonstrated additional linkages between specific fuel assemblages and fire intensity at small spatial scales. In this study, we build upon both patterns by using long-term datasets to examine the relationship between fire and specific fuel types, and how the combination of these two elements contributes to ground cover species diversity. We used 11 yr of monitoring data from longleaf pine forests at Eglin Air Force Base, Florida (USA), to parameterize a structural equation model that examines causal relationships between fuels and fire history on ground cover plant diversity. Overstory-derived fuels, including pine needle litter, pine cones, and other 10 and 100-h woody fuels, had the greatest positive impact on diversity in relatively open-canopied, frequently burned reference stands. A second model examined surface fuel components originating from the forest overstory as characterized by airborne light detection and ranging and found that pine needle litter was positively associated with canopy density. Our parameter estimates for causal relationships between easily measured variables and plant diversity will allow for the development of management models at the stand scale while being informed by fuels measured at the plot scale.

Recent developments in molecular techniques have allowed researchers to identify previously uncultured organisms, which has propelled a vast expansion of our knowledge regarding our commensal microbiota. Interest in the microbiome specific to HIV grew from earlier findings suggesting that bacterial translocation from the intestines is the cause of persistent immune activation despite effective viral suppression with antiretroviral therapy (ART). Studies of SIV infected primates have demonstrated that Proteobacteria preferentially translocate and that mucosal immunity can be restored with probiotics. Pathogenic SIV infection results in a massive expansion of the virome, whereas non-pathogenic SIV infection does not. Human HIV infected cohorts have been shown to have microbiota distinctive from that of HIV negative controls and efforts to restore the intestinal microbiome via probiotics have often had positive results on host markers. The microbiota of the genital tract may play a significant role in acquisition and transmission of HIV. Modification of commensal microbial communities likely represents an important therapeutic adjunct to treatment of HIV. Here we review the literature regarding human microbiome in HIV infection.

The relationship between markers of monocyte/macrophage activation (sCD14 and sCD163) and components of the Veterans Aging Cohort Study (VACS) score, which predict mortality in patients with HIV, in immunologic nonresponders (INRs) is not defined. HIV+ subjects with >12 months of continuous virologic suppression and persistent CD4 <250 cells/mm(3) were enrolled at the CORE Center, Chicago. Subjects had a single visit where history was taken and blood drawn. ELISA assays for sCD14 and sC163 were performed at Blood Systems, CA. Descriptive statistics were performed using SAS. We enrolled 43 subjects with persistent CD4 <250 after a median of 32 months of continuous viral suppression. We found elevated markers of monocyte/macrophage activation; sCD14 and sCD163 correlated with higher VACS scores as well as hepatitis C virus (HCV) coinfection and FIB-4 score, components of the VACS index. In this cohort of immunologic nonresponders, there was a significant correlation between markers of monocyte/macrophage activation and the VACS score. Among components of the VACS index, we did not find a significant association between HCV coinfection and sCD14; however, there was a significant association between HCV coinfection and sCD163.

Results of the randomized complete block design ANCOVA for ground-cover evenness at the treatment scale by year.