scholarly journals Understanding Barriers to Borrelia burgdorferi Dissemination during Infection Using Massively Parallel Sequencing

2013 ◽  
Vol 81 (7) ◽  
pp. 2347-2357 ◽  
Author(s):  
Erin B. Troy ◽  
Tao Lin ◽  
Lihui Gao ◽  
David W. Lazinski ◽  
Andrew Camilli ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Massively Parallel Sequencing ◽  
Host Immune System ◽  
Multiple Time ◽  
Population Bottlenecks ◽  
Chronic Infections ◽  
Content Type ◽  
Transposon Mutants ◽  
Adapter Molecule ◽  
Multiple Time Points

ABSTRACTBorrelia burgdorferiis an invasive spirochete that can cause acute and chronic infections in the skin, heart, joints, and central nervous system of infected mammalian hosts. Little is understood about where the bacteria encounter the strongest barriers to infection and how different components of the host immune system influence the population as the infection progresses. To identify population bottlenecks in a murine host, we utilized Tn-seq to monitor the composition of mixed populations ofB. burgdorferiduring infection. Both wild-type mice and mice lacking the Toll-like receptor adapter molecule MyD88 were infected with a pool of infectiousB. burgdorferitransposon mutants with insertions in the same gene. At multiple time points postinfection, bacteria were isolated from the mice and the compositions of theB. burgdorferipopulations at the injection site and in distal tissues determined. We identified a population bottleneck at the site of infection that significantly altered the composition of the population. The magnitude of this bottleneck was reduced in MyD88−/−mice, indicating a role for innate immunity in limiting early establishment ofB. burgdorferiinfection. There is not a significant bottleneck during the colonization of distal tissues, suggesting that founder effects are limited and there is not a strict limitation on the number of organisms able to initiate populations at distal sites. These findings further our understanding of the interactions betweenB. burgdorferiand its murine host in the establishment of infection and dissemination of the organism.

Structural elaboration in police organizations: an exploration

2017 ◽  
Vol 40 (2) ◽  
pp. 351-365 ◽  
Author(s):  
Alicia L. Jurek ◽  
Matthew C. Matusiak ◽  
Randa Embry Matusiak
Keyword(s):  
Large Scale ◽  
Structural Complexity ◽  
Essential Elements ◽  
Multiple Time ◽  
Police Departments ◽  
Content Type ◽  
Police Organizations ◽  
The Usa ◽  
Multiple Time Points ◽  
American Police

Purpose The current research explores the structural elaboration of municipal American police organizations, specifically, the structural complexity of police organizations and its relationship to time. The purpose of this paper is to describe and test essential elements of the structural elaboration hypothesis. Design/methodology/approach The authors explore the structural elaboration hypothesis utilizing a sample of 219 large police departments across the USA. Data are drawn from multiple waves of the Law Enforcement Management and Administrative Statistics survey and are analyzed using tobit and OLS regression techniques. Findings While there is some evidence that police departments are becoming more elaborate, little evidence for the structural elaboration hypothesis as a function of time is found. Originality/value This project is the first to specifically explore the structural elaboration hypothesis across multiple time points. Additionally, results highlight structural trends across a panel of large American police organizations and provide potential explanations for changes. Suggestions for large-scale policing data collection are also provided.

scholarly journals Fluorescence-Based Reporter for Gauging Cyclic Di-GMP Levels in Pseudomonas aeruginosa

2012 ◽  
Vol 78 (15) ◽  
pp. 5060-5069 ◽  
Author(s):  
Morten T. Rybtke ◽  
Bradley R. Borlee ◽  
Keiji Murakami ◽  
Yasuhiko Irie ◽  
Morten Hentzer ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Biofilm Formation ◽  
Fluorescent Protein ◽  
Subsequent Development ◽  
Cellular Level ◽  
Host Immune System ◽  
Chronic Infections ◽  
Content Type ◽  
Genes Encoding ◽  
Green Fluorescent

ABSTRACTThe increased tolerance toward the host immune system and antibiotics displayed by biofilm-formingPseudomonas aeruginosaand other bacteria in chronic infections such as cystic fibrosis bronchopneumonia is of major concern. Targeting of biofilm formation is believed to be a key aspect in the development of novel antipathogenic drugs that can augment the effect of classic antibiotics by decreasing antimicrobial tolerance. The second messenger cyclic di-GMP is a positive regulator of biofilm formation, and cyclic di-GMP signaling is now regarded as a potential target for the development of antipathogenic compounds. Here we describe the development of fluorescent monitors that can gauge the cellular level of cyclic di-GMP inP. aeruginosa. We have created cyclic di-GMP level reporters by transcriptionally fusing the cyclic di-GMP-responsivecdrApromoter to genes encoding green fluorescent protein. We show that the reporter constructs give a fluorescent readout of the intracellular level of cyclic di-GMP inP. aeruginosastrains with different levels of cyclic di-GMP. Furthermore, we show that the reporters are able to detect increased turnover of cyclic di-GMP mediated by treatment ofP. aeruginosawith the phosphodiesterase inducer nitric oxide. Considering that biofilm formation is a necessity for the subsequent development of a chronic infection and therefore a pathogenicity trait, the reporters display a significant potential for use in the identification of novel antipathogenic compounds targeting cyclic di-GMP signaling, as well as for use in research aiming at understanding the biofilm biology ofP. aeruginosa.

A systematic review of the methodologies used in research related to adult drug and alcohol rehabilitation in therapeutic communities published 2000-2013

2015 ◽  
Vol 36 (4) ◽  
pp. 193-208 ◽  
Author(s):  
Cassandra Perryman ◽  
Genevieve Dingle
Keyword(s):  
Systematic Review ◽  
Psychiatric Symptoms ◽  
Well Being ◽  
Size Analysis ◽  
Multiple Time ◽  
Therapeutic Communities ◽  
Diverse Range ◽  
Content Type ◽  
Time Points ◽  
Multiple Time Points

Purpose – The purpose of this paper is to summarize research conducted in long-term residential rehabilitation centers, including therapeutic communities (TCs), in order to further clarify the effectiveness of this treatment approach and to evaluate the quality of TC research conducted in the period 2000-2013. Design/methodology/approach – The composite search engine UQ database Summon were used to find articles with “Therapeutic Community” as title words, and the search was limited to adult participants, peer-reviewed articles, published between January 2000 and June 2013 in the English language. The review was conducted using Cochrane Collaboration methods and reported under the Preferred Reporting Items for Systematic Review and Meta-analyses guidelines. Findings – In total, 25 studies met inclusion criteria for the review and represented data from n=5,923 participants in the USA, Australia, Spain, England, and Belgium. Evidence supports the TC approach for a diverse range of individuals who misuse a range of substances. Several studies reported a relationship between retention and outcomes however dropout from treatment is a widespread issue. A paucity of research using multiple time points precludes any firm conclusions regarding the optimal length of treatment in a TC. There is a lack of research on the interplay between individual and community-level factors on client well-being, retention, and longer term outcomes. Research limitations/implications – This review highlights the need for TC research that includes multiple time points and follow-up assessments, and measures of change in theoretically meaningful constructs alongside standard measures of demographics, substance use, and psychiatric symptoms. Practical implications – The reporting format of TC research should be better standardized in order to create a better basis for research comparison. More standardized reporting would also allow for effect size analysis, and create a more efficacious evidence base. Originality/value – This updates the systematic review body of research.

Are “youth days” effective at motivating new sport participation? Evidence from a pre-post event research design

2019 ◽  
Vol 11 (1) ◽  
pp. 89-104
Author(s):  
Jordan Taylor Bakhsh ◽  
Luke R. Potwarka ◽  
Ryan Snelgrove
Keyword(s):  
Sport Participation ◽  
Control Group ◽  
Multiple Time ◽  
Elite Sport ◽  
Cross Sectional ◽  
Content Type ◽  
Sport Competition ◽  
Research Designs ◽  
Multiple Time Points ◽  
Motivation To Participate

Purpose The purpose of this paper is to explore the effects that exposure to a youth day event at an elite sport competition has on youth spectators’ motivations to participate in the sport on display. Design/methodology/approach The paper was underpinned by the theory of planned behavior (TPB). Pre- and post-event questionnaires were administered to local grade seven and eight students (n=318) as part of a youth day event at the 2016 Milton International Track Cycling Challenge in Ontario, Canada. Questionnaires assessed each TPB construct one week before the youth day and immediately following the event. Findings The paper provides empirical insights about the shifts from pre- to post-event behavioral antecedent measures. Results suggest youth day events can be effective at driving positive shifts in participation intention and subjective norm among youth populations. Research limitations/implications A control group was not possible as an ethical limitation was created from the school boards which did not allow for some students/classes within the study to not experience the event. Researchers are encouraged to develop a study which allows for a youth control group and assesses the shift in behavioral antecedents at multiple time points post-event. Practical implications The paper includes implications for how to leverage subjective norms as a means of motivating post-event participation. Originality/value The paper fulfils a methodological gap to move beyond cross-sectional data and employ pre-post event research designs to measure the effect spectating an elite sport competition can have on youth’s motivation to participate in the sport on display.

Understanding demonstration effects among youth sport spectators: cognitive and affective explanations

2020 ◽  
Vol 10 (2) ◽  
pp. 187-206
Author(s):  
Luke R. Potwarka ◽  
Ryan Snelgrove ◽  
Laura Wood ◽  
Georgia Teare ◽  
Daniel Wigfield
Keyword(s):  
Multiple Time ◽  
Content Type ◽  
Before And After ◽  
Intention To Participate ◽  
Affective Components ◽  
The Spectator ◽  
Multiple Time Points ◽  
Cycling Event ◽  
Intentions To Participate ◽  
Track Cycling

PurposeThe purpose of this study was to examine whether watching a live track cycling event could increase youths' intention to participate in the sport, and to identify cognitive and affective mechanisms associated with post-event intentions.Design/methodology/approachA sample of youth spectators (n = 362) who experienced the 2016 Milton International Track Cycling Challenge completed pre- and post-event questionnaires to assess intention to participate and cognitive and affective components of their spectator experience.FindingsRespondents' intentions to participate post-event were significantly higher than pre-event. Results also indicated that state inspiration mediated relationships between three cognitive dimensions of sport spectator experiences (i.e. fantasy, flow, evaluation) and intention to participate.Practical implicationsSport managers should design youth day events to engage with youth prior to the event to increase their knowledge of the sport. This prior engagement may help youth to evaluate performances effectively. Moreover, event experience should be designed to incorporate vicarious and immersive experiences tailored to youth spectators.Originality/valueThe present study is one of the first to assess intentions to participate among youth spectators at multiple time points (i.e. before and after an event) and identifies specific mechanism within the spectator experience that may lead to a demonstration effect.

scholarly journals Borrelia burgdorferi, the Causative Agent of Lyme Disease, Forms Drug-Tolerant Persister Cells

2015 ◽  
Vol 59 (8) ◽  
pp. 4616-4624 ◽  
Author(s):  
Bijaya Sharma ◽  
Autumn V. Brown ◽  
Nicole E. Matluck ◽  
Linden T. Hu ◽  
Kim Lewis
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Stationary Phase ◽  
Causative Agent ◽  
Late Stage ◽  
The United States ◽  
Chronic Infections ◽  
Content Type ◽  
Stage Disease ◽  
Late Stage Disease

ABSTRACTBorrelia burgdorferiis the causative agent of Lyme disease, which affects an estimated 300,000 people annually in the United States. When treated early, the disease usually resolves, but when left untreated, it can result in symptoms such as arthritis and encephalopathy. Treatment of the late-stage disease may require multiple courses of antibiotic therapy. Given that antibiotic resistance has not been observed forB. burgdorferi, the reason for the recalcitrance of late-stage disease to antibiotics is unclear. In other chronic infections, the presence of drug-tolerant persisters has been linked to recalcitrance of the disease. In this study, we examined the ability ofB. burgdorferito form persisters. Killing growing cultures ofB. burgdorferiwith antibiotics used to treat the disease was distinctly biphasic, with a small subpopulation of surviving cells. Upon regrowth, these cells formed a new subpopulation of antibiotic-tolerant cells, indicating that these are persisters rather than resistant mutants. The level of persisters increased sharply as the culture transitioned from the exponential to stationary phase. Combinations of antibiotics did not improve killing. Daptomycin, a membrane-active bactericidal antibiotic, killed stationary-phase cells but not persisters. Mitomycin C, an anticancer agent that forms adducts with DNA, killed persisters and eradicated growing and stationary cultures ofB. burgdorferi. Finally, we examined the ability of pulse dosing an antibiotic to eliminate persisters. After addition of ceftriaxone, the antibiotic was washed away, surviving persisters were allowed to resuscitate, and the antibiotic was added again. Four pulse doses of ceftriaxone killed persisters, eradicating all live bacteria in the culture.

scholarly journals BBB07 contributes to, but is not essential for, Borrelia burgdorferi infection in mice

Microbiology ◽  
2020 ◽  
Vol 166 (10) ◽  
pp. 988-994
Author(s):  
Beth Hahn ◽  
Phillip Anderson ◽  
Zouyan Lu ◽  
Rebecca Danner ◽  
Zhipeng Zhou ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Type Species ◽  
Inflammatory Responses ◽  
Synovial Cells ◽  
Single Strain ◽  
Content Type ◽  
Transposon Mutants ◽  
Integrin Ligand

Borrelia burgdorferi, a causative agent of Lyme disease, encodes a protein BBB07 on the genomic plasmid cp26. BBB07 was identified as a candidate integrin ligand based on the presence of an RGD tripeptide motif, which is present in a number of mammalian ligands for β1 and β3 integrins . Previous work demonstrated that BBB07 in recombinant form binds to β1 integrins and induces inflammatory responses in synovial cells in culture. Several transposon mutants in bbb07 were attenuated in an in vivo screen of the transposon library in mice. We therefore tested individual transposon mutant clones in single-strain infections in mice and found that they were attenuated in terms of ID50 but did not have significantly reduced tissue burdens in mice. Based on data presented here we conclude that BBB07 is not essential for, but does contribute to, B. burgdorferi infectivity in mice.

scholarly journals Tapering Courses of Oral Vancomycin Induce Persistent Disruption of the Microbiota That Provide Colonization Resistance to Clostridium difficile and Vancomycin-Resistant Enterococci in Mice

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Myreen E. Tomas ◽  
Thriveen S. C. Mana ◽  
Brigid M. Wilson ◽  
Michelle M. Nerandzic ◽  
Samira Joussef-Piña ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Anaerobic Bacteria ◽  
Multiple Time ◽  
Colonization Resistance ◽  
Content Type ◽  
Vancomycin Resistant Enterococci ◽  
Indigenous Microbiota ◽  
Vancomycin Resistant ◽  
Multiple Time Points ◽  
The Impact

ABSTRACT Vancomycin taper regimens are commonly used for the treatment of recurrent Clostridium difficile infections. One rationale for tapering and pulsing of the dose at the end of therapy is to reduce the selective pressure of vancomycin on the indigenous intestinal microbiota. Here, we used a mouse model to test the hypothesis that the indigenous microbiota that provide colonization resistance against C. difficile and vancomycin-resistant enterococci (VRE) is repopulated during tapering courses of vancomycin. Mice were treated orally with vancomycin daily for 10 days, vancomycin in a tapering dose for 42 days, fidaxomicin for 10 days, or saline. To assess colonization resistance, subsets of mice were challenged with 10 4 CFU of C. difficile or VRE at multiple time points during and after completion of treatment. The impact of the treatments on the microbiome was measured by cultures, real-time PCR for selected anaerobic bacteria, and deep sequencing. Vancomycin taper-treated mice developed alterations of the microbiota and disruption of colonization resistance that was persistent 18 days after treatment. In contrast, mice treated with a 10-day course of vancomycin exhibited recovery of the microbiota and of colonization resistance by 15 days after treatment, and fidaxomicin-treated mice maintained intact colonization resistance. These findings demonstrate that alteration of the indigenous microbiota responsible for colonization resistance to C. difficile and VRE persist during and after completion of tapering courses of vancomycin.

scholarly journals Pseudomonas aeruginosa PA14 Enhances the Efficacy of Norfloxacin against Staphylococcus aureus Newman Biofilms

2020 ◽  
Vol 202 (18) ◽  
Author(s):  
Giulia Orazi ◽  
Fabrice Jean-Pierre ◽  
George A. O’Toole
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Agents ◽  
Respiratory Infections ◽  
Multiple Infection ◽  
Bacterial Biofilms ◽  
Interspecies Interactions ◽  
Chronic Infections ◽  
Content Type

ABSTRACT The thick mucus within the airways of individuals with cystic fibrosis (CF) promotes frequent respiratory infections that are often polymicrobial. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most prevalent pathogens that cause CF pulmonary infections, and both are among the most common etiologic agents of chronic wound infections. Furthermore, the ability of P. aeruginosa and S. aureus to form biofilms promotes the establishment of chronic infections that are often difficult to eradicate using antimicrobial agents. In this study, we found that multiple LasR-regulated exoproducts of P. aeruginosa, including 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), siderophores, phenazines, and rhamnolipids, likely contribute to the ability of P. aeruginosa PA14 to shift S. aureus Newman norfloxacin susceptibility profiles. Here, we observe that exposure to P. aeruginosa exoproducts leads to an increase in intracellular norfloxacin accumulation by S. aureus. We previously showed that P. aeruginosa supernatant dissipates the S. aureus membrane potential, and furthermore, depletion of the S. aureus proton motive force recapitulates the effect of the P. aeruginosa PA14 supernatant on shifting norfloxacin sensitivity profiles of biofilm-grown S. aureus Newman. From these results, we hypothesize that exposure to P. aeruginosa PA14 exoproducts leads to increased uptake of the drug and/or an impaired ability of S. aureus Newman to efflux norfloxacin. Surprisingly, the effect observed here of P. aeruginosa PA14 exoproducts on S. aureus Newman susceptibility to norfloxacin seemed to be specific to these strains and this antibiotic. Our results illustrate that microbially derived products can alter the ability of antimicrobial agents to kill bacterial biofilms. IMPORTANCE Pseudomonas aeruginosa and Staphylococcus aureus are frequently coisolated from multiple infection sites, including the lungs of individuals with cystic fibrosis (CF) and nonhealing diabetic foot ulcers. Coinfection with P. aeruginosa and S. aureus has been shown to produce worse outcomes compared to infection with either organism alone. Furthermore, the ability of these pathogens to form biofilms enables them to cause persistent infection and withstand antimicrobial therapy. In this study, we found that P. aeruginosa-secreted products dramatically increase the ability of the antibiotic norfloxacin to kill S. aureus biofilms. Understanding how interspecies interactions alter the antibiotic susceptibility of bacterial biofilms may inform treatment decisions and inspire the development of new therapeutic strategies.

scholarly journals Physical activity levels among ovarian cancer survivors: a prospective longitudinal cohort study

2021 ◽  
pp. ijgc-2020-002107
Author(s):  
Tamara Jones ◽  
Carolina Sandler ◽  
Dimitrios Vagenas ◽  
Monika Janda ◽  
Andreas Obermair ◽  
...  
Keyword(s):  
Physical Activity ◽  
Ovarian Cancer ◽  
Stage Iv ◽  
Multiple Time ◽  
Activity Levels ◽  
Prospective Longitudinal Study ◽  
Physical Activity Advice ◽  
Physical Activity Levels ◽  
Multiple Time Points ◽  
Prospective Longitudinal

ObjectivePhysical activity following cancer diagnosis is associated with improved outcomes, including potential survival benefits, yet physical activity levels among common cancer types tend to decrease following diagnosis and remain low. Physical activity levels following diagnosis of less common cancers, such as ovarian cancer, are less known. The objectives of this study were to describe physical activity levels and to explore characteristics associated with physical activity levels in women with ovarian cancer from pre-diagnosis to 2 years post-diagnosis.MethodsAs part of a prospective longitudinal study, physical activity levels of women with ovarian cancer were assessed at multiple time points between pre-diagnosis and 2 years post-diagnosis. Physical activity levels and change in physical activity were described using metabolic equivalent task hours and minutes per week, and categorically (sedentary, insufficiently, or sufficiently active). Generalized Estimating Equations were used to explore whether participant characteristics were related to physical activity levels.ResultsA total of 110 women with ovarian cancer with a median age of 62 years (range 33–88) at diagnosis were included. 53–57% of the women were sufficiently active post-diagnosis, although average physical activity levels for the cohort were below recommended levels throughout the 2-year follow-up period (120–142.5min/week). A decrease or no change in post-diagnosis physical activity was reported by 44–60% of women compared with pre-diagnosis physical activity levels. Women diagnosed with stage IV disease, those earning a lower income, those receiving chemotherapy, and those currently smoking or working were more likely to report lower physical activity levels and had increased odds of being insufficiently active or sedentary.ConclusionsInterventions providing patients with appropriate physical activity advice and support for behavior change could potentially improve physical activity levels and health outcomes.

Sign in / Sign up

Export Citation Format

Share Document