scholarly journals Gold Standard Cholera Diagnostics Are Tarnished by Lytic Bacteriophage and Antibiotics

2020 ◽  
Vol 58 (9) ◽  
Author(s):  
E. J. Nelson ◽  
J. A. Grembi ◽  
D. L. Chao ◽  
J. R. Andrews ◽  
L. Alexandrova ◽  
...  
Keyword(s):  
Pathogen Detection ◽  
Diarrheal Disease ◽  
Etiologic Agent ◽  
Lytic Bacteriophage ◽  
Negative Effects ◽  
First Line ◽  
Field Methods ◽  
Content Type ◽  
Stool Samples ◽  
Large Enrollment

ABSTRACT A fundamental, clinical, and scientific concern is how lytic bacteriophage, as well as antibiotics, impact diagnostic positivity. Cholera was chosen as a model disease to investigate this important question, because cholera outbreaks enable large enrollment, field methods are well established, and the predatory relationship between lytic bacteriophage and the etiologic agent Vibrio cholerae share commonalities across bacterial taxa. Patients with diarrheal disease were enrolled at two remote hospitals in Bangladesh. Diagnostic performance was assessed as a function of lytic bacteriophage detection and exposure to the first-line antibiotic azithromycin, detected in stool samples by mass spectrometry. Among diarrheal samples positive by nanoliter quantitative PCR (qPCR) for V. cholerae (n = 78/849), the odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by 89% (odds ratio [OR], 0.108; 95% confidence interval [CI], 0.002 to 0.872) and 87% (OR, 0.130; 95% CI, 0.022 to 0.649), respectively, when lytic bacteriophage were detected. The odds that an RDT or qPCR was positive was reduced by more than 99% (OR, 0.00; 95% CI, 0.00 to 0.28) and 89% (OR, 0.11; 95% CI, 0.03 to 0.44), respectively, when azithromycin was detected. Analysis of additional samples from South Sudan found similar phage effects on RDTs; antibiotics were not assayed. Cholera burden estimates may improve by accommodating for the negative effects of lytic bacteriophage and antibiotic exposure on diagnostic positivity. One accommodation is using bacteriophage detection as a proxy for pathogen detection. These findings have relevance for other diagnostic settings where bacterial pathogens are vulnerable to lytic bacteriophage predation.

scholarly journals Comparative Evaluation of Enteric Bacterial Culture and a Molecular Multiplex Syndromic Panel in Children with Acute Gastroenteritis

2019 ◽  
Vol 57 (6) ◽  
Author(s):  
Thomas Kellner ◽  
Brendon Parsons ◽  
Linda Chui ◽  
Byron M. Berenger ◽  
Jianling Xie ◽  
...  
Keyword(s):  
Pathogen Detection ◽  
Rectal Swab ◽  
Bacterial Pathogen ◽  
Positive Culture ◽  
Content Type ◽  
Negative Culture ◽  
Percent Agreement ◽  
Stool Samples ◽  
Culture Positive ◽  
Culture Negative

ABSTRACTAlthough enteric multianalyte syndromic panels are increasingly employed, direct comparisons with traditional methods and the inclusion of host phenotype correlations are limited. Luminex xTAG gastrointestinal pathogen panel (GPP) and culture results are highly concordant. However, phenotypic and microbiological confirmatory testing raises concerns regarding the accuracy of the GPP, especially forSalmonellaspp. A total of 3,089 children with gastroenteritis submitted stool specimens, rectal swab specimens, and clinical data. The primary outcome was bacterial pathogen detection agreement for shared targets between culture and the Luminex xTAG GPP. Secondary analyses included phenotype assessment, additional testing of GPP-negative/culture-positive isolate suspensions with the GPP, and in-house and commercial confirmatory nucleic acid testing of GPP-positive/culture-negative extracts. The overall percent agreement between technologies was >99% for each pathogen.Salmonellaspp. were detected in specimens from 64 participants: 12 (19%) by culture only, 9 (14%) by GPP only, and 43 (67%) by both techniques. Positive percent agreement forSalmonellaspp. was 78.2% (95% confidence interval [CI], 64.6%, 87.8%). Isolate suspensions from the 12 participants with specimens GPP negative/culture positive forSalmonellatested positive by GPP. Specimens GPP positive/culture negative forSalmonellaoriginated in younger children with less diarrhea and more vomiting. GPP-positive/culture-negative specimen extracts tested positive using additional assays for 0/2Campylobacter-positive specimens, 0/4Escherichia coliO157-positive specimens, 0/9Salmonella-positive specimens, and 2/3Shigella-positive specimens. For both rectal swab and stool samples, the median cycle threshold (CT) values, determined using quantitative PCR, were higher for GPP-negative/culture-positive samples than for GPP-positive/culture-positive samples (for rectal swabs, 36.9 [interquartile range {IQR}, 33.7, 37.1] versus 30.0 [IQR, 26.2, 33.2], respectively [P = 0.002]; for stool samples, 36.9 [IQR, 33.7, 37.1] versus 29.0 [IQR, 24.8, 30.8], respectively [P = 0.001]). GPP and culture have excellent overall agreement; however, for specific pathogens, GPP is less sensitive than culture and, notably, identifies samples false positive forSalmonellaspp.

scholarly journals Draft Genome Sequences of 13 Vibrio cholerae Strains from the Rio Grande Delta

2021 ◽  
Vol 10 (22) ◽  
Author(s):  
Jeffrey W. Turner ◽  
Jorge Duran-Gonzalez ◽  
David A. Laughlin ◽  
Daniel Unterweger ◽  
David Silva ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Diarrheal Disease ◽  
Draft Genome ◽  
Rio Grande ◽  
Etiologic Agent ◽  
Genome Sequences ◽  
Content Type

Vibrio cholerae is the etiologic agent of cholera, an acute and often fatal diarrheal disease that affects millions globally. We report the draft genome sequences of 13 non-O1/O139 V. cholerae strains isolated from the Rio Grande Delta, TX, USA. These genomes will aid future analyses of environmental serovars.

Sustainable Lean in psychiatry? Assessment through socio-technical principles

2016 ◽  
Vol 8 (1) ◽  
pp. 53-71 ◽  
Author(s):  
Pernilla Lindskog ◽  
Annika Vänje ◽  
Åsa Törnkvist ◽  
Jörgen Eklund
Keyword(s):  
Practical Implication ◽  
Research Area ◽  
Negative Effects ◽  
First Line ◽  
Senior Managers ◽  
Line Managers ◽  
Lean Implementation ◽  
Content Type ◽  
Technical Principles ◽  
Power And Authority

Purpose – This paper aims to identify conditions affecting sustainability of Lean implementations in Swedish psychiatric healthcare, from a socio-technical perspective. Design/methodology/approach – Longitudinal focus group interviews were conducted with 24 first-line managers within Swedish psychiatric healthcare. The analysis was made using Cherns’ ten socio-technical principles and a framework for sustainable development work in healthcare. Findings – The most critical socio-technical principles for a sustainable Lean implementation were boundary location; power and authority; and compatibility. At hospital level, socio-technical principles were inhibited by the weak ownership of the Lean implementation. However, strong ownership at division level meant the same principles were supported. Unclear goals made follow-ups difficult which had negative effects on the learning processes in the Lean implementation. The role and responsibility of first-line managers were unclear in that they perceived they lacked power and authority resulting in negative effects on the participation – an important sustainability concept. Originality/value – Empirically based papers assessing Lean implementations in psychiatry are rare. This study is a contribution to the research area of sustainable Lean implementations in healthcare. The practical implication of this study is that decision makers, senior managers, first-line managers and psychiatrists can be supported in reaching sustainable implementations of Lean.

scholarly journals Evidence of a Dominant Lineage of Vibrio cholerae-Specific Lytic Bacteriophages Shed by Cholera Patients over a 10-Year Period in Dhaka, Bangladesh

mBio ◽  
2011 ◽  
Vol 2 (1) ◽  
Author(s):  
Kimberley D. Seed ◽  
Kip L. Bodi ◽  
Andrew M. Kropinski ◽  
Hans-Wolfgang Ackermann ◽  
Stephen B. Calderwood ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Diarrheal Disease ◽  
Molecular Genetic ◽  
Diarrhoeal Disease ◽  
Comparative Sequence Analysis ◽  
Open Reading Frames ◽  
Surveillance Period ◽  
Content Type ◽  
Stool Samples ◽  
High Level

ABSTRACT Lytic bacteriophages are hypothesized to contribute to the seasonality and duration of cholera epidemics in Bangladesh. However, the bacteriophages contributing to this phenomenon have yet to be characterized at a molecular genetic level. In this study, we isolated and sequenced the genomes of 15 bacteriophages from stool samples from cholera patients spanning a 10-year surveillance period in Dhaka, Bangladesh. Our results indicate that a single novel bacteriophage type, designated ICP1 (for the International Centre for Diarrhoeal Disease Research, Bangladesh cholera phage 1 ) is present in all stool samples from cholera patients, while two other bacteriophage types, one novel (ICP2) and one T7-like (ICP3), are transient. ICP1 is a member of the Myoviridae family and has a 126-kilobase genome comprising 230 open reading frames. Comparative sequence analysis of ICP1 and related isolates from this time period indicates a high level of genetic conservation. The ubiquitous presence of ICP1 in cholera patients and the finding that the O1 antigen of lipopolysaccharide (LPS) serves as the ICP1 receptor suggest that ICP1 is extremely well adapted to predation of human-pathogenic V. cholerae O1. IMPORTANCE The severe diarrheal disease cholera is caused by the bacterium Vibrio cholerae, which can be transmitted to humans from the aquatic environment. Factors that affect V. cholerae in the environment can impact the occurrence of cholera outbreaks; one of these factors is thought to be the presence of bacterial viruses, or bacteriophages. Bacteriophages that prey on V. cholerae in the environment, and potentially in humans, have not been extensively genetically characterized. Here, we isolated and sequenced the genomes of bacteriophages from cholera patient stool samples collected over a 10-year period in Dhaka, Bangladesh, a region that suffers from regular cholera outbreaks. We describe a unique bacteriophage present in all samples, infer its evolution by sequencing multiple isolates from different patients over time, and identify the host receptor that shows that the bacteriophage specifically predates the serogroup of V. cholerae responsible for the majority of disease occurrences.

scholarly journals Gold-standard diagnostics are tarnished by lytic bacteriophage

2020 ◽  
Author(s):  
E.J. Nelson ◽  
J.A. Grembi ◽  
D.L. Chao ◽  
J.R. Andrews ◽  
L. Alexandrova ◽  
...  
Keyword(s):  
Diagnostic Test ◽  
Rapid Diagnostic Test ◽  
Gold Standard ◽  
Diagnostic Performance ◽  
Diarrheal Disease ◽  
Current Approach ◽  
Lytic Bacteriophage ◽  
Antibiotic Exposure ◽  
First Line ◽  
Negative Effect

ABSTRACTBackgroundA fundamental clinical and scientific concern is how lytic bacteriophage, as well as antibiotics, impact diagnostic positivity.MethodsCholera was chosen as a model disease to investigate this important question. Patients with diarrheal disease were enrolled at two remote hospitals in Bangladesh. Diagnostic performance was assessed as a function of lytic bacteriophage detection, as well as exposure to the first-line antibiotic azithromycin detected by mass spectrometry.ResultsAmong diarrheal samples positive by nanoliter quantitative PCR for Vibrio cholerae (n=78/849), the odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by 89% (OR 0.108; 95%CI 0.002-0.872) and 87% (OR 0.130; 95%CI 0.022-0.649) when lytic bacteriophage were detected, respectively. The odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by more than 99% (OR 0.00; 95% CI: 0.00-0.28) and 89% (OR 0.11; 95% CI: 0.03-0.44) when azithromycin was detected, respectively.ConclusionsEstimations of cholera burden may improve by accommodating for the negative effect of antimicrobial exposure on diagnostic positivity. Furthermore, the findings herein challenge our current approach to interpreting and developing bacterial diagnostics given variable rates of lytic bacteriophage and antibiotic exposure.

The More Control, the Better?

2014 ◽  
Vol 26 (2) ◽  
pp. 81-91 ◽  
Author(s):  
Jeeyun Oh ◽  
Mun-Young Chung ◽  
Sangyong Han
Keyword(s):  
Mixed Design ◽  
Negative Effects ◽  
Story Structure ◽  
Content Type ◽  
High User ◽  
User Control ◽  
Rigorous Research ◽  
Control Versus ◽  
The Media ◽  
The Impact

Despite of the popularity of interactive movie trailers, rigorous research on one of the most apparent features of these interfaces – the level of user control – has been scarce. This study explored the effects of user control on users’ immersion and enjoyment of the movie trailers, moderated by the content type. We conducted a 2 (high user control versus low user control) × 2 (drama film trailer versus documentary film trailer) mixed-design factorial experiment. The results showed that the level of user control over movie trailer interfaces decreased users’ immersion when the trailer had an element of traditional story structure, such as a drama film trailer. Participants in the high user control condition answered that they were less fascinated with, absorbed in, focused on, mentally involved with, and emotionally affected by the movie trailer than participants in the low user control condition only with the drama movie trailer. The negative effects of user control on the level of immersion for the drama trailer translated into users’ enjoyment. The impact of user control over interfaces on immersion and enjoyment varies depending on the nature of the media content, which suggests a possible trade-off between the level of user control and entertainment outcomes.

Overcoming counter-knowledge through telemedicine communication technologies

2017 ◽  
Vol 31 (7/8) ◽  
pp. 730-745 ◽  
Author(s):  
Jorge Cegarra-Sanchez ◽  
Juan-Gabriel Cegarra-Navarro ◽  
Anthony Wensley ◽  
Jose Diaz Manzano
Keyword(s):  
Learning Process ◽  
Design Methodology ◽  
Communication Technologies ◽  
Regional Hospital ◽  
Potential Contribution ◽  
Exploration And Exploitation ◽  
Negative Effects ◽  
Content Type

Purpose Knowledge acquired from sources of unverified information such as gossip, partial truths or lies, in this paper it is termed as “counter-knowledge.” The purpose of this paper is to explore this topic through an exploration of the links between a Hospital-in-the-Home Units (HHUs) learning process (LP), counter-knowledge, and the utilization of communication technologies. The following two questions are addressed: Does the reduction of counter-knowledge result in the utilization of communication technologies? Does the development of counter-knowledge hinder the LP? Design/methodology/approach This paper examines the relevance of communication technologies to the exploration and exploitation of knowledge for 252 patients of a (HHU) within a Spanish regional hospital. The data collected was analyzed using the PLS-Graph. Findings To HHU managers, this study offers a set of guidelines to assist in their gaining an understanding of the role of counter-knowledge in organizational LPs and the potential contribution of communication technologies. Our findings support the proposition that the negative effects of counter-knowledge can be mitigated by using communication technologies. Originality/value It is argued in this paper that counter-knowledge may play a variety of different roles in the implementation of LPs. Specifically, the assignment of communication technologies to homecare units has given them the means to filter counter-knowledge and prevent users from any possible problems caused by such counter-knowledge.

scholarly journals Spo0A Suppresses sin Locus Expression in Clostridioides difficile

mSphere ◽  
2020 ◽  
Vol 5 (6) ◽  
Author(s):  
Babita Adhikari Dhungel ◽  
Revathi Govind
Keyword(s):  
Diarrheal Disease ◽  
Toxin Production ◽  
The United States ◽  
Upstream Region ◽  
Pcr Analysis ◽  
Bacterial Cells ◽  
Master Regulator ◽  
Content Type ◽  
Clostridioides Difficile

ABSTRACT Clostridioides difficile is the leading cause of nosocomial infection and is the causative agent of antibiotic-associated diarrhea. The severity of the disease is directly associated with toxin production, and spores are responsible for the transmission and persistence of the organism. Previously, we characterized sin locus regulators SinR and SinR′ (we renamed it SinI), where SinR is the regulator of toxin production and sporulation. The SinI regulator acts as its antagonist. In Bacillus subtilis, Spo0A, the master regulator of sporulation, controls SinR by regulating the expression of its antagonist, sinI. However, the role of Spo0A in the expression of sinR and sinI in C. difficile had not yet been reported. In this study, we tested spo0A mutants in three different C. difficile strains, R20291, UK1, and JIR8094, to understand the role of Spo0A in sin locus expression. Western blot analysis revealed that spo0A mutants had increased SinR levels. Quantitative reverse transcription-PCR (qRT-PCR) analysis of its expression further supported these data. By carrying out genetic and biochemical assays, we show that Spo0A can bind to the upstream region of this locus to regulates its expression. This study provides vital information that Spo0A regulates the sin locus, which controls critical pathogenic traits such as sporulation, toxin production, and motility in C. difficile. IMPORTANCE Clostridioides difficile is the leading cause of antibiotic-associated diarrheal disease in the United States. During infection, C. difficile spores germinate, and the vegetative bacterial cells produce toxins that damage host tissue. In C. difficile, the sin locus is known to regulate both sporulation and toxin production. In this study, we show that Spo0A, the master regulator of sporulation, controls sin locus expression. Results from our study suggest that Spo0A directly regulates the expression of this locus by binding to its upstream DNA region. This observation adds new detail to the gene regulatory network that connects sporulation and toxin production in this pathogen.

scholarly journals Differential Response of the Human Renal Proximal Tubular Epithelial Cell Line HK-2 to Shiga Toxin Types 1 and 2

2011 ◽  
Vol 79 (9) ◽  
pp. 3527-3540 ◽  
Author(s):  
Erin K. Lentz ◽  
Dinorah Leyva-Illades ◽  
Moo-Seung Lee ◽  
Rama P. Cherla ◽  
Vernon L. Tesh
Keyword(s):  
Epithelial Cell ◽  
Cell Line ◽  
Shiga Toxin ◽  
Renal Damage ◽  
Diarrheal Disease ◽  
Shigella Dysenteriae ◽  
Parp Cleavage ◽  
Epithelial Cell Line ◽  
Cytotoxic Action ◽  
Content Type

ABSTRACTShiga toxins (Stxs) are expressed by the enteric pathogensShigella dysenteriaeserotype 1 and certain serotypes ofEscherichia coli. Stx-producing bacteria cause bloody diarrhea with the potential to progress to acute renal failure. Stxs are potent protein synthesis inhibitors and are the primary virulence factors responsible for renal damage that may follow diarrheal disease. We explored the use of the immortalized human proximal tubule epithelial cell line HK-2 as anin vitromodel of Stx-induced renal damage. We showed that these cells express abundant membrane Gb3and are differentially susceptible to the cytotoxic action of Stxs, being more sensitive to Shiga toxin type 1 (Stx1) than to Stx2. At early time points (24 h), HK-2 cells were significantly more sensitive to Stxs than Vero cells; however, by 72 h, Vero cell monolayers were completely destroyed while some HK-2 cells survived toxin challenge, suggesting that a subpopulation of HK-2 cells are relatively toxin resistant. Fluorescently labeled Stx1 B subunits localized to both lysosomal and endoplasmic reticulum (ER) compartments in HK-2 cells, suggesting that differences in intracellular trafficking may play a role in susceptibility to Stx-mediated cytotoxicity. Although proinflammatory cytokines were not upregulated by toxin challenge, Stx2 selectively induced the expression of two chemokines, macrophage inflammatory protein-1α (MIP-1α) and MIP-1β. Stx1 and Stx2 differentially activated components of the ER stress response in HK-2 cells. Finally, we demonstrated significant poly(ADP-ribose) polymerase (PARP) cleavage after exposure to Stx1 or Stx2. However, procaspase 3 cleavage was undetectable, suggesting that HK-2 cells may undergo apoptosis in response to Stxs in a caspase 3-independent manner.

Social capital and national innovation system: a cross-country analysis

2014 ◽  
Vol 21 (4) ◽  
pp. 453-475 ◽  
Author(s):  
Sepehr Ghazinoory ◽  
Ali Bitaab ◽  
Ardeshir Lohrasbi
Keyword(s):  
Social Capital ◽  
National Level ◽  
Innovation System ◽  
Negative Effects ◽  
Content Type ◽  
Research Findings ◽  
Different Dimensions ◽  
The Impact ◽  
Positive Effect

Purpose – In the last two decades, researchers have paid much attention to the role of cultural values on economic and social development. In particular, the crucial role of different aspects of culture on the development of innovation has been stressed in the literature. Consequently, it is vital to understand how social capital, as a core cultural value, affects the innovation process and the innovative performance at the national level. However, to date, the impact of different dimensions of social capital and innovation has not been properly portrayed or explained. Thus, the purpose of this paper is to investigate the influence of four different dimensions of social capital (institutional and interpersonal, associational life and norms) on two of the main functions of national innovation system (NIS) (entrepreneurship and knowledge creation) based on over 50,000 observations in 34 countries. Design/methodology/approach – In this regard, national-level data from the World Values Survey database was employed to quantify social capital. Entrepreneurship is, in turn, assumed to consist of three sub-indexes and 14 indicators based on the Global Entrepreneurship Index. Knowledge creation is also measured through US Patent Office applications. Also, exploratory factor analysis and structural equation modeling approach were used to build the measurement model and investigate the impact that each factor of social capital had on entrepreneurship and knowledge application, respectively. Measurement and structural models were built and their reliability and validity were tested using various fit indices. Research findings suggest the strong positive effect of institutional trust and networking on entrepreneurship. Also, interpersonal trust and networks were shown to have high influence on knowledge development at the national level. Norms appear to have naïve to medium negative effects on both functions. Findings – Research findings suggest the strong positive effect of institutional trust and networking on entrepreneurship. Also, interpersonal trust and networks were shown to have high influence on knowledge development at the national level. Norms appear to have naïve to medium negative effects on both functions. Originality/value – However, to date, the impact of different dimensions of social capital and innovation has not been properly portrayed or explained.

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