bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacterial Pathogen Emergence Requires More than Direct Contact with a Novel Passerine Host
Authors: Staley Molly , Hill Geoffrey E. , Josefson Chloe C. , Armbruster Jonathan W. , Bonneaud Camille 
Published: January 2018

ABSTRACT

While direct contact may sometimes be sufficient to allow a pathogen to jump into a new host species, in other cases, fortuitously adaptive mutations that arise in the original donor host are also necessary. Viruses have been the focus of most host shift studies, so less is known about the importance of ecological versus evolutionary processes to successful bacterial host shifts. Here we tested whether direct contact with the novel host was sufficient to enable the mid-1990s jump of the bacterium
Mycoplasma gallisepticum
from domestic poultry to house finches (
Haemorhous mexicanus
). We experimentally inoculated house finches with two genetically distinct
M. gallisepticum
strains obtained either from poultry (Rlow) or from house finches (HF1995) during an epizootic outbreak. All 15 house finches inoculated with HF1995 became infected, whereas Rlow successfully infected 12 of 15 (80%) inoculated house finches. Comparisons among infected birds showed that, relative to HF1995, Rlow achieved substantially lower bacterial loads in the host respiratory mucosa and was cleared faster. Furthermore, Rlow-infected finches were less likely to develop clinical symptoms than HF1995-infected birds and, when they did, displayed milder conjunctivitis. The lower infection success of Rlow relative to HF1995 was not, however, due to a heightened host antibody response to Rlow. Taken together, our results indicate that contact between infected poultry and house finches was not, by itself, sufficient to explain the jump of
M. gallisepticum
to house finches. Instead, mutations arising in the original poultry host would have been necessary for successful pathogen emergence in the novel finch host.
Vaccine-Linked Chemotherapy Improves Benznidazole Efficacy for Acute Chagas Disease
Authors: Jones Kathryn , Versteeg Leroy , Damania Ashish , Keegan Brian , Kendricks April , Pollet Jeroen , Cruz-Chan Julio Vladimir , Gusovsky Fabian , Hotez Peter J. , Bottazzi Maria Elena 
Published: January 2018

ABSTRACTChagas disease affects 6 to 7 million people worldwide, resulting in significant disease burdens and health care costs in countries of endemicity. Chemotherapeutic treatment is restricted to two parasiticidal drugs, benznidazole and nifurtimox. Both drugs are highly effective during acute disease but are only minimally effective during chronic disease and fraught with significant adverse clinical effects. In experimental models, vaccines can be used to induce parasite-specific balanced TH1/TH2 immune responses that effectively reduce parasite burdens and associated inflammation while minimizing adverse effects. The objective of this study was to determine the feasibility of vaccine-linked chemotherapy for reducing the amount of benznidazole required to significantly reduce blood and tissue parasite burdens. In this study, we were able to achieve a 4-fold reduction in the amount of benznidazole required to significantly reduce blood and tissue parasite burdens by combining the low-dose benznidazole with a recombinant vaccine candidate, Tc24 C4, formulated with a synthetic Toll-like 4 receptor agonist, E6020, in a squalene oil-in-water emulsion. Additionally, vaccination induced a robust parasite-specific balanced TH1/TH2 immune response. We concluded that vaccine-linked chemotherapy is a feasible option for advancement to clinical use for improving the tolerability and efficacy of benznidazole.
Activities of Thrombin and Factor Xa Are Essential for Replication of Hepatitis E Virus and Are Possibly Implicated in ORF1 Polyprotein Processing
Authors: Kanade Gayatri D. , Pingale Kunal D. , Karpe Yogesh A. 
Published: January 2018

ABSTRACT

Hepatitis E virus (HEV) is a clinically important positive-sense RNA virus. The ORF1 of HEV encodes a nonstructural polyprotein of 1,693 amino acids. It is not clear whether the ORF1 polyprotein (pORF1) is processed into distinct enzymatic domains. Many researchers have attempted to understand the mechanisms of pORF1 processing. However, these studies gave various results and could never convincingly establish the mechanism of pORF1 processing. In this study, we demonstrated the possible role of thrombin and factor Xa in pORF1 processing. We observed that the HEV pORF1 polyprotein bears conserved cleavage sites of thrombin and factor Xa. Using a reverse genetics approach, we demonstrated that an HEV replicon having mutations in the cleavage sites of either thrombin or factor Xa could not replicate efficiently in cell culture. Further, we demonstrated
in vitro
processing when we incubated recombinant pORF1 fragments with thrombin, and we observed the processing of pORF1 polyprotein. The treatment of a liver cell line with a serine protease inhibitor as well as small interfering RNA (siRNA) knockdown of thrombin and factor Xa resulted in significant reduction in the replication of HEV. Thrombin and factor Xa have been well studied for their roles in blood clotting. Both of these proteins are believed to be present in the active form in the blood plasma. Interestingly, in this report, we demonstrated the presence of biologically active thrombin and factor Xa in a liver cell line. The results suggest that factor Xa and thrombin are essential for the replication of HEV and may be involved in pORF1 polyprotein processing of HEV.

IMPORTANCE
Hepatitis E virus (HEV) causes a liver disorder called hepatitis in humans, which is mostly an acute and self-limiting infection in adults. A high mortality rate of about 30% is observed in HEV-infected pregnant women in developing countries. There is no convincing opinion about HEV ORF1 polyprotein processing owing to the variability of study results obtained so far. HEV pORF1 has cleavage sites for two host cellular serine proteases, thrombin and factor Xa, that are conserved among HEV genotypes. For the first time, this study demonstrated that thrombin and factor Xa cleavage sites on HEV pORF1 are obligatory for HEV replication. Intracellular biochemical activities of the said serine proteases are also essential for efficient HEV replication in cell culture and must be involved in pORF1 processing. This study sheds light on the presence and roles of clotting factors with respect to virus replication in the cells.
Mechanical stress potentiates the differentiation of periodontal ligament stem cells into keratocytes
Authors: Chen Jialin , Zhang Wei , Backman Ludvig J , Kelk Peyman , Danielson Patrik 
Published: January 2018

AimsTo explore the role of corneal-shaped static mechanical strain on the differentiation of human periodontal ligament stem cells (PDLSCs) into keratocytes and the possible synergistic effects of mechanics and inducing medium.MethodsPDLSCs were exposed to 3% static dome-shaped mechanical strain in a Flexcell Tension System for 3 days and 7 days. Keratocyte phenotype was determined by gene expression of keratocyte markers. Keratocyte differentiation (inducing) medium was introduced in the Flexcell system, either continuously or intermittently combined with mechanical stimulation. The synergistic effects of mechanics and inducing medium on keratocyte differentiation was evaluated by gene and protein expression of keratocyte markers. Finally, a multilamellar cell sheet was assembled by seeding PDLSCs on a collagen membrane and inducing keratocyte differentiation. The transparency of the cell sheet was assessed, and typical markers of native human corneal stroma were evaluated by immunofluorescence staining.ResultsDome-shaped mechanical stimulation promoted PDLSCs to differentiate into keratocytes, as shown by the upregulation of ALDH3A1, CD34, LUM, COL I and COL V. The expression of integrins were also upregulated after mechanical stimulation, including integrin alpha 1, alpha 2, beta 1 and non-muscle myosin II B. A synergistic effect of mechanics and inducing medium was found on keratocyte differentiation. The cell sheets were assembled under the treatment of mechanics and inducing medium simultaneously. The cell sheets were transparent, multilamellar and expressed typical markers of corneal stroma.ConclusionDome-shaped mechanical stimulation promotes differentiation of PDLSCs into keratocytes and has synergistic effects with inducing medium. Multilamellar cell sheets that resemble native human corneal stroma show potential for future clinical applications.
Risk factors for incidence of trachomatous scarring in a cohort of women in low endemic district
Authors: Karani Rabia , Wolle Meraf , Mkocha Harran , Muñoz Beatriz , West Sheila K 
Published: January 2018

Background/aimsTo determine the incidence of scarring in women in a trachoma low endemic district of rural Tanzania and to determine the effects of lifetime cooking fire exposure and markers of lower socioeconomic status on incidence of scarring in these women.MethodsA prospective cohort study was conducted over a 3.5-year period from 2013 to 2016 in 48 villages in Kongwa, Tanzania where trachoma at baseline was 5.2% in children. A random sample of 2966 women aged 15 and older who were at risk for incident scarring were eligible for follow-up. Data on demographic factors, cooking fire exposure and trachomatous scarring were gathered at baseline and follow-up. An index of lifetime exposure to cooking fire exposure was created and bivariate analysis, age-adjusted logistic regression and multivariable logistic models were used to look for associations of demographic factors and cooking fire exposure with incident trachomatous scarring.ResultsThe cumulative incidence of scarring was 7.1% or 2.0% per year. Incidence of scarring increased with age and exposure to markers of lower socioeconomic status. A multivariable logistic regression model adjusting for confounding factors did not find an association between lifetime cooking fire exposure and incidence of scarring (OR=0.92; 95% CI 0.68 to 1.24, P=0.58).ConclusionsThere was still incident scarring in women in Tanzania despite low rates of active trachoma. There was no association between exposure to cooking fires and incident scarring. More research is needed to understand the factors that contribute to new scarring in these women.
Binocular stereo acuity affects monocular three-dimensional shape perception in patients with strabismus
Authors: Sawamura Hiromasa , Gillebert Céline R , Todd James T , Orban Guy A 
Published: January 2018

Background/aimsTo evaluate the perception of three-dimensional (3D) shape in patients with strabismus and the contributions of stereopsis and monocular cues to this perception.MethodsTwenty-one patients with strabismus with and 20 without stereo acuity as well as 25 age-matched normal volunteers performed two tasks: (1) identifying the closest vertices of 3D shapes from monocular shading (3D-SfS), texture (3D-SfT) or motion cues (3D-SfM) and from binocular disparity (3D-SfD), (2) discriminating 1D elementary features of these cues.ResultsDiscrimination of the elementary features of luminance, texture and motion did not differ across groups. When the distances between reported and actual closest vertices were resolved into sagittal and frontoparallel plane components, sagittal components in 3D-SfS and frontoparallel components in 3D-SfT indicated larger errors in patients with strabismus without stereo acuity than in normal subjects. These patients could not discriminate one-dimensional elementary features of binocular disparity. Patients with strabismus with stereo acuity performed worse for both components of 3D-SfD and frontoparallel components of 3D-SfT compared with normal subjects. No differences were observed in the perception of 3D-SfM across groups. A comparison between normal subjects and patients with strabismus with normal stereopsis revealed no deficit in 3D shape perception from any cue.ConclusionsBinocular stereopsis is essential for fine perception of 3D shape, even when 3D shape is defined by monocular static cues. Interaction between these cues may occur in ventral occipitotemporal regions, where 3D-SfS, 3D-SfT and 3D-SfD are processed in the same or neighbouring cortical regions. Our findings demonstrate the perceptual benefit of binocular stereopsis in patients with strabismus.
Implementation of medical retina virtual clinics in a tertiary eye care referral centre
Authors: Kortuem Karsten , Fasler Katrin , Charnley Amanda , Khambati Hussain , Fasolo Sandro , Katz Menachem , Balaskas Konstantinos , Rajendram Ranjan , Hamilton Robin , Keane Pearse A , Sim Dawn A 
Published: January 2018

BackgroundThe increasing incidence of medical retinal diseases has created capacity issues across UK. In this study, we describe the implementation and outcomes of virtual medical retina clinics (VMRCs) at Moorfields Eye Hospital, South Division, London. It represents a promising solution to ensure that patients are seen and treated in a timely fashionMethodsFirst attendances in the VMRC (September 2016–May 2017) were included. It was open to non-urgent external referrals and to existing patients in a face-to-face clinic (F2FC). All patients received visual acuity testing, dilated fundus photography and optical coherence tomography scans. Grading was performed by consultants, fellows and allied healthcare professionals. Outcomes of these virtual consultations and reasons for F2FC referrals were assessed.ResultsA total number of 1729 patients were included (1543 were internal and 186 external referrals). The majority were diagnosed with diabetic retinopathy (75.1% of internal and 46.8% of external referrals). Of the internal referrals, 14.6% were discharged, 54.5% continued in VMRC and 30.9% were brought to a F2FC. Of the external referrals, 45.5% were discharged, 37.1% continued in VMRC and 17.4% were brought to a F2FC. The main reason for F2FC referrals was image quality (34.7%), followed by detection of potentially treatable disease (20.2%).ConclusionVMRC can be implemented successfully using existing resources within a hospital eye service. It may also serve as a first-line rapid-access clinic for low-risk referrals. This would enable medical retinal services to cope with increasing demand and efficiently allocate resources to those who require treatment.
Characteristic optical coherence tomography findings in patients with primary vitreoretinal lymphoma: a novel aid to early diagnosis
Authors: Barry Robert J , Tasiopoulou Anastasia , Murray Philip I , Patel Praveen J , Sagoo Mandeep S , Denniston Alastair K , Keane Pearse A 
Published: January 2018

BackgroundThe diagnosis of primary vitreoretinal lymphoma (PVRL) poses significant difficulties; presenting features are non-specific and confirmation usually necessitates invasive vitreoretinal biopsy. Diagnosis is often delayed, resulting in increased morbidity and mortality. Non-invasive imaging modalities such as spectral domain optical coherence tomography (SD-OCT) offer simple and rapid aids to diagnosis. We present characteristic SD-OCT images of patients with biopsy-positive PVRL and propose a number of typical features, which we believe are useful in identifying these lesions at an early stage.MethodsMedical records of all patients attending Moorfields Eye Hospital between April 2010 and April 2016 with biopsy-positive PVRL were reviewed. Pretreatment SD-OCT images were collected for all eyes and were reviewed independently by two researchers for features suggestive of PVRL.ResultsPretreatment SD-OCT images of 32 eyes of 22 patients with biopsy-proven PVRL were reviewed. Observed features included hyper-reflective subretinal infiltrates (17/32), hyper-reflective infiltration in inner retinal layers (6/32), retinal pigment epithelium (RPE) undulation (5/32), clumps of vitreous cells (5/32) and sub-RPE deposits (3/32). Of these, the hyper-reflective subretinal infiltrates have an appearance unique to PVRL, with features not seen in other diseases.ConclusionWe have identified a range of SD-OCT features, which we believe to be consistent with a diagnosis of PVRL. We propose that the observation of hyper-reflective subretinal infiltrates as described is highly suggestive of PVRL. This case series further demonstrates the utility of SD-OCT as a non-invasive and rapid aid to diagnosis, which may improve both visual outcomes and survival of patients with intraocular malignancies such as PVRL.
Serum lactate cut-offs asarisk stratification tool for in-hospital adverse outcomes in emergency department patients screened for suspected sepsis
Authors: Shetty Amith L , Thompson Kelly , Byth Karen , Macaskill Petra , Green Malcolm , Fullick Mary , Lander Harvey , Iredell Jonathan 
Published: January 2018

ObjectivesWe investigated specific lactate thresholds for adverse outcomes in patients presenting to emergency departments (EDs) with suspected sepsis identified based on the performance of a sepsis screening algorithm.Design and settingA standardised sepsis bundle was implemented across public hospitals in New South Wales, Australia, as a quality improvement initiative. A register of all adult ED presentations (≥18 years) meeting predefined criteria for sepsis was created, using a combination of data linkage and direct reporting from 97 participating sites.ParticipantsA total of 12 349 adult ED presentations with 8310 (67.3%) having serum lactate analysis on arrival. Analysis of outcomes was based on dataset for 12 349 subjects obtained through multiple imputation for missing data.InterventionsA sepsis management bundle including early antibiotic prescribing, fluid therapy and referral to intensive care unit (ICU) services was implemented.Outcome measuresA primary composite adverse event (AE) outcome of inhospital mortality (IHM) and/or prolonged ICU stay ≥72 hours (ICU 72 hours) was used for this study.ResultsThere was statistically significant increase both in the ORs of AE and IHM with each integer increase in serum lactate values. After adjusting for the presence of hypotension, the estimated ORs for the combined AE outcome were 2.71 (95% CI 2.05 to 3.57), 2.65 (95% CI 2.29 to 3.08), 3.10 (95% CI 2.71 to 3.53) and 3.89 (95% CI 3.36 to 4.50) for serum lactate levels at or above 1, 2, 3 and 4 mmol/L, respectively. The corresponding ORs for IHM were 2.93 (95% CI 2.08 to 4.13), 2.77 (95% CI 2.34 to 3.29), 3.26 (95% CI 2.80 to 3.80) and 4.01 (95% CI 3.40 to 4.73), respectively (all P<0.0001). More than 10% of patients with suspected sepsis and with serum lactate ≥2 mmol/L experienced a prolonged ICU stay or died in hospital.ConclusionsED sepsis screening algorithms intended to identify patient adverse outcomes should incorporate a serum lactate cut-off of ≥2 mmol/L as a threshold for the initiation of specific interventions and increased monitoring.
Process evaluation of the Data-driven Quality Improvement in Primary Care (DQIP) trial: quantitative examination of variation between practices in recruitment, implementation and effectiveness
Authors: Dreischulte Tobias , Grant Aileen , Hapca Adrian , Guthrie Bruce 
Published: January 2018

ObjectivesThe cluster randomised trial of the Data-driven Quality Improvement in Primary Care (DQIP) intervention showed that education, informatics and financial incentives for general medical practices to review patients with ongoing high-risk prescribing of non-steroidal anti-inflammatory drugs and antiplatelets reduced the primary end point of high-risk prescribing by 37%, where both ongoing and new high-risk prescribing were significantly reduced. This quantitative process evaluation examined practice factors associated with (1) participation in the DQIP trial, (2) review activity (extent and nature of documented reviews) and (3) practice level effectiveness (relative reductions in the primary end point).Setting/participantsInvited practices recruited (n=33) and not recruited (n=32) to the DQIP trial in Scotland, UK.Outcome measures(1) Characteristics of recruited versus non-recruited practices. Associations of (2) practice characteristics and ‘adoption’ (self-reported implementation work done by practices) with documented review activity and (3) of practice characteristics, DQIP adoption and review activity with effectiveness.Results(1) Recruited practices had lower performance in the quality and outcomes framework than those declining participation. (2) Not being an approved general practitioner training practice and higher self-reported adoption were significantly associated with higher review activity. (3) Effectiveness ranged from a relative increase in high-risk prescribing of 24.1% to a relative reduction of 77.2%. High-risk prescribing and DQIP adoption (but not documented review activity) were significantly associated with greater effectiveness in the final multivariate model, explaining 64.0% of variation in effectiveness.ConclusionsIntervention implementation and effectiveness of the DQIP intervention varied substantially between practices. Although the DQIP intervention primarily targeted review of ongoing high-risk prescribing, the finding that self-reported DQIP adoption was a stronger predictor of effectiveness than documented review activity supports that reducing initiation and/or re-initiation of high-risk prescribing is key to its effectiveness.Trial registration numberNCT01425502; Post-results.
Knowledge, opinions and compliance related to the 100% smoke-free law in hospitality venues in Kampala, Uganda: cross-sectional results from theKOMPLY Project
Authors: Gravely Shannon , Nyamurungi Kellen Namusisi , Kabwama Steven Ndugwa , Okello Gabriel , Robertson Lindsay , Heng Kelvin Khow Chuan , Ndikum Achiri Elvis , Oginni Adeniyi Samuel , Rusatira Jean Christophe , Kakoulides Socrates , Huffman Mark D , Yusuf Salim , Bianco Eduardo 
Published: January 2018

ObjectiveThis study evaluated knowledge, opinions and compliance related to Uganda’s comprehensive smoke-free law among hospitality venues in Kampala Uganda.DesignThis multi-method study presents cross-sectional findings of the extent of compliance in the early phase of Uganda’s comprehensive smoke-free law (2 months postimplementation; pre-enforcement).SettingBars, pubs and restaurants in Kampala Uganda.Procedure and participantsA two-stage stratified cluster sampling procedure was used to select hospitality sites stratified by all five divisions in Kampala. A total of 222 establishments were selected for the study. One hospitality representative from each of the visited sites agreed to take part in a face-to-face administered questionnaire. A subsample of hospitality venues were randomly selected for tobacco air quality testing (n=108). Data were collected between June and August 2016.Outcome measuresKnowledge and opinions of the smoke-free law among hospitality venue staff and owners. The level of compliance with the smoke-free law in hospitality venues through: (1) systematic objective observations (eg, active smoking, the presence of designated smoking areas, ‘no smoking’ signage) and (2) air quality by measuring the levels of tobacco particulate matter (PM2.5) in both indoor and outdoor venues.ResultsActive smoking was observed in 18% of venues, 31% had visible ‘no smoking’ signage and 47% had visible cigarette remains. Among interviewed respondents, 57% agreed that they had not been adequately informed about the smoke-free law; however, 90% were supportive of the ban. Nearly all respondents (97%) agreed that the law will protect workers’ health, but 32% believed that the law would cause financial losses at their establishment. Indoor PM2.5levels were hazardous (267.6 µg/m3) in venues that allowed smoking and moderate (29.6 µg/m3) in smoke-free establishments.ConclusionsIn the early phase of Uganda’s smoke-free law, the level of compliance in hospitality venues settings in Kampala was suboptimal. Civil society and the media have strong potential to inform and educate the hospitality industry and smokers of the benefits and requirements of the smoke-free law.