bluuebunny/crossref_metadata_2025_split huggingface dataset:
The K186E Amino Acid Substitution in the Canine Influenza Virus H3N8 NS1 Protein Restores Its Ability To Inhibit Host Gene Expression
Authors: Nogales Aitor , Chauché Caroline , DeDiego Marta L. , Topham David J. , Parrish Colin R. , Murcia Pablo R. , Martínez-Sobrido Luis 
Published: August 2017

ABSTRACT
Canine influenza viruses (CIVs) are the causative agents of canine influenza, a contagious respiratory disease in dogs, and include the equine-origin H3N8 and the avian-origin H3N2 viruses. Influenza A virus (IAV) nonstructural protein 1 (NS1) is a virulence factor essential for counteracting the innate immune response. Here, we evaluated the ability of H3N8 CIV NS1 to inhibit host innate immune responses. We found that H3N8 CIV NS1 was able to efficiently counteract interferon (IFN) responses but was unable to block general gene expression in human or canine cells. Such ability was restored by a single amino acid substitution in position 186 (K186E) that resulted in NS1 binding to the 30-kDa subunit of the cleavage and polyadenylation specificity factor (CPSF30), a cellular protein involved in pre-mRNA processing. We also examined the frequency distribution of K186 and E186 among H3N8 CIVs and equine influenza viruses (EIVs), the ancestors of H3N8 CIV, and experimentally determined the impact of amino acid 186 in the ability of different CIV and EIV NS1s to inhibit general gene expression. In all cases, the presence of E186 was responsible for the control of host gene expression. In contrast, the NS1 protein of H3N2 CIV harbors E186 and blocks general gene expression in canine cells. Altogether, our results confirm previous studies on the strain-dependent ability of NS1 to block general gene expression. Moreover, the observed polymorphism on amino acid 186 between H3N8 and H3N2 CIVs might be the result of adaptive changes acquired during long-term circulation of avian-origin IAVs in mammals.

IMPORTANCE
Canine influenza is a respiratory disease of dogs caused by two CIV subtypes, the H3N8 and H3N2 viruses, of equine and avian origins, respectively. Influenza NS1 is the main viral factor responsible for the control of host innate immune responses, and changes in NS1 can play an important role in host adaptation. Here we assessed the ability of H3N8 CIV NS1 to inhibit host innate immune responses and gene expression. The H3N8 CIV NS1 did not block host gene expression, but this activity was restored by a single amino acid substitution (K186E), which was responsible for NS1 binding to the host factor CPSF30. In contrast, the H3N2 CIV NS1, which contains E186, blocks general gene expression. Our results suggest that the ability to block host gene expression is not required for influenza virus replication in mammals but might be important in the long-term adaptation of avian-origin influenza viruses to mammals.
PrP P102L and Nearby Lysine Mutations Promote Spontaneous
In Vitro
Formation of Transmissible Prions
Authors: Kraus Allison , Raymond Gregory J. , Race Brent , Campbell Katrina J. , Hughson Andrew G. , Anson Kelsie J. , Raymond Lynne D. , Caughey Byron 
Published: August 2017

ABSTRACT

Accumulation of fibrillar protein aggregates is a hallmark of many diseases. While numerous proteins form fibrils by prion-like seeded polymerization
in vitro
, only some are transmissible and pathogenic
in vivo
. To probe the structural features that confer transmissibility to prion protein (PrP) fibrils, we have analyzed synthetic PrP amyloids with or without the human prion disease-associated P102L mutation. The formation of infectious prions from PrP molecules
in vitro
has required cofactors and/or unphysiological denaturing conditions. Here, we demonstrate that, under physiologically compatible conditions without cofactors, the P102L mutation in recombinant hamster PrP promoted prion formation when seeded by minute amounts of scrapie prions
in vitro
. Surprisingly, combination of the P102L mutation with charge-neutralizing substitutions of four nearby lysines promoted spontaneous prion formation. When inoculated into hamsters, both of these types of synthetic prions initiated substantial accumulation of prion seeding activity and protease-resistant PrP without transmissible spongiform encephalopathy (TSE) clinical signs or notable glial activation. Our evidence suggests that PrP's centrally located proline and lysine residues act as conformational switches in the
in vitro
formation of transmissible PrP amyloids.

IMPORTANCE
Many diseases involve the damaging accumulation of specific misfolded proteins in thread-like aggregates. These threads (fibrils) are capable of growing on the ends by seeding the refolding and incorporation of the normal form of the given protein. In many cases such aggregates can be infectious and propagate like prions when transmitted from one individual host to another. Some transmitted aggregates can cause fatal disease, as with human iatrogenic prion diseases, while other aggregates appear to be relatively innocuous. The factors that distinguish infectious and pathogenic protein aggregates from more innocuous ones are poorly understood. Here we have compared the combined effects of prion seeding and mutations of prion protein (PrP) on the structure and transmission properties of synthetic PrP aggregates. Our results highlight the influence of specific sequence features in the normally unstructured region of PrP that influence the infectious and neuropathogenic properties of PrP-derived aggregates.
Overweight and obese children do not consult their general practitioner more often than normal weight children for musculoskeletal complaints during a 2-year follow-up
Authors: van Leeuwen Janneke , van Middelkoop Marienke , Paulis Winifred D , Bueving Herman J , Bindels Patrick J E , Koes Bart W 
Published: August 2017

BackgroundChildhood obesity is associated with self-reported musculoskeletal complaints, injuries and fractures. In the current study, we investigated the association between weight status of children and the frequency and type of musculoskeletal consultations at the general practitioner (GP) during a 2-year follow-up.MethodsData from a prospective longitudinal cohort study including children aged 2–18 years presenting in general practices in the Netherlands were used. Height and weight were measured at baseline, at 6-month, 1-year and 2-year follow-ups. Electronic medical files were used to collect information on the frequency and type of consultations at the GP during the 2-year follow-up period. Associations between weight status and frequency and type of GP consultations were calculated.ResultsOf the 617 included children, 111 (18%) were overweight or obese and 506 (82%) were non-overweight. Overweight children were significantly older (mean age in years (SD): 9.8 (3.6)vs7.8 (4.0), p=0.004). Overweight children consulted the GP in general significantly more frequent during the 2-year follow-up than non-overweight children (mean (SD): 7.3 (5.7)vs6.7 (5.4), OR 1.09, 95% CI 1.01 to 1.18). No significant difference was seen in the number of overweight and non-overweight children consulting their GP for musculoskeletal complaints (OR 1.20 (0.86 to 1.68)). Additionally, no significant difference between overweight and non-overweight children was seen for the number of consultations for further specified musculoskeletal disorders.ConclusionNo association was seen between childhood weight status and the frequency and type of musculoskeletal consultations at the GP during a 2-year follow-up.
Impact of child death on paediatric trainees
Authors: Hollingsworth Clare E , Wesley Carla , Huckridge Jaymie , Finn Gabrielle M , Griksaitis Michael J 
Published: August 2017

ObjectiveTo assess the prevalence of symptoms of acute stress reactions (ASR) and post-traumatic stress disorder (PTSD) in paediatric trainees following their involvement in child death.DesignA survey designed to identify trainees’ previous experiences of child death combined with questions to identify features of PTSD. Quantitative interpretation was used alongside a χ2 test. A p value of <0.05 was considered significant.Setting604 surveys were distributed across 13 UK health education deaneries.Participants303/604 (50%) of trainees completed the surveys.Results251/280 (90%) of trainees had been involved with the death of a child, although 190/284 (67%) had no training in child death. 118/248 (48%) of trainees were given a formal debrief session following their most recent experience. 203/251 (81%) of trainees reported one or more symptoms or behaviours that could contribute to a diagnosis of ASR/PTSD. 23/251 (9%) of trainees met the complete criteria for ASR and 13/251 (5%) for PTSD. Attending a formal debrief and reporting feelings of guilt were associated with an increase in diagnostic criteria for ASR/PTSD (p=0.036 and p<0.001, respectively).ConclusionsPaediatric trainees are at risk of developing ASR and PTSD following the death of a child. The feeling of guilt should be identified and acknowledged to allow prompt signposting to further support, including psychological assessment or intervention if required. Clear recommendations need to be made about the safety of debriefing sessions as, in keeping with existing evidence, our data suggest that debrief after the death of a child may be associated with the development of symptoms suggestive of ASR/PTSD.
Developing standards for the development of glaucoma virtual clinics using a modified Delphi approach
Authors: Kotecha Aachal , Longstaff Simon , Azuara-Blanco Augusto , Kirwan James F , Morgan James Edwards , Spencer Anne Fiona , Foster Paul J 
Published: August 2017

PurposeTo obtain consensus opinion for the development of a standards framework for the development and implementation of virtual clinics for glaucoma monitoring in the UK using a modified Delphi methodology.MethodsA modified Delphi technique was used that involved sampling members of the UK Glaucoma and Eire Society (UKEGS). The first round scored the strength of agreement to a series of standards statements using a 9-point Likert scale. The revised standards were subjected to a second round of scoring and free-text comment. The final standards were discussed and agreed by an expert panel consisting of seven glaucoma subspecialists from across the UK. A version of the standards was submitted to external stakeholders for a 3-month consultation.ResultsThere was a 44% response rate of UKEGS members to rounds 1 and 2, consisting largely of consultant ophthalmologists with a specialist interest in glaucoma. The final version of the standards document was validated by stakeholder consultation and contains four sections pertaining to the patient groups, testing methods, staffing requirements and governance structure of NHS secondary care glaucoma virtual clinic models.ConclusionsUse of a modified Delphi approach has provided consensus agreement for the standards required for the development of virtual clinics to monitor glaucoma in the UK. It is anticipated that this document will be useful as a guide for those implementing this model of service delivery.
Social capital, neighbourhood characteristics and utilisation of local public health services among domestic migrants in China: a cross-sectional study
Authors: Hou Zhiyuan , Lin Senlin , Zhang Donglan 
Published: August 2017

ObjectivesWe examined the association between structural social capital and public health services use, and explored the modifiable effect of neighbourhood factors on this association among domestic migrants in China.MethodsData were from a 2014 nationally representative cross-sectional sample of domestic migrants aged 15–59 years in China. Survey-weighted logistic regression models were applied to assess the association between structural social capital, measured by participation in social organisations and social activities, and use of public health services. Interaction terms between neighbourhood urban status, neighbourhood composition and social capital were further assessed in the models.ResultsMigrants who participated in social organisations were more likely to establish health records (OR 1.467, 95% CI 1.201 to 1.793) and receive health education information (OR 1.729, 95% CI 1.484 to 2.016) than those who did not. Participation in social activities was positively associated with establishing health records only in urban communities (OR 1.853, 95% CI 1.060 to 3.239), and it was positively linked to receiving health education information among those living with a higher percentage of local neighbours (OR 1.451, 95% CI 1.044 to 2.017).ConclusionsStructural social capital was related to an increased utilisation of local public health services among migrants. The findings of this study provided new evidence for the differential influences of social capital by neighbourhood characteristics in China, which suggested the importance to enhance social capital in rural/suburban communities and communities where the majority of the residents were migrants.
A novel income security intervention to address poverty in a primary care setting: a retrospective chart review
Authors: Jones Marcella K , Bloch Gary , Pinto Andrew D 
Published: August 2017

ObjectiveTo examine the development and implementation of a novel income security intervention in primary care.DesignA retrospective, descriptive chart review of all patients referred to the Income Security Heath Promotion service during the first year of the service (December 2013–December 2014).SettingA multisite interdisciplinary primary care organisation in inner city Toronto, Canada, serving over 40 000 patients.ParticipantsThe study population included 181 patients (53% female, mean age 48 years) who were referred to the Income Security Health Promotion service and engaged in care.InterventionThe Income Security Health Promotion service consists of a trained health promoter who provides a mixture of expert advice and case management to patients to improve income security. An advisory group, made up of physicians, social workers, a community engagement specialist and a clinical manager, supports the service.Outcome measuresSociodemographic information, health status, referral information and encounter details were collected from patient charts.ResultsEncounters focused on helping patients with increasing their income (77.4%), reducing their expenses (58.6%) and improving their financial literacy (26.5%). The health promoter provided an array of services to patients, including assistance with taxes, connecting to community services, budgeting and accessing free services. The service could be improved with more specific goal setting, better links to other members of the healthcare team and implementing routine follow-up with each patient after discharge.ConclusionsIncome Security Health Promotion is a novel service within primary care to assist vulnerable patients with a key social determinant of health. This study is a preliminary look at understanding the functioning of the service. Future research will examine the impact of the Income Security Health Promotion service on income security, financial literacy, engagement with health services and health outcomes.
Development and validation of clinical prediction models for mortality, functional outcome and cognitive impairment after stroke: a study protocol
Authors: Fahey Marion , Rudd Anthony , Béjot Yannick , Wolfe Charles , Douiri Abdel 
Published: August 2017

IntroductionStroke is a leading cause of adult disability and death worldwide. The neurological impairments associated with stroke prevent patients from performing basic daily activities and have enormous impact on families and caregivers. Practical and accurate tools to assist in predicting outcome after stroke at patient level can provide significant aid for patient management. Furthermore, prediction models of this kind can be useful for clinical research, health economics, policymaking and clinical decision support.Methods2869 patients with first-ever stroke from South London Stroke Register (SLSR) (1995–2004) will be included in the development cohort. We will use information captured after baseline to construct multilevel models and a Cox proportional hazard model to predict cognitive impairment, functional outcome and mortality up to 5 years after stroke. Repeated random subsampling validation (Monte Carlo cross-validation) will be evaluated in model development. Data from participants recruited to the stroke register (2005–2014) will be used for temporal validation of the models. Data from participants recruited to the Dijon Stroke Register (1985–2015) will be used for external validation. Discrimination, calibration and clinical utility of the models will be presented.EthicsPatients, or for patients who cannot consent their relatives, gave written informed consent to participate in stroke-related studies within the SLSR. The SLSR design was approved by the ethics committees of Guy’s and St Thomas’ NHS Foundation Trust, Kings College Hospital, Queens Square and Westminster Hospitals (London). The Dijon Stroke Registry was approved by the Comité National des Registres and the InVS and has authorisation of the Commission Nationale de l’Informatique et des Libertés.
Protocol for an economic evaluation of the randomised controlled trial of culprit lesion only PCI versus immediate multivessel PCI in acute myocardial infarction complicated by cardiogenic shock: CULPRIT-SHOCK trial
Authors: Quayyum Zahidul , Briggs Andrew , Robles-Zurita Jose , Oldroyd Keith , Zeymer Uwe , Desch Steffen , Waha Suzanne de , Thiele Holger 
Published: August 2017

IntroductionEmergency percutaneous coronary intervention (PCI) of the culprit lesion for patients with acute myocardial infarctions is an accepted practice. A majority of patients present with multivessel disease with additional relevant stenoses apart from the culprit lesion. In haemodynamically stable patients, there is increasing evidence from randomised trials to support the practice of immediate complete revascularisation. However, in the presence of cardiogenic shock, the optimal management strategy for additional non-culprit lesions is unknown. A multicentre randomised controlled trial, CULPRIT-SHOCK, is examining whether culprit vessel only PCI with potentially subsequent staged revascularisation is more effective than immediate multivessel PCI. This paper describes the intended economic evaluation of the trial.Methods and analysisThe economic evaluation will be conducted using a pre-trial decision model and within-trial analysis. The modelling-based analysis will provide expected costs and health outcomes, and incremental cost-effectiveness ratio over the lifetime for the cohort of patients included in the trial. The within-trial analysis will provide estimates of cost per life saved at 30 days and in 1 year, and estimates of health-related quality of life. Bootstrapping and cost-effectiveness acceptability curves will be used to address any uncertainty around these estimates. Different types of regression models within a generalised estimating equation framework will be used to examine how the total cost and quality-adjusted life years are explained by patients’ characteristics, revascularisation strategy, country and centre. The cost-effectiveness analysis will be from the perspective of each country’s national health services, where costs will be expressed in euros adjusted for purchasing power parity.Ethics and disseminationEthical approval for the study was granted by the local Ethics Committee at each recruiting centre. The economic evaluation analyses will be published in peer-reviewed journals of the concerned literature and communicated through the profiles of the authors atwww.twitter.comandwww.researchgate.net.Trial registration numberNCT01927549; Pre-results.
A prospective cohort study of hospital separations among people who inject drugs in Australia: 2008–2013
Authors: Nambiar Dhanya , Stoové Mark , Hickman Matthew , Dietze Paul 
Published: August 2017

ObjectivesInjecting drug use is a persistent behaviour that increases the risk of morbidities and mortality. We assessed the burden of hospital separations among people who inject drugs (PWID), the excess compared to the general population and characteristics of separations associated with frequent use.DesignProspective cohort study.SettingAll public and private hospitals in Victoria.Participants757 community-based PWID with hospital separations between January 2008 and June 2013 identified through record linkage, who contributed over 3729 person-years.Primary and secondary outcome measuresCounts, proportions and rates of hospital separations, descriptive administrative data including all diagnoses, comparison of separation rates to the general population, trend in separations and factors associated with frequent separations.ResultsThere were 2106 separations in the cohort. The most common principal diagnoses were related to mental and behavioural disorders (31%), but social circumstances influencing health was the most common group of diagnoses (61%) when all contributing diagnoses for each patient were considered. Separation rates were up to three times higher than in the age-matched population, and there was a 12% increase in separations every 6 months. Over a quarter (29%) of the cohort had frequent separations (defined as two or more separations in a calendar year), which were associated with mental health-related diagnoses, being discharged to locations other than a patient’s residence, having a medical as opposed to surgical intervention, seasonal patterns, relationship status and gender.ConclusionsMental health conditions and other characteristics associated with separations and frequent separations in particular, emphasise the importance of providing referrals to harm reduction, social services and mental health services at discharge in order to reduce excess hospital separations among PWID.
School staff perpetration of physical violence against students in Uganda: a multilevel analysis of risk factors
Authors: Merrill Katherine G , Knight Louise , Glynn Judith R , Allen Elizabeth , Naker Dipak , Devries Karen M 
Published: August 2017

ObjectiveTo conduct a multilevel analysis of risk factors for physical violence perpetration by school staff against Ugandan students.DesignMultilevel logistic regression analysis of cross-sectional survey data from 499 staff and 828 caregivers of students at 38 primary schools, collected in 2012 and 2014 during the Good Schools Study.SettingLuwero District, Uganda.Main outcome measurePast-week use of physical violence by school staff against students was measured using the International Society for the Prevention of Child Abuse and Neglect 'Child Abuse Screening Tool- Child International' and the WHO Multi-Country Study on Women’s Health and Domestic Violence against Women.ResultsOf 499 staff, 215 (43%) reported perpetration of physical violence against students in the past week. Individual risk factors associated with physical violence perpetration included being a teacher versus another type of staff member (p<0.001), approving of physical discipline practices (p<0.001), having children (p<0.01), being age 30–39 years (p<0.05), using physical violence against non-students (p<0.05) and being a victim of intimate partner violence (IPV) (p<0.05). We observed weak evidence (p=0.06) that male staff members who had been a victim of IPV showed higher odds of violence perpetration compared with male staff who had not been a victim of IPV. No evidence was observed for school- or community-level risk factors.ConclusionsPhysical violence perpetration from school staff is widespread, and interventions are needed to address this issue. Staff who have been victims of violence and who use violence against people other than students may benefit from additional interventions. Researchers should further investigate how school and community contexts influence staff’s physical violence usage, given a lack of associations observed in this study.