bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mildly Acidic pH Triggers an Irreversible Conformational Change in the Fusion Domain of Herpes Simplex Virus 1 Glycoprotein B and Inactivation of Viral Entry
Authors: Weed Darin J. , Pritchard Suzanne M. , Gonzalez Floricel , Aguilar Hector C. , Nicola Anthony V. 
Published: December 2016

ABSTRACT
Herpes simplex virus (HSV) entry into a subset of cells requires endocytosis and endosomal low pH. Preexposure of isolated virions to mildly acidic pH of 5 to 6 partially inactivates HSV infectivity in an irreversible manner. Acid inactivation is a hallmark of viruses that enter via low-pH pathways; this occurs by pretriggering conformational changes essential for fusion. The target and mechanism(s) of low-pH inactivation of HSV are unclear. Here, low-pH-treated HSV-1 was defective in fusion activity and yet retained normal levels of attachment to cell surface heparan sulfate and binding to nectin-1 receptor. Low-pH-triggered conformational changes in gB reported to date are reversible, despite irreversible low-pH inactivation. gB conformational changes and their reversibility were measured by antigenic analysis with a panel of monoclonal antibodies and by detecting changes in oligomeric conformation. Three-hour treatment of HSV-1 virions with pH 5 or multiple sequential treatments at pH 5 followed by neutral pH caused an irreversible >2.5 log infectivity reduction. While changes in several gB antigenic sites were reversible, alteration of the H126 epitope was irreversible. gB oligomeric conformational change remained reversible under all conditions tested. Altogether, our results reveal that oligomeric alterations and fusion domain changes represent distinct conformational changes in gB, and the latter correlates with irreversible low-pH inactivation of HSV. We propose that conformational change in the gB fusion domain is important for activation of membrane fusion during viral entry and that in the absence of a host target membrane, this change results in irreversible inactivation of virions.

IMPORTANCE
HSV-1 is an important pathogen with a high seroprevalence throughout the human population. HSV infects cells via multiple pathways, including a low-pH route into epithelial cells, the primary portal into the host. HSV is inactivated by low-pH preexposure, and gB, a class III fusion protein, undergoes reversible conformational changes in response to low-pH exposure. Here, we show that low-pH inactivation of HSV is irreversible and due to a defect in virion fusion activity. We identified an irreversible change in the fusion domain of gB following multiple sequential low-pH exposures or following prolonged low-pH treatment. This change appears to be separable from the alteration in gB quaternary structure. Together, the results are consistent with a model by which low pH can have an activating or inactivating effect on HSV depending on the presence of a target membrane.
A systematic review on the effect of the organisation of hospital discharge on patient health outcomes
Authors: Couturier Bérengère , Carrat Fabrice , Hejblum Gilles 
Published: December 2016

ObjectiveThe transition from hospital to home represents a key step in the management of patients and several problems related to this transition may arise, with potential adverse effects on patient health after discharge. The purpose of our study was to explore the association between components of the hospital discharge process including subsequent continuity of care and patient outcomes in the post-discharge period.DesignSystematic review of observational and interventional studies.SettingWe conducted a combined search in the Medline and Web of Science databases. Additional studies were identified by screening the bibliographies of the included studies. The data collection process was conducted using a standardised predefined grid that included quality criteria.ParticipantsA standard patient population returning home after hospitalisation.Primary and secondary outcomesAdverse health outcomes occurring after hospital discharge.ResultsIn the 20 studies fulfilling our eligibility criteria, the main discharge-process components explored were: discharge summary (n=2), discharge instructions (n=2), drug-related problems at discharge (n=4), transition from hospital to home (n=5) and continuity of care after hospital discharge (n=7). The major subsequent patient health outcomes measured were: rehospitalisations (n=18), emergency department visits (n=8) and mortality (n=5). Eight of the 18 studies exploring rehospitalisations and two of the eight studies examining emergency department visits reported at least one significant association between the discharge process and these outcomes. None of the studies investigating patient mortality reported any significant such associations between the discharge process and these outcomes.ConclusionsIrrespective of the component of the discharge process explored, the outcome considered (composite or not), the sample size and the study design, no consistent statistical association between hospital discharge and patient health outcome was identified. This systematic review highlights a wide heterogeneity between studies, especially in terms of the component(s) of the hospital discharge process investigated, study designs, outcomes and follow-up durations.
Clinical practitioners’ views on the management of patients with medically unexplained physical symptoms (MUPS): a qualitative study
Authors: Brownell A Keith W , Atkins Chloe , Whiteley Andrea , Woollard Robert F , Kornelsen Jude 
Published: December 2016

ObjectivesBy identifying strategies that practicing physicians use in managing patients with medically unexplained physical symptoms (MUPS), we present an interim practical management guide (IPMG) that clinical practitioners may find useful in their clinical practices and that may help guide future research.DesignA qualitative research study based on interview data from practicing physicians with experience in dealing with MUPS and known to the physician members of the research team. A parallel exploration of patient experiences was carried out simultaneously and is reported elsewhere.Setting2 urban centres in 2 different Canadian provinces in a healthcare system where family physicians provide the majority of primary care and self-referral to specialists rarely occurs.ParticipantsThe physician members of the research team invited practicing family and specialty physicians to participate in the study.ResultsWe characterise the care of patients with MUPS in terms of a 4-part framework: (1) the challenge of diagnosis; (2) the challenge of management/treatment; (3) the importance of communication and (4) the importance of the therapeutic relationship.ConclusionsOn the basis of the details in the different parts of the framework, we propose an IPMG that practitioners may find useful to facilitate the clinical care of patients with MUPS. The guide can be readily implemented into the practice of any physician who cares for patients with MUPS.
Nairobi Newborn Study: a protocol for an observational study to estimate the gaps in provision and quality of inpatient newborn care in Nairobi City County, Kenya
Authors: Murphy Georgina A V , Gathara David , Aluvaala Jalemba , Mwachiro Jacintah , Abuya Nancy , Ouma Paul , Snow Robert W , English Mike 
Published: December 2016

IntroductionProgress has been made in Kenya towards reducing child mortality as part of efforts aligned with the fourth Millennium Development Goal. However, little advancement has been made in reducing mortality among newborns, which now accounts for 45% of all child deaths. The frequently unanticipated nature of neonatal illness, its severity and the high dependency of sick newborns on skilled care make the provision of inpatient hospital services one key component of strategies to improve newborn survival.Methods and analysesThis project aims to assess the availability and quality of inpatient newborn care in hospitals in Nairobi City County across the public, private and not-for-profit sectors and align this to the estimated need for such services, providing a description of the quantity and quality gaps between capacity and demand. The population level burden of disease will be estimated using morbidity incidence estimates from a literature review applied to subcounty estimates of population-adjusted births, providing a spatially disaggregated estimate of need within the county. This will be followed by a survey of neonatal services across all health facilities providing 24/7 inpatient newborn care in the county. The survey will include: a retrospective audit of admission registers to estimate the usage of facilities and case-mix of patients; a structural assessment of facilities to gain insight into capacity; a questionnaire to nursing staff focusing on the process of delivering key obstetric and neonatal interventions; and a retrospective case audit to assess adherence to guidelines by clinicians.Ethics and disseminationThis study has been approved by the Kenya Medical Research Institute Scientific and Ethics Review Unit (SSC protocol No.2999). Results will be disseminated: to participating facilities through individualised reports and a joint workshop; to local and national stakeholders through meetings and a summary report; and to the international community through peer-review publication and international meetings.
Burden of multimorbidity in relation to age, gender and immigrant status: a cross-sectional study based on administrative data
Authors: Lenzi Jacopo , Avaldi Vera Maria , Rucci Paola , Pieri Giulia , Fantini Maria Pia 
Published: December 2016

ObjectivesMany studies have investigated multimorbidity, whose prevalence varies according to settings and data sources. However, few studies on this topic have been conducted in Italy, a country with universal healthcare and one of the most aged populations in the world. The aim of this study was to estimate the prevalence of multimorbidity in a Northern Italian region, to investigate its distribution by age, gender and citizenship and to analyse the correlations of diseases.DesignCross-sectional study based on administrative data.SettingEmilia-Romagna, an Italian region with ∼4.4 million inhabitants, of which almost one-fourth are aged ≥65 years.ParticipantsAll adults residing in Emilia-Romagna on 31 December 2012. Hospitalisations, drug prescriptions and contacts with community mental health services from 2003 to 2012 were traced to identify the presence of 17 physical and 9 mental health disorders.Primary and secondary outcome measuresDescriptive analysis of differences in the prevalence of multimorbidity in relation to age, gender and citizenship. The correlations of diseases were analysed using exploratory factor analysis.ResultsThe study population included 622 026 men and 751 011women, with a mean age of 66.4 years. Patients with multimorbidity were 33.5% in 75 years and >60% among patients aged ≥90 years; among patients aged ≥65 years, the proportion of multimorbidity was 39.9%. After standardisation by age and gender, multimorbidity was significantly more frequent among Italian citizens than among immigrants. Factor analysis identified 5 multimorbidity patterns: (1) psychiatric disorders, (2) cardiovascular, renal, pulmonary and cerebrovascular diseases, (3) neurological diseases, (4) liver diseases, AIDS/HIV and substance abuse and (5) tumours.ConclusionsMultimorbidity was highly prevalent in Emilia-Romagna and strongly associated with age. This finding highlights the need for healthcare providers to adopt individualised care plans and ensure continuity of care.
Surgical versus conservative treatment for lumbar disc herniation: a prospective cohort study
Authors: Gugliotta Marinella , da Costa Bruno R , Dabis Essam , Theiler Robert , Jüni Peter , Reichenbach Stephan , Landolt Hans , Hasler Paul 
Published: December 2016

ObjectivesEvidence comparing the effectiveness of surgical and conservative treatment of symptomatic lumbar disc herniation is controversial. We sought to compare short-term and long-term effectiveness of surgical and conservative treatment in sciatica symptom severity and quality of life in patients with lumbar disc herniation in a routine clinical setting.MethodsA prospective cohort study of a routine clinical practice registry consisting of 370 patients. Outcome measures were the North American Spine Society questionnaire and the 36-Item Short-Form Health Survey to assess patient-reported back pain, physical function, neurogenic symptoms and quality of life. Primary outcomes were back pain at 6 and 12 weeks. Standard open discectomy was assessed versus conservative interventions at 6, 12, 52 and 104 weeks. We filled in missing outcome variable values with multiple imputation, accounted for repeated measures within patients with mixed-effects models and adjusted baseline group differences in relevant prognostic indicators by inverse probability of treatment weighting.ResultsSurgical treatment patients reported less back pain at 6 weeks than those receiving conservative therapy (−0.97; 95% CI −1.89 to −0.09), were more likely to report ≥50% decrease in back pain symptoms from baseline to 6 weeks (48% vs 17%, risk difference: 0.34; 95% CI 0.16 to 0.47) and reported less physical function disability at 52 weeks (−3.7; 95% CI −7.4 to −0.1). The other assessments showed minimal between-group differences with CIs, including the null effect.ConclusionsCompared with conservative therapy, surgical treatment provided faster relief from back pain symptoms in patients with lumbar disc herniation, but did not show a benefit over conservative treatment in midterm and long-term follow-up.
Estimating change in cardiovascular disease and diabetes burdens due to dietary and metabolic factors in Korea 1998–2011: a comparative risk assessment analysis
Authors: Cho Yoonsu , Cudhea Frederick , Park Ju-Hyun , Lee Jong-Tae , Mozaffarian Dariush , Singh Gitanjali , Shin Min-Jeong 
Published: December 2016

ObjectivesOver the past 10 years, the burden of chronic diseases in Korea has increased. However, there are currently no quantitative estimates of how changes in diet and metabolic factors have contributed to these shifting burdens. This study aims to evaluate the contributions of dietary and metabolic risk factors to death from cardiometabolic diseases (CMDs) such as cardiovascular conditions, strokes and diabetes in Korea, and to estimate how these contributions have changed over the past 10 years (1998–2011).Design and methodsWe used data on 6 dietary and 4 metabolic risk factors by sex, age and year from the Korea National Health and Nutrition Examination Survey. The relative risks for the effects of the risk factors on CMD mortality were obtained from meta-analyses. The population-attributable fraction attributable to the risk factors was calculated by using a comparative risk assessment approach across sex and age strata (males and females, age groups 25–34, 35–44, 45–54, 55–64, 65–74 and 75+ years) from 1998 to 2011.ResultsThe results showed that a suboptimal diet and high blood pressure were the main risk factors for CMD mortality in Korea. High blood pressure accounted for 127 096 (95% uncertainty interval (UI): 121 907 to 132 218) deaths from CMD. Among the individual dietary risk factors, a high intake of sodium (42 387 deaths; 95% UI: 42 387 to 65 094) and a low intake of fruit (50 244 deaths; 95% UI: 40 981 to 59 178) and whole grains (54 248 deaths; 95% UI: 47 020 to 61 343) were responsible for the highest number of CMD deaths in Korea.ConclusionsIndicating the relative importance of risk factors in Korea, the results suggest that metabolic and dietary risk factors were major contributors to CMD mortality.
‘It promoted a positive culture around falls prevention’: staff response to a patient education programme—a qualitative evaluation
Authors: Hill Anne-Marie , Waldron Nicholas , Francis-Coad Jacqueline , Haines Terry , Etherton-Beer Christopher , Flicker Leon , Ingram Katharine , McPhail Steven M 
Published: December 2016

ObjectivesThe purpose of this study was to understand how staff responded to individualised patient falls prevention education delivered as part of a cluster randomised trial, including how they perceived the education contributed to falls prevention on their wards.DesignA qualitative explanatory study.Methods5 focus groups were conducted at participatory hospital sites. The purposive sample of clinical staff (including nurses, physiotherapists and quality improvement staff) worked on aged care rehabilitation wards when a cluster randomised trial evaluating a patient education programme was conducted. During the intervention period, an educator, who was a trained health professional and not a member of staff, provided individualised falls prevention education to patients with good levels of cognition (Mini-Mental State Examination >23/30). Clinical staff were provided with training to support the programme and their feedback was sought after the trial concluded, to understand how they perceived the programme impacted on falls prevention. Data were thematically analysed using NVivo qualitative data analysis software.Results5 focus groups were conducted at different hospitals (n=30 participants). Staff perceived that the education created a positive culture around falls prevention and further, facilitated teamwork, whereby patients and staff worked together to address falls prevention. The educator was perceived to be a valuable member of the team. Staff reported that they developed increased knowledge and awareness about creating a safe ward environment. Patients being proactive and empowered to engage in falls prevention strategies, such as ringing the bell for assistance, was viewed as supporting staff falls prevention efforts and motivating staff to change practice.ConclusionsStaff responded positively to patient falls prevention education being delivered on their wards. Providing individualised patient education to older patients with good levels of cognition can empower staff and patients to work as a team to address falls prevention on hospital rehabilitation wards.
Protocol for developing, disseminating and implementing a core outcome set for endometriosis
Authors: Hirsch Martin , Duffy James M N , Barker Claire , Hummelshoj Lone , Johnson Neil P , Mol Ben , Khan Khalid S , Farquhar Cindy 
Published: December 2016

IntroductionEndometriosis is a common gynaecological disease characterised by pain and subfertility. Randomised controlled trials evaluating treatments for endometriosis have reported many different outcomes and outcome measures. This variation restricts effective data synthesis limiting the usefulness of research to inform clinical practice. To address these methodological concerns, we aim to develop, disseminate and implement a core outcome set for endometriosis engaging with key stakeholders, including healthcare professionals, researchers and women with endometriosis.Methods and analysisAn international steering group has been established, including healthcare professionals, researchers and patient representatives. Potential outcomes identified from a systematic review of the literature will be entered into a modified Delphi method. Key stakeholders will be invited to participate including healthcare professionals, researchers and women with endometriosis. Participants will be invited to score individual outcomes on a nine-point Likert scale anchored between 1 (not important) and 9 (critical). Repeated reflection and rescoring should promote whole and individual stakeholder group converge towards consensus, ‘core’, outcomes. High-quality outcome measures will be associated with core outcomes.Ethics and disseminationThe implementation of a core outcome set for endometriosis within future clinical trials, systematic reviews and clinical guidelines will enhance the availability of comparable data to facilitate evidence-based patient care. This study was prospectively registered with Core Outcome Measures in Effectiveness Trials Initiative; number: 691.
Safety and feasibility of sublingual microcirculation assessment in the emergency department for civilian and military patients with traumatic haemorrhagic shock: a prospective cohort study
Authors: Naumann David N , Mellis Clare , Smith Iain M , Mamuza Jasna , Skene Imogen , Harris Tim , Midwinter Mark J , Hutchings Sam D 
Published: December 2016

ObjectivesSublingual microcirculatory monitoring for traumatic haemorrhagic shock (THS) may predict clinical outcomes better than traditional blood pressure and cardiac output, but is not usually performed until the patient reaches the intensive care unit (ICU), missing earlier data of potential importance. This pilot study assessed for the first time the feasibility and safety of sublingual video-microscopy for THS in the emergency department (ED), and whether it yields useable data for analysis.SettingA safety and feasibility assessment was undertaken as part of the prospective observational MICROSHOCK study; sublingual video-microscopy was performed at the UK-led Role 3 medical facility at Camp Bastion, Afghanistan, and in the ED in 3 UK Major Trauma Centres.ParticipantsThere were 15 casualties (2 military, 13 civilian) who presented with traumatic haemorrhagic shock with a median injury severity score of 26. The median age was 41; the majority (n=12) were male. The most common injury mechanism was road traffic accident.Primary and secondary outcome measuresSafety and feasibility were the primary outcomes, as measured by lack of adverse events or clinical interruptions, and successful acquisition and storage of data. The secondary outcome was the quality of acquired video clips according to validated criteria, in order to determine whether useful data could be obtained in this emergency context.ResultsVideo-microscopy was successfully performed and stored for analysis for all patients, yielding 161 video clips. There were no adverse events or episodes where clinical management was affected or interrupted. There were 104 (64.6%) video clips from 14 patients of sufficient quality for analysis.ConclusionsEarly sublingual microcirculatory monitoring in the ED for patients with THS is safe and feasible, even in a deployed military setting, and yields videos of satisfactory quality in a high proportion of cases. Further investigations of early microcirculatory behaviour in this context are warranted.Trial registration numberNCT02111109.
Vertical distribution of helium and
40
Ar/
36
Ar in porewaters of the Eastern Paris Basin (Bure/Haute-Marne): constraints on transport processes through the sedimentary sequence
Authors: Jean-Baptiste P. , Lavielle B. , Fourre E. , Smith T. , Pagel M. 
Published: December 2016

Abstract

As part of its ongoing project on repositories for high-activity, long-lived radioactive waste, a 2000 m deep borehole was drilled by the French Nuclear Waste Agency (ANDRA) in the layered structure of alternating aquifers and aquitards of the Eastern Paris Basin. Among the information retrieved from this borehole, the vertical distribution of chloride in porewaters showed that, in addition to vertical diffusion, lateral advection in the aquifers plays a major part in transporting chlorine away from the study area. Helium concentrations were also measured in porewaters along the borehole. Because the helium input function is different from that of chlorine, it represents an excellent alternative tracer to further constrain transport characteristics. We applied an advection–diffusion model to the helium profiles with the appropriate source term for
4
He based on U–Th measured concentrations of uranium and thorium.
40
Ar/
36
Ar data, which were available along the whole sequence, were also simulated. The modelled and measured
4
He profiles were in good agreement, indicating that the transport parameters used for the chlorine simulations were robust.
40
Ar/
36
Ar simulations also gave coherent results and confirmed that most of the radiogenic
40
Ar remained trapped in the rocks (primarily in clays and feldspars).