bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parallels between lumbosacral radiculopathy and complex regional pain syndrome: α1-adrenoceptor upregulation, reduced dermal nerve fibre density, and hemisensory disturbances in postsurgical sciatica
Authors: Drummond Peter D. , Morellini Natalie , Visser Eric , Finch Philip M. 
Published: April 2019

Abstract
Residual lower-limb pain after low back surgery (postsurgical sciatica) and complex regional pain syndrome (CRPS) involving a lower limb are separate conditions but may share some mechanisms (eg, tissue inflammation, neuroimmune disturbances, and central neuroplasticity). As adrenergically evoked pain contributes, in part, to CRPS, whether an adrenergic mechanism also contributes to postsurgical sciatica was investigated in this study. Immunohistochemistry was used to identify α1-adrenoceptors (α1-AR) on nerve fibres and other targets in the affected and contralateral skin of 25 patients with postsurgical sciatica, and α1-AR expression was investigated in relation to pain and pinprick hyperalgesia after intradermal injection of the α1-AR agonist phenylephrine. In addition, quantitative sensory testing was performed on all 4 limbs and on each side of the forehead. α1-AR expression was greater in keratinocytes (but not blood vessels or nerve fibres) in the symptomatic than contralateral leg, and dermal nerve fibre density was reduced in both legs. However, distal adrenergic involvement in pain in postsurgical sciatica seems unlikely, as neither heightened α1-AR expression in keratinocytes nor reduced dermal nerve fibre density were associated with pain or hyperalgesia to intradermal phenylephrine injection. Sensitivity to pressure-pain, pinprick, and cold-pain was greater in the ipsilateral than contralateral forehead of the entire cohort, but sensory disturbances were most pronounced in patients with additional CRPS-like features. Together, these findings suggest that bilateral distal neuropathy and central neuroplastic changes are involved not only in the pathophysiology of CRPS but also in postsurgical sciatica. This may have treatment implications for patients with postsurgical sciatica.
Injury, Sleep, and Functional Outcome in Hospital Patients With Traumatic Brain Injury
Authors: Williams Ellita T. , Buchanan Diana Taibi , Buysse Daniel J. , Thompson Hilaire J. 
Published: April 2019

ABSTRACT

Problem: Uninterrupted nighttime sleep is associated with better cognition and functional outcomes in healthy adults, but the relationship between sleep and functional outcome in individuals hospitalized with severe traumatic brain injury (TBI) remains to be clarified. Objective: The aims of this study were to (1) describe nighttime rest-activity variables—wake bouts (counts), total wake time (minutes), and sleep efficiency (SE) (percentage; time asleep/time in bed)—in people on a neuroscience step-down unit (NSDU) post-TBI and (2) describe the association between injury and nighttime rest-activity on post-TBI functional outcome (using Functional Independence Measure [FIM] at discharge from inpatient care). Methods: This study is a cross-sectional, descriptive pilot study. We recruited participants from the NSDU (n = 17 [age: mean (SD), 63.4 (17.9)]; 82% male, 94% white) who wore wrist actigraphy (source of nighttime rest-activity variables) for up to 5 nights. For injury variables, we used Glasgow Coma Scale (GCS) score and Injury Severity Score (ISS). We used Spearman ρ and regression to measure associations. Results: Glasgow Coma Scale mean (SD) score was 8.8 (4.9), ISS mean (SD) score was 23.6 (6.7), and FIM mean (SD) score was 48 (14.5). Averages of nighttime rest-activity variables (8 PM–7 AM) were as follows: SE, 73% (SD, 16); wake bouts, 41 counts (SD, 18); total wake time, 74 minutes (SD, 47). Correlations showed significance between FIM and GCS (P = .005) and between SE and GCS (P = .015). GCS was the only statistically significant variable associated with FIM (P = .013); we eliminated other variables from the model as nonsignificant (P > .10). Sleep efficiency and FIM association was nonsignificant (P = .40). In a separate model (ISS, GCS, and SE [dependent variable]), GCS was significant (P = .04), but ISS was not (P = .25). Conclusion: Patients with severe TBI on the NSDU have poor actigraphic sleep at night. GCS has a stronger association to functional outcome than nighttime rest-activity variables.
The Effect of Low Back Pain on Daily Activities and Sleep Quality in Patients With Lumbar Disc Herniation: A Pilot Study
Authors: Kose Gulsah , Tastan Sevinc , Temiz Nail Caglar , Sari Melek , Izci Yusuf 
Published: April 2019

ABSTRACT
The aim of this study was to determine the effect of low back pain on the daily activities and sleep quality of patients with lumbar disc herniation. This cross-sectional study was performed between January and July 2015 in 77 patients. A visual analog scale (VAS), the Oswestry Disability Index (ODI), and the Pittsburgh Sleep Quality Index were used for patient assessment. The mean (SD) ODI score was 58.84 (9.51), and the mean (SD) VAS score of patients was 73.26 (24.37) mm. The VAS and ODI scores increased with age. This disability was mainly observed during weight lifting (67.6%), walking (48.1%), and standing (50.7%). A positive correlation was found between VAS score and ODI (r = 0.49, P < .001) and Pittsburgh Sleep Quality Index (r = 0.23, P = .039) scores. In patients with lumbar disc herniation, disability in activities of daily living and sleep quality are directly affected by low back pain and increase with pain intensity. Findings of this study provide useful information for healthcare professionals.
Changing pattern of chronic hepatitis C in renal transplant patients over 20 years
Authors: Emori Christini T. , Uehara Sílvia N.O. , Carvalho-Filho Roberto J. , Amaral Ana Cristina , de Souza e Silva Ivonete S. , Lanzoni Valéria P. , Moreira Sílvia R. , Silva-Souza Ana Lúcia , Gama Raimundo A. , Nunes Eunice J.S. , Leopércio Ana Paula.S. , Appel Flávia , Silva Antônio Eduardo B. , Medina-Pestana José O. , Ferraz Maria L.G. 
Published: April 2019

Background
The prevalence and clinical epidemiological profile of hepatitis C virus (HCV) infection have changed over time.

Aim
This study aimed to evaluate these changes in renal transplant recipients (RTx) comparing two different decades.

Materials and methods
RTx with HCV referred to RTx from 1993 to 2003 (A) and from 2004 to 2014 (B) were studied retrospectively. The demographic and clinical characteristics and different outcomes were compared between groups A and B. Variables that were statistically different were tested for inclusion in a multivariate Cox proportional hazard model predicting patient survival within the group.

Results
Among 11 715 RTx, the prevalence of HCV was 7% in A and 4.9% in B. In the more recent period (B), the mean age was older (46.2 vs. 39.5 years), with more males (72 vs. 60.7%), larger number of deceased donors (74 vs. 55%), higher percentage of previous RTx (27 vs. 13.7%), less frequent history of blood transfusion (81 vs. 89.4%), lower prevalence of hepatitis B virus coinfection (4.7 vs. 21.4%), and higher percentage of cirrhotic patients (13 vs. 5%). Patients of group B more frequently underwent treatment of HCV (29 vs. 9%), less frequently used azathioprine (38.6 vs. 60.7%) and cyclosporine (11.8 vs. 74.7%), and more frequently used tacrolimus (91 vs. 27.3%). In the outcomes, graft loss showed no difference between periods; however, decompensation was more frequent (P = 0.007) and patients’ survival was lower in the more recent period (P = 0.032) compared with the earlier one.

Conclusion
The profile of RTx with HCV has changed over the last 20 years. Despite a decrease in the prevalence of HCV, new clinical challenges have emerged, such as more advanced age and a higher prevalence of cirrhosis.
Impact of pretransplant antibodies on outcomes after heart transplantation
Authors: Nunoda Shinichi 
Published: April 2019

Purpose of review
Since the discovery of human leukocyte antigen (HLA) in the 1950s, there has been great interest in the role of antibodies in posttransplant rejection. The development of the lymphocyte toxicity test by Terasaki et al. in the 1960s was the first step toward understanding the role of antibodies in posttransplant rejection.

Recent findings
Subsequently, various organs have been transplanted and improving posttransplant outcomes have become a focus of research. In particular, methods to measure antibodies that affect posttransplant outcomes, including anti-HLA antibodies, and methods to desensitize patients from specific antibodies have been explored. One recent method for measuring antibodies is called the solid-phase assay, which uses purified HLA fixed to microbeads. This assay does not use donor lymphocytes and allows clinicians to test the reactivity of patient serum against a panel of antibodies. It has also enabled the identification of specific anti-HLA antibodies using a single HLA.

Summary
In addition to advances in methods to measure and analyze anti-HLA antibodies, the clinical impact of non-HLA antibodies has also received much attention recently.
Differential Intraoperative Effect of Liver Transplant in Different Inborn Errors of Metabolism
Authors: Porta Francesco , Romagnoli Renato , Busso Marta , Tandoi Francesco , Spada Marco 
Published: April 2019

ABSTRACTLiver transplant (LT) is a therapeutic option for a growing number of inborn errors of metabolism (IEM), including some disorders not confined to the liver. Clinical advantages of LT in maple syrup urine disease (MSUD), methylmalonic acidemia (MMA), and argininosuccinic aciduria (ASA) have been reported. However, no information on the early metabolic effect of LT after portal reperfusion is available in these disorders. Here we describe the intraoperative differential metabolic outcome of LT in MSUD, MMA, and ASA. In these IEM, LT promptly cleared toxic metabolites to safe concentrations. In MSUD, leucine concentration reached physiological concentration within 12 hours after portal reperfusion. In MMA and ASA, LT allowed faster clearance of methylmalonate and argininosuccinate, respectively, both dropping by ~90% within the first hour after portal reperfusion. The early biochemical benefits of LT in MSUD, MMA, and ASA demonstrate its immediate effectiveness in protecting patients from intercurrent metabolic decompensations.
Medicolegal Investigation for Cremation Clearance
Authors: Gill James R. , Olko Holly G. , DeJoseph Maura E. 
Published: April 2019

AbstractThis study on cremation clearance examines whether physical inspections detect more unnatural unreported deaths than medicolegal investigations without inspections. We reviewed all deaths reported to the medical examiner for cremation clearance during 2 distinct years and compared subsequent amendments of death certificates after 2 different investigative methodologies (1 with and 1 without physical inspection). Of 10,367 deaths in 2012, there were 86 deaths (0.83%) in which the investigation with physical inspection resulted in amendments to the death certificate. Of 11,906 deaths in 2016 without physical inspection, there were 153 that resulted in amendments (1.3%) including 2 homicides. For the detection of accidents, there was no statistically significant difference (χ2= 0.8119,P= 0.367552). For cremation investigations, the work effort and costs of performing physical inspections do not appear justified given the similar detection rates (approximately 1%) for unnatural deaths among the 2 groups. Both methods, however, do detect unreported unnatural deaths.
Development of a Quality Improvement Curriculum in a Pediatric Emergency Medicine Fellowship
Authors: Carney Kevin P. , Topoz Irina , Vu Tien T. , Mistry Rakesh D. , DiStefano Michael 
Published: April 2019

AbstractQuality improvement (QI) is a science of systematic analysis and improvement of health care delivery systems. Working knowledge of QI models is imperative to professional development of future pediatric emergency medicine practitioners. The Accreditation Council for Graduate Medical Education has established a list of QI and patient safety expectations for trainees. In order to address educational needs in this area, we have created a novel QI curriculum for pediatric emergency medicine fellows that include didactic sessions, active participation in QI projects, and mentorship by QI faculty. As a part of the curriculum, fellows are required to participate in variety of QI and patient safety activities, such as Morbidity and Mortality conferences, QI and Patient Case Review committees, and Clinical Care Guideline work groups. As a measure of success, fellows who have participated in this curriculum have shared their successful QI work at the local and national levels. This goal of this report is to share our experience in order to provide other institutions a framework for their own curriculum development.
Tenure and Turnover Among State Health Officials From the SHO-CASE Survey: Correlates and Consequences of Changing Leadership
Authors: Menachemi Nir , Danielson Elizabeth C. , Tilson Hugh A. , Yeager Valerie A. , Sellers Katie , Halverson Paul K. ,   for the SHO-CASE Steering Committee
Published: April 2019

Objective:
To examine characteristics associated with tenure length of State Health Officials (SHOs) and examine reasons and consequences for SHO turnover.

Design:
Surveys of current and former SHOs linked with secondary data from the United Health Foundation.

Setting:
Original survey responses from SHOs in the United States.

Participants:
Respondents included SHOs who served between 1973 and 2017.

Main Outcome Measures:
Tenure length and consequences of SHO turnover.

Results:
Average completed tenure among SHOs was 5.3 years (median = 4) and was shorter in recent time periods compared with decades prior. Older age at appointment (β = −0.109, P = .005) and those holding a management degree (β = −1.835, P = .017) and/or a law degree (β = −3.553, P < .001) were each associated with shorter SHO tenures. State Health Officials from states in the top quartile for health rankings had significantly longer average tenures (β = 1.717, P = .036). Many former SHOs believed that their tenure was too short and reported that their departure had either a significant or very large effect on their agency's ability to fulfill its mission.

Conclusions:
State Health Official tenures have become shorter over time and continue to be shorter than industry chief executive officers and best practice recommendations from organizational researchers. States have an opportunity to consider and address how factors within their control influence the stability of the SHO position.
Reduced Biventricular Volumes and Myocardial Dysfunction Long-term After Pediatric Heart Transplantation Assessed by CMR
Authors: Latus Heiner , Hachmann Pauline , Voges Inga , Mueller Simon , Gummel Kerstin , Reich Bettina , Sarikouch Samir , Peters Brigitte , Mazhari Nona , Behnke-Hall Kachina , Jux Christian , Apitz Christian , Thul Josef , Akintuerk Hakan , Bauer Juergen , Schranz Dietmar 
Published: April 2019

Background.
Long-term cardiac remodeling after heart transplantation (HT) in children has been insufficiently characterized. The aim of our study was to evaluate ventricular size in HT patients using cardiovascular magnetic resonance (CMR) imaging, to find underlying factors related to potentially abnormal cardiac dimensions and to study its impact on functional class and ventricular function.

Methods.
Seventy-five pediatric HT recipients (age 14.0 ± 4.2 y) were assessed by using CMR 11.2 ± 5.4 years after HT. Right ventricular (RV) and left ventricular (LV) volumes and mass were derived from short-axis cine images and myocardial strain/strain rate was assessed using myocardial feature tracking technique. Results were compared with a healthy reference population (n = 79, age 13.7 ± 3.7 y).

Results.
LV end-diastolic ventricular volumes were smaller (64 ± 12 versus 84 ± 12 mL/m2; P < 0.001) while mass-to-volume ratio (0.86 ± 0.18 versus 0.65 ± 0.11; P < 0.001) and heart rate (92 ± 14 versus 78 ± 13 beats/min; P < 0.001) were higher in HT patients. LV-ejection fraction (EF) was preserved (66% ± 8% versus 64% ± 6%; P = 0.18) but RV-EF (58 ± 7 versus 62% ± 4%, P = 0.004), LV systolic longitudinal strain (−12 ± 6 versus −15% ± 5%; P = 0.05), diastolic strain rate (1.2 ± 0.6 versus 1.5 ± 0.6 1/s; P = 0.03), and intra and interventricular synchrony were lower in the HT group. Smaller LV dimensions were primarily related to longer follow-up time since HT (β = −0.38; P < 0.001) and were associated with worse functional class and impaired ventricular systolic and diastolic performance.

Conclusions.
Cardiac remodeling after pediatric HT is characterized by reduced biventricular size and increased mass-to-volume ratio. These adverse changes evolve gradually and are associated with impaired functional class and ventricular dysfunction suggesting chronic maladaptive processes affecting allograft health.
Post-treatment human papillomavirus antibody kinetics in cervical cancer patients
Authors: Piontek Till , Harmel Christoph , Pawlita Michael , Carow Katrin , Schröter Juliane , Runnebaum Ingo B. , Dürst Matthias , Graw Frederik , Waterboer Tim 
Published: April 2019

Antibodies to the E6 and E7 oncoproteins of high-risk human papillomavirus (HPV) types are strongly associated with HPV-driven cancer, while antibodies against the capsid protein L1 are considered cumulative exposure markers. To test the hypothesis that L1 antibody levels are stable over time, whereas E6 and E7 levels undergo decay after cervical cancer (CxCa) treatment, we performed multiplex serology for HPV16 and 18 antigens E6, E7 and L1 in a post-treatment study of 184 patients with invasive CxCa that were characterized with a median follow-up time of 725 days, and 2–12 sera per patient. Antibody titers significantly decreased within the first six months for HPV16 E6 and E7 but not L1, and stabilized for the following 12 months on a high level, with few patients showing seroreversion. Of 67 patients seropositive for HPV16 E6 at diagnosis, 28 (41.8%) showed a decrease in antibody titers of at least 50% within the first 18 months. Similarly, of 50 HPV16 E7 seropositives, 33 (66.0%) showed decreasing antibody levels, whereas antibody decay was less frequent for HPV16 L1 (12 of 47, 25.5%). Using a power-law mathematical model to characterize antibody decay kinetics, the mean (±s.e.) durations to a 50% reduction in antibody titers within individual patients were estimated to be 56.9 (±26.1) and 56.3 (±19.0) days for HPV16 E6 and E7, respectively. In summary, HPV16 E6 and E7 antibodies undergo a slow but significant decrease in antibody titers within the first 6–18 months following CxCa treatment. However, larger studies are needed to confirm the utility of serology for prediction of disease progression and time to relapse based on antibody decay kinetics.
This article is part of the theme issue ‘Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses'.
The scope of viral causation of human cancers: interpreting virus density from an evolutionary perspective
Authors: Ewald Paul W. , Swain Ewald Holly A. 
Published: April 2019

Most known oncogenic viruses of humans use DNA as their genomic material. Research over the past quarter century has revealed that their oncogenicity results largely from direct interference with barriers to oncogenesis. In contrast to viruses that have been accepted causes of particular cancers, candidate viral causes tend to have fewer viral than cellular genomes in the tumours. These low viral loads have caused researchers to conclude that the associated viruses are not primary causes of the associated cancers. Consideration of differential survival, reproduction and infiltration of cells in a tumour suggest, however, that viral loads could be low even when viruses are primary causes of cancer. Resolution of this issue has important implications for human health because medical research tends to be effective at preventing and controlling infectious diseases. Mathematical models may clarify the problem and help guide future research by assessing whether low viral loads are likely outcomes of the differential survival, reproduction, and infiltration of cells in a tumour and, more generally, the extent to which viruses contribute to cancer.
This article is part of the theme issue ‘Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses’.
Complement in human pre-implantation embryos: attack and defense
Authors: Reichhardt Martin P. , Lundin Karolina , Lokki A. Inkeri , Recher Gaëlle , Vuoristo Sanna , Katayama Shintaro , Tapanainen Juha , Kere Juha , Meri Seppo , Tuuri Timo 
Published: April 2019

AbstractIt is essential for early human life that immunological responses to developing embryos are tightly regulated. An imbalance in the activation and regulation of the human complement system occurs in pregnancy complications, such as pre-eclampsia and recurrent miscarriage. We hereby present the first full analysis of the expression and deposition of complement molecules in human pre-implantation embryos. Thus far, immunological imbalance has been considered in stages of pregnancy following implantation. We here show that complement activation and deposition takes place on developing human embryos already at the pre-implantation stage. Using confocal microscopy, we observed deposition of activation products such as C1q, C3 and C5 on healthy developing embryos, which highlights the need for strict complement regulation. The early embryos express the complement membrane inhibitors CD46, CD55 and CD59 and bind the soluble regulators C4bp and factor H. These findings show that complement targets human embryos, and indicate potential adverse pregnancy outcomes, if regulation of activation fails. In addition, single-cell RNA sequencing of embryos at oocyte, zygote, 4-cell and 8-cell stages showed expression of complement genes, e.g. C1s, C2, C3, C5, factor B and factor D. This shows that the embryonic cells themselves have the capacity to express C3 and C5, which may become activated and function as mediators of cellular signaling. The specific local embryonic expression of complement components, regulators, and deposition of activation products on the surface of embryos suggests that complement has immunoregulatory functions and may impact cellular homeostasis and differentiation at the earliest stage of human life.Statement of significanceWhile canonical functions of the complement system relate to pathogen-defence, it is known to drive certain immune pathologies. The work here described shows, for the first time, expression and localization of a full range of complement molecules in human pre-implantation embryos. We demonstrate complement attack against early embryos, and show presence of embryonic defence mechanisms. Furthermore, we reveal early embryonic production of complement activators, suggesting non-canonical roles in cell signalling and development. Our findings thus reveal a fundamental role for complement at the earliest stages of human embryogenesis. Our data opens up for future studies into the role of complement, both in relation to infertility and pregnancy complications, as well as basic cellular processes during early human development.