bluuebunny/crossref_metadata_2025_split huggingface dataset:
Invasive Group A Streptococcus Infection in Children in Southern Israel Before and After the Introduction of Varicella Vaccine
Authors: Hasin Ori , Hazan Guy , Rokney Assaf , Dayan Roy , Sagi Orli , Ben-Shimol Shalom , Greenberg David , Danino Dana 
Published: February 2019

Abstract
The annual rates of group A Streptococcus bacteremia per 100 000 children in southern Israel declined after introduction of the varicella vaccine to the national immunization program, from 2.43 (95% confidence interval, 1.73–3.13) in 1995–2002 to 1.30 (95% confidence interval, 0.91–1.72) in 2010–2016 (P = .04). This reduction correlated with the disappearance of varicella rash as a predisposing factor.
Faculties, Knowledge, and Reasons for Doubt in the Cartesian Circle
Authors: Clark Matthew 
Published: February 2019

AbstractThis paper argues for a novel solution to the Cartesian Circle by emphasising the important epistemic role of the Second Meditation and Descartes’ faculty epistemology. I argue that, for Descartes: doubt requires a ‘good reason’ to doubt (§2.1); whether a reason qualifies as a ‘good reason’ depends on which faculty produces that reason (§2.2); and for distinct metaphysical perceptions from the faculty of the intellect, no other faculty can provide ‘good reasons’ to doubt (§2.3). The upshot of §2 is that the doubts raised up to the Third Meditation do not apply to the distinct metaphysical perceptions of the intellect, and in particular do not apply to the premises of the proof of the existence of God. I present the role of God as primarily to secure clear and distinct perceptions beyond the intellect, and knowledge of conclusions when those conclusions are no longer being clearly and distinctly perceived (§3.1). Finally, I give an account of Descartes’ use of ‘cognoscere’, ‘scire’, and ‘scientia’ as three distinct epistemic levels, providing a valuable structure within which one can see the meditator progress (§3.2).
Developing Physician Leadership in Hospital Policy Development: A Case Study of Resident-Driven Policy Initiatives in the Department of Neurosurgery at the University of Alabama at Birmingham
Authors: Shank Christopher D , Kuhn Elizabeth N , Hadley Mark N , Walters Beverly C 
Published: February 2019

Abstract
The bulk of a resident's daily work is patient care related; however, other aspects of residency training are vital both to a resident's education and to the advancement of the field. Basic science and clinical research are the more common academic activities in which residents participate after completion of daily patient care objectives. Less frequently, residents participate in a process vital to the delivery of efficient, cost-effective, and safe patient care: hospital policy development.
Two policies were identified as outdated or absent: (1) the process for the declaration of brain death and (2) a policy for the use of hypertonic saline in the Neurosciences Intensive Care Unit. The policies were rewritten after review of the existing policy (when applicable), other institutions’ examples, national guidelines, and state and federal laws. Once written, proposals were reviewed by department leadership, hospital ethics, legal counsel, ad hoc specialty committees, the Medical Directors Council, and the Medical Executive Committee. After multiple revisions, each proposal was endorsed by the above bodies and ratified as hospital policy.
Residents may make a substantial impact on patient care through active participation in the authorship and implementation of hospital policy. The inclusion of residents in policy development has improved the process for declaring brain death and management of patients with devastating neurological pathology. Resident involvement in hospital policy initiatives can be successful, valuable to the institution, and beneficial to patient care. Resident involvement is predicated on faculty and institutional support of such endeavors.
The proper strategy to compress and protect plasmid DNA in the Pluronic L64-electropulse system for enhanced intramuscular gene delivery
Authors: He Yutong , Liu Yili , Sun Zhe , Han Fei , Tang James Zhenggui , Gao Rong , Wang Gang 
Published: February 2019

Abstract
Intramuscular expression of functional proteins is a promising strategy for therapeutic purposes. Previously, we developed an intramuscular gene delivery method by combining Pluronic L64 and optimized electropulse, which is among the most efficient methods to date. However, plasmid DNAs (pDNAs) in this method were not compressed, making them unstable and inefficient in vivo. We considered that a proper compression of pDNAs by an appropriate material should facilitate gene expression in this L64-electropulse system. Here, we reported our finding of such a material, Epigallocatechin gallate (EGCG), a natural compound in green teas, which could compress and protect pDNAs and significantly increase intramuscular gene expression in the L64-electropulse system. Meanwhile, we found that polyethylenimine (PEI) could also slightly improve exogenous gene expression in the optimal procedure. By analysing the characteristic differences between EGCG and PEI, we concluded that negatively charged materials with strong affinity to nucleic acids and/or other properties suitable for gene delivery, such as EGCG, are better alternatives than cationic materials (like PEI) for muscle-based gene delivery. The results revealed that a critical principle for material/pDNA complex benefitting intramuscular gene delivery/expression is to keep the complex negatively charged. This proof-of-concept study displays the breakthrough in compressing pDNAs and provides a principle and strategy to develop more efficient intramuscular gene delivery systems for therapeutic applications.
Epigenome-wide association study identifies Behçet’s disease-associated methylation loci in Han Chinese
Authors: Yu Hongsong , Du Liping , Yi Shenglan , Wang Qingfeng , Zhu Yunyun , Qiu Yiguo , Jiang Yan , Li Minghui , Wang Detao , Wang Qing , Yuan Gangxiang , Cao Qingfeng , Kijlstra Aize , Yang Peizeng 
Published: February 2019

Abstract

Objective
The aetiology of Behçet’s disease (BD), known as a systemic vasculitis, is not completely understood. Increasing evidence suggests that aberrant DNA methylation may contribute to the pathogenesis of BD. The aim of this epigenome-wide association study was to identify BD-associated methylation loci in Han Chinese.

Methods
Genome-wide DNA methylation profiles were compared between 60 BD patients and 60 healthy controls using the Infinium Human Methylation 450 K Beadchip. BD-associated methylation loci were validated in 100 BD patients and 100 healthy controls by pyrosequencing. Gene expression and cytokine production was quantified by real-time PCR and ELISA.

Results
A total of 4332 differentially methylated CpG sites were associated with BD. Five differentially methylated CpG sites (cg03546163, cg25114611, cg20228731, cg23261343 and cg14290576) revealed a significant hypomethylation status across four different genes (FKBP5, FLJ43663, RUNX2 and NFIL3) and were validated by pyrosequencing. Validation results showed that the most significant locus was located in the 5’UTR of FKBP5 (cg03546163, P = 3.81E-13). Four CpG sites with an aberrant methylation status, including cg03546163, cg25114611, cg23261343 and cg14290576, may serve as a diagnostic marker for BD (area under the receiver operating curve curve = 83.95%, 95% CI 78.20, 89.70%). A significantly inverse correlation was found between the degree of methylation at cg03546163 as well as cg25114611 and FKBP5 mRNA expression. Treatment with a demethylation agent, 5-Aza-2’-deoxycytidine resulted in an increase of FKBP5 mRNA expression and a stimulated IL-1β production.

Conclusion
Our findings suggest that aberrant DNA methylation, independently of previously known genetic variants, plays a vital role in the pathogenesis of BD.

Trial registration
Chinese Clinical Trial Registry, chictr.org.cn, ChiCTR-CCC-12002184.
Adverse Drug Reactions, still masquerading after all these years?
Authors: Gray Laurence A. , Routledge Philip A. 
Published: February 2019

Summary
In this journal in 1976, Professor Duncan Vere suggested that some adverse drug reactions could behave as “masqueraders”, sometimes evading detection for a considerable time after a medicine was introduced into clinical practice. Using contemporary examples, we illustrate why we believe the five main reasons he cited for adverse drug reactions masquerading in this manner remain just as relevant today. Although newer methods of investigation are increasingly contributing to improved surveillance, individual case reports and spontaneous reporting systems for suspected adverse drug reactions remain a cornerstone of pharmacovigilance and should continue during the whole of the time that medicines continue to be used therapeutically.
10-year Follow-up of Mod Quad and Triangle Tilt Surgeries in Obstetric Brachial Plexus Injury
Authors: Nath Rahul K. , Somasundaram Chandra 
Published: February 2019

Aim:
To evaluate whether obstetric brachial plexus injury (OBPI) children who had mod Quad and triangle tilt surgeries maintained their recovered upper extremity functional movements over 10 years.

Background:
The short-term outcomes of surgery in OBPI patients are well documented. However, only a few publications with results over 10-year postoperative follow-up exist. We have previously reported the outcomes of these 2 surgeries in OBPI after 1, 2, and 5 years. Here, we report the successful outcomes in 17 of these patients over 10 years.

Methods:
Seventeen OBPI patients, who had mod Quad, a modified muscle release operation and triangle tilt, a bony surgical procedure with us between 2005 and 2008, had postoperative follow-up of 10 years and met the inclusion criteria. Patients who had multiple surgeries and did not have 10-year follow-up are excluded in this study.

Results:
Fifteen of 17 children maintain their recovered upper extremity functions for extended long period (mean, 10 years; range, 9–13 years). There was statistically significant improvement in total functional Mallet score after 3 years (mean, 18.8 ± 2.1; P ≤ 0.01) from the preoperative mean total Mallet score of 14.5 ± 1.2. This improvement was not only maintained for extended period but also improved (mean total Mallet score, 20.35 ± 2.3; P ≤ 0.01) in some patients.

Conclusions:
Overall, all upper extremity functions improved greatly after mod Quad and triangle tilt surgeries in OBPI children, and they were able to maintain their recovered functional movements over extended period of 10 years.
Determining Reliability of Arthroscopic Classifications for Hip Labral Tears
Authors: Guimarães Barros Antônio Augusto , Vassalo Carlos César , Costa Lincoln Paiva , de Oliveira Paganini Vinícius , de Carvalho Guedes Euler , Percope de Andrade Marco Antônio 
Published: February 2019

Objective:
Evaluate interobserver and intraobserver reliability of hip arthroscopic classifications for labral tears.

Design:
Retrospective diagnostic study of nonconsecutive patients.

Setting:
Institutional study.

Patients:
From a database of 278 hip arthroscopy videos for treatment of femoroacetabular impingement, 70 videos were chosen by simple random sampling. Exclusion criteria included presence of radiological arthrosis (Tonnis > 2), previous hip surgery, inadequate lesion palpation, poor image quality, and refusal to participate in the study. The final sample included 60 videos.

Interventions:
Four hip surgeons evaluated the videos twice at 1-month intervals and classified the lesions according to Lage, Seldes, and Beck classifications for hip labral tears.

Main Outcome Measures:
Interobserver and intraobserver reliability with the percent of agreement and weighted Cohen kappa values.

Results:
Patients had a mean age of 33 years (SD, 7; range, 18-47 years), and 32 (53%) were men. Femoroacetabular impingement types included combined (CAM and pincer) in 31 (52%), CAM in 27 (45%), and pincer in 2 (3%). For interobserver reliability, the average weighted kappa values were 0.68, 0.65, and 0.78 for the Lage, Seldes, and Beck classifications, respectively. For intraobserver reliability, the mean weighted kappa values were 0.87, 0.64, and 0.93 for the Lage, Seldes, and Beck classifications, respectively.

Conclusions:
Beck classification had the highest average values for interobserver and intraobserver agreements. Lage, Seldes, and Beck scores for acetabular labrum tears showed substantial interobserver agreement. In the intraobserver evaluation, the Seldes system presented substantial agreement, whereas Lage and Beck classifications were considered excellent agreement.
The Art of Living With Symptoms: A Qualitative Study Among Patients With Primary Brain Tumors Receiving Proton Beam Therapy
Authors: Langegård Ulrica , Ahlberg Karin , Björk-Eriksson Thomas , Fransson Per , Johansson Birgitta , Ohlsson-Nevo Emma , Witt-Nyström Petra , Sjövall Katarina 
Published: February 2019

Background
Symptom management in conjunction with proton beam therapy (PBT) from patient's perspective has not been explored. Such knowledge is essential to optimize the care in this relatively new treatment modality.

Objective
The aim of this study was to explore the process of symptom management in patients with brain tumor receiving PBT.

Methods
Participants were 22 patients with primary brain tumor who received PBT, recruited in collaboration with a national center for proton therapy and 2 oncology clinics at 2 university hospitals in Sweden. Interviews using open-ended questions were conducted before, during, and/or after treatment. Verbatim interview transcripts were analyzed using classic Grounded Theory.

Results

“The art of living with symptoms” emerged as the core concept. This encompassed 3 interconnected symptom management concepts: “Adapting to limited ability,” “Learning about oneself,” and “Creating new routines.” These concepts were summarized in a substantive theoretical model of symptom management. Despite the struggle to manage symptoms, participants lived a satisfactory life.

Conclusions
Symptom management in conjunction with PBT comprises a process of action, thoughts, and emotions. The concepts that emerged indicated patients' symptom management strategies were based on their own resources.

Implications for Practice
It is important that PBT facilities develop an approach that facilitates the symptom management process based on patients' experiences of symptoms, as well as their actions and available resources.
Therapeutic Hypothermia After Perinatal Asphyxia in Infants With Severe, Ductal-Dependent Congenital Heart Disease*
Authors: Boos Vinzenz , Tietze Anna , Berger Felix , Bührer Christoph 
Published: February 2019

Objectives:
Patients with severe congenital heart disease and cardiac anomalies such as restrictive foramen ovale, intact atrial septum, or narrowing of ductus arteriosus are at risk for perinatal asphyxia, leading to hypoxic-ischemic encephalopathy. We hypothesize that therapeutic hypothermia can be applied to these patients and seek to investigate feasibility and safety of this method.

Design:
A retrospective observational study.

Setting:
The Department of Neonatology of Charité, University Hospital, Berlin, Germany.

Patients:
Newborns with severe congenital heart disease and perinatal asphyxia were retrospectively analyzed over a 6-year period.

Interventions:
Application of therapeutic hypothermia.

Measurements and Main Results:
Ten patients with perinatal asphyxia were enrolled in this study. All patients received low-dose prostaglandin E1 for ductal maintenance. Three patients without evidence for hypoxic-ischemic encephalopathy did not receive therapeutic hypothermia. One patient died at the age of 15 hours, and therapeutic hypothermia was discontinued after 19 hours in another patient with severe arterial hypotension. Adverse effects during hypothermia included respiratory insufficiency (100%), arterial hypotension (71%), the need for inotropic support (71%), and pulmonary hypertension (43%), the latter associated with prolonged postoperative inotropic support. No neurologic complications occurred before or after the surgery. Operative outcome of surviving patients was excellent. Early brain MRI scans were suggestive of good neurodevelopmental prognosis for most patients.

Conclusions:
Therapeutic hypothermia can be applied to patients with severe congenital heart disease and hypoxic-ischemic encephalopathy. Low-dose prostaglandin E1 infusions are safe for ductal maintenance during cooling, but cardiopulmonary adverse effects should be anticipated.
Hypotensive Response to IV Acetaminophen in Pediatric Cardiac Patients*
Authors: Achuff Barbara-Jo , Moffett Brady S. , Acosta Sebastian , Lasa Javier J. , Checchia Paul A. , Rusin Craig G. 
Published: February 2019

Objectives:
Acetaminophen is ubiquitously used as antipyretic/analgesic administered IV to patients undergoing surgery and to critically ill patients when enteral routes are not possible. Widely believed to be safe and free of adverse side effects, concerns have developed in adult literature regarding the association of IV acetaminophen and transient hypotension. We hypothesize that there are hemodynamic effects after IV acetaminophen in the PICU and assess the prevalence of such in a large pediatric cardiovascular ICU population using high-fidelity data.

Design:
Observational study analyzing an enormous set of continuous physiologic data including millions of beat to beat blood pressures surrounding medication administration.

Setting:
Quaternary pediatric cardiovascular ICU between January 1, 2013, and November 13, 2017.

Patients:
All patients less than or equal to 18 years old who received IV acetaminophen. Mechanical support devices excluded.

Interventions:
None.

Measurements and Main Results:
Physiologic vital sign data were analyzed in 5-minute intervals starting 60 minutes before through 180 minutes after completion. Hypotension defined as mean arterial pressure –15% from baseline and relative hypotension defined –10%. Only doses where patients received no other medications, including vasopressors, within the previous hour were included. t test and a correlation matrix were used to eliminate correlated factors before a logistic regression analysis was performed. Six-hundred eight patients received 777 IV acetaminophen doses. Median age was 8.8 months (interquartile range, 2–62 mo) with a dose of 12.5 mg/kg (interquartile range, 10–15 mg/kg). Data were normalized for age and reference values. One in 20 doses (5%) were associated with hypotension, and one in five (20%) associated with relative hypotension. Univariate analysis revealed hypotension associated with age, baseline mean arterial pressure, and skin temperature (p = 0.05, 0.01, and 0.09). Logistic regression revealed mean arterial pressure (p = 0.01) and age (p = 0.05) remained predictive for hypotension.

Conclusions:
In isolation of other medication, a hemodynamic response to IV acetaminophen has a higher prevalence in critically ill children with cardiac disease than previously thought and justifies controlled studies in the perioperative and critical care setting. The added impact on individual patient hemodynamics and physiologic instability will require further study.
Psychological Traits, Heart Rate Variability, and Risk of Coronary Heart Disease in Healthy Aging Women—The Women's Health Initiative
Authors: Salmoirago-Blotcher Elena , Hovey Kathleen M. , Andrews Cristopher A. , Allison Matthew , Brunner Robert L. , Denburg Nathalie L. , Eaton Charles , Garcia Lorena , Sealy-Jefferson Shawnita M. , Zaslavsky Oleg , Kang Joseph , López Lenny , Post Stephen G. , Tindle Hilary , Wassertheil-Smoller Sylvia 
Published: February 2019

ABSTRACT

Objective
Psychological traits such as optimism and hostility affect coronary heart disease (CHD) risk, but mechanisms for this association are unclear. We hypothesized that optimism and hostility may affect CHD risk via changes in heart rate variability (HRV).

Methods
We conducted a longitudinal analysis using data from the Women's Health Initiative Myocardial Ischemia and Migraine Study. Participants underwent 24-hour ambulatory electrocardiogram monitoring 3 years after enrollment. Optimism (Life Orientation Test-Revised), cynical hostility (Cook-Medley), demographics, and coronary risk factors were assessed at baseline. HRV measures included standard deviation of average N-N intervals (SDNN); standard deviation of average N-N intervals for 5 minutes (SDANN); and average heart rate (HR). CHD was defined as the first occurrence of myocardial infarction, angina, coronary angioplasty, and bypass grafting. Linear and Cox regression models adjusted for CHD risk factors were used to examine, respectively, associations between optimism, hostility, and HRV and between HRV and CHD risk.

Results
Final analyses included 2655 women. Although optimism was not associated with HRV, hostility was inversely associated with HRV 3 years later (SDANN: adjusted β = −0.54; 95% CI = −0.97 to −0.11; SDNN: −0.49; 95% CI = −0.93 to −0.05). HRV was inversely associated with CHD risk; for each 10-millisecond increase in SDNN or SDANN, there was a decrease in CHD risk of 9% (p = .023) and 12% (p = .006), respectively.

Conclusions
HRV did not play a major role in explaining why more optimistic women seem to be somewhat protected from CHD risk. Although hostility was inversely associated with HRV, its role in explaining the association between hostility and CHD risk remains to be established.
Implanted Nerve Electrical Stimulation allows to Selectively Restore Hand and Forearm Movements in Patients with a Complete Tetraplegia
Authors: Tigra Wafa , Azevedo Christine , Teissier Jacques , Gelis Anthony , Coulet Bertrand , Divoux Jean-Louis , Guiraud David 
Published: February 2019

AbstractBackgroundFunctional Electrical Stimulation (FES) is used for decades in rehabilitation centers. For patients with a spinal cord injury (SCI), FES can prevent muscular atrophy, reduce spasticity and/or restore limb movements. To this last aim, FES external devices can be used, but elicit imprecise movements. FES implanted devices used neuromuscular stimulation and required implantation of one electrode for each site (muscle) to stimulate, an heavy surgical procedure and 10 times more electrical charges than nerve stimulation. Moreover, complications related to the numerous implanted components could appear over time. The purpose of this work is to evaluate whether a multi-contact nerve cuff electrode can selectively activate forearm and hand muscles and restore functional movements in patient with a complete tetraplegia.MethodsA 12-contacts cuff electrode was designed to selectively activate, without damage it, multi fascicular peripheral nerve (1). Six subjects rwith at least one extensor or one flexor muscle stimulable by surface electrical stimulation, have been enrolled into the study. During the surgical procedure, radial or median nerve was stimulated through up to 35 different configurations of stimulation at an intensity up to 2.1 mA (25 Hz, pulse width 250 µs, inter-pulse 100 µs). Surface electrodes were positioned upon the forearm to record compound muscle action potentials elicited by nerve electrical stimulation. Recruitments curves and videos were recorded.ResultsThe multicontact cuff electrode allowed us to selectively activate group of muscles to produce multiple, independent and functional hand and forearm movements in persons with tetraplegia. A surface electrical stimulation did not allow all those movements.