bluuebunny/crossref_metadata_2025 huggingface dataset:
Translating biased signaling in the ghrelin receptor system into differential in vivo functions
Authors: Mende Franziska , Hundahl Cecilie , Plouffe Bianca , Skov Louise Julie , Sivertsen Bjørn , Madsen Andreas Nygaard , Lückmann Michael , Diep Thi Ai , Offermanns Stefan , Frimurer Thomas Michael , Bouvier Michel , Holst Birgitte
Published: October 2018

Significance

Obesity is a major health threat of the twenty-first century, impacting individual patients and healthcare expenditure. Due to safety concerns, few antiobesity treatments with only moderate effect remain on the market. The ghrelin receptor is an attractive target for the development of novel antiobesity drugs, since ghrelin increases both fat accumulation and food intake. However, ghrelin also modulates a variety of additional physiological functions. Thus, drugs targeting the ghrelin receptor may induce unacceptable side effects and have limited clinical use. We demonstrate that biased ligands, which selectively activate only a subset of the molecular signaling pathways, may be powerful tools to obtain drugs that efficaciously reduce body weight without inducing adverse effects by selectively modulating appetite and energy expenditure.
Human mitochondrial degradosome prevents harmful mitochondrial R loops and mitochondrial genome instability
Authors: Silva Sonia , Camino Lola P. , Aguilera Andrés
Published: October 2018

Significance

R loops form during transcription when the mRNA hybridizes back to the template DNA forming a stable DNA–RNA hybrid. Stable R loops can block replication and transcription machineries, leading to genome instability and human diseases. We report that the human mitochondrial degradosome (mtEXO), formed by SUV3 and PNPase, plays an important role in R-loop metabolism in the mitochondria apart from preventing dsRNA accumulation, with implications in replication and preventing instability of the mitochondrial genome. Our findings help establish a connection between the RNA processing activities of the mtEXO and mitochondrial genome stability, affecting mitochondria homeostasis, cellular metabolism, and human diseases.
Identification of SLAC1 anion channel residues required for CO
2
/bicarbonate sensing and regulation of stomatal movements
Authors: Zhang Jingbo , Wang Nuo , Miao Yinglong , Hauser Felix , McCammon J. Andrew , Rappel Wouter-Jan , Schroeder Julian I.
Published: October 2018

Significance

Plants optimize CO
2
influx for photosynthesis and water loss by regulating gas exchange between the inside of leaves and the atmosphere via stomatal pores. Respiration in darkness and the continuing atmospheric [CO
2
] rise cause closing of stomatal pores, thus affecting plant water loss globally. However, the mechanisms by which plant guard and mesophyll cells sense CO
2
/bicarbonate for CO
2
regulation of stomata remain unknown. Here, a computer-aided modeling approach and multiple experimental assays suggest that the anion channel SLAC1 plays an important role in CO
2
/bicarbonate sensing in guard cells. This work will aid in the understanding of how plants cope with the increasing CO
2
concentration and can further lead to new approaches for developing crop plants to adapt to climate change.
Activity-dependent bulk endocytosis proteome reveals a key presynaptic role for the monomeric GTPase Rab11
Authors: Kokotos A. C. , Peltier J. , Davenport E. C. , Trost M. , Cousin M. A.
Published: October 2018

Significance

The maintenance of neurotransmission by synaptic vesicle (SV) recycling is critical to brain function. The dominant SV recycling mode during intense activity is activity-dependent bulk endocytosis (ADBE), suggesting it will perform a pivotal role in neurotransmission. However, the role of ADBE is still undetermined, due to the absence of identified molecules specific for this process. The determination of the bulk endosome proteome (a key ADBE organelle) revealed that it has a unique molecular signature and identified a role for Rab11 in presynaptic function. This work provides the molecular inventory of ADBE, a resource that will be of significant value to researchers wishing to modulate neurotransmission during intense neuronal activity in both health and disease.
Characterizing posttranslational modifications in prokaryotic metabolism using a multiscale workflow
Authors: Brunk Elizabeth , Chang Roger L. , Xia Jing , Hefzi Hooman , Yurkovich James T. , Kim Donghyuk , Buckmiller Evan , Wang Harris H. , Cho Byung-Kwan , Yang Chen , Palsson Bernhard O. , Church George M. , Lewis Nathan E.
Published: October 2018

Significance

Understanding roles and mechanisms of protein posttranslational modifications (PTMs) would greatly impact multiple scientific domains, from bioengineering to biomedical science. PTMs are known to interfere with drug action and influence biochemical networks of engineered organisms. Many PTM sites have been identified, but it remains unclear under which conditions these sites are modified. Furthermore, there is a need to understand how the cell utilizes PTMs to increase fitness. Here, we approach this challenge by integrating tools from molecular biology, biochemistry, and systems biology to unravel mechanisms through which PTMs regulate enzymes throughout
Escherichia coli
metabolism and demonstrate how these individual PTMs further regulate pathways and ultimately cell phenotypes. This workflow could be applied to study PTMs and their roles across species.
Language alternation in peer interaction in content and language integrated learning (CLIL)
Authors: Morton Tom , Evnitskaya Natalia
Published: October 2018

This chapter explores language alternation (LA) practices in peer interaction in a CLIL (Content and Language Integrated Learning) science classroom in the context of recent calls for rethinking language use in multilingual education, notably the concept of “translanguaging”. While most studies attempt to identify functions for LA practices in multilingual education, the conversation analytic perspective of this study examines LA from a participants’ (emic) perspective. The analyses explore LA practices at both the “local” level of turn construction and sequence organisation, and the “overall” level of participants’ orientation to medium of instruction. The findings suggest that improving understanding of learners’ LA practices in peer interaction in multilingual education contexts could contribute to achieving the goals of this type of education.
Recurring patterns of language alternation practices by EFL novice teachers in Vietnam
Authors: Giang Lam Hoang Thi
Published: October 2018

This study adopts the methods of conversation analysis to track the recurring patterns in the language alternation practices of three English as a Foreign Language (EFL) novice teachers’ in a Vietnamese tertiary context. The analysis focused on alternation from English (the L2) to Vietnamese (the L1) during their teaching. Findings show that in instructional elicitation sequences when teachers pursued students’ comprehension and response, there was a gap before the teachers switched to the L1. Also, when teachers provided the students with quickly stated instructions, checked and confirmed their comprehension and further elaborated their own instructions, the L1 was the medium of choice. Such switches to the L1 were frequently conducted without a gap.
A macrorole approach to dative subjects
Authors: Farrell Patrick , Willgohs Beatriz
Published: October 2018

The arguments of certain Spanish verbs of psychological experience exhibit morphosyntactic properties similar to those of Germanic “oblique subject” verbs, as described, for example, in Barðdal (2001) and Barðdal & Eythórsson (2005). In this article, we show how the behavior of dative experiencers looks neither “quirky” nor “non-canonical” when grammatical privilege is accounted for directly in terms of semantic macroroles in the sense of Role and Reference Grammar (Van Valin 2005), provided that the standard set of Actor (A) and Undergoer (U) macroroles is augmented to include a third, i.e., Receptor (R), that corresponds roughly to Fillmore’s (1968) Dative category of semantic case and the Relational Grammar indirect object relation (Perlmutter 1984). Adding R to the set of macroroles enables us to account straightforwardly for the subject and non-subject properties of dative experiencers in Spanish, as well as parallel properties of possessor/recipient arguments across construction types, without having anything hinge either on dative case per se or on the notion of subject.
The diachrony of non-canonical subjects in Northwest Semitic
Authors: Pat-El Na'ama
Published: October 2018

A syntactic pattern involving non-canonical subject marking in some Northwest-Semitic languages is fascinating for two reasons: (1) it cannot be reconstructed to the proto-language and it must have developed relatively late in the history of the family, which affords us an opportunity to observe its development through textual attestations (cf. Barðdal & Eythórsson 2009); (2) the predication is by and large non-verbal, which seems to counter explanations based on passive derivations and agentivity as a possible origin (Haspelmath 2001). I suggest instead that non-canonical subjects originated from free datives in clauses where the typical agreement cannot be applied. In such cases, the dative, which is animate, definite and associated with the subject, eventually outranked the original subject, which is typically a nominalization and never animate or definite. I further discuss the special features of the non-canonical subject and argue that it is quite stable.
Frequency as a key to language change and reorganisation
Authors: Breder Birkenes Magnus
Published: October 2018

This paper deals with the case of apparent subtraction in number and case morphology, which is a special phenomenon shared by many German dialects. Taking a vast amount of material from all over the German-speaking area into consideration, this paper treats subtraction within a usage-based approach. Subtractive forms are seen as diachronically transparent, but synchronically a case of weak suppletion, whose retention is governed by frequency. It is argued that phonological rules lead to grammatical variation (allomorphy) that is eliminated over time. In most dialects, other more type-frequent patterns like zero-marking or additive endings prevail (perhaps due to influence from the standard language), but in a few dialects, the subtractive pattern remains strong and even expands to other lexemes. This aspect of variation has, as of yet, not been adequately explained by previous rule-based approaches to subtraction in German dialects.
Genesis and diachronic persistence of overabundance
Authors: Cappellaro Chiara
Published: October 2018

This article investigates the genesis and diachronic persistence of ‘overabundance’ (Thornton 2011) or variation at the level of individual cells in a lexeme’s paradigm (e.g. Italian pst.ptcp forms sepolto/seppellito ‘buried’). Two main genetic paths are identified: emergence (i) via form competition (e.g. Italian ella/essa ‘she’) and (ii) via rule competition (e.g. Ladin talaranes/talarane/talaràs ‘spiders’). Building on previous work (Cappellaro 2013, 2017), the present study proposes that persistence correlates positively with low frequency and later acquisition, but also addresses the question whether there is a link between genetic type (form/rule competition) and persistence. In the case of Italian sepolto/seppellito < Latin sepultus/sepelitus, persistence over millennia is metachronic – a function of analogical pressures inherent in the system, which can, in principle, operate at any given time.
Reorganising voice in the history of Greek
Authors: Lavidas Nikolaos
Published: October 2018

In this study, I analyse the reorganisation of voice variation in Greek in terms of an increase or decrease in complexity. I support the view of split complexity (E[xternal]- vs. I[nternal]-complexity), and I add the role of parametric routes to the whole picture of grammatical complexity in cases of reorganisation of variation. In this respect, the new active anticausatives resulted in a lower degree of complexity in terms of derivation; conversely, the parametric route became more complex because a microparameter determines the lexically constrained group of active anticausatives. In terms of E-complexity, the option of this microparameter results in lower complexity because it is related to frequent elements. However, E-complexity is also affected by a prescriptive rule that favours elements that are less frequent (nonactive anticausatives).
Power analysis in a SMART design: sample size estimation for determining the best embedded dynamic treatment regime
Authors: Artman William J , Nahum-Shani Inbal , Wu Tianshuang , Mckay James R , Ertefaie Ashkan
Published: October 2018

Sequential, multiple assignment, randomized trial (SMART) designs have become increasingly popular in the field of precision medicine by providing a means for comparing more than two sequences of treatments tailored to the individual patient, i.e., dynamic treatment regime (DTR). The construction of evidence-based DTRs promises a replacement to ad hoc one-size-fits-all decisions pervasive in patient care. However, there are substantial statistical challenges in sizing SMART designs due to the correlation structure between the DTRs embedded in the design (EDTR). Since a primary goal of SMARTs is the construction of an optimal EDTR, investigators are interested in sizing SMARTs based on the ability to screen out EDTRs inferior to the optimal EDTR by a given amount which cannot be done using existing methods. In this article, we fill this gap by developing a rigorous power analysis framework that leverages the multiple comparisons with the best methodology. Our method employs Monte Carlo simulation to compute the number of individuals to enroll in an arbitrary SMART. We evaluate our method through extensive simulation studies. We illustrate our method by retrospectively computing the power in the Extending Treatment Effectiveness of Naltrexone (EXTEND) trial. An R package implementing our methodology is available to download from the Comprehensive R Archive Network.
Sildenafil for the treatment of preeclampsia, an update: should we still be enthusiastic?
Authors: Simon-Tillaux Noémie , Lecarpentier Edouard , Tsatsaris Vassilis , Hertig Alexandre
Published: October 2018

Preeclampsia is a hypertensive disorder of pregnancy and the clinical manifestation of severe endothelial dysfunction associated with maternal and foetal morbidity and mortality. The primum movens of the disease is the defect of invasion of the uterine arteries by foetal syncytiotrophoblasts, which causes a maladaptive placental response to chronic hypoxia and the secretion of the soluble form of type 1 vascular growth endothelial factor receptor, also called soluble fms-like tyrosine kinase 1 (sFlt-1), the major player in the pathophysiology of the disease. Among its different effects, sFlt-1 induces abnormal sensitivity of the maternal vessels to the vasoconstrictor angiotensin II. This leads to the hypertensive phenotype, recently shown to be abrogated by the administration of sildenafil citrate, which can potentiate the vasodilatory mediator nitrite oxide. This review focuses on the mechanisms of maternal endothelial dysfunction in preeclampsia and discusses the therapeutic window of sildenafil use in the context of preeclampsia, based on the results from preclinical studies and clinical trials. Safety issues recently reported in neonates have considerably narrowed this window.
Risk Factors and Outcomes Associated With Acquisition of Daptomycin and Linezolid–Nonsusceptible Vancomycin-Resistant Enterococcus
Authors: Greene Matthew H , Harris Bryan D , Nesbitt Whitney J , Watson Marley L , Wright Patty W , Talbot Thomas R , Nelson George E
Published: October 2018

Background

Vancomycin-resistant enterococcus (VRE) causes substantial health care–associated infection with increasing reports of resistance to daptomycin or linezolid. We conducted a case–control study reporting 81 cases of daptomycin and linezolid–nonsusceptible VRE (DLVRE), a resistance pattern not previously reported.

Methods

We reviewed VRE isolates from June 2010 through June 2015 for nonsusceptibility to both daptomycin (minimum inhibitory concentration [MIC] > 4) and linezolid (MIC ≥ 4). We matched cases by year to control patients with VRE susceptible to both daptomycin and linezolid and performed retrospective chart review to gather risk factor and outcome data.

Results

We identified 81 DLVRE cases. Resistance to both daptomycin and linezolid was more common than resistance to either agent individually. Compared with susceptible VRE, DLVRE was more likely to present as bacteremia without focus (P < 0.01), with DLVRE patients more likely to be immune suppressed (P = .04), to be neutropenic (P = .03), or to have had an invasive procedure in the prior 30 days (P = .04). Any antibiotic exposure over the prior 30 days conferred a 4-fold increased risk for DLVRE (odds ratio [OR], 4.25; 95% confidence interval [CI], 1.43−12.63; P = .01); multivariate analysis implicated daptomycin days of therapy (DOT) over the past year as a specific risk factor (OR, 1.10; 95% CI, 1.01−1.19; P = .03). DLVRE cases had longer hospitalizations (P = .04) but no increased risk for in-hospital death.

Conclusions

DLVRE is an emerging multidrug-resistant pathogen associated with immune suppression, neutropenia, and recent invasive procedure. Prior antibiotic exposure, specifically daptomycin exposure, confers risk for acquisition of DLVRE.
Improving Opioid Management and Resource Utilization in an Internal Medicine Residency Clinic: A Before-After Study over Two Plan-Do-Study-Act Cycles
Authors: Wong Rachel , Carroll William , Muttreja Astha , Garcia Victor , Taub Erin , Fernan Alice
Published: October 2018

Objective Chronic pain and opioid management are challenging in primary care, especially for trainees with discontinuous ambulatory schedules and less practice experience. The study objective was to improve adherence to quality metrics and office visit utilization in a resident clinic.

Design Before-after quality improvement intervention over two Plan-Do-Study-Act cycles.

Setting Suburban, university-affiliated Internal Medicine resident clinic.

Methods During the 2015–2017 academic years, two sequential interventions were implemented: 1) use of electronic pain and opioid management templates and workflow redesign routing opioid renewals through a registered nurse (RN); 2) RN previsit planning and daily nurse–physician huddles before patient visits. Outcomes included adherence to annual toxicology screening, risk assessment and opioid agreements, opioid dose prescribed, and office visit utilization.

Results The template and workflow redesign intervention increased annual toxicology from 53% to 81% (P < 0.0015), annual opioid agreement from 13.8% to 53.5% (P < 0.0001), and risk assessment from 0% to 75.9% (P < 0.0001). Average daily morphine milligram equivalents (MME) decreased from 96.6 MME to 67.7 MME (P < 0.0001), and annual office visits decreased from 11.1 to 8.9 (P = 0.0004). Previsit planning and huddles did not show incremental increases in adherence to quality measures but did improve clinic utilization and maintained high levels of adherence to quality measures.

Conclusions Quality improvement interventions can improve adherence to quality measures and clinic utilization. A critical role is served by midlevel nursing providers to provide continuity to patients and trainees. Teaching clinics need to develop sustainable systems of care to moderate quality assurance in opioid prescribing.
Comparison of Methodologies Used in Homicide Investigations to Collect, Prioritize, and Eliminate Persons of Interest: A Case Study of Three Dutch Real-World Homicide Cases
Authors: Sutmuller August Daniel , den Hengst Marielle , Barros Ana Isabel , van Gelder P H A J M
Published: October 2018

This paper provides a comparison between four methodologies that assist criminal investigators in homicide investigations. The Person of Interest Priority Assessment Tool, Trace Investigate and Evaluate, Rasterfahndung, and Analysis of Competing Hypotheses are compared on their performance in the collection, prioritization, and elimination phase of homicide cases in today’s digital era. Three recent Dutch homicide cases are used. The use of categories during collection can assist criminal investigators in the early inclusion of the perpetrator into the investigation, however, in this digital era, the number of persons of interest becomes too large to humanly handle. All four methodologies use techniques to assign weight to pieces of evidence; further research is required to evaluate the effectiveness of these techniques when the amount of pieces of evidence explodes. The use of pre-set elimination categories shows the least promising result leaving most persons of interest not-eliminated by the currently used methodologies.
Monetary Policy Spillovers and Currency Networks in Cross-Border Bank Lending: Lessons from the 2013 Fed Taper Tantrum*
Authors: Avdjiev Stefan , Takáts Előd
Published: October 2018

We show that currency networks in cross-border bank lending have a significant impact on the size, distribution, and direction of international monetary policy spillovers. Utilizing a novel dataset, we map the major currency networks in international banking and show that the US dollar dominates at the global level. Next, we provide evidence that during the 2013 Fed taper tantrum, the degree of exposure to US dollar lending had a significant impact on cross-border bank lending growth. Most notably, it had a strong negative impact on cross-border flows to emerging markets.
Experience with definitive instrumented final fusion after posterior-based distraction lengthening in patients with early-onset spinal deformity: single center results
Authors: Murphy Robert F. , Pacult Mark A. , Barfield William R. , Gross Richard H. , Mooney James F.
Published: October 2018

Limited reports exist with regard to clinical and radiographic details of patients with early-onset spinal deformity (EOSD) undergoing definitive instrumented final fusion (FF) following implantation of a growing construct. Charts and radiographs were queried for all patients who underwent FF after management of EOSD with a distraction-based posterior construct at a single institution from 2006 to 2017. Patients managed during the growth modulation period with either proximal rib or spinal fixation were included. Thirteen patients qualified for inclusion. Spinal deformity etiologies were varied (neuromuscular: 5, idiopathic: 4, congenital: 4). Average age at implantation was 6.5 years, and patients underwent an average of 8.15 lengthening procedures over an average of 69 months. After the growing program, modest correction in main coronal Cobb was obtained at FF (average 52.4° before FF, 37.6° following FF, P<0.001; average percent improvement of 27%). Five patients required posterior column osteotomies. Using criteria proposed by Flynn and colleagues, ‘minimal’ coronal correction was achieved in 23% of patients and ‘moderate’ in 77%. No patient achieved ‘substantial’ (>50%) correction. Subjective poor bone quality was appreciated in 67% of patients, and 85% were noted to have areas of autofusion over previously spanned levels. Two (15%) patients sustained a total of four complications. After growth modulation procedures, EOSD deformities are generally stiff, bone quality is often subjectively poor, and autofusion is common, even after use of proximally rib-based systems. Modestly improved coronal Cobb correction can be obtained at FF but may require single or multiple posterior osteotomies. Intraoperative difficulties can be expected, and clinicians should be alert for intraoperative and postoperative complications.
Combined Reconstruction of the Medial Patellofemoral Ligament (MPFL) and Medial Quadriceps Tendon-Femoral Ligament (MQTFL) for Patellar Instability in Children and Adolescents: Surgical Technique and Outcomes
Authors: Spang Robert C. , Tepolt Frances A. , Paschos Nikolaos K. , Redler Lauren H. , Davis Eric A. , Kocher Mininder S.
Published: October 2018

Objectives:

A variety of surgical options exist to treat the challenging problem of recurrent patellar instability in children and adolescents. The goal of the current study is to describe a novel combined reconstruction technique of both the medial patellofemoral ligament (MPFL) and the medial quadriceps tendon-femoral ligament (MQTFL) and report patient outcomes of a single-surgeon series.

Methods:

All patients studied underwent simultaneous MPFL and MQTFL reconstruction for patellar instability using gracilis allograft. Demographic, clinical, and radiographic data were collected. Subjective outcomes were assessed for a minimum of 1 year postoperatively.

Results:

Twenty-five patients (27 knees), including 15 female and 10 male individuals with an average age of 15.0±2.2 years (range, 10.3 to 18.9), were included. Prior ipsilateral patellofemoral surgery had been performed in 6 of 25 (24%) patients. Simultaneous hemiepiphysiodesis for valgus deformity at the time of combined reconstruction was performed in 5 of 25 (20%) patients. Preoperative imaging showed a mean tibial tubercle-trochlear groove of 17.2±3.8, Caton-Deschamps Index (CDI) of 1.13±0.16, and trochlear dysplasia Dejour A/B [22/26 (85%)] or Dejour C/D [4/26 (15%)]. A total of 18 patients (19 knees, 72%) returned outcomes questionnaires at a mean 2.0±0.5 years after surgery. Mean Kujala, Pedi-IKDC, and Lysholm scores were 85.9±13.9, 81.5±15.2, and 84.3±13.5, respectively. Later revision procedure (tibial tubercle osteotomy) for recurrent patellar instability was required in 2 of 25 patients (8%) patients, and another patient reported persistent instability not requiring revision. Return to sports was possible in 10 of 13 self-reported athletes (77%) at a mean of 5.8±3.9 months (range, 2 to 15).

Conclusions:

The present study describes a combined MPFL-MQTFL reconstruction technique with favorable short-term results. Although particularly useful in the skeletally immature patient where tibial tubercle osteotomy should be avoided and patellar fixation minimized, combined reconstruction may potentially be appropriate for older patients with patellofemoral instability as well. This technique more closely recreates the native anatomy of both the MPFL and MQTFL, may decrease the risk of patellar fracture, and can be useful in the revision setting.

Level of Evidence:

Level IV.
Utilization of a Wide Array of Nonvalidated Outcome Scales in Pediatric Orthopaedic Publications: Can’t We All Measure the Same Thing?
Authors: Truong Walter H. , Price Meghan J. , Agarwal Kunal N. , Suryavanshi Joash R. , Somasegar Sahana , Thompson Micha , Fabricant Peter D. , Dodwell Emily R.
Published: October 2018

Purpose:

Clinical changes are best evaluated with standardized, validated outcomes, including both patient-reported outcome measures and surgeon-reported outcome measures (PROMs and SROMs). The purpose of this study was to describe the spectrum of outcome measures used in pediatric orthopaedic publications over the past 10 years and to determine the proportion that are in fact age-appropriate, validated, and appropriately applied in terms of condition and population.

Methods:

The Journal of Bone and Joint Surgery, The Bone and Joint Journal, Journal of Pediatric Orthopaedics A and B, and Journal of Children’s Orthopaedics were systematically searched for studies including children aged 18 and below, over a 10-year period from January 2005 to December 2014. Economic evaluations, letters, editorials, review articles, and clinical guidelines were excluded. SROMs and PROMs used were extracted, as were details on subject age and condition for which they were used. Each outcome scale was assessed for validity, and the proportion of scales used appropriately was calculated. Cochrane-Armitage test of trend was used to determine changes in PROM and SROM utilization over the study period.

Results:

A total of 4614 articles were identified, of which 2251 met inclusion and exclusion criteria. In total, 259 (11.5%) of studies used a PROM, whereas 326 (14.5%) used a SROM. A total of 230 different outcome scales were identified; 115 were patient reported and 115 were surgeon reported. However, only 18.7% of SROMs and 38.3% of PROMs were applied to an age and disease-appropriate demographic. Overall, there was a significant increase in the overall utilization of PROMs during the study period (P=0.004), but no corresponding increase in pediatric-validated PROMs (P=0.164). SROM utilization did not significantly change over the study period (P=0.337).

Conclusions:

Within the field of pediatric orthopaedics, an expansive variety of outcome scales are used, many of which have not been validated in children. Improved uniformity in reporting of outcomes and use of disease and age-validated outcomes scales is essential to improve multicenter research collaboration and data quality to generate appropriate evidence-based conclusions and treatment strategies in pediatric orthopaedics.

Level of Evidence:

Level IV—systematic review.
Surgical Management of the Posttraumatic Stiff Elbow: A Step-Wise Algorithm for Open Osteocapsular Release
Authors: Gauger Erich M. , Rhee Peter C.
Published: October 2018

Posttraumatic elbow stiffness is common with the primary indication for contracture release being limited motion that affects functional activities which has not adequately improved after intensive therapy and rehabilitation. Preoperative evaluation focuses on the history of previous nonoperative and/or operative treatment, physical exam with particular attention paid to the status of the ulnar nerve, and imaging consisting of radiographs and computed tomography. There are multiple intrinsic and extrinsic causes of posttraumatic contracture. In general, limitation of motion in one direction can be attributed to a mechanical block and/or opposing contracture or tightness. Open elbow contracture release has been shown to improve motion, patient health status and disability scores with the specific surgical approach based upon the contracture pathology and surgeon preference. A step-wise algorithm is presented for open osteocapsular release. An anterior and posterior release is performed first through a lateral approach with the addition of a medial approach if ulnar nerve dysfunction exists or inadequate release has been obtained from the lateral approach. A previous posterior incision can be utilized by raising full thickness flaps. After release, gentle manipulation is performed and intraoperative stability is assessed with stress testing under fluoroscopy. Postoperatively, pain is managed with an in-dwelling nerve catheter and rehabilitation commences immediately. Significant improvement in range of motion can be expected with adequate surgical release and postoperative rehabilitation.
Associations Among Pregnancy, Parturition, and Open-angle Glaucoma: Korea National Health and Nutrition Examination Survey 2010 to 2011
Authors: Lee Jae Yeun , Kim Joon Mo , Kim Seong Ho , Kim In Tae , Kim Hyun Tae , Chung Pil-Wook , Bae Jeong Hun , Won Yu Sam , Lee Mi Yeon , Park Ki Ho
Published: October 2018

Purpose:

The purpose of this study was to investigate the association between factors associated with parturition and open-angle glaucoma (OAG) in Korean females.

Methods:

A population-based, cross-sectional survey was performed from the Korean National Health and Nutrition Examination Survey from 2010 to 2011 and enrolled postmenopausal female participants (n=1798). We obtained information on demographics, comorbidities, and health-related behaviors and performed comprehensive ophthalmic examinations. Multivariate regression analysis was used to assess the correlation between pregnancy and delivery and the prevalence of OAG in all enrolled subjects.

Results:

The prevalence of OAG among study participants was 6.42%. There was a significant difference in the number of deliveries and age at first delivery between the OAG group and the nonglaucoma group. In multiple linear regression models adjusted for age, hypertension, and intraocular pressure only pregnancy 1 was associated with higher risk of OAG compared with pregnancy 2 (P=0.023). Subjects who had 3 or 4 deliveries were at higher risk of OAG compared with subjects with 2 deliveries (P=0.027). An age at first delivery of 16 to 20 years or 21 to 23 years was associated with increased OAG risk compared with the reference group (P<0.05).

Conclusions:

A history of three or more deliveries and an age at first delivery younger than 23 years were associated with increased risk of OAG. These results suggest that changes or events during the period from pregnancy to delivery affect the development of glaucoma.
A Prospective Evaluation of the Repeatability and Reliability of New Steady-state Pattern Electroretinogram Parameters
Authors: Gillmann Kevin , Mansouri Kaweh , Rao Harsha L. , Ouabas Adel , Chaudhary Ankita , Bravetti Giorgio E. , Mermoud André
Published: October 2018

Purpose:

The purpose of this study was to determine the repeatability and reproducibility of a new Pattern Electroretinography (PERG) device in healthy subjects.

Methods:

A total of 40 eyes of 20 healthy subjects (45.6±6.8 y, 70% female) were enrolled in this prospective study. Steady-state PERG were recorded using the Diopsys NOVA (Diopsys Inc., NJ) to obtain the Magnitude, MagnitudeD, MagnitudeD/Magnitude Ratio, and Signal to Noise Ratio. Subjects underwent 2 “contrast sensitivity” protocols with the same electrodes and 2 after changing electrodes, by a single examiner. Eyes were stimulated separately using high and low contrast patterns. The same examination was repeated by a different operator following the same protocol 6 months after the baseline measures. Repeatability and reproducibility of the readings were calculated using intraclass correlation coefficient (ICC). A Bland-Altman plot was used to analyze the agreement between measures.

Results:

ICC of Magnitude, MagnitudeD, MagnitudeD/Magnitude ratio, and SNR were 0.87, 0.81, 0.36, and 0.81, respectively between measures taken with the same electrodes (repeatability). After changing electrodes, ICC of the Magnitude, MagD, MagD/Mag ratio, and SNR were 0.79, 0.85, 0.51, and 0.83, respectively during the same session as baseline measures, and 0.87, 0.85, 0.40, and 0.76 when repeated after 6 months (reproducibility). The variability of MagD/Mag ratio increased with successive test repetitions.

Conclusions:

Mag, MagD, and SNR were repeatable and reproducible, whereas the MagD/Mag ratio was less repeatable and reproducible. These results suggest that the former parameters are sufficiently reliable to be used in clinical practice.
Concussion Burden, Recovery, and Risk Factors in Elite Youth Ice Hockey Players
Authors: Schneider Kathryn J. , Nettel-Aguirre Alberto , Palacios-Derflingher Luz , Mrazik Martin , Brooks Brian L. , Woollings Kaikanani , Blake Tracy , McKay Carly , Lebrun Constance , Barlow Karen , Taylor Kirsten , Lemke Nicole , Meeuwisse Willem H. , Emery Carolyn A.
Published: October 2018

Objective:

To examine rates of concussion and more severe concussion (time loss of greater than 10 days) in elite 13- to 17-year-old ice hockey players.

Methods:

This is a prospective cohort study (Alberta, Canada). Bantam (13-14 years) and Midget (15-17 years) male and female elite (top 20% by division of play) youth ice hockey players participated in this study. Players completed a demographic and medical history questionnaire and clinical test battery at the beginning of the season. A previously validated injury surveillance system was used to document exposure hours and injury during one season of play (8 months). Players with a suspected ice hockey–related concussion were referred to the study sport medicine physicians for assessment. Time loss from hockey participation was documented on an injury report form.

Results:

Overall, 778 elite youth ice hockey players (659 males and 119 females; aged 13-17 years) participated in this study. In total, 143 concussions were reported. The concussion incidence rate (IR) was 17.60 concussions/100 players (95% CI, 15.09-20.44). The concussion IR was 1.31 concussions/1000 player-hours (95% CI, 1.09-1.57). Time loss of greater than 10 days was reported in 74% of cases (106/143), and 20% (n = 28) had time loss of greater than 30 days.

Conclusions:

Concussion is a common injury in elite youth ice hockey players. In this study population, a large proportion of concussions (74%) resulted in a time loss of greater than 10 days, possibly reflecting more conservative management or longer recovery in youth athletes.
Velopharyngeal incompetence: role in paediatric swallowing deficits
Authors: Swibel Rosenthal Laura H. , Walsh Kathleen , Thompson Dana M.
Published: October 2018

Purpose of review

The purpose of this manuscript is to highlight the latest advances in diagnosis and management of velopharyngeal incompetence (VPI) as it pertains to swallowing deficits in children. This is timely and relevant as otolaryngologists are often amongst the first to diagnose and treat VPI. Although nasal regurgitation of a bolus is frequently transient, persistent problems can be associated with other swallowing problems and other significant medical problems. Furthermore, velopharyngeal incompetence has implications for speech production.

Recent findings

Persistent VPI associated with a swallowing deficit can be an isolated anomaly with or without a cleft palate or submucous cleft palate. VPI may be secondary to a cranial neuropathy, esophageal abnormality or associated with another airway anomaly, any of which may further contribute to dysphagia. Findings of additional anomalies may be suggestive of a syndrome. Workup should explore these potential causes. When velopharyngeal incompetence is associated with dysphagia, fiberoptic endoscopic evaluation of swallow (FEES) and videofluoroscopic swallow study (VFSS) can be helpful in diagnosis and management. The advantages and disadvantages of FEES and VFSS have been well delineated over the past few years. Similarly, nasopharyngoscopy and fluoroscopy are increasingly used in diagnosis and management of VPI that is associated with hypernasal resonance disorders.

Concurrent medical diagnoses or syndrome manifestations are often associated with or contribute significantly to the cause of dysphagia in children with VPI. As VPI can be a sign of brainstem vagal neuropathy, the clinician should investigate by imaging the CNS if other correlative symptoms of dysphagia and examination findings are present. Endoscopy is advocated for evaluation of vocal fold function. Fluoroscopy is best for further assessment of airway protection or safety of swallow. And, whenever indicated, additional workup is recommended to determine an underlying cause of the swallowing disorder.
Update on sinus disease in children with cystic fibrosis: advances in treatment modalities, microbiology, and health-related quality-of-life instruments
Authors: Gallant Jean-Nicolas , Mitchell Margaret B. , Virgin Frank W.
Published: October 2018

Purpose of review

There is a lack of consensus with regards to the diagnosis and treatment of sinus disease in children with cystic fibrosis. Here, we review literature from the past 18 months in order to highlight the way forward in this contentious field.

Recent findings

Most of the literature (from the past 18 months) on sinus disease in pediatric cystic fibrosis focused on treatment approaches, bacteriology and immunology, and health-related quality-of-life (HRQOL) instruments. Quality studies have demonstrated that functional endoscopic sinus surgery (FESS) is as safe in children with or without cystic fibrosis; that the microbiology of the paranasal sinus in children with cystic fibrosis is different than that of their lungs; and, that HRQOL instruments may prove useful in determining sinonasal disease severity in children with cystic fibrosis.

Medical and surgical approaches appear to be viable in the treatment of sinonasal disease in pediatric cystic fibrosis; the microbiology and immunology of pediatric cystic fibrosis is proving more complex and nuanced than initially believed; and, HRQOL instruments show promise in reconciling differences between observable and clinically relevant sinus disease in pediatric cystic fibrosis patients.
Vocal fold nodules in children
Authors: Mudd Pamela , Noelke Carolyn
Published: October 2018

Purpose of review

Vocal nodules are a common presentation in children, representing the most common cause of dysphonia.

Recent findings

Children with siblings, ADHD, and of male sex are most likely to be affected. Female children, however, tend to have more likely progression into adolescence. Quality-of-life indices can aid in screening for vocal nodules whereas stroboscopy, and possibly, ultrasound are required for definitive diagnosis.

Management has not significantly changed over time and should begin with conservative behavioral and environmental modifications along with voice therapy in those more severely impacted. Though immediate outcomes vary somewhat depending on management direction, the overall prognosis seems to be good even with lack of intervention. It is most critical to ensure a definitive diagnosis, and offer management therapies that are appropriate for the level of impact the vocal nodules have on communication and voice production in the child.
Female athletes: managing risk and maximizing benefit
Authors: Cleary Shannon , Chi Victoria , Feinstein Ronald
Published: October 2018

Purpose of review

The purpose of this review is to provide an updated summary on the unique aspects of caring for female youth and adolescent athletes.

Recent findings

Recent research on female athletes has led to a better understanding of injuries and conditions that are more likely to occur in female youth and adolescent athletes, including the frequency and severity of concussions, musculoskeletal injury such as involving the anterior cruciate ligament, and the female athlete triad. Social factors, such as the growing pressure to specialize in a sport particularly at an early age, also put young female athletes at risk for issues such as overuse injuries. Researchers continue to explore the benefits of athletic participation that extend beyond physical fitness.

Female participation in youth sports has increased dramatically during the past 50 years. This has led to greater research on how to manage risks and maximize benefits for young female athletes, although there is still much to be learned. Providers should educate patients, parents, and coaches on both the increased risks for female athletes and ways to provide better support and accessibility of youth sports to all children.
Infections after xenotransplantation
Authors: Nellore Anoma
Published: October 2018

Purpose of review

Xenotransplantation offers a solution for the global shortage of available organs. However, cross-species transplantation and immunosuppression raises concerns about transmission of zoonotic infections to the recipient as well as to the public.

Recent findings

Here, we review the major infections of concern after xenotransplantation, risks of their transmission, diagnostic, therapeutic as well as prevention modalities for these infections after xenotransplantation. This review is particularly timely in light of recent advances in porcine genome editing technology that allow removal of retroviral sequences.

We cannot appreciate the full risk of infections after xenotransplantation in absence of clinical trials. However, there are guidelines for strict microbiologic monitoring and reporting, infectious diagnostic assay development, breeding and quarantine of graft source animals to limit infectious transmission.
Lung bioengineering: advances and challenges in lung decellularization and recellularization
Authors: Uriarte Juan J. , Uhl Franziska E. , Rolandsson Enes Sara E. , Pouliot Robert A. , Weiss Daniel J.
Published: October 2018

Purpose of review

Bioengineering the lung based on its natural extracellular matrix (ECM) offers novel opportunities to overcome the shortage of donors, to reduce chronic allograft rejections, and to improve the median survival rate of transplanted patients. During the last decade, lung tissue engineering has advanced rapidly to combine scaffolds, cells, and biologically active molecules into functional tissues to restore or improve the lung's main function, gas exchange. This review will inspect the current progress in lung bioengineering using decellularized and recellularized lung scaffolds and highlight future challenges in the field.

Recent findings

Lung decellularization and recellularization protocols have provided researchers with tools to progress toward functional lung tissue engineering. However, there is continuous evolution and refinement particularly for optimization of lung recellularization. These further the possibility of developing a transplantable bioartificial lung.

Bioengineering the lung using recellularized scaffolds could offer a curative option for patients with end-stage organ failure but its accomplishment remains unclear in the short-term. However, the state-of-the-art of techniques described in this review will increase our knowledge of the lung ECM and of chemical and mechanical cues which drive cell repopulation to improve the advances in lung regeneration and lung tissue engineering.
Incidence and Characteristics of Neonatal Herpes: Comparison of Two Population-Based Data Sources, New York City, 2006–2015
Authors: Lao Steven , Flagg Elaine W. , Schillinger Julia A.
Published: October 2018

Background

Neonatal herpes (nHSV) is a potentially fatal disease caused by herpes simplex virus (HSV) infection during the neonatal period. Neonatal herpes simplex virus infections are not nationally notifiable, and varying incidence rates have been reported. Beginning in 2006, New York City (NYC) required reporting of nHSV infections and conducted case investigations. We compared the use of administrative hospital data with active surveillance to monitor trends in nHSV infection.

Methods

We compared the incidence and characteristics of nHSV cases as measured using population-based surveillance and administrative hospital discharge data collected between 2006 and 2015. Surveillance cases were defined as laboratory-confirmed HSV infections in NYC-resident infants aged 60 days or younger at diagnosis. Administrative cases were defined as NYC-resident infants aged 60 days or younger at hospital admission whose records included an HSV diagnosis. Neonatal herpes cases after ritual Jewish circumcision with direct orogenital suction were excluded.

Results

There were 107 surveillance cases (9.9 per 100,000 live births) and 131 administrative cases (12.1 per 100,000 live births). Incidence was highest in infants born to non-Hispanic black mothers aged 20 years or younger (surveillance, 57.2 per 100,000 live births; administrative data, 31.2 per 100,000 live births). The distribution of cases by year did not significantly differ across data sources. Surveillance cases had a higher case-fatality rate (18.7%) compared with administrative cases (8.4%;P= 0.019).

Conclusions

Administrative hospital data can be used to measure the incidence of nHSV infection and describe disease burden across population subgroups in jurisdictions where nHSV reporting is not required. However, administrative data may underascertain nHSV case fatality.