bluuebunny/crossref_metadata_2025 huggingface dataset:
LC3 and STRAP regulate actin filament assembly by JMY during autophagosome formation
Authors: Hu Xiaohua , Mullins R. Dyche
Published: November 2018

During autophagy, actin filament networks move and remodel cellular membranes to form autophagosomes that enclose and metabolize cytoplasmic contents. Two actin regulators, WHAMM and JMY, participate in autophagosome formation, but the signals linking autophagy to actin assembly are poorly understood. We show that, in nonstarved cells, cytoplasmic JMY colocalizes with STRAP, a regulator of JMY’s nuclear functions, on nonmotile vesicles with no associated actin networks. Upon starvation, JMY shifts to motile, LC3-containing membranes that move on actin comet tails. LC3 enhances JMY’s de novo actin nucleation activity via a cryptic actin-binding sequence near JMY’s N terminus, and STRAP inhibits JMY’s ability to nucleate actin and activate the Arp2/3 complex. Cytoplasmic STRAP negatively regulates autophagy. Finally, we use purified proteins to reconstitute LC3- and JMY-dependent actin network formation on membranes and inhibition of network formation by STRAP. We conclude that LC3 and STRAP regulate JMY’s actin assembly activities in trans during autophagy.
Final report, on-going key comparison BIPM.QM-K1, ozone at ambient level, comparison with NIST, September 2017
Authors: Viallon Joële , Idrees Faraz , Moussay Philippe , Wielgosz Robert , Norris James E , Hodges Joseph T
Published: November 2018

As part of the ongoing key comparison BIPM.QM-K1, a comparison has been performed between the ozone national standard of the National Institute of Standards and Technology (NIST) and the common reference standard of the key comparison, maintained by the Bureau International des Poids et Mesures (BIPM). The instruments have been compared over a nominal ozone amount-of-substance fraction range of 0 nmol/mol to 500 nmol/mol.

KEY WORDS FOR SEARCH

Ozone, Standard Reference Photometer

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.

The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
The magneto-optical response of two Faraday crystals from Matesy: a case study
Authors: Espina-Hernández J H , Michlmayr S , Piepgras R , Zagar B
Published: November 2018

This work analyses two Faraday crystals from the company Matesy to elucidate how their differences compromise experimental results for quantitative magnetometry. Our results show that the two crystals have different domain patterns and different hysteresis loops under the influence of a homogeneous magnetic field, which point to the importance of considering carefully the crystal selection and their individual characterization for its successful implementation in a magneto-optic measurement setup.
Estimation of vector uncertainties of multivariable indirect instrumental measurement systems on the star circuit example
Authors: Warsza Zygmunt , Puchalski Jacek
Published: November 2018

Signal processing in a multi-variable indirect measurement system and its uncertainties is considered. It was proposed to extend the vector method of estimating uncertainties, given in Supplement 2 to GUM for the use to describe the accuracy of instrumental systems for indirect multivariable measurements. A formula for the covariance matrix of relative uncertainties is also given. As the example, the covariance matrix for indirect measurements of the star form circuit resistances from its terminals was determined and influence of of the measurement channels uncertainties are analyzed.
Effect Modification by Age on the Benefit or Harm of Antihypertensive Treatment for Elderly Hypertensives: A Systematic Review and Meta-analysis
Authors: Huang Chi-Jung , Chiang Chern-En , Williams Bryan , Kario Kazuomi , Sung Shih-Hsien , Chen Chen-Huan , Wang Tzung-Dau , Cheng Hao-Min
Published: November 2018

BACKGROUND

The influence of age on balance of benefit vs. potential harm of blood pressure (BP)-lowering therapy for elderly hypertensives is unclear. We evaluated the modifying effects of age on BP lowering for various adverse outcomes in hypertensive patients older than 60 years without specified comorbidities.

METHODS

All relevant randomized controlled trials (RCTs) were systematically identified. Coronary heart disease, stroke, heart failure (HF), cardiovascular death, major adverse cardiovascular events (MACE), renal failure (RF), and all-cause death were assessed. Meta-regression analysis was used to explore the relationship between achieved systolic BP (SBP) and the risk of adverse events. Random-effects meta-analysis was used to pool the estimates.

RESULTS

Our study included 18 RCTs (n = 53,993). Meta-regression analysis showed a lower achieved SBP related with a lower risk of stroke and cardiovascular death, but an increased risk of RF. The regression slopes were comparable between populations stratifying by age 75 years. In subgroup analysis, the relative risks of a more aggressive BP lowering strategy were similar between patients aged older or less than 75 years for all outcomes except for RF (P for interaction = 0.02). Compared to treatment with final achieved SBP 140–150 mm Hg, a lower achieved SBP (<140 mm Hg) was significantly associated with decreased risk of stroke (relative risk = 0.68; 95% confidence interval = 0.55–0.85), HF (0.77; 0.60–0.99), cardiovascular death (0.68; 0.52–0.89), and MACE (0.83; 0.69–0.99).

CONCLUSIONS

To treat hypertension in the elderly, age had trivial effect modification on most outcomes, except for renal failure. Close monitoring of renal function may be warranted in the management of elderly hypertension.
A Novel Extended Deep Plane Facelift Technique for Jawline Rejuvenation and Volumization
Authors: Jacono Andrew A , Bryant Lucas M , Ahmedli Nigar N
Published: November 2018

Background

Jawline aging is a complex process. We believe loss of posterior jawline definition and volume depletion is an underappreciated factor in the aging face.

Objectives

The aim of this study was to describe a novel composite, rotational flap modification of an extended deep-plane rhytidectomy. We evaluated long-term efficacy on improving jawline contour and volumization of the posterior mandibular region overlying the gonial angle.

Methods

We performed a prospective study on patients who underwent our modification of extended deep-plane rhytidectomy. We define and introduce the mandibular defining line, a new anatomic metric in evaluating the mandibular contour. We define the area of the posterior lower face overlying the gonion and mandibular angle as the gonial area. Using 3-dimensional photography, we quantify contour changes along the mandibular border and volume change along the gonial area.

Results

Eighty-nine patients (178 hemifaces) were analyzed. The mean gonial area volume gained was 3.5 cc. Average follow-up was 19 months. There was a statistically significant change in the mean mandibular defining line from 7.1 cm preoperatively to 9.8 cm postoperatively. This represents a lengthening of the visual perspective of the mandibular contour of 2.7 cm.

Conclusions

Composite, rotational flap modification of extended deep-plane rhytidectomy provides significant long-term augmentation of volume to the posterior mandibular region and lengthens the visual perspective of the inferior mandibular contour, creating a more youthful jawline. In selected cases, this may obviate the need for other volumization procedures used to improve jawline contour, such as autologous fat grafting.

Level of Evidence: 4
Ledipasvir/Sofosbuvir for 8 Weeks to Treat Acute Hepatitis C Virus Infections in Men With Human Immunodeficiency Virus Infections: Sofosbuvir-Containing Regimens Without Interferon for Treatment of Acute HCV in HIV-1 Infected Individuals
Authors: Naggie Susanna , Fierer Daniel S , Hughes Michael D , Kim Arthur Y , Luetkemeyer Annie , Vu Vincent , Roa Jhoanna , Rwema Steve , Brainard Diana M , McHutchison John G , Peters Marion G , Kiser Jennifer J , Marks Kristen M , Chung Raymond T ,   Acquired Immunodeficiency Syndrome Clinical Trials Group (ACTG) A5327 Study Team, Alston-Smith Beverly , Weichmann Laura , Sise Thucuma , Cosimano Emily , Jennings Cheryl , Moyo Sikhulile , Dadson Oswald , Luetkemeyer Annie , Dwyer Jay , Hughes Valery , Grenade Joanne , Stroberg Todd , Ilmet Tiina , Henn Sarah , Kiger Kristi , Flynn Teri , Sbrolla Amy , Nuffer Kathleen , Wyles David , McGregor Donna , Hawkins Claudia , Williams Brett , Green Tondria , Tebas Pablo , Kim Deborah , Bedimo Roger , Wise Holly , Arduino Roberto C , Villamil Aristoteles
Published: November 2018

Background

Current guidelines for the management of hepatitis C virus (HCV) infections provide varying recommendations for the optimal treatment of acute HCV infections. There are limited data from small cohort studies to provide guidance on the best approach to treatment of this important patient population.

Methods

Sofosbuvir-Containing Regimens Without Interferon for Treatment of Acute HCV in HIV-1 Infected Individuals is an open-label, 2-cohort, Phase 1 clinical trial in which the second cohort assessed the safety and efficacy of 8 weeks of ledipasvir/sofosbuvir for the treatment of acute HCV infections in participants with chronic human immunodeficiency virus (HIV)-1 infections. This final analysis of the second cohort had a planned accrual of 27 participants, based on non-inferiority criteria, compared to the study-defined, historical, sustained virologic response (SVR) of 60% with pegylated-interferon/ribavirin.

Results

We enrolled 27 men (9 Hispanic; 11 White, non-Hispanic; 5 Black, non-Hispanic; 2 Asian or Pacific Islander; median age 46 years). Most (96%) had HCV genotype-1 infection and 59% had the favorable interleukin 28B CC genotype. The median baseline HCV RNA load was 6.17 log10 IU/mL (interquartile range 4.51 – 6.55). All participants (100%) achieved the primary outcome of a sustained virologic response 12 weeks after the date of the last dose of study treatment (90% confidence interval 90–100%), achieving non-inferiority versus the 60% historic benchmark. No treatment discontinuations occurred.

Conclusions

This multicenter clinical trial, investigating 8 weeks of ledipasvir/sofosbuvir for acute HCV infections in men with HIV infections, reports a 100% SVR. This study provides the rationale for larger studies of shortened courses of direct-acting antiviral therapies in persons with HIV infections, including those with high baseline HCV RNA loads.

Clinical Trials Registration

NCT02128217.
A Critical Assessment of the Asia Rebalance
Authors: Katagiri Nori
Published: November 2018

While the Obama administration’s Asia rebalance strategy received some praise from scholars and practitioners, it generated three problems that caused the USA to overlook many opportunities and neglect vital concerns. First, the strategy left Asia less stable by undermining US relations with China and smaller states in Southeast Asia. Secondly, it weakened America’s influence outside Asia by committing fewer resources. Finally, the rebalance was executed out of a relatively small cadre of government officials, allowing primarily civilian agencies to dictate Asia policy and excluding key branches of government. Furthermore, although the strategy competed with the strategies of restraint and offshore balancing, it never had the solid support of any international relations theories, leaving few scholars to directly associate it with a theory. Ultimately, the rebalance’s multiple logics prevented it from achieving intellectual hegemony in the American foreign policy discourse, and its substantive flaws and theoretical inconsistencies made difficult its acceptance as an enduring strategy in the Asia-Pacific region.
Mode classification in fast-rotating stars using a convolutional neural network: model-based regular patterns in δ Scuti stars
Authors: Mirouh Giovanni M , Angelou George C , Reese Daniel R , Costa Guglielmo
Published: November 2018

Oscillation modes in fast-rotating stars can be split into several subclasses, each with their own properties. To date, seismology of these stars cannot rely on regular pattern analysis and scaling relations. However, recently there has been the promising discovery of large separations observed in spectra of fast-rotating δ Scuti stars; they were attributed to the island-mode subclass, and linked to the stellar mean density through a scaling law. In this work, we investigate the relevance of this scaling relation by computing models of fast-rotating stars and their oscillation spectra. In order to sort the thousands of oscillation modes thus obtained, we train a convolutional neural network isolating the island modes with 96 per cent accuracy. Arguing that the observed large separation is systematically smaller than the asymptotic one, we retrieve the observational $\Delta \nu \text{--} \overline{\rho }$ scaling law. This relation will be used to drive forward modelling efforts, and is a first step towards mode identification and inversions for fast-rotating stars.
What Isn’t a Case-Control Study?
Authors: Kicielinski Kimberly P , Dupépé Esther B , Gordon Amber S , Mayo Nancy E , Walters Beverly C
Published: November 2018

BACKGROUND

Confusion exists among neurosurgeons when choosing and implementing an appropriate study design and statistical methods when conducting research. We noticed particular difficulty with mislabeled and inappropriate case-control studies in the neurosurgical literature.

OBJECTIVE

To quantify and to rigorously review this issue for appropriateness in publication and to establish quality of the manuscripts using a rigorous technique.

METHODS

Following a literature search, pairs drawn from 5 independent reviewers evaluated a complete sample of 125 manuscripts claiming to be case-control studies with respect to basic case-control criteria. Seventy-five papers were then subjected to a more rigorous appraisal for quality using the SIGN Methodology Checklist for case-control studies.

RESULTS

Fifty publications were rejected based on basic criteria used to identify case-control design. Of the 75 subjected to quality analysis, 46 were felt to be acceptable for publication. Only 11 papers (9%) achieved the designation of high quality. Of the original 125 papers evaluated, 79 (63%) were inappropriately labeled case-control studies.

CONCLUSION

Mislabeling and use of inappropriate study design are common in the neurosurgical literature. Manuscripts should be evaluated rigorously by reviewers and readers, and neurosurgical training programs should include instruction on choice of appropriate study design and critical appraisal of the literature.
Inhibition of Manual Movements at Speech Arrest Sites in the Posterior Inferior Frontal Lobe
Authors: Breshears Jonathan D , Southwell Derek G , Chang Edward F
Published: November 2018

BACKGROUND

Intraoperative stimulation of the posterior inferior frontal lobe (IFL) induces speech arrest, which is often interpreted as demonstration of essential language function. However, prior reports have described “negative motor areas” in the IFL, sites where stimulation halts ongoing limb motor activity.

OBJECTIVE

To investigate the spatial and functional relationship between IFL speech arrest areas and negative motor areas (NMAs).

METHODS

In this retrospective cohort study, intraoperative stimulation mapping was performed to localize speech and motor function, as well as arrest of hand movement, hand posture, and guitar playing in a set of patients undergoing awake craniotomy for dominant hemisphere pathologies. The incidence and localization of speech arrest and motor inhibition was analyzed.

RESULTS

Eleven patients underwent intraoperative localization of speech arrest sites and inhibitory motor areas. A total of 17 speech arrest sites were identified in the dominant frontal lobe, and, of these, 5 sites (29.4%) were also identified as NMAs. Speech arrest and arrest of guitar playing was also evoked by a single IFL site in 1 subject.

CONCLUSION

Inferior frontal gyrus speech arrest sites do not function solely in speech production. These findings provide further evidence for the complexity of language organization, and suggest the need for refined mapping strategies that discern between language-specific sites and inhibitory motor areas.
Surgical Stabilization Improves 30-day Mortality in Patients With Traumatic Flail Chest: A Comparative Case Series at a Major Trauma Center
Authors: Walters Samuel T. , Craxford Simon , Russell Rebecca , Khan Tanvir , Nightingale Jessica , Moran Chris G. , Taylor Andrew M. , Forward Daren P. , Ollivere Benjamin J.
Published: November 2018

Objectives:

To evaluate the outcomes including early mortality after surgical rib fixation using a locking plate system as part of a newly introduced chest trauma pathway.

Design:

Prospective cohort study with retrospective case-controlled matching with a minimum of 1-year follow-up.

Setting:

Regional Level 1 trauma center.

Patients/Participants:

Consecutive patients undergoing surgical rib fixation were prospectively recruited over a 3-year period (56 patients) and matched to similar patients managed nonoperatively (89 patients) using our local trauma registry. Matching was based on injury severity scores and patient demographics.

Intervention:

Surgical rib fixation with locking plates.

Main Outcome Measurements:

The primary outcome measure was 30-day mortality with secondary outcomes of hospital length of stay, intensive care unit length of stay, and patient-reported outcome measures including quality of life (EuroQol—EQ-5D-5L). Official causes of death were obtained from the coroner including postmortem results.

Results:

There was a significant reduction in 30-day mortality in the fixed patients with 1.8% (1/56) compared to 12.4% (11/89) of the nonfixed patients (P = 0.03). This difference remained significant after further exclusion of other nonsurvivable injuries (P = 0.046). Although hospital length of stay was significantly longer in the fixed group, there was no difference on multivariable analysis. Other secondary outcomes were comparable between the groups with no significant differences in any patient-reported measures.

Conclusions:

Mortality was significantly lower in patients who underwent rib stabilization. Quality of life and other patient-reported measures were similar, demonstrating no evidence of detrimental longer-term effects of rib stabilization.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Biomarkers for immune checkpoint inhibitors in advanced nonsmall cell lung cancer
Authors: Pirker Robert
Published: November 2018

Purpose of review

Immune checkpoint inhibitors have been established as a new class of anticancer drugs for patients with advanced nonsmall cell lung cancer. Predictive biomarkers might help to select those patients who will derive the greatest benefit from these expensive drugs. This review summarizes the current status of predictive biomarkers for immune checkpoint inhibitors in advanced nonsmall cell lung cancer.

Recent finding

Programmed death ligand 1 (PD-L1) staining on tumor cells and immune cells has been studied as a predictive biomarker for immune checkpoint inhibitors. Higher PD-L1 levels appeared to be associated with greater benefit from these drugs in many studies, although such an association was absent in some studies. Tumor mutational load was associated with benefit from the combination of nivolumab plus ipilimumab. Immune checkpoint inhibitors combined with first-line chemotherapy improved survival compared to chemotherapy alone. These improvements were clinically relevant also in patients with PD-L1 expression in less than 1% of tumor cells.

PD-L1 expression on tumor and immune cells and tumor mutational load allow better selection of patients for treatment with immune checkpoint inhibitors as single agents. The role of PD-L1 for the selection of patients for chemoimmuntherapy remains to be seen.
Cardiovascular Diseases and Long-term Self-reported Exposure to Pollution
Authors: Salameh Pascale , Zeidan Rouba Karen , Hallit Souheil , Farah Rita , Chahine Mirna , Asmar Roland , Hosseini Hassan
Published: November 2018

Background:

Cardiovascular diseases (CVDs) are linked to high mortality and morbidity, particularly in developing countries. Some studies have linked indoor and outdoor pollution to CVD, but results are inconsistent. Our objective was to assess this association in Lebanon, a Middle Eastern country.

Methods:

A national cross-sectional study was conducted across Lebanon. CVD prevalence, which included prevalent ischemic heart and cerebrovascular diseases, was assessed. Moreover, in addition to self-reported items of pollution exposure, we assessed potential predictors of CVD, including sociodemographic characteristics, self-reported health information, and biological measurements.

Results:

We assessed the dose-effect relationship of pollution items in relation with CVD. Self-reported indoor and outdoor pollution exposures were associated with CVD, with or without taking biological values into account. Moreover, we found a dose-effect relationship of exposure with risk of disease (44% increase in risk of CVD for every additional pollution exposure item), after adjustment for sociodemographic and biological characteristics.

Conclusion:

Although additional studies would be necessary to confirm these findings, interventions should start to sensitize the population about the effect of pollution on chronic diseases and the work of reducing pollution and improving air quality should be implemented to decrease the disease burden on the population and health system.
Minimizing Endothelial Cell Loss Caused by Orientation Stamps on Preloaded Descemet Membrane Endothelial Keratoplasty Grafts
Authors: Newman Lara R. , Tran Khoa D. , Odell Kelly , Dye Philip K. , Galloway Joshua , Sales Christopher S. , Straiko Michael D. , Terry Mark A.
Published: November 2018

Purpose:

To quantify endothelial cell loss (ECL) caused by orientation stamps on prestripped and preloaded Descemet membrane endothelial keratoplasty (DMEK) grafts, and to examine a method for reducing ECL using a smaller stamp.

Methods:

Ten prestripped and 10 preloaded DMEK grafts were prepared with S-stamps. Ten additional preloaded DMEK grafts were prepared with both an S-stamp and a smaller F-stamp in different paracentral areas of the graft. The footprint of each stamp was measured using ink on cardstock. DMEK grafts were stored in viewing chambers filled with 20 mL of Optisol-GS for 3 days at 4°C. ECL was quantified using Calcein-AM staining and FIJI Weka Segmentation.

Results:

S-stamps on prestripped DMEK grafts contributed an average ECL of 1.1% ± 0.5% (range: 0.6%–2.2%) toward total graft damage, whereas S-stamps on preloaded DMEK grafts contributed approximately twice that amount (average ECL: 2.0% ± 0.7%, range: 1.3%–3.1%, P = 0.004). Overall ECL for prestripped grafts (average: 7.1% ± 3.3%, range: 3.3%–13.7%) and preloaded grafts (average: 11.3% ± 4.2%, range: 6.9%–19.4%) was similar to previous reports. The footprint of the S-stamp was approximately 45% larger than that of the F-stamp. In 10 preloaded grafts marked with both stamps, the S-stamp caused an average ECL of 1.9% ± 0.6% (range: 1.2%–3.2%), whereas the smaller F-stamp caused an average ECL of 1.0% ± 0.2% (range: 0.8%–1.4%, P = 0.0002).

Conclusions:

Loss of endothelial cells associated with graft-stamping was greater in preloaded tissue than in prestripped tissue and was less with a smaller F-stamp than with a larger S-stamp. Using a smaller stamp could help minimize ECL in prestripped and preloaded DMEK grafts.
Concomitant Left Atrial Reduction in Rheumatic Mitral Valve Disease with Giant Left Atrium
Authors: Adalti Sudhir , Patel Kartik G. , Doshi Chirag P. , Ananthnarayanan Chandrashekhar , Mehta Chintan N. , Wadhawa Vivek A. , Gupta Vijay , Patel Sanjay K.
Published: November 2018

Objective

The giant left atrium is a frequent finding with rheumatic heart disease. The enlarged left atrium was found to be a risk factor for early mortality and postoperative higher thromboembolic events, but its management remains controversial. Most of the surgeons just do the mitral valve procedure without any intervention for enlarged left atrium. We present our center's experience of patients with giant left atrium who underwent a newer technique of left atrium reduction concomitant with mitral valve procedure.

Methods

Between January 2012 and February 2015, 25 patients, who underwent surgery for concomitant left atrium reduction with mitral valve disease, were included in the study after institute's ethics committee clearance. Patients having combined aortic and mitral valve disease were excluded. Preoperative, intraoperative, and postoperative data were collected. All the patients were also followed up clinically and echocardiographically in postoperative period.

Results

There were 15 (60%) females. The mean ± SD age of the patients was 36.92 ± 5.4 years. Preoperatively, all patients were in long-standing persistent atrial fibrillation. The mean ± SD bypass and aortic cross-clamp time were 74.56 ± 3.85 and 51.72 ± 4.32 minutes, respectively. There was a significant reduction of left atrium diameter and volume from 94.48 ± 11.0 mm to 40.08 ± 1.35 mm and 348.3 ± 121.1 to 26.57 ± 2.9 mL/m2, respectively. There was no early or late mortality. At a mean ± SD follow-up of 42.28 ± 12.1 months, all patients were in New York Heart Association I or II class and 24 (96%) patients were in normal sinus rhythm.

Conclusions

Concurrent left atrium reduction with mitral valve procedure is a feasible and effective technique for event-free survival of the patients having giant left atrium with mitral disease.
Determinants of Influenza and Pertussis Vaccination Uptake in Pregnancy
Authors: Wilcox Christopher R. , Calvert Anna , Metz Jane , Kilich Eliz , MacLeod Rachael , Beadon Kirsten , Heath Paul T. , Khalil Asma , Finn Adam , Snape Matthew D. , Vandrevala Tushna , Nadarzynski Tom , Coleman Matthew A. , Jones Christine E.
Published: November 2018

Introduction:

Uptake rates of antenatal vaccination remain suboptimal. Our aims were to determine (1) the acceptability of routine vaccination among pregnant women, (2) the confidence of maternity healthcare professionals (HCPs) discussing vaccination and (3) HCP opinion regarding the optimum healthcare site for vaccine administration.

Methods:

Separate questionnaires for pregnant women and HCPs were distributed within 4 national health service (NHS) trusts in South England (July 2017 to January 2018).

Results:

Responses from 314 pregnant women and 204 HCPs (18% obstetricians, 75% midwives, 7% unidentified) were analyzed. Previous/intended uptake of influenza and pertussis vaccination was 78% and 92%, respectively. The commonest reason for declining vaccination was feared side effects for their child. White British women (79%) were significantly more accepting of influenza [85% vs. 61%; odds ratio (OR) 3.25; 95% confidence interval [CI], 1.67–6.32] and pertussis vaccination (96% vs. 83%; OR 4.83; 95% CI: 1.77–13.19) compared with nonwhite British women. Among HCPs, 25% were slightly or not at all confident discussing vaccination. Obstetricians felt significantly more confident discussing pertussis vaccination than midwives (68% vs. 55% were very/moderately confident; OR 2.05; 95% CI: 1.02–4.12). Among HCPs, 53%, 25% and 16% thought vaccines should be administered in primary care (general practice), community midwifery and in hospital, respectively.

Conclusion:

Misconceptions exist regarding safety/efficacy of antenatal vaccination, and framing information towards the child’s safety may increase uptake. Education of HCPs is essential, and vaccine promotion should be incorporated into routine antenatal care, with an emphasis on women from ethnic minorities. Administration of vaccines in primary care presents logistical barriers; however, support for alternative sites appears low among HCPs.
Use of the Intrepid Dynamic Exoskeletal Orthosis in the Management of Common Peroneal Nerve Palsy after Knee Dislocation
Authors: Quacinella Michael , Mazzone Brittney , Kuhn Kevin , Wyatt Marilynn
Published: November 2018

Introduction

The intrepid dynamic exoskeletal orthosis (IDEO) is a custom high-level floor reaction ankle-foot orthosis (AFO) designed specifically for the war limb salvage military population. The use of the IDEO has not been described in the management of foot drop after common peroneal nerve (CPN) palsy after knee dislocation. We present two case reports demonstrating the efficacy the IDEO in treating active-duty service members with foot drop after CPN palsy.

Method

Two active-duty male Marines sustained CPN injury and foot drop after knee dislocation as a result of noncontact sports injuries. The IDEO was selected based on both patients' functional limitations despite surgical reconstruction. Both expressed a desire to return to unrestricted active-duty military duty. The IDEO was selected for treatment based on prior successes in limb salvage patients. A three-dimensional gait analysis was performed with the patient ambulating at a self-selected speed under three conditions: 1) barefoot, 2) shod without orthosis, and 3) IDEO with shod. Variables of interest were spatiotemporal and gait kinematics, return to active-duty status, gait symmetry, and Comprehensive High-Level Activity Mobility Predictor (CHAMP) scores.

Results

Sagittal plane kinematics improved while ambulating with the IDEO demonstrating improved steppage gait. Spatiotemporal variables, specifically velocity and cadence, were improved with both the AFO and the IDEO. The most symmetrical gait pattern was observed while using the IDEO. The patients demonstrated their ability to run by completing the CHAMP test with the IDEO. Both patients were cleared for active duty.

Conclusions

The measured improvements in gait kinematics, spatiotemporal variables, gait symmetry, and CHAMP scores as a result of the IDEO show significant functional benefit, making it a useful adjuvant therapy in patients who are motivated to achieve the maximal functional outcome after this devastating injury.
Typical Versus Atypical Antipsychotics for Acute Mania
Authors: Medici Clara Reece , Kai Linda Marie , Kristensen Simon Bang , Kirkedal Christian , Munk-Jørgensen Povl , Straszek Sune
Published: November 2018

Background:

Mania is challenging to treat. Typical antipsychotics may be more efficient compared with atypical antipsychotics, however, with unfavorable side effects.

Study Question:

To investigate the courses of acute manic episodes and correlations between changes of severity during manic episodes and type of antipsychotic treatment.

Study Design:

This case record study included patients admitted with mania (International Classification of Diseases 10th revision code F30, F31.0, F31.1, F31.2 or F31.6) at the Department of Affective Disorders, Aarhus University Hospital from June 1, 2013 to April 1, 2016.

Measures and Outcomes:

The doses of typical and atypical antipsychotics were standardized as defined daily dose according to the World Health Organization's guidelines. The severity of mania was measured up to 3 times daily with the Modified Bech–Rafaelsen Mania Scale (MAS-M), a nurse administered scale. We applied a linear regression in a mixed model approach to compare MAS-M score over time under the influence of typical plus atypical antipsychotics and atypical antipsychotics only. We further analyzed by mania with and without psychosis and by concomitant use of lithium and/or antiseizure medication.

Results:

We included 56 admissions on 46 patients. The courses of the manic episodes measured by MAS-M varied between patients—both daily variations and changes over time. Patients receiving typical antipsychotics had higher baseline MAS-M, more recent admissions, and were mechanically constrained more often compared with patients receiving atypical antipsychotics only. Adjusted for age, gender, mechanical constraint, and dosage of antipsychotics, the difference in reduction of mania was −0.02 MAS-M points/d (95% confidence interval, −0.05 to 0.01) higher in the group receiving atypical antipsychotics only; however, it is not statistically or clinically significant.

Conclusions:

The rate of improvement of mania was similar in the two groups which supports that atypical antipsychotics can be recommended over typical antipsychotics to reduce risk of severe side effects.
Preventive Effect of l-Carnitine on Scar Formation During Acute Pyelonephritis: A Randomized Placebo-Controlled Trial
Authors: Gheissari Alaleh , Aslani Nahid , Eshraghi Azadeh , Moslehi Masoud , Merikhi Alireza , Keikhah Mojtaba , Haghjoo Javanmard Shaghayegh , Vaseghi Golnaz
Published: November 2018

Background:

Urinary tract infection and pyelonephritis are clinical problems that frequently occur in children. Several factors are responsible for renal tissue injury, morbidity, and renal scarring after pyelonephritis. The aim of this study was to evaluate the preventive effect of l-carnitine on renal scarring in acute pyelonephritis.

Methods:

A randomized double-blind clinical trial was conducted on 65 children aged 6 months to 10 years. Patients were randomized into 2 groups to receive 7-day treatment with only antibiotics without l-carnitine (control group; n = 32) and 7-day treatment with l-carnitine (case group; n = 33) during the acute phase of infection. Technetium-99m-labeled dimercaptosuccinic acid (DMSA) scintigraphy was performed for all children during the acute phase (in 2–7 days of hospitalization) and late phase. P-value less than 0.05 was statistically significant.

Results:

We recruited 65 participants in the study: 32 children in control group and 33 children in case group. Three children in the control group and 2 children in the case group refused to perform the second DMSA scan. Overall, data analysis at the end of the study was done on 60 patients. Age distribution of girl patients with upper urinary infection was 6.5% in girl children aged between 6 months and 12 months, 41.1% aged between 1 and 5 years, 33.3% aged between 5 and 10 years, respectively. There was no significant difference between 2 groups in age and sex. There was no significant difference between 2 groups in systolic blood pressure, diastolic blood pressure, the lab data including urine white blood cells and serum erythrocyte sedimentation rate, and antibiogram profiles. Voiding dysfunction was detected in 10% of the participants. The baseline DMSA was not significantly difference in 2 groups, but worsening of kidney lesions was significantly higher in control group after 6 months (P = 0.012).

Conclusion:

Our study showed that l-carnitine significantly decreased renal scarring because of acute pyelonephritis.
Comparison of Immune Reconstitution After Allogeneic Versus Autologous Stem Cell Transplantation in 182 Pediatric Recipients
Authors: Wiegering Verena , Eyrich Matthias , Winkler Beate , Schlegel Paul G.
Published: November 2018

Hematopoietic stem cell transplantation (HSCT) is a life-saving procedure for children with a variety of malignant and nonmalignant conditions. However, even if immune reconstitution after HSCT has been studied extensively, until now, data on the comparison of immune reconstitution after autologous versus allogeneic HSCT are scarce, but might provide important clinical implications. We examined immune reconstitution (T cells, B cells, and NK cells) at defined timepoints in 147 children who received 182 HSCTs. Differences in the time course of immune reconstitution were analyzed in autologous versus allogeneic HSCT. We identified a quicker immune reconstitution in the T-cell compartment, especially in the CD4 and naive subset after autologous HSCT, whereas recipients of allogeneic transplants showed a higher TCRgd proportion. B-cell reconstitution showed a delayed immune reconstitution after allogeneic HSCT in the first 2 years after HSCT. However, a reconstitution of all lymphocyte subsets after HSCT could be achieved in all patients. Children undergoing an HSCT show a different pattern of immune reconstitution in the allogeneic and autologous setting. This might influence the outcome and should affect the clinical handling of infectious prophylaxis and revaccinations.
Outcomes and Patterns of Healthcare Utilization After Hospitalization for Pediatric Critical Illness Due to Respiratory Failure*
Authors: Yagiela Lauren M. , Barbaro Ryan P. , Quasney Michael W. , Pfarr Marie A. , Ursu Dan C. , Prosser Lisa A. , Odetola Fola O.
Published: November 2018

Objectives:

To quantify home care needs, healthcare utilization, and 2-year mortality after pediatric critical illness due to respiratory failure, and evaluate the impact of new morbidity and abnormal function at hospital discharge on resource use and outcomes.

Design:

Retrospective cohort study.

Setting:

Quaternary care PICU.

Patients:

Patients less than or equal to 18 years with respiratory failure from January 1, 2013, to December 31, 2014.

Measurements and Main Results:

Patient demographics, hospitalization characteristics, and healthcare utilization were quantified and compared according to morbidity development and discharge functional status. Multivariable regression methods evaluated 2-year readmission rates and mortality by morbidity development and discharge functional status. Of 163 patients, the median age was 2.1 years (interquartile range, 0.6–10.9 yr), 61 (37.4%) had a comorbidity, and 73 (44.8%) had abnormal function at admission. Median ventilation duration was 6.0 days (interquartile range, 3.0–11.7 d), and median PICU and hospital length of stay were 8 (interquartile range, 4–15) and 14 days (interquartile range, 8–23 d), respectively. At hospital discharge, eight of 163 (4.9%) had died, and 14 of 163 (8.6%) had a new morbidity. Of the surviving 155 patients at hospital discharge, 87 (56.1%) had abnormal function, 120 (77.4%) had new medications, 24 (15.5%) had new medical devices, and 43 (27.7%) had new home care equipment. Cumulative 2-year mortality was 14 of 163 (8.6%) with six of 163 (3.7%) occurring after discharge. Within 2 years, 81 of 155 of patients (52.2%) were readmitted, often (58/81, 71.6%) to the PICU. Abnormal function at discharge was associated with elevated odds of readmission to the hospital (odds ratio, 1.49; 1.28–1.74; p < 0.0001) and PICU (odds ratio, 1.47; 1.27–1.71; p < 0.0001) within 2 years.

Conclusions:

After critical illness, children have significant new healthcare burdens heretofore unrecognized. Abnormal functional status at hospital discharge was associated with increased healthcare utilization up to 2 years thereafter.
Rethinking the causes of pain in herpes zoster and postherpetic neuralgia: the ectopic pacemaker hypothesis
Authors: Devor Marshall
Published: November 2018

Introduction:

Pain in herpes zoster (HZ) and postherpetic neuralgia (PHN) is traditionally explained in terms of 2 processes: irritable nociceptors in the rash-inflamed skin and, later, deafferentation due to destruction of sensory neurons in one virally infected dorsal root ganglion.

Objectives and methods:

Consideration of the evidence supporting this explanation in light of contemporary understanding of the pain system finds it wanting. An alternative hypothesis is proposed as a replacement.

Results:

This model, the ectopic pacemaker hypothesis of HZ and PHN, proposes that pain in both conditions is driven by hyperexcitable ectopic pacemaker sites at various locations in primary sensory neurons affected by the causative varicella zoster virus infection. This peripheral input is exacerbated by central sensitization induced and maintained by the ectopic activity.

Conclusions:

The shift in perspective regarding the pain mechanism in HZ/PHN has specific implications for clinical management.
Validating a Trigger Tool for Detecting Adverse Drug Events in Elderly Patients With Multimorbidity (TRIGGER-CHRON)
Authors: Toscano Guzmán María Dolores , Banqueri Mercedes Galván , Otero María José , Fidalgo Susana Sánchez , Noguera Isabel Font , Guerrero María Concepción Pérez
Published: November 2018

Purpose

The aims of the study were to evaluate the performance of an initial list developed to detect adverse drug events (ADEs) in elderly patients with multimorbidity in clinical practice, to explore the possibility of shortening the list, and to use this tool to study the incidence and characteristics of the ADEs among this population.

Methods

This observational study was conducted at 12 Spanish hospitals. A random sample of five charts from each hospital was selected weekly for retrospective review for a 12-week period. We included patients aged 65 years and older with multimorbidity, hospitalized more than 48 hours. Adverse drug events were detected using a list of 51 triggers previously selected by an expert panel by means of a modified Delphi method. The number of triggers identified and ADEs detected were recorded. The severity and preventability of the ADEs were evaluated. The positive predictive value (PPV) of each trigger was calculated and used to select the most efficient triggers.

Results

In 720 charts reviewed, 1430 positive triggers were identified that led to detect 215 ADEs in 178 patients (24.7%), of which 13% were serious. One hundred nineteen ADEs (55.3%) were preventable and mainly related to inadequate treatment monitoring and prescribing errors. Triggers with a PPV of 5% or less were eliminated, resulting in a final list of 32 triggers (TRIGGER-CHRON) with a PPV of 22.1%, which accounted for 98.9% of all ADEs detected and 98.6% of the preventable ADEs.

Conclusions

The shorter final validated TRIGGER-CHRON tool is an efficient list for identifying ADEs in elderly patients with multimorbidity, detecting ADEs in one-fourth of hospitalized patients in internal medicine or geriatric units.
Sentinel Lymph Node Biopsy in Small Papillary Thyroid Cancer
Authors: Garau Ludovico M. , Rubello Domenico , Morganti Riccardo , Boni Giuseppe , Volterrani Duccio , Colletti Patrick M. , Manca Gianpiero
Published: November 2018

Purpose

The aim of this study was to compare reported results on available techniques for sentinel lymph node detection rate (SDR) in papillary thyroid cancer (PTC).

Methods

The MEDLINE database was searched via a PubMed interface to identify original articles regarding sentinel lymph node biopsy (SNB) in thyroid cancer. Studies were stratified according to the sentinel lymph node (SLN) detection technique: vital-dye (VD), 99mTc-nanocolloid planar lymphoscintigraphy with the use of intraoperative hand-held gamma probes (LS), both 99mTc-nanocolloid planar lymphoscintigraphy with intraoperative use of hand-held gamma probe and VD (LS + VD), 99mTc-nanocolloid planar lymphoscintigraphy with the additional contribution of preoperative SPECT/CT, and intraoperative use of hand-held gamma probe (LS-SPECT/CT). Pooled SDR values were presented with a 95% confidence interval (CI) for each SLN detection techniques. A Z-test was used to compare pooled SDR estimates. False-negative rates were summarized for each method.

Results

Forty-five studies were included. Overall SDRs for the VD, LS, LS + VD, and LS-SPECT/CT techniques were 83% (95% CI, 77%–88%; I
2 = 78%), 96% (95% CI, 90%–98%; I
2 = 68%), 87% (95% CI, 65%–96%; I
2 = 75%), and 93% (95% CI, 86%–97%; I
2 = 0%), respectively. False-negative rates were 0% to 38%, 0% to 40%, 0% to 17%, and 7% to 8%, respectively.

Conclusions

In patients with PTC, 99mTc-nanocolloids offer a higher SDR than that of the VD technique. The addition of SPECT/CT improved identification of metastatic SLNs outside the central neck compartment.
SEAPI Incontinence Classification System: 1-Year Postoperative Results Following Midurethral Sling Placement
Authors: Glass Allison , Durbin-Johnson Blythe , Rothschild Jennifer , Gomelsky Alexander
Published: November 2018

Objective

There are limited long-term data that has examined postoperative quality-of-life measures following placement of midurethral sling (MUS) for stress urinary incontinence (SUI). The SEAPI incontinence questionnaire includes 5 data points that rate severity of specific urinary symptoms. Our aim was to describe changes in SEAPI questionnaire outcomes 1 year following sling placement.

Methods

We retrospectively reviewed women who underwent MUS for SUI from 2005 to 2012. We included those women who had completed preoperative and postoperative (>12 months) SEAPI scores. Individual S, E, A, P, I score cure was defined as postoperative score of 0 (>0 preoperative). Logistic regression analysis was used to model the effects of patient characteristics on incontinence cure and S, E, A, P, I scores.

Results

A total of 584 women were included. Median follow-up was 25.4 months (12–126.8 months). Follow-up duration and baseline S, P, and I scores were associated with significantly lower odds of overall incontinence cure, whereas rectocele grade has positive association (odds ratio, 1.31; P = 0.040). Type of sling did not impact overall incontinence cure or cure of individual SEAPI scores.

Conclusions

Preoperative S, P, and I scores had negative association with stress incontinence cure. Cure of individual S, E, A, P, I scores was impacted differently by various patient factors. The SEAPI questionnaire provides a unique profile of patient-reported and functional measures in women with SUI and may be helpful in those who undergo MUS.
Activation of dopamine receptor 2 (DRD2) prompts transcriptomic and metabolic plasticity in glioblastoma
Authors: Caragher Seamus P. , Shireman Jack M. , Huang Mei , Miska Jason , Baisiwala Shivani , Park Cheol Hong , Saathoff Miranda R. , Warnke Louisa , Xiao Ting , Lesniak Maciej S. , James C. David , Meltzer Herbert , Tryba Andrew K. , Ahmed Atique U
Published: November 2018

Glioblastoma (GBM) is one of the most aggressive and lethal tumor types. Evidence continues to accrue indicating that the complex relationship between GBM and the brain microenvironment contributes to this malignant phenotype. However, the interaction between GBM and neurotransmitters, signaling molecules involved in neuronal communication, remains incompletely understood. Here we examined, in both sexes of humans and mice, how the monoamine dopamine influences GBM cells. We demonstrate that GBM cells express DRD2, with elevated expression in the glioma-initiating cell (GIC) population. Stimulation of DRD2 caused neuron-like depolarization exclusively in GICs. In addition, long-term activation of DRD2 heightened the sphere-forming capacity of GBM cells as well as tumor engraftment efficiency. Mechanistic investigation revealed that DRD2 signaling activates the hypoxia response and functionally alters metabolism. Finally, we found that GBM cells synthesize and secrete dopamine themselves, suggesting a potential autocrine mechanism. These results identify dopamine signaling as a potential therapeutic target in GBM and further highlight neurotransmitters as a key feature of the pro-tumor microenvironment.

Significance Statement

This work offers critical insight into the role of the neurotransmitter dopamine in the progression of GBM. We show that dopamine induces specific changes in the state of tumor cells, augmenting their growth and shifting them to a more stem-cell like state. Further, we show that dopamine can alter the metabolic behavior of GBM cells, increasing glycolysis. Finally, we show that GBM cells, including tumor samples from patients, can synthesize and secrete dopamine, suggesting an autocrine signaling process underlying these results. These results describe a novel connection between neurotransmitters and brain cancer, further highlighting the critical influence of the brain milieu on GBM.