bluuebunny/crossref_metadata_2025 huggingface dataset:
Reading and Theory of Mind in Adolescents with Cochlear Implant
Authors: Figueroa Mario , Darbra Sònia , Silvestre Núria
Published: October 2019

Previous research has shown a possible link between reading comprehension and theory of mind (ToM), but these findings are unclear in adolescents with cochlear implants (CI). In the present study, reading comprehension and ToM were assessed in adolescents with CI and the relation between both skills was also studied. Two sessions were performed on two groups of adolescents aged between 12 and 16 years of age (36 adolescents with CI and 54 participants with typical hearing, TH). They were evaluated by means of a standardized reading battery, a false belief task, and Faux Pas stories. The results indicated that reading and cognitive ToM were more developed in the TH group than in adolescents with CI. However, early-CI and binaural group performance were close to the TH group in narrative and expository comprehension and cognitive ToM. The results also indicated that cognitive ToM and reading comprehension appear to be related in deaf adolescents.
Nuclear magnetic resonance investigation of water transport through the plasma membrane of various yeast species
Authors: Šoltésová Mária , Elicharová Hana , Srb Pavel , Růžička Michal , Janisova Larisa , Sychrová Hana , Lang Jan
Published: October 2019

A specific technique of nuclear magnetic resonance (NMR) spectroscopy, filter-exchange spectroscopy (FEXSY), was employed to investigate water transport through the plasma membrane in intact yeast cells. This technique allows water transport to be monitored directly, thus avoiding the necessity to subject the cells to any rapid change in the external conditions, e.g. osmotic shock. We established a sample preparation protocol, a data analysis procedure and verified the applicability of FEXSY experiments. We recorded the exchange rates in the temperature range 10–40°C for Saccharomyces cerevisiae. The resulting activation energy of 29 kJ mol−1 supports the hypothesis that water exchange is facilitated by water channels—aquaporins. Furthermore, we measured for the first time water exchange rates in three other phylogenetically unrelated yeast species (Schizosaccharomyces pombe, Candida albicans and Zygosaccharomyces rouxii) and observed remarkably different water exchange rates between these species. Findings of our work contribute to a better understanding of as fundamental a cell process as the control of water transport through the plasma membrane.
Insights into wild-type dynamin 2 and the consequences of DNM2 mutations from transgenic zebrafish
Authors: Zhao Mo , Smith Lindsay , Volpatti Jonathan , Fabian Lacramioara , Dowling James J
Published: October 2019

Dynamin 2 (DNM2) encodes a ubiquitously expressed large GTPase with membrane fission capabilities that participates in the endocytosis of clathrin-coated vesicles. Heterozygous mutations in DNM2 are associated with two distinct neuromuscular disorders, Charcot–Marie–Tooth disease (CMT) and autosomal dominant centronuclear myopathy (CNM). Despite extensive investigations in cell culture, the role of dynamin 2 in normal muscle development is poorly understood and the consequences of DNM2 mutations at the molecular level in vivo are not known. To address these gaps in knowledge, we developed transgenic zebrafish expressing either wild-type dynamin 2 or dynamin 2 with either a CNM or CMT mutation. Taking advantage of the live imaging capabilities of the zebrafish embryo, we establish the localization of wild-type and mutant dynamin 2 in vivo, showing for the first time distinctive dynamin 2 subcellular compartments. Additionally, we demonstrate that CNM-related DNM2 mutations are associated with protein mislocalization and aggregation. Lastly, we define core phenotypes associated with our transgenic mutant fish, including impaired motor function and altered muscle ultrastructure, making them the ideal platform for drug screening. Overall, using the power of the zebrafish, we establish novel insights into dynamin 2 localization and dynamics and provide the necessary groundwork for future studies examining dynamin 2 pathomechanisms and therapy development.
Splicing factor DHX15 affects tp53 and mdm2 expression via alternate splicing and promoter usage
Authors: McElderry John , Carrington Blake , Bishop Kevin , Kim Erika , Pei Wuhong , Chen Zelin , Ramanagoudr-Bhojappa Ramanagouda , Prakash Anupam , Burgess Shawn M , Liu P Paul , Sood Raman
Published: October 2019

DHX15, a DEAH box containing RNA helicase, is a splicing factor required for the last step of splicing. Recent studies identified a recurrent mutational hotspot, R222G, in DHX15 in ∼ 6% of acute myeloid leukemia (AML) patients that carry the fusion protein RUNX1-RUNX1T1 produced by t (8;21) (q22;q22). Studies using yeast mutants showed that substitution of G for the residue equivalent to R222 leads to loss of its helicase function, suggesting that it is a loss-of-function mutation. To elucidate the role of DHX15 during development, we established the first vertebrate knockout model with CRISPR/Cas9 in zebrafish. Our data showed that dhx15 expression is enriched in the brain, eyes, pectoral fin primordia, liver and intestinal bulb during embryonic development. Dhx15 deficiency leads to pleiotropic morphological phenotypes in homozygous mutant embryos starting at 3 days post fertilization (dpf) that result in lethality by 7 dpf, revealing an essential role during embryonic development. RNA-seq analysis suggested important roles of Dhx15 in chromatin and nucleosome assembly and regulation of the Mdm2-p53 pathway. Interestingly, exons corresponding to the alternate transcriptional start sites for tp53 and mdm2 were preferentially expressed in the mutant embryos, leading to significant upregulation of their alternate isoforms, Δ113p53 (orthologous to Δ133p53 isoform in human) and mdm2-P2 (isoform using distal promoter P2), respectively. We speculate that these alterations in the Mdm2-p53 pathway contribute to the development of AML in patients with t(8;21) and somatically mutated DHX15.
Pharmacokinetics and Pharmacodynamics of Linezolid in Patients With Sepsis Receiving Continuous Venovenous Hemofiltration and Extended Daily Hemofiltration
Authors: Zheng Junbo , Sun Zhidan , Sun Lei , Zhang Xing , Hou Guiying , Han Qiuyuan , Li Xianghui , Liu Gaofeng , Gao Yang , Ye Ming , Wang Hongliang , Yu Kaijiang
Published: October 2019

Background

This prospective study compared pharmacokinetics (PK) and pharmacodynamics (PD) of linezolid in patients with sepsis receiving continuous venovenous hemofiltration (CVVH) with patients receiving extended daily hemofiltration (EDH).

Methods

Patients with sepsis treated with linezolid and CVVH or EDH were included. Serial blood samples were collected and linezolid concentrations measured. PKs were analyzed using Pmetrics. Monte Carlo simulations were used to evaluate PD target achievement.

Results

From 20 patients, 320 blood samples were collected for PK and PD analysis. PK profiles of linezolid were best described by a 2-compartment model. PK parameters were not significantly different between EDH and CVVH groups and were associated with body weight, renal replacement therapy (RRT) duration, and sequential organ failure assessment score. Monte Carlo simulations showed poor fractional target attainment for a minimum inhibitory concentration (MIC) of 2 mg/L with standard 600 mg intravenous administration every 12 hours.

Conclusions

Patients with sepsis receiving RRT exhibited variability in PK/PD parameters for linezolid. PK parameters were not significantly different between CVVH- and EDH-treated patients. Higher probability of target attainment would be achievable at a MIC of 2 mg/L in EDH patients. Higher linezolid doses should be considered for patients on RRT to achieve adequate blood levels.
‘Onward to the End of the Nineteenth Century’: Edward Prime-Stevenson’s Queer Musicological Nostalgia
Authors: Franseen Kristin M
Published: October 2019

Relatively little known today, Edward Prime-Stevenson (1858–1942) was a man of hidden depths. Despite success as a music critic, Prime-Stevenson left the United States around the turn of the century to pursue (in his words) ‘studies in a branch of sexual psychology’ in Europe. Following this move, he published two books on homosexuality under the pseudonym Xavier Mayne. While ‘Mayne’s’ work has been analysed in depth by LGBTQ+ literary scholars in the past twenty years, Prime-Stevenson’s musical writings have received substantially less attention. This article considers the intertextual relationships between his musical and sexological writings—in particular, his approach to secret messages in instrumental music, musings on musical intimacy, and attempts at queer canon-building—as both a scholarly attempt at creating a proto-‘queer musicology’ through sheer force of will and a deeply personal voicing of queer musical nostalgia.
Diverse outcomes of planet formation and composition around low-mass stars and brown dwarfs
Authors: Miguel Y , Cridland A , Ormel C W , Fortney J J , Ida S
Published: October 2019

The detection of Earth-size exoplanets around low-mass stars –in stars such as Proxima Centauri and TRAPPIST-1– provide an exceptional chance to improve our understanding of the formation of planets around M stars and brown dwarfs. We explore the formation of such planets with a population synthesis code based on a planetesimal-driven model previously used to study the formation of the Jovian satellites. Because the discs have low mass and the stars are cool, the formation is an inefficient process that happens at short periods, generating compact planetary systems. Planets can be trapped in resonances and we follow the evolution of the planets after the gas has dissipated and they undergo orbit crossings and possible mergers. We find that formation of planets above Mars mass and in the planetesimal accretion scenario, is only possible around stars with masses M⋆ ≥ 0.07Msun and discs of Mdisc ≥ 10−2 Msun. We find that planets above Earth-mass form around stars with masses larger than 0.15 Msun, while planets larger than 5 M⊕ do not form in our model, even not under the most optimal conditions (massive disc), showing that planets such as GJ 3512b form with another, more efficient mechanism. Our results show that the majority of planets form with a significant water fraction; that most of our synthetic planetary systems have 1, 2 or 3 planets, but planets with 4,5,6 and 7 planets are also common, confirming that compact planetary systems with many planets should be a relatively common outcome of planet formation around small stars.
Design and synthesis of pleated DNA origami nanotubes with adjustable diameters
Authors: Berengut Jonathan F , Berengut Julian C , Doye Jonathan P K , Prešern Domen , Kawamoto Akihiro , Ruan Juanfang , Wainwright Madeleine J , Lee Lawrence K
Published: October 2019

DNA origami allows for the synthesis of nanoscale structures and machines with nanometre precision and high yields. Tubular DNA origami nanostructures are particularly useful because their geometry facilitates a variety of applications including nanoparticle encapsulation, the construction of artificial membrane pores and as structural scaffolds that can uniquely spatially arrange nanoparticles in circular, linear and helical arrays. Here we report a system of parametrization for the design of radially symmetric DNA origami nanotubes with adjustable diameter, length, crossover density, pleat angle and chirality. The system is implemented into a computational algorithm that provides a practical means to navigate the complex geometry of DNA origami nanotube design. We apply this in the design, synthesis and characterization of novel DNA origami nanotubes. These include structures with pleated walls where the same number of duplexes can form nanotubes with different diameters, and to vary the diameter within the same structure. We also construct nanotubes that can be reconfigured into different chiral shapes. Finally, we explore the effect of strain on the local and global geometry of DNA origami nanotubes and demonstrate how pleated walls can provide a strategy to rigidify nanotubes and to construct closely packed parallel duplexes.
Single molecule analysis of effects of non-canonical guide RNAs and specificity-enhancing mutations on Cas9-induced DNA unwinding
Authors: Okafor Ikenna C , Singh Digvijay , Wang Yanbo , Jung Minhee , Wang Haobo , Mallon John , Bailey Scott , Lee Jungjoon K , Ha Taekjip
Published: October 2019

Cas9 has made a wide range of genomic manipulation possible. However, its specificity continues to be a challenge. Non-canonical gRNAs and new engineered variants of Cas9 have been developed to improve specificity, but at the cost of the on-target activity. DNA unwinding is a checkpoint before cleavage by Cas9, and was shown to be made more sensitive to sequence mismatches by specificity-enhancing mutations in engineered Cas9s. Here we performed single-molecule FRET-based DNA unwinding experiments using various combinations of non-canonical gRNAs and different Cas9s. All engineered Cas9s were less promiscuous than wild type when canonical gRNA was used, but HypaCas9 had much-reduced on-target unwinding. Cas9-HF1 and eCas9 showed the best balance between low promiscuity and high on-target activity with canonical gRNA. When extended gRNAs with one or two non-matching guanines added to the 5′ end were used, Sniper1-Cas9 showed the lowest promiscuity while maintaining high on-target activity. Truncated gRNA generally reduced unwinding and adding a non-matching guanine to the 5′ end of gRNA influenced unwinding in a sequence-context dependent manner. Our results are consistent with cell-based cleavage data and provide a mechanistic understanding of how various Cas9/gRNA combinations perform in genome engineering.
New developments on the Encyclopedia of DNA Elements (ENCODE) data portal
Authors: Luo Yunhai , Hitz Benjamin C , Gabdank Idan , Hilton Jason A , Kagda Meenakshi S , Lam Bonita , Myers Zachary , Sud Paul , Jou Jennifer , Lin Khine , Baymuradov Ulugbek K , Graham Keenan , Litton Casey , Miyasato Stuart R , Strattan J Seth , Jolanki Otto , Lee Jin-Wook , Tanaka Forrest Y , Adenekan Philip , O’Neill Emma , Cherry J Michael
Published: October 2019

The Encyclopedia of DNA Elements (ENCODE) is an ongoing collaborative research project aimed at identifying all the functional elements in the human and mouse genomes. Data generated by the ENCODE consortium are freely accessible at the ENCODE portal (https://www.encodeproject.org/), which is developed and maintained by the ENCODE Data Coordinating Center (DCC). Since the initial portal release in 2013, the ENCODE DCC has updated the portal to make ENCODE data more findable, accessible, interoperable and reusable. Here, we report on recent updates, including new ENCODE data and assays, ENCODE uniform data processing pipelines, new visualization tools, a dataset cart feature, unrestricted public access to ENCODE data on the cloud (Amazon Web Services open data registry, https://registry.opendata.aws/encode-project/) and more comprehensive tutorials and documentation.
Unrestricted Direct Access to Physical Therapist Services Is Associated With Lower Health Care Utilization and Costs in Patients With New-Onset Low Back Pain
Authors: Garrity Brigid M , McDonough Christine M , Ameli Omid , Rothendler James A , Carey Kathleen M , Cabral Howard J , Stein Michael D , Saper Robert B , Kazis Lewis E
Published: October 2019

Background

Low back pain (LBP) is one of the most prevalent conditions for which patients seek physical therapy in the United States. The American Physical Therapy Association categorizes direct access to physical therapist services into 3 levels: limited, provisional, and unrestricted.

Objective

The objective of this study was to evaluate the association of level of access to physical therapist services with LBP-related health care utilization and costs.

Design

This was a retrospective cohort study of patients with new-onset LBP between 2008 and 2013; data were from OptumLabs Data Warehouse.

Methods

We identified 59,670 individuals who were 18 years old or older, who had new-onset LBP, and who had commercial or Medicare Advantage insurance through a private health plan. We examined 2 samples. The first was health care utilization among individuals who saw a physical therapist first in states with either unrestricted access or provisional access. The second was LBP-related costs among individuals who saw either a physical therapist or a primary care physician first.

Results

Individuals who saw a physical therapist first in states with provisional access had significantly higher measures of health care utilization within 30 days, including plain imaging and frequency of physician visits, than individuals who saw a physical therapist first in states with unrestricted access. Compared with individuals who saw a primary care physician first, pooled across provisional-access and unrestricted-access states, those who saw a physical therapist first in provisional-access states had 25% higher relative costs at 30 days and 32% higher relative costs at 90 days, whereas those who saw a physical therapist first in unrestricted-access states had 13% lower costs at 30 days and 32% lower costs at 90 days.

Limitations

This was a claims-based study with limited information on patient characteristics, including severity and duration of pain.

Conclusions

Short-term LBP-related health care utilization and costs were lower for individuals in unrestricted-access states than in provisional-access states.
Diagnosis of giant cell arteritis
Authors: Ponte Cristina , Martins-Martinho Joana , Luqmani Raashid Ahmed
Published: October 2019

GCA is the most common form of primary systemic vasculitis affecting older people. It is considered a clinical emergency because it can lead to irreversible blindness in around 20% of untreated cases. High doses of glucocorticoids should be initiated promptly to prevent disease-related complications; however, glucocorticoids therapy usually results in significant toxicity. Therefore, correct diagnosis is crucial. For many years, temporal artery biopsy has been considered the diagnostic ‘gold standard’ for GCA, but it has many limitations (including low sensitivity). US has proven to be effective for diagnosing GCA and can reliably replace temporal artery biopsy in particular clinical settings. In cases of suspected GCA with large-vessel involvement, other imaging modalities can be used for diagnosis (e.g. CT and PET). Here we review the current evidence for each diagnostic modality and propose an algorithm to diagnose cranial-GCA in a setting with rapid access to high quality US.
Smoking cessation is associated with lower disease activity and predicts cardiovascular risk reduction in rheumatoid arthritis patients
Authors: Roelsgaard Ida K , Ikdahl Eirik , Rollefstad Silvia , Wibetoe Grunde , Esbensen Bente A , Kitas George D , van Riel Piet , Gabriel Sherine , Kvien Tore K , Douglas Karen , Wållberg-Jonsson Solveig , Rantapää Dahlqvist Solbritt , Karpouzas George , Dessein Patrick H , Tsang Linda , El-Gabalawy Hani , Hitchon Carol A , Pascual-Ramos Virginia , Contreras-Yáñez Irazú , Sfikakis Petros P , González-Gay Miguel A , Crowson Cynthia S , Semb Anne Grete
Published: October 2019

Objectives

Smoking is a major risk factor for the development of both cardiovascular disease (CVD) and RA and may cause attenuated responses to anti-rheumatic treatments. Our aim was to compare disease activity, CVD risk factors and CVD event rates across smoking status in RA patients.

Methods

Disease characteristics, CVD risk factors and relevant medications were recorded in RA patients without prior CVD from 10 countries (Norway, UK, Netherlands, USA, Sweden, Greece, South Africa, Spain, Canada and Mexico). Information on CVD events was collected. Adjusted analysis of variance, logistic regression and Cox models were applied to compare RA disease activity (DAS28), CVD risk factors and event rates across categories of smoking status.

Results

Of the 3311 RA patients (1012 former, 887 current and 1412 never smokers), 235 experienced CVD events during a median follow-up of 3.5 years (interquartile range 2.5–6.1). At enrolment, current smokers were more likely to have moderate or high disease activity compared with former and never smokers (P < 0.001 for both). There was a gradient of worsening CVD risk factor profiles (lipoproteins and blood pressure) from never to former to current smokers. Furthermore, former and never smokers had significantly lower CVD event rates compared with current smokers [hazard ratio 0.70 (95% CI 0.51, 0.95), P = 0.02 and 0.48 (0.34, 0.69), P < 0.001, respectively]. The CVD event rates for former and never smokers were comparable.

Conclusion

Smoking cessation in patients with RA was associated with lower disease activity and improved lipid profiles and was a predictor of reduced rates of CVD events.
CONTEMPORARY RADIATION DOSES IN INTERVENTIONAL CARDIOLOGY: A NATIONWIDE STUDY OF PATIENT SKIN DOSES IN FINLAND
Authors: Järvinen Jukka , Sierpowska Joanna , Siiskonen Teemu , Husso Minna , Järvinen Hannu , Kiviniemi Tuomas , Rissanen Tuomas T , Lindholm Carita , Matikka Hanna , Larjava Heli R S , Mäkelä Timo J , Strengell Satu , Eskola Markku , Parviainen Teuvo , Hallinen Elina , Pirinen Markku , Kivelä Antti , Teräs Mika
Published: October 2019

In contemporary interventional cardiology, for typical elderly patients, the most severe radiation-related harm to patients can be considered to come from skin exposures. In this paper, maximum local skin doses in cardiological procedures are explored with Gafchromic film dosimetry. Film and reader calibrations and reading were performed at the Secondary Standards Dosimetry Laboratory of the Radiation and Nuclear Safety Authority (STUK), and data were gathered from seven hospitals in Finland. As alert levels for early transient erythema, 200 Gycm2 kerma area product (KAP) and 2000 mGy air kerma levels for transcatheter aortic valve implantations (TAVI) procedures are proposed. The largest doses were measured in TAVI (4158.8 mGy) and percutaneous coronary interventions (PCI) (941.68 mGy). Accuracies of the GE DoseWatch and Siemens CareMonitor skin dose estimates were reasonable, but more results are needed to reliably assess and validate the tools’ capabilities and reliabilities. Uncertainty of the Gafchromic dosimetry was estimated as 9.1% for a calibration with seven data points and 19.3% for a calibration with five data points.
Epigenetic regulation of TIMP1 expression by 8‐oxoguanine DNA glycosylase‐1 binding to DNA:RNA hybrid
Authors: Pan Lang , Wang Hui , Luo Jinhua , Zeng Ji , Pi Jiao , Liu Huijun , Liu Chi , Ba Xueqing , Qu Xiangping , Xiang Yang , Boldogh Istvan , Qin Xiaoqun
Published: October 2019

8‐Oxoguanine DNA glycosylase‐1 (OGG1)‐initiated base excision repair pathway is primarily responsible for 7, 8‐dihydro‐8‐oxoguanine (8‐oxoG) removal from DNA. Recent studies, however, have shown that 8‐oxoG in gene regulatory elements may serve as an epigenetic mark, and OGG1 has distinct functions in modulating gene expression. Genome‐wide mapping of oxidative stress‐induced OGG1 enrichment within introns was documented, but its significance has not yet been fully characterized. Here, we explored whether OGG1 recruited to intron 1 of tissue inhibitor of metalloproteinase‐1 (TIMP1) gene and modulated its expression. Using chromatin and DNA:RNA hybrid immunoprecipitation assays, we report recruitment of OGG1 to the DNA:RNA hybrid in intron 1, where it increases nascent RNA but lowers mRNA levels in O3‐exposed human airway epithelial cells and mouse lungs. Decrease in TIMP1 expression is alleviated by antioxidant administration, small interfering RNA depletion, or inhibition of OGG1 binding to its genomic substrate.In vitrostudies revealed direct interaction between OGG1 and 8‐oxoG containing DNA:RNA hybrid, without excision of its substrate. Inhibition of OGG1 binding to DNA:RNA hybrid translated into an increase in TIMP1 expression and a decrease in oxidant‐induced lung inflammatory responses as well as airway remodeling. Data documented here reveal a novel molecular link between OGG1 at damaged sites and transcription dynamics that may contribute to oxidative stress‐induced cellular and tissue responses.—Pan, L., Wang, H., Luo, J., Zeng J., Pi, J., Liu, H., Liu, C., Ba, X., Qu, X., Xiang Y., Boldogh, I., Qin, X. Epigenetic regulation of TIMP1 expression by 8‐oxoguanine DNA glycosylase‐1 binding to DNA:RNA hybrid. FASEB J. 33, 14159‐14170 (2019).www.fasebj.org
Lamotrigine vs. Carbamazepine Monotherapy for Epilepsy Treatment
Authors: Pich Jacqueline
Published: October 2019

Editor's note: This is a summary of a nursing care–related systematic review from the Cochrane Library. For more information, see http://nursingcare.cochrane.org.
Diabetes Mellitus
Authors: Kelley Carly E. , Weaver Anne
Published: October 2019

Diabetes mellitus is a chronic illness with increased morbidity and mortality. The prevalence of diabetes mellitus is increasing among women of all ages. This monograph provides an overview of the pathophysiology, evaluation, and management of diabetes mellitus and comorbidities in women. Management approaches in pediatric, adolescent, reproductive-aged, perimenopausal, and postmenopausal patients are addressed.
Functional and radiographic outcomes of Gartland type II supracondylar humerus fractures managed by closed reduction under nitrous oxide as conscious sedation
Authors: Pierantoni Silvia , Alberghina Flavia , Cravino Mattia , Paonessa Matteo , Canavese Federico , Andreacchio Antonio
Published: October 2019

The management of Gartland type II supracondylar fractures remains controversial. This study aimed to evaluate the clinical, functional, and radiographic outcomes of Gartland type II supracondylar fractures treated by immediate closed reduction and casting in the emergency department using equimolar nitrous oxide as conscious sedation. All patients were treated non-operatively using equimolar nitrous oxide as conscious sedation during closed reduction and cast immobilization. Three out of 34 patients (three elbows; 8.8%) were lost during follow-up. The mean follow-up time was 26.4 months (range: 6–48). The mean Quick DASH score at cast removal was 22.4 (range: 19–40) and 2.3 (range: 0–9) at the last follow-up visit in patients without secondary displacement (n = 26; 76.5%). The mean Quick-DASH score of patients (n = 5; 16.1%) requiring closed reduction and percutaneous pinning under general anesthesia because of secondary displacement was 21.4 (range: 19–25) at cast removal and 0.9 (range: 0–2.3) at the last follow-up visit. No significant differences between the two groups were found at any time (P = 0.38 and P = 0.48, respectively). The two groups also showed a comparable radiographic outcome and similar Flynn’s criteria. The mean Numeric Pain Intensity was three (range: 0–6). No complications related to the administration of equimolar nitrous oxide were recorded. The use of equimolar nitrous oxide as conscious sedation for closed reduction and casting appears to be a safe, inexpensive, and appropriate conservative method of treatment for displaced Gartland type II supracondylar fractures in children. A regular follow-up is mandatory to detect early secondary displacement, as 16.1% of fractures required additional closed reduction and percutaneous pinning under general anesthesia. Level IV, retrospective study.
Intertrochanteric Imhäuser osteotomy combined with osteochondroplasty in treatment of moderate-severe stable slipped capital femoral epiphysis: a case series study
Authors: Abdelaziz Tarek Hassan , Elbeshry Shady Samir , Goda Ayman Hussein , Fayyad Tamer A. , Aly Ahmad Saeed , Mahmoud Shady Abdulghaffar
Published: October 2019

The aim of the study is to assess the safety and efficacy of Imhäuser osteotomy combined with osteochondroplasty in the treatment of moderate-severe stable slipped capital femoral epiphysis (SCFE) on short-term basis. Nineteen patients (20 hips) with moderate-severe stable SCFE were surgically treated by Imhäuser osteotomy combined with osteochondroplasty and followed up for 3–4 years. The cases aged between 12 and 18 years at the time of surgery and complained of a variety of symptoms and signs that included pain, limping, limited range of motion (ROM), and/or abductor weakness. The outcomes were assessed using clinical and radiological parameters as well as functional outcome measures: “Harris hip score” (HHS) and “The Western Ontario and McMaster Universities Osteoarthritis Index” (WOMAC). There were statistically significant improvements in flexion, internal rotation, and abduction ROM. HHS and WOMAC improved significantly with final follow-up scores at 86.76 and 6.4%, respectively. The radiological parameters showed significant improvement regarding Southwick angle (mean 12.8°), alpha angle of Nötzli (mean 29.85°), Hilgenreiner epiphyseal angle (mean 37.65°), neck shaft angle (mean 140.63°), and acetabulo-trochanteric distance (median14.1 mm) at the end of follow-up period. Imhäuser osteotomy combined with osteochondroplasty is a good option in moderate-severe stable SCFE treatment.
Assessing the effect of physeal biopsy on angular deformity in a rabbit model
Authors: Stevens Peter , Epperson Richard T. , Taylor Nicholas B. , Dickerson Mary , Williams Dustin L.
Published: October 2019

Obtaining a biopsy of the physis in a pediatric/juvenile could provide the ability to diagnose and manage children with physeal abnormalities. However, it has not yet been determined whether a physeal biopsy procedure affects angular deformity. We employed a rabbit model to collect biopsies of the distal femoral and proximal tibial physes on anesthetized, 8-week old New Zealand rabbits. The contralateral limb served as a control. At 8 (n = 5) and 16 (n = 5) weeks postbiopsy, animals were euthanized. Micro-computed tomography (CT) was employed to estimate percentage of the physis biopsied and assess structural abnormalities resulting from biopsy. Bone samples were embedded in polymethylmethacrylate and analyzed. The percentage of physis sampled was ≤1.5% of the total femoral physis while all but one of the tibiae had ≤2.3% removed. There were no iatrogenic clinical or radiographic deformities (frontal or sagittal). Micro-CT and histological analysis suggested that physeal defects had signs of healing that did not lead to subsequent angular deviation. A defect caused by physeal biopsy may not lead to angular deformity. Long-term data could help determine the safety and efficacy of collecting biopsies for histological analyses. Advanced imaging may demonstrate a detailed picture of anatomic or structural alteration of a given physis, but provides no functional information. The diagnostic and therapeutic information that could be gleaned from one or more serial biopsy samples could be invaluable in decision making and clinical management (e.g. skeletal dysplasias and metabolic conditions), so long as subsequent deformity is not a future possibility.
What Is the Causal Interpretation of Sibling Comparison Designs?
Authors: Petersen Anne Helby , Lange Theis
Published: October 2019

Sibling comparison designs have long been used to assess causal effects of exposures for which randomized studies are impossible and measurement of all relevant confounding is unobtainable. The idea is to utilize the fact that siblings often share a lot of unobserved variables. Therefore, it is proposed that in certain cases, comparing siblings is equivalent to comparing exchangeable individuals, which is the foundation for causal inference based on randomized controlled trials (RCTs). However, this intuition—and the publication of highly important sibling studies—vastly predate modern causal inference theory. Full causal descriptions of sibling comparison designs are essentially nonexistent, and therefore it is not clear exactly how or if we can interpret their estimated effects as causal. We fill this theoretical gap by proposing a counterfactual-based framework for sibling comparison designs. Moreover, we employ this framework to derive precise causal interpretations for three commonly used sibling model estimators stemming from fixed-effects ordinary least squares (OLS), conditional logistic regression, and stratified Cox regression. We establish that, for the latter two, the obtained effect parameter describes a causal effect on the full sibling group, not the individuals, and thus it does not correspond to the prevailing intuition from the RCT analogue. For fixed-effects OLS estimation, the parameter describes a causal effect on an individual, but may depend on an intervention on the whole sibling group. OLS estimation thus results in an estimator that can be given a simple causal interpretation that is similar, but not equal to, the RCT parallel. See video abstract at, http://links.lww.com/EDE/B618.
Therapeutic Drug Monitoring Can Improve Linezolid Dosing Regimens in Current Clinical Practice: A Review of Linezolid Pharmacokinetics and Pharmacodynamics
Authors: Rao Gauri G. , Konicki Robyn , Cattaneo Dario , Alffenaar Jan-Willem , Marriott Deborah J. E. , Neely Michael ,   On behalf of the IATDMCT Antimicrobial Scientific Committee
Published: October 2019

Linezolid is an antibiotic used to treat infections caused by drug-resistant gram-positive organisms, including vancomycin-resistantEnterococcus faecium, multi-drug resistantStreptococcus pneumoniae, and methicillin-resistantStaphylococcus aureus. The adverse effects of linezolid can include thrombocytopenia and neuropathy, which are more prevalent with higher exposures and longer treatment durations. Although linezolid is traditionally administered at a standard 600 mg dose every 12 hours, the resulting exposure can vary greatly between patients and can lead to treatment failure or toxicity. The efficacy and toxicity of linezolid are determined by the exposure achieved in the patient; numerous clinical and population pharmacokinetics (popPK) studies have identified threshold measurements for both parameters. Several special populations with an increased need for linezolid dose adjustments have also been identified. Therapeutic Drug Monitoring (TDM) is a clinical strategy that assesses the response of an individual patient and helps adjust the dosing regimen to maximize efficacy while minimizing toxicity. Adaptive feedback control and model-informed precision dosing are additional strategies that use Bayesian algorithms and PK models to predict patient-specific drug exposure. TDM is a very useful tool for patient populations with sparse clinical data or known alterations in pharmacokinetics, including children, patients with renal insufficiency or those receiving renal replacement therapy, and patients taking co-medications known to interact with linezolid. As part of the clinical workflow, clinicians can use TDM with the thresholds summarized from the current literature to improve linezolid dosing for patients and maximize the probability of treatment success.
Immediate Prepectoral Breast Reconstruction in Suboptimal Patients Using an Air-filled Spacer
Authors: Becker Hilton , Mathew Prakash J.
Published: October 2019

Introduction:

Immediate prepectoral breast reconstruction offers excellent aesthetic results with less pain and elimination of animation deformity due to avoidance of pectoralis dissection and subpectoral implant placement. Concerns about the effects of prostheses on flap perfusion have limited use of the technique to highly selected patients. We present a series of “suboptimal” patients that have undergone immediate prepectoral breast reconstruction utilizing an air-filled “spacer” implant.

Methods:

A single surgeon’s experience with immediate, single-stage prepectoral breast reconstruction using a Spectrum implant was retrospectively reviewed. Patient demographics, adjuvant therapies, risk factors for threatened flaps, and complications, including those that required subsequent intervention, were evaluated.

Results:

Twenty-five patients (39 breasts) underwent immediate prepectoral reconstruction with a Spectrum implant. Ten patients had minor complications, 6 of whom required intervention with successful correction. There was a single case of implant loss in the series; this patient had prior radiation.

Conclusions:

Utilizing the spacer concept, immediate single-stage prepectoral breast reconstruction is a viable alternative to subpectoral implant placement or delay procedures. The technique delivers aesthetic results with less postoperative pain, quicker operative times, and avoidance of animation deformity. It can be considered for any patient, including high-risk patients such as those with radiation exposure, thin/threatened skin flaps, significant ptosis, and obesity.
Dissociation between hypertrophy and fibrosis in the left ventricle early after experimental kidney transplantation
Authors: Krebber Merle M. , Papazova Diana A. , Oosterhuis Nynke R. , Mokry Michal , Cramer Maarten J. , Cheng Caroline , Joles Jaap A. , Verhaar Marianne C.
Published: October 2019

Objective:

Left ventricular (LV) hypertrophy is the most common cardiac alteration in patients with chronic kidney disease (CKD). Normalization of hypertension in CKD patients receiving a healthy kidney allograft often reverses LV hypertrophy, but effects on LV fibrosis remain unclear. To study causal interactions between graft and environment on LV hypertrophy, fibrosis and inflammation, we applied cross-kidney transplantation

Methods:

Orthotopic transplantation was performed after inducing CKD in rats by two-third bilateral ablation of kidney mass: Healthy kidney (K) donor to healthy heart (H) recipient (healthy-K→healthy-H); CKD-K→healthy-H; healthy-K→CKD-H; CKD-K→CKD-H; N= 6 per group.

Results:

At week 6 after transplantation, mean arterial pressure (MAP) and LV mass index (LVMI) increased in CKD-K versus healthy-K irrespective of recipient. Contrarily, LV fibrosis was more severe in CKD-H versus healthy-H recipients irrespective of graft. Indeed, MAP and plasma creatinine correlated with LVMI but not with LV fibrosis. Increased LVMI in CKD-K→CKD-H not accompanied by cardiomyocyte cross-sectional area gain is consistent with eccentric remodelling. Cardiac RNA sequencing found a strong transcriptional response associated with LV fibrosis but only sparse changes associated with LV hypertrophy. This response was, among others, characterized by changes in extracellular matrix (ECM) and inflammatory gene expression.

Conclusion:

LVMI reversed and MAP and renal function were normalized early after transplantation of a healthy kidney. However, LV fibrosis persisted, dissociating LV hypertrophy from LV fibrosis within 6 weeks. Elucidating cardiac ECM dynamics in CKD patients, although challenging, appears promising.
ASSESSING THE ACTIVITY OF MYOPIC CHOROIDAL NEOVASCULARIZATION
Authors: Li Songshan , Sun Limei , Zhao Xiujuan , Huang Sijian , Luo Xiaoling , Zhang Aiyuan , Chen Chonglin , Wang Zhirong , Liu Chengxi , Ding Xiaoyan
Published: October 2019

Purpose:

This study aims to suggest a novel strategy for assessing the activity of myopic choroidal neovascularization (mCNV) based on optical coherence tomography angiography (OCTA) and to compare it with traditional fundus fluorescein angiography as the gold standard.

Methods:

Macular OCTA images were obtained using RTVue XR Avanti with AngioVue. Morphologic features of mCNV lesions were analyzed. Characteristics of OCTA in 41 eyes with active mCNV and 41 eyes with inactive mCNV were analyzed. Optical coherence tomography angiography parameters associated with mCNV activity and the clinical significance of their sensitivity and specificity were analyzed using fundus fluorescein angiography as the reference.

Results:

Of the total 108 patients, 82 had OCTA images with good quality which were included in this study. Several anatomical features of the CNV lesions, including overall appearance, branching with tiny vessels, presence of anastomoses/loops, and choroidal dark halo, were considered the possible parameters associated with mCNV activity. The intra- and interobserver agreements were substantial. To evaluate the CNV activity, sensitivity of overall appearance, tiny vascular branching, and presence of anastomoses or loops were 65.9%, 82.9%, and 73.2%, respectively, whereas the specificity was 87.8%, 90.2%, and 92.7%, respectively. However, the choroidal dark halo showed low specificity (46.3%) and failed in terms of evaluating the activity of mCNV. A novel comprehensive procedure integrating branching as a major parameter and overall appearance and presence of anastomoses/loops as minor parameters was developed to evaluate mCNV activity with sensitivity of 95.1% and specificity of 85.4%.

Conclusion:

In mCNV, the acquisition rate of clear OCTA images was 75.9%. A novel comprehensive diagnostic procedure combining mCNV appearance, vascular branching, and anastomoses/loops by OCTA may be a valuable strategy to evaluate neovascular activity in mCNV.
OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY DETECTS SUBCLINICAL RADIAL PERIPAPILLARY CAPILLARY DENSITY REDUCTION AFTER PLAQUE RADIOTHERAPY FOR CHOROIDAL MELANOMA
Authors: Chien Jason L. , Sioufi Kareem , Ferenczy Sandor R. , Say Emil A. T. , Shields Carol L.
Published: October 2019

Purpose:

To evaluate radial peripapillary capillary density (RPCD) in irradiated eyes without radiation papillopathy clinically.

Methods:

Patients treated with plaque radiotherapy for unilateral choroidal melanoma without radiation papillopathy clinically received optical coherence tomography and optical coherence tomography angiography imaging at ∼12- to 24-month follow-up. Comparison of RPCD globally and meridian closest to plaque and meridian farthest to plaque of irradiated versus nonirradiated eyes was performed.

Results:

Mean age was 55 years (n = 10). Mean largest basal diameter and thickness were 10.1 and 4.4 mm, respectively. Mean radiation dose to the optic nerve head and foveola was 41.7 and 66.2 Gy, respectively. No radiation papillopathy was detected by ophthalmoscopy throughout follow-up (mean:14 months). Radial peripapillary capillary density was significantly reduced globally (all P < 0.02). Meridian closest to plaque RPCD was significantly reduced (P < 0.01), but not meridian farthest to plaque RPCD (P = 0.07). Circumpapillary retinal nerve fiber layer thickness was not significantly reduced (P > 0.26). Radiation dose to the optic nerve head was correlated with meridian closest to plaque RPCD reduction (r = 0.76; P < 0.01). Mean radiation dose to the optic nerve head for <5% and ≥5% RPCD reductions was 35.9 ± 12.2 and 55.2 ± 6.4 Gy, respectively.

Conclusion:

Radial peripapillary capillary density reduction was found in irradiated eyes before clinical evidence of radiation papillopathy and circumpapillary retinal nerve fiber layer thickness reduction. Radial peripapillary capillary density reduction is correlated to plaque location and radiation dose to the optic nerve head.
Effect of Scleral Lens Wear on Central Corneal Thickness and Intraocular Pressure in Patients With Ocular Surface Disease
Authors: Shahnazi Kevin C. , Isozaki Veronica L. , Chiu Gloria B.
Published: October 2019

Objectives:

To determine the effect of scleral lens wear on central corneal thickness (CCT) and intraocular pressure (IOP).

Methods:

Twenty-five subjects (46 eyes), fit with scleral lenses that ranged in diameter from 17.0 to 18.0 mm, were included in this retrospective study at the University of Southern California, Department of Ophthalmology. All subjects had ocular surface disease and were categorized into the following groups based on etiology of their dry eye: chronic graft versus host disease, Stevens–Johnson syndrome, Sjögren syndrome, or general dry eye syndrome. Measurements of CCT and IOP were obtained at the initial scleral lens consultation (pre-CCT and pre-IOP) and at follow-up visits (post-CCT and post-IOP) immediately after lens removal.

Results:

The total average difference between pre-CCT and post-CCT was 7.19 μm (544.90±31.29 vs. 552.09±30.30 μm), which was a statistically significant increase of 1.01% (P≤0.05). On the other hand, the total average difference between pre-IOP and post-IOP was −0.89 mm Hg (14.47±3.63 vs. 13.58±3.61 mm Hg), which was not statistically significant (P≥0.05). There were no statistically significant correlations between change in CCT (ΔCCT) and visual acuity (P≥0.05), between ΔCCT or change in IOP (ΔIOP) in relation to lens diameter (P≥0.05), between etiology of dry eye affecting ΔCCT or ΔIOP (P≥0.05), between wearing time today and ΔCCT or ΔIOP (P≥0.05), and between average wearing time (AWT) and ΔCCT (P≥0.05). In addition, there was no statistically significant correlation between AWT and ΔIOP (R
2=0.0796) over a range of wear time hours.

Conclusion:

There was a statistically significant increase in CCT after scleral lens wear in subjects with ocular surface disease, which may be attributed to subclinical hypoxic conditions created by scleral lens wear. No significant relationship was found between scleral lens wear and IOP.
Real-world clinical outcomes of anticancer treatments in patients with advanced melanoma in China: retrospective, observational study
Authors: Cui Chuanliang , Yan Xieqiao , Liu Shusen , Deitz Anne C. , Si Lu , Chi Zhihong , Sheng Xinan , Lian Bin , Li Jianfeng , Ge Jun , Wang Xuan , Mao Lili , Tang Bixia , Zhou Li , Bai Xue , Li Siming , Li Ben , Wu Haiyan , Guo Jun
Published: October 2019

Introduction:

Treatment options for advanced melanoma in China are lacking, particularly second-line therapies. The aim of this retrospective observational study was to describe the real-world effectiveness of available anticancer therapies in patients with locally advanced/metastatic melanoma in China.

Methods:

Adult patients with unresectable stage III or IV melanoma treated between January 1, 2014, and December 31, 2015, at the Beijing Cancer Hospital (BCH) were eligible (data cutoff: December 31, 2017). Data were obtained from patient electronic medical records. Responders were adjudicated per Response Evaluation Criteria in Solid Tumors, version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.

Results:

Of 248 eligible patients, 221 and 116 were treated with anticancer therapies in first-line and second-line settings, respectively (89 received both at BCH). Approximately 95% of patients had stage IV melanoma; 40.7% had acral melanoma, and 30.6% had mucosal histology. By data cutoff, 195 of 248 (78.6%) patients had died. Median OS for all patients was 10.5 months; 12-month OS rate was 43.9%. In the first-line setting, the objective response rate was 6.3% (95% confidence interval, 3.5%–10.4%) and the median duration of response was 9.1 months. Median PFS was 3.5 months and 12-month PFS rate was 10.6%; median OS was 10.5 months and 12-month OS rate was 43.5%. In the second-line setting, objective response rate was 3.4% (95% confidence interval, 0.9%–8.6%) and median duration of response was 7.5 months. Median PFS was 2.3 months and 12-month PFS rate was 5.2%; median OS was 7.5 months and 12-month OS rate was 30.5%.

Conclusion:

In China, first-line and second-line anticancer therapy seems to be associated with suboptimal clinical outcomes in advanced melanoma, indicating a need for effective therapies.