bluuebunny/crossref_metadata_2025 huggingface dataset:
Exosomal lncRNAs and cancer: connecting the missing links
Authors: Naderi-Meshkin Hojjat , Lai Xin , Amirkhah Raheleh , Vera Julio , Rasko John E J , Schmitz Ulf
Published: June 2018

Motivation

Extracellular vesicles (EVs), including exosomes and microvesicles, are potent and clinically valuable tools for early diagnosis, prognosis and potentially the targeted treatment of cancer. The content of EVs is closely related to the type and status of the EV-secreting cell. Circulating exosomes are a source of stable RNAs including mRNAs, microRNAs and long non-coding RNAs (lncRNAs).

Results

This review outlines the links between EVs, lncRNAs and cancer. We highlight communication networks involving the tumor microenvironment, the immune system and metastasis. We show examples supporting the value of exosomal lncRNAs as cancer biomarkers and therapeutic targets. We demonstrate how a system biology approach can be used to model cell–cell communication via exosomal lncRNAs and to simulate effects of therapeutic interventions. In addition, we introduce algorithms and bioinformatics resources for the discovery of tumor-specific lncRNAs and tools that are applied to determine exosome content and lncRNA function. Finally, this review provides a comprehensive collection and guide to databases for exosomal lncRNAs.

Supplementary information

Supplementary data are available at Bioinformatics online.
Revisiting the larval dispersal black box in the Anthropocene
Authors: Chan Kit Yu Karen , Sewell Mary A , Byrne Maria
Published: June 2018

Many marine organisms have a multi-phase life history and rely on their planktonic larvae for dispersal. Despite the important role of larvae in shaping population distribution and abundance, the chemical, physical, and biological factors that shape larval fate are still not fully understood. Shedding light into this larval dispersal “black box” has become critical in the face of global climate change, primarily due to the importance of larval dispersal in formulating sound conservation and management strategies. Focusing on two major stressors, warming and acidification, we highlight the limitations of the current species-by-species, lab-based study approach, and particularly the lack of consideration of the larval experience along the dispersive pathway. Measuring organismal responses to environmentally relevant climate change stress demands an improved documentation of the physical and biological conditions that larvae experience through ontogeny, which in turn requires updated empirical and theoretical approaches. While there are meaningful between taxa comparisons to be made by larval ecologists, to peek into the dispersal black box and to investigate the larger scale consequences of altered dispersal requires innovative collaborations between ecologists, oceanographers, molecular biologists, statisticians, and mathematicians.
Routine Prophylactic Endoscopic Clipping Is Not Efficacious in the Prevention of Delayed Post-Polypectomy Bleeding: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Forbes Nauzer , Frehlich Levi , James Matthew T , Hilsden Robert J , Kaplan Gilaad G , Wilson Todd A , Lorenzetti Diane L , Tate David J , Bourke Michael J , Heitman Steven J
Published: June 2018

Background and Aims

Colorectal cancer (CRC) can be prevented through colonoscopic polypectomy, but this exposes patients to risks, including delayed post-polypectomy bleeding (DPPB). Endoscopists increasingly use clips prophylactically with the aim of preventing DPPB. However, clips are costly, and data to support their efficacy in this context are inconsistent. We performed a systematic review and meta-analysis of randomized controlled trials to assess the efficacy of prophylactic clipping for preventing DPPB.

Methods

We searched electronic databases and other relevant sources for randomized controlled trials assessing the efficacy of prophylactic clipping versus no clipping for the prevention of DPPB. Pooled relative risks were determined using a fixed-effects model. Subgroup analyses were also performed.

Results

A total of 2305 citations were initially screened. Seven randomized controlled trials satisfied all criteria for inclusion. The quality of included studies was generally low to moderate. A total of 2851 patients underwent 5405 polypectomies. Delayed post-polypectomy bleeding occurred at an overall pooled rate of 2.5%. No overall benefit of clipping for preventing DPPB was observed, with a pooled relative risk of 0.86 (95% confidence interval [CI], 0.55 to 1.36). No significant patient or polyp factors predicting DPPB were found through subgroup analyses. No publication bias was identified.

Conclusions

Randomized trials to date do not demonstrate a protective effect of prophylactic clipping for the prevention of DPPB, and therefore, the practice of routine prophylactic clipping appears unjustified. Additional high quality randomized trials are required to identify higher-risk groups that may benefit from prophylactic clipping.
Effects of Early Auditory Deprivation on Working Memory and Reasoning Abilities in Verbal and Visuospatial Domains for Pediatric Cochlear Implant Recipients
Authors: Davidson Lisa S. , Geers Ann E. , Hale Sandra , Sommers Mitchell M. , Brenner Christine , Spehar Brent
Published: June 2018

Objectives:

The overall goal of this study was to compare verbal and visuospatial working memory in children with normal hearing (NH) and with cochlear implants (CI). The main questions addressed by this study were (1) Does auditory deprivation result in global or domain-specific deficits in working memory in children with CIs compared with their NH age mates? (2) Does the potential for verbal recoding affect performance on measures of reasoning ability in children with CIs relative to their NH age mates? and (3) Is performance on verbal and visuospatial working memory tasks related to spoken receptive language level achieved by children with CIs?

Design:

A total of 54 children ranging in age from 5 to 9 years participated; 25 children with CIs and 29 children with NH. Participants were tested on both simple and complex measures of verbal and visuospatial working memory. Vocabulary was assessed with the Peabody Picture Vocabulary Test (PPVT) and reasoning abilities with two subtests of the WISC-IV (Wechsler Intelligence Scale for Children, 4th edition): Picture Concepts (verbally mediated) and Matrix Reasoning (visuospatial task). Groups were compared on all measures using analysis of variance after controlling for age and maternal education.

Results:

Children with CIs scored significantly lower than children with NH on measures of working memory, after accounting for age and maternal education. Differences between the groups were more apparent for verbal working memory compared with visuospatial working memory. For reasoning and vocabulary, the CI group scored significantly lower than the NH group for PPVT and WISC Picture Concepts but similar to NH age mates on WISC Matrix Reasoning.

Conclusions:

Results from this study suggest that children with CIs have deficits in working memory related to storing and processing verbal information in working memory. These deficits extend to receptive vocabulary and verbal reasoning and remain even after controlling for the higher maternal education level of the NH group. Their ability to store and process visuospatial information in working memory and complete reasoning tasks that minimize verbal labeling of stimuli more closely approaches performance of NH age mates.
Peer Support in Critical Care: A Systematic Review
Authors: Haines Kimberley J. , Beesley Sarah J. , Hopkins Ramona O. , McPeake Joanne , Quasim Tara , Ritchie Kathryn , Iwashyna Theodore J.
Published: June 2018

Objectives:

Identifying solutions to improve recovery after critical illness is a pressing problem. We systematically evaluated studies of peer support as a potential intervention to improve recovery in critical care populations and synthesized elements important to peer support model design.

Data Sources:

A systematic search of Medical Literature Analysis and Retrieval System Online, Cumulative Index to Nursing and Allied Health Literature, PsychINFO, and Excertpa Medica Database was undertaken May 2017. Prospective Register of Systematic Reviews identification number: CRD42017070174.

Study Selection:

Two independent reviewers assessed titles and abstracts against study eligibility criteria. Studies were included where 1) patients and families had experienced critical illness and 2) patients and families had participated in a peer support intervention. Discrepancies were resolved by consensus and a third independent reviewer adjudicated as necessary.

Data Extraction:

Two independent reviewers assessed study quality with the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool, and data were synthesized according to the Preferred Reporting Items for Systematic Reviews guidelines and interventions summarized using the Template for Intervention Description and Replication Checklist.

Data Synthesis:

Two-thousand nine-hundred thirty-two studies were screened. Eight were included, comprising 192 family members and 92 patients including adults (with cardiac surgery, acute myocardial infarction, trauma), pediatrics, and neonates. The most common peer support model of the eight studies was an in-person, facilitated group for families that occurred during the patients’ ICU admission. Peer support reduced psychologic morbidity and improved social support and self-efficacy in two studies; in both cases, peer support was via an individual peer-to-peer model. In the remaining studies, it was difficult to determine the outcomes of peer support as the reporting and quality of studies was low.

Conclusions:

Peer support appeared to reduce psychologic morbidity and increase social support. The evidence for peer support in critically ill populations is limited. There is a need for well-designed and rigorously reported research into this complex intervention.
Nivolumab monotherapy or in combination with ipilimumab for metastatic melanoma: systematic review and meta-analysis of randomized-controlled trials
Authors: Menshawy Amr , Eltonob Abdelrahman A. , Barkat Sarah A. , Ghanem Ahmed , Mniesy Mahmoud M. , Mohamed Ishak , Abdel-Maboud Mohamed , Mattar Omar M. , Elfil Mohamed , Bahbah Eshak I. , Elgebaly Ahmed
Published: June 2018

Nivolumab, a completely human programmed death-1 inhibitor antibody, was first approved by the Food and Drug Administration for patients with advanced malignant melanoma resistant to other modalities of treatment. In 2015, it received approval as the first line of treatment for malignant melanoma. We aimed to synthesize evidence from published randomized-controlled trials on the safety and efficacy of nivolumab, either alone or in combination with ipilimumab, in the management of advanced unresectable melanoma. We searched the following electronic databases: PubMed, Scopus, Web of Science, and Cochrane Central. The records retrieved were screened for eligibility. Time-to-event data were pooled as Hazard ratio using the generic inverse variance method and dichotomous data were pooled as relative risk (RR) in a random-effects model. We used Review Manager 5.3 software for windows. Four unique randomized-controlled trials (five reports) with a total of 1910 patients (nivolumab group, n=1207 and control group, n=703) were included. The overall effect estimate favored nivolumab plus ipilimumab versus ipilimumab alone in terms of the objective response rate [RR: 3.58, 95% confidence interval (CI): 2.08–6.14], the complete response rate (RR: 5.93, 95% CI: 2.45–14.37), the partial response rate (RR: 2.80, 95% CI: 2.16–3.64), the stable disease rate (RR: 0.56, 95% CI: 0.41–0.76), and progression-free survival (hazard ratio: 0.67, 95% CI: 0.60–0.74). The pooled studies were homogenous. Similar results were obtained for nivolumab monotherapy versus chemotherapy comparison. Nivolumab alone or combined with ipilimumab significantly improved the overall and complete response rates compared with ipilimumab alone. In addition, nivolumab resulted in longer progression-free survival with a comparable safety profile.
Population Pharmacokinetic Analysis of Gentamicin in Pediatric Extracorporeal Membrane Oxygenation
Authors: Moffett Brady S. , Morris Jennifer , Galati Marianne , Munoz Flor M. , Arikan Ayse Akcan
Published: June 2018

Background:

Gentamicin pharmacokinetics may be altered in pediatric patients undergoing extracorporeal membrane oxygenation (ECMO). Description of gentamicin pharmacokinetics and relevant variables can improve dosing.

Methods:

A retrospective population pharmacokinetic study was designed, and pediatric patients who received gentamicin while undergoing ECMO therapy over a period of 6 1/2 years were included. Data collection included the following: patient demographics, serum creatinine, albumin, hematocrit, gentamicin dosing and serum concentrations, urine output, and ECMO circuit parameters. Descriptive statistics were used to characterize the patient population. Population pharmacokinetic analysis was performed with NONMEM, and simulation was performed to identify empiric doses to achieve therapeutic serum concentrations.

Results:

A total of 37 patients met study criteria (75.7% male patients), with a median age of 0.17 [interquartile range (IQR) 0.12–0.82] years. Primary indications for ECMO included the following: congenital diaphragmatic hernia (n = 17), persistent pulmonary hypertension (n = 5), and septic shock (n = 4). Patients received a total of 117 gentamicin doses [median 1.8 (IQR 1.4–2.9) mg/kg/dose] and had 125 serum concentrations measured at a median of 22.8 (IQR 15.8–25.5) hours after a dose. Population pharmacokinetic analysis identified a 2-compartment model with additive error as the best fit. Covariates included the following: allometrically scaled fat-free mass on clearance, central and peripheral volume of distribution (VDcentraland VDperipheral), and intercompartmental clearance; serum creatinine on clearance; ultrafiltration rate on central volume of distribution. Simulation identified dosage of 4–5 mg/kg/dose every 24 hours for neonates and infants as an acceptable empiric dosing regimen. Children and adolescents had elevated trough concentrations when dosed according to traditional dosing methods.

Conclusions:

Fat-free mass should be used to dose gentamicin in pediatric ECMO patients. Serum creatinine is a marker of gentamicin clearance and should be used to adjust gentamicin dosing in pediatric ECMO patients.
Evidence for Adaptive Response in a Molecular Epidemiological Study of the Inhabitants of a High Background-radiation Area of Yangjiang, China
Authors: Su Shibiao , Zhou Shanyu , Wen Cuiju , Zou Jianming , Zhang Danying , Geng Jiwu , Yang Min , Liu Ming , Li Lichun , Wen Wei
Published: June 2018

Our previous studies have shown that cancer mortality in high background-radiation areas of China was lower than that in a control area, indicating the possibility of an adaptive response in high background-radiation areas. Our aim is to determine the effect of low-dose radiation on the level of DNA oxidative damage, DNA damage repair, antioxidant capacity, and apoptosis in high background-radiation area and control area populations of Guangdong through a molecular epidemiological study in order to identify adaptive response. Blood samples were collected from male residents aged 50 to 59 y in a high background-radiation area (Yangjiang) and a control area (Enping), and activities of superoxide dismutase, glutathione, catalase, total antioxidant capacity, and expression of O6‐methylguanine-DNA methyltransferase gene (MGMT), human 8‐oxoguanine DNA N-glycosylase 1 gene (hOGG1), proapoptotic genes and antiapoptotic genes, oxidative-stress-related genes, as well as concentrations of 8‐OHdG, TrxR, HSP27, and MT-COX2 were determined. The activities of antioxidative enzymes, relative mRNA expression level of DNA repair genes, antiapoptotic genes, oxidative-stress-related genes HSPB1 and MT-COX2, and the concentration of antioxidant index TrxR in the high background-radiation area population increased significantly compared to the control population (p < 0.05). The relative mRNA expression level of proapoptotic genes and the concentration of DNA oxidative damage index 8‐OHdG were significantly lower in the high background-radiation area compared to those in the control area (p < 0.05). In conclusion, under long-term, natural, high background, ionizing radiation, DNA damage-repair capacity and antioxidant capacity of inhabitants in the high background-radiation area may be enhanced. Additionally, it could induce up regulation of cell-survival gene expression and down regulation of apoptotic gene expression. It might be speculated that enhanced antioxidant and DNA repair capacity and inhibition of apoptosis might play important roles in adaptive response of low-dose radiation in high background-radiation areas.
NEGATIVE EFFECTS OF VITAL DYES AFTER UNEVENTFUL VITREOMACULAR SURGERY
Authors: Röhrig Stephan , Farecki Marie-Louise , Boden Karl T. , Haus Arno , Gutfleisch Matthias , Jung Sascha , Lommatzsch Albrecht , Szurman Peter , Januschowski Kai
Published: June 2018

Purpose:

Vital dyes have become a clinical standard during chromovitrectomy but toxicity remains an issue. We compared the clinical outcome of one supposedly toxic vital dye (AV 17 with 5% mannitol) with a standard vital dye (MBB Dual) and performed a power analysis for future comparative studies.

Methods:

Retrospective analysis of 270 eyes after chromovitrectomy with internal limiting membrane peeling because of macular holes. Primary endpoint was loss in BCVA >2 lines and photoreceptor atrophy as seen on optical coherence tomography examination.

Results:

In 173 eyes, staining of the epiretinal membrane and extracellular matrix was performed using MBB (Group A), and in 97 using AV 17-M (Group B). The mean BCVA was not significantly different after more than 3 months and also not in the early postoperative period after surgery between Group A and Group B. The number of patients suffering from a decline in BCVA of two lines and more was not significantly higher in patients of Group B. There was not a significantly higher percentage of patients with an inner segment/outer segment defect.

Conclusion:

Our rather homogeneous study showed no significant difference between both dyes. Thousand five hundred patients would need to be examined to find a significant difference in future studies.
OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY CHARACTERISTICS OF POLYPOIDAL CHOROIDAL VASCULOPATHY SECONDARY TO CHRONIC CENTRAL SEROUS CHORIORETINOPATHY
Authors: Peiretti Enrico , Iovino Claudio , Sacconi Riccardo , Caminiti Giulia , Querques Giuseppe
Published: June 2018

Purpose:

To report diagnostic capability of optical coherence tomography angiography (OCTA) in detecting polypoidal choroidal vasculopathy and its morphologic characteristics in white patients with chronic central serous chorioretinopathy.

Methods:

Retrospective consecutive series of 20 eyes (17 consecutive patients) with a diagnosis of polypoidal choroidal vasculopathy secondary to chronic central serous chorioretinopathy based on clinical and multimodal imaging were included. All patients underwent a complete ophthalmologic examination, including best-correct visual acuity, fundus autofluorescence, fluorescein and indocyanine green angiography, spectral-domain optical coherence tomography, and OCTA.

Results:

In all eyes (100%), OCTA revealed the branching vascular network as a hyperflow lesion in both choriocapillaris and outer retina layers. Segmentation of the choriocapillaris in OCTA, in correspondence of the polypoidal dilation detected at indocyanine green angiography, showed a hyperflow round structure in 75% of cases and hypoflow round structure in 15%. Two of 20 eyes (10%) had no detectable polyps on OCTA.

Conclusion:

Optical coherence tomography angiography is a noninvasive imaging modality allowing a good visualization of both branching vascular network and polyp dilations. Our findings suggest that OCTA is a useful tool in the investigation of chronic central serous chorioretinopathy complicated by polypoidal choroidal vasculopathy.
RECONSTITUTION OF THE ELLIPSOID ZONE WITH TOCILIZUMAB IN AUTOIMMUNE RETINOPATHY
Authors: Finn Avni P. , Keenan Robert T. , Jaffe Glenn J.
Published: June 2018

Purpose:

To demonstrate improvement and stabilization of retinal findings, including recalcitrant cystoid macular edema, in a patient with nonparaneoplastic autoimmune retinopathy after treatment with tocilizumab, a humanized monoclonal antibody against soluble and membrane-bound IL-6 receptor.

Methods:

Observational case report. A 46-year-old woman was diagnosed with nonparaneoplastic autoimmune retinopathy and followed over 4 years on various immunosuppressive medications with worsening disease and recalcitrant cystoid macular edema. This report describes the rapid improvement and stabilization of her ocular disease once tocilizumab was initiated.

Results:

Tocilizumab, a monoclonal antibody against the IL-6 receptor, was initiated at a dose of 8 mg/kg every 4 weeks. Cystoid macular edema was significantly decreased after just two infusions and nearly resolved after five infusions. Ellipsoid zone and outer retinal integrity also improved on optical coherence tomography. The patient tolerated the medication with limited side effects.

Conclusion:

Long-term immunosuppression is the cornerstone of treatment for nonparaneoplastic autoimmune retinopathy, although success is highly variable. We report a case treated with tocilizumab with dramatic improvement in refractory macular edema and reconstitution of the ellipsoid zone on optical coherence tomography in a patient with nonparaneoplastic autoimmune retinopathy. This case highlights the potential role of treatment with an IL-6 inhibitor in autoimmune retinopathy though further studies are needed.
Endothelial Cell Loss in Obstetric Forceps-Related Corneal Injury: A Longitudinal Specular Microscopic Study
Authors: El Hamouly Ali , Sheung Man Fung Simon , Sami Hamza , Jiandani Dishay , Williams Sara , Mireskandari Kamiar , Ali Asim
Published: June 2018

Purpose:

To assess the impact of ocular trauma associated with obstetric forceps delivery on the corneal endothelium in children.

Methods:

Five patients who attended the Hospital for Sick Children, Toronto, between 2013 and 2016 with a diagnosis of unilateral obstetrical forceps-related corneal injury were included. Clinical presentation, best-corrected visual acuity, corneal endothelial cell density (ECD, cells/mm2), and measures of cellular morphology were obtained.

Results:

The mean follow-up duration was 30 ± 10 months. Mean ECD in the affected eye at initial assessment was significantly lower than that of the fellow eye (2576 ± 733 vs. 3481 ± 288 cells/mm2, P = 0.02). At final follow-up, mean ECD was 3293 ± 175 and 1907 ± 524 cells/mm2 in the normal and affected eyes, respectively (P = 0.004). The mean annual rate of the ECD decrease was higher in the affected eyes than in the normal eyes (9.1% ± 4.2% vs. 2.0% ± 2.5%), although this difference was not statistically significant (P = 0.06).

Conclusions:

In children with forceps-related corneal injury, lower ECD with a higher annual decrease can be assessed with specular microscopy for risk stratification and parental counseling purposes.
Pediatric Amazonian Toxoplasmosis Caused by Atypical Strains in French Guiana, 2002–2017
Authors: Blaizot Romain , Nabet Cécile , Blanchet Denis , Martin Elise , Mercier Aurélien , Dardé Marie-Laure , Elenga Narcisse , Demar Magalie
Published: June 2018

Background:

Amazonian toxoplasmosis is a recently described form of Toxoplasma gondii infection, characterized by severe clinical and biological features and involvement of atypical genetic strains circulating through a forest-based cycle. Though mostly reported in French Guiana since 1998, this disease is probably under-diagnosed in other areas of South America. Few data are available on its specific features in children.

Methods:

We retrospectively included all children seen in Cayenne between 2002 and 2017, diagnosed with acute toxoplasmosis due to an atypical strain. Clinical and biological features and risk factors of Amazonian toxoplasmosis were recorded.

Results:

Eleven children met the inclusion criteria. The main clinical features were fever, lymphadenopathy, hepatomegaly and splenomegaly, as reported in adults. Less expected signs such as rhinorrhea, pharyngitis and maculopapular rash were also frequent. Cutaneous signs were associated with the involvement of a genetically atypical strain. Respiratory involvement was rare but associated with respiratory distress. Outcome was always favorable. Treatment by pyrimethamine/sulfadiazine or trimethoprim/sulfamethoxazole was always justified, efficient and well tolerated. Genetic analysis suggested the involvement of wild mammals in disease transmission, and strain-dependent virulence as one of the prognostic risk factors.

Conclusions:

As in adults, pediatric Amazonian toxoplasmosis requires a systematic treatment. Symptoms such as skin rash, rhinorrhea and pharyngitis should not be mistaken for viral infections, when associated with lymphadenopathy or fever. Pediatricians working in South America should be familiar with these clinical presentations and with the different risk factors of Amazonian toxoplasmosis.
Immunologic-based Diagnosis of Latent Tuberculosis Among Children Younger Than 5 Years of Age Exposed and Unexposed to Tuberculosis in Tanzania
Authors: Said Khadija , Hella Jerry , Ruzegea Mwajabu , Solanki Rajesh , Chiryamkubi Magreth , Mhimbira Francis , Ritz Nicole , Schindler Christian , Mandalakas Anna M. , Manji Karim , Tanner Marcel , Utzinger Jürg , Fenner Lukas
Published: June 2018

Background:

Childhood tuberculosis (TB) is acquired after exposure to an infectious TB case, often within the household. We prospectively screened children 6–59 months of age, exposed and unexposed to an infectious TB case within the same household, for latent tuberculosis infection (LTBI), in Dar es Salaam, Tanzania.

Methods:

We collected medical data and clinical specimens (to evaluate for helminths, TB and HIV coinfections) and performed physical examinations at enrollment and at 3-month and 6-month follow-up surveys. LTBI was assessed using QuantiFERON-TB Gold (QFT) at enrollment and at 3 months.

Results:

In total, 301 children had complete data records (186 with TB exposure and 115 without known TB exposure). The median age of children was 26 months (range: 6–58); 52% were females, and 4 were HIV positive. Eight children (3%) developed TB during the 6-month follow-up. We found equal proportions of children with LTBI among those with and without exposure: 20% (38/186) versus 20% (23/115) QFT-positive, and 2% (4/186) versus 4% (5/115) indeterminate QFT. QFT conversion rate was 7% (22 children) and reversion 8% (25 children). Of the TB-exposed children, 72% initiated isoniazid preventive therapy, but 61% of parents/caregivers of children with unknown TB exposure and positive QFT refused isoniazid preventive therapy.

Conclusions:

In this high burden TB setting, TB exposure from sources other than the household was equally important as household exposure. Nearly one third of eligible children did not receive isoniazid preventive therapy. Evaluation for LTBI in children remains an important strategy for controlling TB but should not be limited to children with documented TB exposure.
Evaluation of composite responder outcomes of pain intensity and physical function in neuropathic pain clinical trials: an ACTTION individual patient data analysis
Authors: Patel Kushang V. , Allen Robert , Burke Laurie , Farrar John T. , Gewandter Jennifer S. , Gilron Ian , Katz Nathaniel P. , Markman John D. , Marshall Scott F. , Resnick Malca , Rice Andrew S.C. , Rowbotham Michael C. , Smith Shannon M. , Vanhove Geertrui F. , Wasan Ajay D. , Zhang Shuyu , Dworkin Robert H. , Turk Dennis C.
Published: June 2018

Integrating information on physical function and pain intensity into a composite measure may provide a useful method for assessing treatment efficacy in clinical trials of chronic pain. Accordingly, we evaluated composite outcomes in trials of duloxetine, gabapentin, and pregabalin. Data on 2287 patients in 9 trials for painful diabetic peripheral neuropathy (DPN) and 1513 patients in 6 trials for postherpetic neuralgia (PHN) were analyzed. All trials assessed pain intensity on a 0 to 10 numeric rating scale and physical function with the 10-item subscale of the Short Form-36, ranging 0 to 100 with higher scores indicating better function. Correlation between change in pain intensity from baseline to posttreatment and change in physical function was small in DPN (ρ = −0.22; P < 0.001) and nonsignificant in PHN (ρ = −0.05; P = 0.08). Assay sensitivities of 10 composite outcomes were examined in a random subsample of patients enrolled in pregabalin trials for DPN and PHN. Of these, a responder outcome of ≥50% improvement in pain intensity, or a ≥20% improvement in pain intensity and ≥30% improvement in physical function was not only significantly associated with pregabalin vs placebo in the development cohorts for both pain conditions but also in the validation cohorts. Furthermore, this composite outcome was cross-validated in trials of gabapentin for PHN and duloxetine for DPN, and had slightly lower number needed to treat than a standard responder outcome of ≥50% reduction in pain intensity. In summary, this study identified a composite outcome of pain intensity and physical function that may improve the assay sensitivity of future neuropathic pain trials.
Colposcopy Evaluation at the Time of Loop Electrosurgical Excision Procedure May Avoid Unnecessary Treatment
Authors: Munmany Meritxell , Torné Aureli , Nonell Roser , Barnadas Esther , Luqui Nerea , Ordi Jaume , del Pino Marta
Published: June 2018

Objective

The aim of the study was to assess the accuracy of colposcopy evaluation at the time of the loop electrosurgical excision procedure (LEEP) to identify women with a previous confirmatory diagnosis of squamous intraepithelial lesion/cervical intraepithelial neoplasia (SIL/CIN) with low probability of dysplasia in the LEEP specimen.

Materials and Methods

We prospectively recruited a cohort of 162 women undergoing LEEP for histological high-grade SIL/CIN 2–3 or low-grade SIL/CIN 1 with high-grade SIL cytology showing a fully visible squamocolumnar junction in the colposcopy evaluation at the time of LEEP. At the referral visit cervical cytology, human papillomavirus and genotype detection, digital colposcopy, colposcopical lesion measurement, and 1 or more biopsies of the transformation zone were obtained. The uterine cervix was colposcopically evaluated intraoperatively.

Results

Thirty-four women (21.0%) had a normal colposcopy evaluation at the time of the LEEP, whereas the remaining 128 women showed abnormal findings. Absence of SIL/CIN in the LEEP specimen was confirmed in 28 (82.3%) of the 34 women with a normal colposcopy at the time of LEEP group and 8 (3.1%) of the 128 women showing abnormal colposcopy at the time of LEEP group (p < .001). A normal colposcopic evaluation at the time of LEEP was associated with an increase in the risk of absence of lesion in the cone specimen compared with cases presenting an abnormal colposcopy (95% CI = 33.8–1,555.1, p < .001). The colposcopy evaluation at the time of LEEP had a positive predictive value of 82.3% (95% CI = 66.5–91.5) and a negative predictive value of 96.9% (95% CI = 92.2–98.8) to predict low probability of SIL/CIN in the specimen.

Conclusions

Colposcopic evaluation at the time of LEEP seems to be accurate to identify SIL/CIN postbiopsy regression; thus, its performance would be considered at the time of the treatment.
Is an Intravenous Injection of Gadolinium Really Necessary for Intralabyrinthine Schwannomas MR Examination?
Authors: Karol Anne , Veillon Francis , Huynh Thaï , Severac François , Charpiot Anne , Venkatasamy Aïna
Published: June 2018

Objectives:

Our aim was to confirm the usefulness of T2-weighted (T2W) gradient-echo sequence for detection and topographic diagnosis of intralabyrinthine schwannomas (ILS) compared with T1W contrast-enhanced sequence as gold standard, to evaluate the necessity of intravenous gadolinium injection for ILS follow-up imaging.

Methods:

Thirty patients with ILS were retrospectively enrolled and compared to a control group of 30 patients with no inner ear pathology. All patients underwent a T2W gradient-echo steady-state free precession (SSFP) acquisition at 3T, which was visually analyzed by two radiologists and compared to contrast-enhanced T1W sequence. A quantitative analysis was also performed, with the measurement of the tumor and inner ear signal on T2W images and the measurement of the tumor length in cochlear schwannomas.

Results:

T2W FIESTA-C sequence correctly diagnosed ILS with a sensitivity (Se) of 95% and a specificity (Sp) of 100%, with matching results for their topographic evaluation (Se 92%, Sp 98%) compared with the gold-standard. The difference between the two sequences was only 2.5%, with excellent interobserver agreement. The tumor signal on T2W images was significantly lower than the normal bright signal of the normal inner ear fluids (mean signal ratio = 0.42 vs 0.98).

Conclusion:

The positive and topographic diagnostic accuracy of T2W FIESTA-C sequence was excellent compared with the T1W contrast-enhanced sequence, even though the latter remains easier and faster to analyze for an untrained radiologist. The performances of T2W gradient-echo sequence at 3T make it a reasonable alternative strategy for following ILS after they are diagnosed.
Comprehensive review of the extended middle cranial fossa approach
Authors: Lipschitz Noga , Kohlberg Gavriel D. , Zuccarello Mario , Samy Ravi N.
Published: June 2018

Purpose of review

To review the current literature on the extended middle cranial fossa (xMCF) approach and to provide a comprehensive description of the relevant anatomy, indications, surgical technique, results, and complications.

Recent findings

The xMCF approach expands the surgical exposure provided by the sMCF approach, allowing access to the internal auditory canal, cerebellopontine angle, prepontine cistern, anterior petrous apex, petrous carotid artery, Meckel's cave, cavernous sinus, mid and upper clivus, and posterior lesions approaching the jugular foramen. Preservation of serviceable hearing is possible with success rates approximating 50% in vestibular schwannoma and meningioma resection, and facial nerve outcome is excellent.

The xMCF is an important approach for difficult to access lesions that additionally offers the possibility of hearing preservation. This approach is also useful for vascular lesions, auditory brainstem implantation, and lesions of mid-brainstem.
Case Series: Bilateral Rhegmatogenous Retinal Detachments in Atopic Dermatitis
Authors: Tan Licia , Teo Lynn , Lee Shu Yen
Published: June 2018

SIGNIFICANCE

Bilateral occurrence of rhegmatogenous retinal detachment is a potentially blinding condition seen most commonly in patients with atopic dermatitis. Poor control of the skin condition may lead to simultaneous or sequential retinal detachment and even development of complications such as proliferative vitreoretinopathy.

PURPOSE

The purpose of this study was to highlight the importance of the dermatologist's role in aggressive treatment of atopic dermatitis to prevent this potentially blinding condition.

CASE REPORTS

A retrospective review of three patients with poorly controlled atopic dermatitis at the Singapore National Eye Centre with bilateral rhegmatogenous retinal detachment was conducted. Two patients presented with sequential rhegmatogenous retinal detachments, and one patient had simultaneous bilateral retinal detachments. At presentation, all three were experiencing atopic dermatitis flares and were either on low-dose oral or topical steroids only. Post–retinal detachment surgery, all eyes except one achieved good visual acuity. The patients were referred to a dermatologist and treated with therapeutic doses of systemic steroids and immunomodulators for their dermatitis flare.

CONCLUSIONS

This case series draws attention to the importance of the eye care provider's comanagement of such patients with atopic dermatitis. Aggressive control of facial atopic dermatitis with consideration of immunomodulators or short-term systemic steroids during flares to control facial eczema and eye rubbing may reduce this potentially blinding ocular complication.
Comparison between Negative-Pressure Fixation and Film Dressing in Wound Management after Tissue Expansion: A Randomized Controlled Trial
Authors: Nagata Takeshi , Miura Katsutoshi , Homma Yoichiro , Fukamizu Hidekazu
Published: June 2018

Wound compression and fixation are important to reduce scarring. Numerous postoperative treatments have been developed to reduce scar formation; however, a simple and effective device that improves the appearance and histochemical properties of incisional scars is needed. Therefore, the authors have devised a novel method, negative-pressure fixation, that applies negative pressure inside polyurethane foam covered with film. In the present study, negative-pressure fixation was applied to incisional wounds resulting from the insertion of a tissue expander in patients undergoing two-stage breast reconstruction. The authors aimed to evaluate the effects of negative-pressure fixation on scar appearance and histochemical properties in comparison to those for film dressing without negative pressure. A prospective, open-label, randomized, single-center study was performed. A half-side test was conducted on the incisional scar resulting from tissue expander insertion during breast reconstruction after mastectomy in 13 female patients. The dressings on both sides of the scar were replaced once per week until the tissue expander was adequately inflated. The outcomes were assessed 6 months later. Scars were photographed before the second operation and were evaluated using a visual analogue scale. All scars were removed and resutured during the final operation, allowing a histochemical analysis. The mean visual analogue scale score for the negative-pressure fixation side was significantly lower compared with that for the film dressing side (p = 0.0025). In addition, the scar on the negative-pressure fixation side was significantly narrower (p = 0.0015). Thus, negative-pressure fixation is a simple and effective device for improving the appearance and histochemical properties of incisional scars.
What Does the Public Think? Examining Plastic Surgery Perceptions through the Twitterverse
Authors: Kalandar Abeer , Al-Youha Sarah , Al-Halabi Becher , Williams Jason
Published: June 2018

Background:

Twitter is a recognized social media platform for communication of health information. Rime reported that emotion is the main motive for social sharing. This study is a content analysis of Twitter that was performed to identify the public’s perceptions and attitudes toward plastic surgery and the emotional triggers that drive social sharing of plastic surgery information.

Methods:

Tweets containing “#PlasticSurgery” or “Plastic Surgery” were archived randomly from August 1, 2014, to December 30, 2016 (n = 4548). Tweets were categorized according to tweet author, specialty, topic, content, multimedia included, emotion, tone, accuracy of information, source, and retweet rate. Statistical analysis was performed to detect significant patterns.

Results:

Tweets on cosmetic surgery (74 percent) were shared mostly on Twitter, predominantly posted by the public [n = 1611 (48 percent)]. More than 13 percent of posts contained “celebrity news” and 42.8 percent contained professional information and resources. The most frequent emotions shared and retweeted were “relaxed/content” (51.5 percent) and “excited/interested” (18.4 percent). Most tweets posted by the public contained inaccurate information [n = 1486 (80 percent)]. Only 154 (11.2 percent) of board-certified plastic surgeons’ tweets were rated as “most accurate.”

Conclusions:

The majority of tweets posted on Twitter contained inaccurate information that can lead to misperception among the public. Understanding emotional triggers for social sharing provides insight into what is most appealing. To enhance public uptake and sharing of tweets, plastic surgeons can use these findings to promote the specialty using relaxed/content emotions or excitement in their social media posts.
Segmental Multiple-Jaw Surgery without Orthodontia: Clear Aligners Alone
Authors: Kankam Hadyn K. N. , Gupta Himank , Sawh-Martinez Rajendra , Steinbacher Derek M.
Published: June 2018

Segmental Le Fort I osteotomy, a complex procedure with many mobile parts, has traditionally required presurgical orthodontics with conventional braces, composed of metal brackets, bands, and archwires. These appliances are not always accepted by patients, particularly older teenagers and professional adults who previously endured traditional orthodontia during adolescence, and now require retreatment because of jaw growth differences necessitating orthognathic surgery. Less obtrusive orthodontic therapies, involving clear aligners (e.g., Invisalign), are becoming increasingly popular, as they are less noticeable and less aesthetically objectionable. They are typically indicated for milder occlusal discrepancies, such as crowding and minor rotations, without significant vertical or transverse problems. Clear aligners in conjunction with orthognathic surgery for severe dentofacial problems are progressive and not widely used. Moreover, the most complicated of orthognathic sequences, segmental double-jaw surgery, has never before been described to be performed using Invisalign. Several potential challenges exist when performing segmental double-jaw surgery with Invisalign (i.e., no bonded or banded appliances, and no archwire). The purpose of this article is to review the feasibility of segmental double-jaw surgery without orthodontia (Invisalign only), report a series of cases, and review the technical steps involved.
The lncRNA, H19 Mediates the Protective Effect of Hypoxia Postconditioning Against Hypoxia-Reoxygenation Injury to Senescent Cardiomyocytes by Targeting microRNA-29b-3p
Authors: Zhang Xuan , Cheng Long , Xu Longhe , Zhang Yunliang , Yang Yitian , Fu Qiang , Mi Weidong , Li Hao
Published: June 2018

Background:

Ischemic postconditioning (I/Post) is an endogenous protection mechanism that reduces injury induced by ischemia-reperfusion (I/R). It remains controversial whether I/Post protects against I/R injury to the aging heart. The long non-coding RNA, H19 protects H9c2 cells against hypoxia-induced injury. This study aimed to elucidate the role of H19 in the hypoxic postconditioning (H/Post) of aged cardiomyocytes.

Methods:

Senescence induced by D-galactose in primary cardiomyocytes from neonatal Sprague–Dawley rats was measured by senescence-associated β-galactosidase staining. Hypoxic injury was evaluated by cell viability and apoptosis assays. H19 expression before and after hypoxia-reoxygenation (H/R) and H/Post was evaluated by real-time polymerase chain reactions. miR-29b-3p-binding sites in H19 and the cellular inhibitor of apoptosis protein 1 (cIAP1) were predicted by bioinformatics analysis, and interaction was verified by luciferase assay. The effects of altered H19, miR-29b-3p, and cIAP1 expression on the viability and apoptosis of senescent cardiomyocytes following H/Post were determined.

Results:

H/Post prevented H/R injury in normal but not senescent cardiomyocytes. H19 expression was remarkably down-regulated after H/Post in senescent compared with normal cardiomyocytes. Small interfering RNA-mediated knockdown of H19 in senescent cardiomyocytes increased H/Post-induced injury. miR-29b-3p was regulated by H19 and led to a greater injury. miR-29b-3p directly targeted the 3′-untranslated region of cIAP1 and suppressed its expression. Furthermore, knockdown of cIAP1 damaged senescent cardiomyocytes following H/Post.

Conclusions:

These findings suggest that H19 mediated the antiapoptotic effect of H/Post against H/R-induced injury to aged cardiomyocytes by inhibiting miR-29b-3p expression.
Knockdown of butyrylcholinesterase but not inhibition by chlorpyrifos alters early differentiation mechanisms in human neural stem cells
Authors: Tiethof Angela K. , Richardson Jason R. , Hart Ronald P.
Published: June 2018

Butyrylcholinesterase (BChE) is the evolutionary counterpart to acetylcholinesterase (AChE). Both are expressed early in nervous system development prior to cholinergic synapse formation. The organophosphate pesticide chlorpyrifos (CPF) primarily exerts toxicity through inhibition of AChE, which results in excess cholinergic stimulation at the synapse. We hypothesized that inhibition of AChE and BChE by CPF may impair early neurogenesis in neural stem cells (NSCs). To model neurodevelopment in vitro, we used human NSCs derived from induced pluripotent stem cells (iPSCs) with a focus on initial differentiation mechanisms. Over six days of NSC differentiation, BChE activity and mRNA expression significantly increased, while AChE activity and expression remained unchanged. CPF treatment (10 μM) caused 82% and 92% inhibition of AChE and BChE, respectively. CPF exposure had no effect on cell viability or the expression of differentiation markers HES5, DCX or MAP2. However, shRNA-knockdown of BChE expression resulted in decreased or delayed expression of transcription factors HES5 and HES3. BChE may have a role in the differentiation of NSCs independent of, or in addition to, its enzymatic activity.
TetrahymenaRIB72A and RIB72B are Microtubule Inner Proteins in the ciliary doublet microtubules
Authors: Stoddard Daniel , Zhao Ying , Bayless Brian A. , Gui Long , Louka Panagiota , Dave Drashti , Suryawanshi Swati , Tomasi Raphaël F.-X. , Dupuis-Williams Pascale , Baroud Charles N. , Gaertig Jacek , Winey Mark , Nicastro Daniela
Published: June 2018

Doublet and triplet microtubules are essential and highly stable core structures of centrioles, basal bodies, cilia and flagella. In contrast to dynamic cytoplasmic microtubules, their luminal surface is coated with regularly arranged Microtubule Inner Proteins (MIPs). However, the protein composition and biological function(s) of MIPs remain poorly understood. Using genetic, biochemical and imaging techniques we identifiedTetrahymenaRIB72A and RIB72B proteins as ciliary MIPs. Fluorescence imaging of tagged RIB72A and RIB72B showed that both proteins co-localize toTetrahymenacilia and basal bodies, but assemble independently. Cryo-electron tomography ofRIB72Aand/orRIB72Bknockout strains revealed major structural defects in the ciliary A-tubule involving MIP1, MIP4 and MIP6 structures. The defects of individual mutants were complementary in the double mutant. All mutants had reduced swimming speed and ciliary beat frequencies, and high-speed video imaging revealed abnormal highly curved cilia during power stroke. Our results show that RIB72A and RIB72B are crucial for the structural assembly of ciliary A-tubule MIPs and are important for proper ciliary motility.

Microtubule Inner Proteins (MIPs) bind to the luminal surface of highly stable microtubules. Combining cell biology and cryo-electron tomography, Stoddardet al.show that RIB72A and RIB72B are conserved MIPs in ciliary doublet microtubules and that they are important for proper ciliary motility.