Αρχειοθήκη ιστολογίου

Πέμπτη 5 Απριλίου 2018

Wheezing in infants: A pandemic condition that need to be treated with patience

Publication date: May–June 2018
Source:Allergologia et Immunopathologia, Volume 46, Issue 3
Author(s): L. Garcia-Marcos




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A Multi-Institutional Validation of Gleason Score Derived from Tissue Microarray Cores

Abstract

To test the agreement between high-grade PCa at RP and TMA, and the ability of TMA to predict BCR. Validation of concordance between tissue microarray (TMA) and radical prostatectomy (RP) high-grade prostate cancer (PCa) is crucial because latter determines the treated natural history of PCa. We hypothesized that TMA Gleason score is in agreement with RP pathology and capable of accurately predicting biochemical recurrence (BCR). Data were provided from a multi-institutional Canadian sample of 1333 TMA and RP specimens with complete clinicopathological data. First, rate of agreement between TMA and high-grade Gleason at RP or biopsy and RP was tested. Second, ability of RP, TMA and biopsy to predict BCR was compared. Multivariable (MVA) Cox regression models were fitted and BCR rates were illustrated with Kaplan-Meier plots. Agreement between RP and TMA and between RP and biopsy was 72.6% (95% CI:69.7–75.5) and 60.4% (95% CI:57.2–63.6), respectively. In MVA predicting BCR, the accuracy for RP, TMA and biopsy was 0.73, 0.72 and 0.68, respectively. TMA added discriminatory ability among exclusively low-grade Gleason RP patients (p = 0.02), but did not improve BCR discrimination in exclusive high-grade PCa RP patients (p = 0.8). TMA Gleason grade accurately reflects presence of high-grade Gleason in RP specimen, accurately predicts BCR rates after RP and improves prediction of BCR in low-grade Gleason patients at RP.



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Outcome of Pancreaticoduodenectomy at Low-Volume Centre in Tier-II City of India

Abstract

Currently, pancreaticoduodenectomy (PD) is considered a common and feasibly performed surgery for periampullary tumours, but it is still a high-risk surgical procedure with potential morbidity and mortality rates. Previously, it was emphasised for the need of high-volume centres to perform specialised surgery such as PD. The authors have made an attempt to know the relation between low-volume centre and outcomes of PD. The study was conducted in a Tier-II city referral hospital located in Karnataka, India. A total of 37 patients with suspected periampullary neoplasms underwent surgical exploration with curative intent over a period of 4 years, i.e. from May 2012 to May 2016. Out of 37 patients, 26 underwent PD, either classic Whipple resection (n = 01) or pylorus-preserving modification (n = 25). In 11 patients, resection was not possible, where biliary and gastric drainage procedures were done. All patients were treated by standardised post-operative care protocols for pancreatic resection used at our centre. We recorded the perioperative outcome along with demographics, indications for surgery, and pre- and intra-operative factors of PD. Post-operative pancreatic fistulae were evident in 4 patients. Two patients had hepaticojejunostomy leak. One patient had chyle leak. Three patients had infection at the surgical site. One patient had post-operative pneumonia leading to mortality. None of the patients had post-op haemorrhage. The surgeon volume and surgeon experience may have minimal contributing factor in post-operative morbidity, especially if there is availability of well-equipped ICU and imaging facilities, along with well-experienced personnel like oncosurgeon, anaesthesiologist, intensivist, radiologist, and nursing staff. There is a need of a multicentre study from Tier-II city hospitals/low-volume centres and high-volume centres to come with perioperative surgical outcomes following PD.



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Managing Gait, Balance, and Posture in Parkinson’s Disease

Abstract

Purpose of Review

Postural instability and gait difficulties inexorably worsen with Parkinson's disease (PD) progression and become treatment resistant, with a severe impact on autonomy and quality of life. We review the main characteristics of balance instability, gait disabilities, and static postural alterations in advanced PD, and the available treatment strategies.

Recent Findings

It remains very difficult to satisfactorily alleviate gait and postural disturbances in advanced PD. Medical and surgical interventions often fail to provide satisfactory or durable alleviation of these axial symptoms, that may actually call for differential treatments. Exercise and adapted physical activity programs can contribute to improving the patients' condition.

Summary

Gait, balance, and postural disabilities are often lumped together under the Postural Instability and Gait Difficulties umbrella term. This may lead to sub-optimal patients' management as data suggest that postural, balance, and gait problems might depend on distinct underlying mechanisms. We advocate for a multidisciplinary approach from the day of diagnosis.



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Genomic and Functional Approaches to Understanding Cancer Aneuploidy

Publication date: Available online 2 April 2018
Source:Cancer Cell
Author(s): Alison M. Taylor, Juliann Shih, Gavin Ha, Galen F. Gao, Xiaoyang Zhang, Ashton C. Berger, Steven E. Schumacher, Chen Wang, Hai Hu, Jianfang Liu, Alexander J. Lazar, Andrew D. Cherniack, Rameen Beroukhim, Matthew Meyerson
Aneuploidy, whole chromosome or chromosome arm imbalance, is a near-universal characteristic of human cancers. In 10,522 cancer genomes from The Cancer Genome Atlas, aneuploidy was correlated with TP53 mutation, somatic mutation rate, and expression of proliferation genes. Aneuploidy was anti-correlated with expression of immune signaling genes, due to decreased leukocyte infiltrates in high-aneuploidy samples. Chromosome arm-level alterations show cancer-specific patterns, including loss of chromosome arm 3p in squamous cancers. We applied genome engineering to delete 3p in lung cells, causing decreased proliferation rescued in part by chromosome 3 duplication. This study defines genomic and phenotypic correlates of cancer aneuploidy and provides an experimental approach to study chromosome arm aneuploidy.

Graphical abstract

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Teaser

Analyzing >10,000 human cancers, Taylor et al. show that aneuploidy is correlated with somatic mutation rate, expression of proliferation genes, and decreased leukocyte infiltration. Loss of chromosome arm 3p is common in squamous cancers, but deletion of chromosome 3p reduces cell proliferation in vitro.


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Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

Publication date: Available online 2 April 2018
Source:Cancer Cell
Author(s): Yang Liu, Nilay S. Sethi, Toshinori Hinoue, Barbara G. Schneider, Andrew D. Cherniack, Francisco Sanchez-Vega, Jose A. Seoane, Farshad Farshidfar, Reanne Bowlby, Mirazul Islam, Jaegil Kim, Walid Chatila, Rehan Akbani, Rupa S. Kanchi, Charles S. Rabkin, Joseph E. Willis, Kenneth K. Wang, Shannon J. McCall, Lopa Mishra, Akinyemi I. Ojesina, Susan Bullman, Chandra Sekhar Pedamallu, Alexander J. Lazar, Ryo Sakai, Vésteinn Thorsson, Adam J. Bass, Peter W. Laird
We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for insertions/deletions, representing microsatellite instability cases with epigenetic silencing of MLH1 in the context of CpG island methylator phenotype, plus tumors with elevated single-nucleotide variants associated with mutations in POLE. Tumors with chromosomal instability were diverse, with gastroesophageal adenocarcinomas harboring fragmented genomes associated with genomic doubling and distinct mutational signatures. We identified a group of tumors in the colon and rectum lacking hypermutation and aneuploidy termed genome stable and enriched in DNA hypermethylation and mutations in KRAS, SOX9, and PCBP1.

Graphical abstract

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Teaser

Liu et al. analyze 921 gastrointestinal (GI) tract adenocarcinomas and find that hypermutated tumors are enriched for insertions/deletions, upper GI tumors with chromosomal instability harbor fragmented genomes, and a group of genome-stable colorectal tumors are enriched in mutations in SOX9 and PCBP1.


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A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers

Publication date: Available online 2 April 2018
Source:Cancer Cell
Author(s): Ashton C. Berger, Anil Korkut, Rupa S. Kanchi, Apurva M. Hegde, Walter Lenoir, Wenbin Liu, Yuexin Liu, Huihui Fan, Hui Shen, Visweswaran Ravikumar, Arvind Rao, Andre Schultz, Xubin Li, Pavel Sumazin, Cecilia Williams, Pieter Mestdagh, Preethi H. Gunaratne, Christina Yau, Reanne Bowlby, A. Gordon Robertson, Daniel G. Tiezzi, Chen Wang, Andrew D. Cherniack, Andrew K. Godwin, Nicole M. Kuderer, Janet S. Rader, Rosemary E. Zuna, Anil K. Sood, Alexander J. Lazar, Akinyemi I. Ojesina, Clement Adebamowo, Sally N. Adebamowo, Keith A. Baggerly, Ting-Wen Chen, Hua-Sheng Chiu, Steve Lefever, Liang Liu, Karen MacKenzie, Sandra Orsulic, Jason Roszik, Carl Simon Shelley, Qianqian Song, Christopher P. Vellano, Nicolas Wentzensen, John N. Weinstein, Gordon B. Mills, Douglas A. Levine, Rehan Akbani
We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks. Pathway analysis identified subtypes with high leukocyte infiltration, raising potential implications for immunotherapy. Using 16 key molecular features, we identified five prognostic subtypes and developed a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories.

Teaser

By performing molecular analyses of 2,579 TCGA gynecological (OV, UCEC, CESC, and UCS) and breast tumors, Berger et al. identify five prognostic subtypes using 16 key molecular features and propose a decision tree based on six clinically assessable features that classifies patients into the subtypes.


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GKAP Acts as a Genetic Modulator of NMDAR Signaling to Govern Invasive Tumor Growth

Publication date: Available online 29 March 2018
Source:Cancer Cell
Author(s): Leanne Li, Qiqun Zeng, Arjun Bhutkar, José A. Galván, Eva Karamitopoulou, Daan Noordermeer, Mei-Wen Peng, Alessandra Piersigilli, Aurel Perren, Inti Zlobec, Hugh Robinson, M. Luisa Iruela-Arispe, Douglas Hanahan
Genetic linkage analysis previously suggested that GKAP, a scaffold protein of the N-methyl-D-aspartate receptor (NMDAR), was a potential modifier of invasion in a mouse model of pancreatic neuroendocrine tumor (PanNET). Here, we establish that GKAP governs invasive growth and treatment response to NMDAR inhibitors of PanNET via its pivotal role in regulating NMDAR pathway activity. Combining genetic knockdown of GKAP and pharmacological inhibition of NMDAR, we implicate as downstream effectors FMRP and HSF1, which along with GKAP demonstrably support invasiveness of PanNET and pancreatic ductal adenocarcinoma cancer cells. Furthermore, we distilled genome-wide expression profiles orchestrated by the NMDAR-GKAP signaling axis, identifying transcriptome signatures in tumors with low/inhibited NMDAR activity that significantly associate with favorable patient prognosis in several cancer types.

Graphical abstract

image

Teaser

Li et al. show that GKAP, a scaffold protein of NMDAR, and its downstream effectors FMRP and HSF1 play important roles in the invasive growth of pancreatic tumors. In several cancer types, low NMDAR activity, based on a transcriptomic signature, associates with favorable patient prognosis.


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lncRNA Epigenetic Landscape Analysis Identifies EPIC1 as an Oncogenic lncRNA that Interacts with MYC and Promotes Cell-Cycle Progression in Cancer

Publication date: Available online 2 April 2018
Source:Cancer Cell
Author(s): Zehua Wang, Bo Yang, Min Zhang, Weiwei Guo, Zhiyuan Wu, Yue Wang, Lin Jia, Song Li, Wen Xie, Da Yang
We characterized the epigenetic landscape of genes encoding long noncoding RNAs (lncRNAs) across 6,475 tumors and 455 cancer cell lines. In stark contrast to the CpG island hypermethylation phenotype in cancer, we observed a recurrent hypomethylation of 1,006 lncRNA genes in cancer, including EPIC1 (epigenetically-induced lncRNA1). Overexpression of EPIC1 is associated with poor prognosis in luminal B breast cancer patients and enhances tumor growth in vitro and in vivo. Mechanistically, EPIC1 promotes cell-cycle progression by interacting with MYC through EPIC1's 129–283 nt region. EPIC1 knockdown reduces the occupancy of MYC to its target genes (e.g., CDKN1A, CCNA2, CDC20, and CDC45). MYC depletion abolishes EPIC1's regulation of MYC target and luminal breast cancer tumorigenesis in vitro and in vivo.

Graphical abstract

image

Teaser

Wang et al. characterize the epigenetic landscape of lncRNAs genes across a large number of human tumors and cancer cell lines and observe recurrent hypomethylation of lncRNA genes, including EPIC1. EPIC1 RNA promotes cell-cycle progression by interacting with MYC and enhancing its binding to target genes.


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Maintenance of Improved Attitudes Toward Stuttering

Purpose
This study sought to determine the extent to which experimentally induced positive attitudes in high school students in a previous investigation were maintained 7 years later.
Method
Authors and assistants recruited 36 adults in their early 20s (Follow-up group) who, in high school, had witnessed either a live oral talk by a person who stutters or a professionally made video on stuttering designed for teens followed by a short talk by the same speaker. The Public Opinion Survey of Human Attributes–Stuttering was administered before and after the interventions in high school and 7 years later such that pre–post group comparisons were made. Previously, the Follow-up group had demonstrated highly positive changes in their attitudes after the interventions. In addition, a control group of 56 former high school students from the same state, who did not participate in the interventions, were recruited and compared to the Follow-up group.
Results
The Follow-up group, which was found to be representative of the original high school cohort, held more positive Public Opinion Survey of Human Attributes–Stuttering mean ratings than the Control group, although somewhat less positive than their previous postintervention ratings.
Conclusions
The Follow-up group maintained many of the positive changes in their beliefs and self reactions regarding stuttering that were induced 7 years earlier after witnessing personal stories and facts about stuttering.

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Consonant and Vowel Identification in Cochlear Implant Users Measured by Nonsense Words: A Systematic Review and Meta-Analysis

Purpose
The purpose of this systematic review and meta-analysis was to establish a baseline of the vowel and consonant identification scores in prelingually and postlingually deaf users of multichannel cochlear implants (CIs) tested with consonant–vowel–consonant and vowel–consonant–vowel nonsense syllables.
Method
Six electronic databases were searched for peer-reviewed articles reporting consonant and vowel identification scores in CI users measured by nonsense words. Relevant studies were independently assessed and screened by 2 reviewers. Consonant and vowel identification scores were presented in forest plots and compared between studies in a meta-analysis.
Results
Forty-seven articles with 50 studies, including 647 participants, thereof 581 postlingually deaf and 66 prelingually deaf, met the inclusion criteria of this study. The mean performance on vowel identification tasks for the postlingually deaf CI users was 76.8% (N = 5), which was higher than the mean performance for the prelingually deaf CI users (67.7%; N = 1). The mean performance on consonant identification tasks for the postlingually deaf CI users was higher (58.4%; N = 44) than for the prelingually deaf CI users (46.7%; N = 6). The most common consonant confusions were found between those with same manner of articulation (/k/ as /t/, /m/ as /n/, and /p/ as /t/).
Conclusions
The mean performance on consonant identification tasks for the prelingually and postlingually deaf CI users was found. There were no statistically significant differences between the scores for prelingually and postlingually deaf CI users. The consonants that were incorrectly identified were typically confused with other consonants with the same acoustic properties, namely, voicing, duration, nasality, and silent gaps. A univariate metaregression model, although not statistically significant, indicated that duration of implant use in postlingually deaf adults predict a substantial portion of their consonant identification ability. As there is no ceiling effect, a nonsense syllable identification test may be a useful addition to the standard test battery in audiology clinics when assessing the speech perception of CI users.

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Radiation induces age-dependent deficits in cortical synaptic plasticity

Abstract
Background
Radiation-induced cognitive dysfunction is a significant side effect of cranial irradiation for brain tumors. Clinically, pediatric patients are more vulnerable than adults. However, the underlying mechanisms of dysfunction, including reasons for age dependence, are still largely unknown. Previous studies have focused on the loss of hippocampal neuronal precursor cells and deficits in memory. However, survivors may also experience deficits in attention, executive function, or other non-hippocampal–dependent cognitive domains. We hypothesized that brain irradiation induces age-dependent deficits in cortical synaptic plasticity.
Methods
In vivo recordings were used to test neuronal plasticity along the direct pathway from the CA1/subicular region to the prefrontal cortex (PFC). Specifically, long-term potentiation (LTP) in the CA1/subicular-PFC pathway was assessed after cranial irradiation of juvenile and adult Sprague Dawley rats. We further assessed a potential role for glutamate toxicity by evaluating the potential neuroprotective effects of memantine.
Results
LTP was greatly inhibited in both adult and juvenile animals at 3 days after radiation but returned to near-normal levels by 8 weeks—only in adult rats. Memantine given before, but not after, irradiation partially prevented LTP inhibition in juvenile and adult rats.
Conclusion
Cranial radiation impairs neuroplasticity along the hippocampal-PFC pathway; however, its effects vary by age. Pretreatment with memantine offered protection to both juvenile and adult animals. Deficits in cortical plasticity may contribute to radiation-induced cognitive dysfunction, including deficits in attention and age-dependent sensitivity of such pathways, which may underlie differences in clinical outcomes between juveniles and adults after cranial irradiation.

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Validation of post-operative residual contrast enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma

Abstract
Background
In the current study, we pooled imaging data in newly diagnosed GBM patients from international multicenter clinical trials, single institution databases, and multicenter clinical trial consortiums to identify the relationship between post-operative residual enhancing tumor volume and overall survival (OS).
Methods
Data from 1,511 newly diagnosed GBM patients from 5 data sources were included in the current study: 1) a single institution database from UCLA (N=398; Discovery); 2) patients from the Ben and Cathy Ivy Foundation for Early Phase Clinical Trials Network Radiogenomics Database (N=262 from 8 centers; Confirmation); 3) the chemoradiation placebo arm from an international phase III trial (AVAglio; N=394 from 120 locations in 23 countries; Validation); 4) the experimental arm from AVAglio examining chemoradiation plus bevacizumab (N=404 from 120 locations in 23 countries; Exploratory Set 1); and 5) an Alliance (N0874) Phase I/II trial of vorinostat plus chemoradiation (N=53; Exploratory Set 2). Post-surgical, residual enhancing disease was quantified using T1 subtraction maps. Multivariate Cox regression models were used to determine influence of clinical variables, MGMT status, and residual tumor volume on OS.
Results
A log-linear relationship was observed between post-operative, residual enhancing tumor volume and OS in newly diagnosed GBM treated with standard chemoradiation. Post-operative tumor volume is a prognostic factor for OS (P<0.01), regardless of therapy, age, and MGMT promoter methylation status.
Conclusion
Post-surgical, residual contrast-enhancing disease significantly negatively influences survival in patients with newly diagnosed glioblastoma treated with chemoradiation with or without concomitant experimental therapy.

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Modeling the diffusion of D-2-hydroxyglutarate from IDH1 mutant gliomas in the central nervous system

Abstract
Background
20-30% of diffusely infiltrative gliomas in adults contain a point mutation in isocitrate dehydrogenase 1 (IDH1mut), which increases production of D-2-hydroxyglutarate (D2HG). This is so efficient that D2HG often reaches 30 mM within IDH1mut gliomas. Yet, while up to 100 µM D2HG can be detected in the circulating cerebrospinal fluid of IDH1mut glioma patients, the exposure of nonneoplastic cells within and surrounding an IDH1mut glioma to D2HG is unknown and difficult to measure directly.
Methods
Conditioned medium from patient-derived IDH1wt and IDH1mut glioma cells was analyzed for D2HG by liquid chromatography-mass spectrometry (LC-MS). Mathematical models of D2HG release and diffusion around an IDH1mut glioma were independently generated based on fluid dynamics within the brain, and on previously reported intratumoral and cerebrospinal D2HG concentrations.
Results
LC-MS analysis indicates that patient-derived IDH1mut glioma cells release 3.7-97.0 pg D2HG per cell per week. Extrapolating this to an average-sized tumor (30 mL glioma volume and 1x108cells/mL tumor), the rate of D2HG release by an IDH1mut glioma (SA) is estimated at 3.2-83.0x10-12 moles/ml/sec. Mathematical models estimate an SA of 2.9-12.9x10-12 moles/ml/sec, within the range of the in vitro LC-MS data. In even the most conservative of these models, the extracellular concentration of D2HG exceeds 3 mM within a 2 cm radius from the center of an IDH1mut glioma.
Conclusions
The microenvironment of an IDH1mut glioma is likely being exposed to high concentrations of D2HG, in the low millimolar range. This has implications for understanding how D2HG affects nonneoplastic cells in an IDH1mut glioma.

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Volumetric response quantified using T1 subtraction predicts long-term survival benefit from cabozantinib monotherapy in recurrent glioblastoma

Abstract
Background
To overcome challenges with traditional response assessment in anti-angiogenc agents, the current study uses T1 subtraction maps to quantify volumetric radiographic response in cabozantinib monotherapy, an orally bioavailable tyrosine kinase inhibitor with activity against VEGFR2, MET, and AXL, in an open-label, phase II trial in patients with recurrent glioblastoma (NCT00704288).
Methods
A total of 108 patients with adequate imaging data and confirmed recurrent GBM were included in this retrospective study from a phase II multicenter trial of cabozantinib monotherapy (XL184-201) at either 100mg (N=87) or 140mg (N=21) per day. Contrast enhanced T1-weighted digital subtraction maps were used to define volume of contrast enhancing tumor at baseline and subsequent follow-up time points. Volumetric radiographic response (>65% reduction in contrast enhancing tumor volume from pre-treatment baseline tumor volume sustained for more than 4 weeks) was tested as an independent predictor of overall survival (OS).
Results
Volumetric response rate (VRR) for all therapeutic doses was 38.9% (41.4% and 28.6% for 100mg and 140mg doses, respectively). A log-linear association between baseline tumor volume and OS (P=0.0006) and a linear correlation between initial change in tumor volume and OS (P=0.0256) were observed. A significant difference in OS was observed between responders (median OS=20.6 months) and non-responders (median OS=8.0 months) (HR=0.3050, P<0.0001). Multivariable analyses showed continuous measures of baseline tumor volume (HR=1.0233, P<0.0001) and volumetric response (HR=0.2240, P<0.0001) were independent predictors of OS.
Conclusions
T1 subtraction maps provide value in determining response in recurrent GBM treated with cabozantinib and correlated with survival benefit.

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A Role for Satb1 in Thyroid Autoimmunity?

Thyroid, Ahead of Print.


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An Online Survey of Hypothyroid Patients Demonstrates Prominent Dissatisfaction

Thyroid, Ahead of Print.


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Targeting the human epidermal growth factor receptor 2 (HER2) oncogene in colorectal cancer

Abstract
BACKGROUND
Human epidermal growth factor receptor 2 (HER2) is an oncogenic driver, and a well-established therapeutic target in breast and gastric cancers. Using functional and genomic analyses of patient-derived xenografts, we previously showed that a subset (approximately 5%) of metastatic colorectal cancer (CRC) tumors are driven by amplification or mutation of HER2.
MATERIALS AND METHODS
This paper reviews the role of HER2 as an oncogenic driver, a prognostic and predictive biomarker, and a clinically actionable target in CRC, considering the specifics of HER2 testing in this tumor type.
RESULTS
While the role of HER2 as a biomarker for prognosis in CRC remains uncertain, its relevance as a therapeutic target has been established. Indeed, independent studies documented substantial clinical benefit in patients treated with biomarker-driven HER2-targeted therapies, with an impact on response rates and duration of response that compared favorably with immunotherapy and other examples of precision oncology.
CONCLUSION
HER2-targeted therapeutic strategies have the potential to change the treatment paradigm for a clinically relevant subgroup of metastatic CRC patients.

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Clinical challenges of glioma and pregnancy: a systematic review

Abstract

Introduction

This review aims to summarize challenges in clinical management of concomitant gliomas and pregnancy and provides suggestions for this management based on current literature.

Methods

PubMed and Embase databases were systematically searched for studies on glioma and pregnancy. Observational studies and articles describing expert opinions on clinical management were included. The strength of evidence was categorized as arguments from observational studies, consensus in expert opinions, or single expert opinions. Risk of bias was assessed by the Newcastle-Ottawa Scale (NOS).

Results

27 studies were selected, including 316 patients with newly diagnosed (n = 202) and known (n = 114) gliomas during pregnancy. The median sample size was 6 (range 1–65, interquartile range 1–9). Few recommendations originated from observational studies; the remaining arguments originated from consensus in expert opinions.

Conclusion

Findings from observational studies of adequate quality include (1) There is no known effect of pregnancy on survival in low-grade glioma patients; (2) Pregnancy can provoke clinical deterioration and tumor growth on MRI; (3) In stable women at term, there is no benefit of cesarean section over vaginal delivery, with respect to adverse events in mother or child. Unanswered questions include when pregnancy should be discouraged, what best monitoring schedule is for both mother and fetus, and if and how chemo- and radiation therapy can be safely administered during pregnancy. A multicenter individual patient level meta-analysis collecting granular information on clinical management and related outcomes is needed to provide scientific evidence for clinical decision-making in pregnant glioma patients.



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Placebo Effects in Traumatic Brain Injury

Journal of Neurotrauma, Ahead of Print.


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Differential Adaptations of the Musculoskeletal System after Spinal Cord Contusion and Transection in Rats

Journal of Neurotrauma, Ahead of Print.


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Gene Profiling of Nucleus Basalis Tau Containing Neurons in Chronic Traumatic Encephalopathy: A Chronic Effects of Neurotrauma Consortium Study

Journal of Neurotrauma, Ahead of Print.


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Estimating Pressure Reactivity Using Noninvasive Doppler-Based Systolic Flow Index

Journal of Neurotrauma, Ahead of Print.


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Effects of Treadmill Training Combined with Serotonergic Interventions on Spasticity after Contusive Spinal Cord Injury

Journal of Neurotrauma, Ahead of Print.


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Food Protein-Induced Enterocolitis Syndrome (FPIES): Review of Recent Guidelines

Abstract

Purpose of Review

To increase understanding of food protein-induced enterocolitis syndrome (FPIES), a non-immunoglobulin E (IgE)-mediated reaction to food, by reviewing a growing body of literature, including recently published international consensus guidelines.

Recent Findings

FPIES primarily affects infants and young children and is characterized by the delayed onset of gastrointestinal symptoms, predominantly repetitive vomiting, in response to a trigger food. Symptoms are often severe and can lead to shock. Diagnosis can be challenging due to a wide differential diagnoses and lack of disease biomarkers. FPIES is a clinical diagnosis, with allergy testing playing a very limited role, if any. Medically supervised oral food challenges are used to monitor resolution of disease, which generally occurs in early childhood.

Summary

FPIES is an important condition presenting to clinicians in a variety of settings. Recent international consensus guidelines and a growing body of literature can better equip practitioners to care for these often-challenging patients.



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Dentin sealing and antibacterial effects of silver-doped bioactive glass/mesoporous silica nanocomposite: an in vitro study

Abstract

Objectives

To synthesize a silver-doped bioactive glass/mesoporous silica nanoparticle (Ag-BGN@MSN), as well as to investigate its effects on dentinal tubule occlusion, microtensile bond strength (MTBS), and antibacterial activity.

Materials and methods

Ag-BGN@MSN was synthesized using a modified "quick alkali-mediated sol-gel" method. Demineralized tooth disc models were made and divided into four groups; the following treatments were then applied: group 1—no treatment, group 2—bioglass, group 3—MSN, group 4—Ag-BGN@MSN. Next, four discs were selected from each group and soaked into 6 wt% citric acid to test acid-resistant stability. Dentinal tubule occlusion, as well as the occlusion ratio, was observed using field-emission scanning electron microscopy. The MTBS was also measured to evaluate the desensitizing effect of the treatments. Cytotoxicity was examined using the MTT assay. Antibacterial activity was detected against Lactobacillus casei, and ion dissolution was evaluated using inductively coupled plasma optical emission spectrometry.

Results

Ag-BGN@MSN effectively occluded the dentinal tubule and formed a membrane-like layer. After the acid challenge, Ag-BGN@MSN had the highest rate of dentinal tubule occlusion. There were no significant differences in MTBS among the four groups (P > 0.05). All concentrations of Ag-BGN@MSN used had a relative cell viability above 72%.

Conclusions

Ag-BGN@MSN was successfully fabricated using a modified sol-gel method. The Ag-BGN@MSN biocomposite effectively occluded dentinal with acid-resistant stability, did not decrease bond strength in self-etch adhesive system, had low cytotoxicity, and antibacterial effect.

Clininal relevance

Dentinal tubule sealing induced by Ag-BGN@MSN biocomposite with antibacterial effect is likely to increase long-term stability in DH.



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Assessment of Radiology Training During Radiation Oncology Residency

Abstract

A strong foundation in diagnostic imaging is essential to the practice of radiation oncology. This study evaluated radiology training in radiation oncology residency. An online survey was distributed to current radiation oncology residents in the USA by e-mail in 2017. Responses were summarized using frequency and percentages and compared with chi-square test and Spearman's rank correlation when appropriate. One hundred five residents completed the survey. Although most residents felt that a strong knowledge base in diagnostic radiology was moderately or extremely important (87%, n = 90/104), the majority were only somewhat confident in their radiology skills (61%, n = 63/104) and were only somewhat, minimally, or not at all satisfied with their training (79%, n = 81/103). Although there was an association between increasing post-graduate training and confidence level (p = 0.01062, ρ = 0.24959), the majority of graduating residents feel only somewhat confident in radiology skills (63%, n = 12/19). Residents were most commonly exposed to radiology via multidisciplinary conferences (96%, n = 100/104), though only 15% (n = 16/104) of residents ranked these as the most beneficial component of their radiology training and 13% (n = 13/101) of residents felt these were the least beneficial. Most residents (60%, n = 63/105) believe there is a need for dedicated radiology training during residency, preferring monthly formal didactics (68%, n = 71/105) co-taught by a radiologist and radiation oncologist (58%, n = 61/105). Radiation oncology residents feel their radiology training is suboptimal, suggesting a need for more guidance and standardization of radiology curriculum. A preferred option may be monthly didactics co-taught by radiologists and radiation oncologists; however, future studies should assess the effectiveness of this model.



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Assessment of Histopathological Grade and Ki-67 Expression in Tobacco and Non-tobacco Habitual Buccal Mucosa Cancer

Abstract

Although there are various risk factors in the literature, the established primary risk factor for oral cancer is tobacco and betal-nut chewing habits. It is believed that pathogenesis of oral cancer depends on the aetiology. To assess the histopathological grade and Ki-67 expression in tobacco (smoking/smokeless) and non-tobacco (betal nut/pan masala) habitual buccal mucosa cancer. The cross-sectional study was carried out in Regional cancer centre, Tamilnadu. Proliferative marker, Ki-67 expression was determined by immunohistochemistry using biotin-streptavidin method. The study includes 117 buccal mucosa cancer patients (61 male and 56 female). According to WHO grading system, high frequency observed with well differentiated squamous cell carcinoma 48 (41%) followed by moderate 46 (39.3%) and poorly differentiated 23 (19.7%). The cut-off value 50% was used to categorize Ki-67 expression into low and high labelling index (LI); 96 (82%) buccal mucosa cancer and 4 (3.4%) adjacent normal mucosa patients showed high Ki-67 expression. The present study showed highly significant association of histopathological tumor grade and Ki-67 expression by Chi square and paired t test p < 0.05. All the patients were grouped as tobacco 87 (74.4%) and non-tobacco habitual 30 (25.6%) in 3:1, respectively. Further, the risk habits identified with significant differences of tumor grade (p = 0.028) and Ki-67 at p < 0.05. Thus, the study revealed that the nature of cell differentiation and proliferation was strongly related to consumption of carcinogen in both tobacco and non-tobacco form. Therefore, histopathological grade and Ki-67 could be used as a reliable biomarker to understand the biological behaviour of risk habits which might helpful for further treatment therapeutics.



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STR1720, a potential sensitizer for radiotherapy and cytotoxicity effects of NVB-BEZ235 in metastatic breast cancer cells

Publication date: Available online 5 April 2018
Source:Pathology - Research and Practice
Author(s): Daryoush Fatehi, Amin Soltani, Mahdi Ghatrehsamani
BackgroundChemo-radio therapy (CRT) resistance is a main barrier in treating the triple negative breast cancer (TNBC). The success of conventional treatment may be ameliorated by elevating the responsiveness of the cancer cells to CRT. NVP-BEZ235 as a PI3K/AKT/mTOR dual inhibitor has been shown promising results in treating breast cancer cells. However, potential radiation-sensitizing effect of NVP-BEZ235 in TNBC remained unclear. In addition, SIRT-1 activation state and environmental cytokine were identified as being responsible for cancer cells responses to CRT. Herein, we investigate the role of interleukin 6 (IL-6) as a tumor environmental cytokine and SIRT1 in the effectiveness of NVP-BEZ235 plus radiotherapy.Material and methodsTNBC cells were pre-treated with/without IL-6 and were exposed to single and combination of SRT1720 (SIRT1 activator)/EX-527 (SIRT1 inhibitor) and/or NVP-BEZ235 and/or gamma radiation. The effect of our treatments on cellular growth was determined by MTT and the cellular death and CSCs percentage were determined by Flow cytometry. Senescence detection kit was used to assay the effect of our treatments on cellular senescence induction.ResultsActivation of SIRT1 via SRT1720 increased the efficacy of CRT in TNBC cells, especially when IL-6 exists in tumor microenvironment. Additionally, IL-6 pre-treatment followed by exposure to SRT1720 and NVP-BEZ235 significantly increased sensitivity of the cancer stem cells to radiation (p < 0.05).ConclusionOur result shows that combination of NVP-BEZ235 and SRT1720 may effectively improve late stage breast cancer cells therapeutics approach. Activation of SIRT1 and STAT3 in resistance breast cancer cells improve the in-vitro therapeutic efficacy of CRT.



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Investigation of miR-136-5p key target genes and pathways in lung squamous cell cancer based on TCGA database and bioinformatics analysis

Publication date: Available online 5 April 2018
Source:Pathology - Research and Practice
Author(s): Zu-cheng Xie, Tian-tian Li, Bin-liang Gan, Xiang Gao, Li Gao, Gang Chen, Xiao-hua Hu
BackgroundLung squamous cell cancer (LUSC) is a common but challenging malignancy. It is important to illuminate the molecular mechanism of LUSC. Thus, we aim to explore the molecular mechanism of miR-136-5p in relation to LUSC.MethodsWe used the Cancer Genome Atlas (TCGA) database to investigate the expression of miR-136-5p in relation to LUSC. Then, we identified the possible miR-136-5p target genes through intersection of the predicted miR-136-5p target genes and LUSC upregulated genes from TCGA. Bioinformatics analysis was performed to determine the key miR-136-5p targets and pathways associated with LUSC. Finally, the expression of hub genes, correlation between miR-136-5p and hub genes, and expected significance of hub genes were evaluated via the TCGA and Genotype-Tissue Expression (GTEx) project.ResultsMiR-136-5p was significantly downregulated in LUSC patients. Glucuronidation, glucuronosyltransferase, and the retinoic acid metabolic process were the most enriched metabolic interactions in LUSC patients. Ascorbate and aldarate metabolism, pentose and glucuronate interconversions, and retinol metabolism were identified as crucial pathways. Seven hub genes (UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A10, SRD5A1, and ADH7) were found to be upregulated, and UGT1A1, UGT1A3, UGT1A6, UGT1A7, and ADH7 were negatively correlated with miR-136-5p. UGT1A7 and ADH7 were the most significantly involved miR-136-5p target genes, and high expression of these genes was correlated with better overall survival and disease-free survival of LUSC patients.ConclusionsDownregulated miR-136-5p may target UGT1A7 and ADH7 and participate in ascorbate and aldarate metabolism, pentose and glucuronate interconversions, and retinol metabolism. High expression of UGT1A7 and ADH7 may indicate better prognosis of LUSC patients.



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The effects of air pollution on daily cardiovascular diseases hospital admissions in Wuhan from 2013 to 2015

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Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Xiaoying Wang, Wangcheng Wang, Shilin Jiao, Jing Yuan, Chunping Hu, Lin Wang
To evaluate the short-term effect of ambient air pollution on cardiovascular hospital admissions and capture the susceptible subpopulations in Wuhan, China, we adopted a generalized additive model to quantitatively analyze the influences of air pollutants on daily cardiovascular diseases hospital admissions and examine the influences of different subgroups. The largest significant effects for PM2.5, SO2 and NO2 on cardiovascular hospital admissions were observed at lag0, lag02 and lag02, respectively, and a 10μg/m3 increment in concentration of PM2.5, SO2 and NO2 were associated with 0.87% (95%CI: 0.05%–1.7%), 3.41% (95%CI: −0.21%-7.17%) and 2.98% (95%CI: 0.66%–5.37%) increases in cardiovascular hospital admissions. Nearly linear relationships were found for NO2 and PM2.5 with cardiovascular hospital admissions, and the J-shaped exposure-response relationship was observed for SO2 with cardiovascular hospital admissions. NO2 might have independent health effects of PM2.5 on the population at risk. The effect estimates for PM2.5 and SO2 were not sensitive with the inclusion of the co-pollutant adjustment. The gender, age and seasonal specific association between three pollutants and cardiovascular disease didn't show obvious differences in the magnitude and trend of the effects except that the seasonal difference of SO2 was significant. This study showed that PM2.5 and NO2 had effects on cardiovascular diseases, and the multiple pollutants should be considered together in the hazard models. In addition, the government should remind the resident to protect themselves and wear masks to avoid the harmful effect of air pollution, especially for the susceptible population.



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Unicentric epithelioid hemangioendothelioma of the calcaneus: a case report and review of literature

Abstract

Background

This review of the literature combined with a clinical case will allow the illustration of a favorable outcome of this variable low grade malignancy, display a role for limb salvage surgery with intralesional treatment, and offer a clinical example of epithelioid hemangioendothelioma, a rare malignancy.

Case presentation

The case report presents a case of solitary epithelioid hemangioendothelioma (EHE) of the calcaneus in a 60-year-old male. Primary vascular tumors of the bone are rare; however, EHE is one of the most common primary malignant vascular tumors to occur in bone. A review of the literature found few cases that involved the calcaneus; those cases found that involved the calcaneus were either part of a multifocal or metastatic disease process. Our case presents a 45-month clinical follow-up of solitary EHE in the calcaneus treated with surgical excision by curettage and cementing.

Conclusion

This case has clinical follow-up greater than 2 years post-operatively and could be a guide for treatment of a rare disorder with a substantial paucity of literature.



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Vocal function exercises for normal voice: With and without semi-occlusion.

Related Articles

Vocal function exercises for normal voice: With and without semi-occlusion.

Int J Speech Lang Pathol. 2018 Apr 03;:1-7

Authors: Bane M, Brown M, Angadi V, Croake DJ, Andreatta RD, Stemple JC

Abstract
PURPOSE: This study examined the effect of varying degrees of vocal tract (VT) occlusion used during Vocal Function Exercises (VFEs) on attainment of maximum phonation time (MPT) goals in normal voice. Greater VT occlusion was expected to result in increased MPT. The overarching goal was to determine whether the semi-occluded vocal tract (SOVT) posture used during VFEs could be modified while preserving efficacy.
METHOD: Twenty-six females ages 18-30 participated in this pre-post longitudinal group study. Participants were randomly assigned to three experimental groups and completed a six-week VFE protocol. The first group performed exercises using the prescribed SOVT posture; the second group used the vowel /o/; group three used the vowel /a/. The primary outcome measure was MPT as performed on the exercise tasks using the assigned vocal tract posture.
RESULT: MPT significantly improved in the prescribed SOVT group, but did not significantly improve in the modified /o/ and /a/ groups.
CONCLUSION: The SOVT posture used during VFEs is modifiable to a small extent without significantly undermining efficacy. Changes in MPT are less robust with reduced VT occlusion. Research in a clinical population is warranted.

PMID: 29614887 [PubMed - as supplied by publisher]



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Cost‐effectiveness of the BRECONDA decision aid for women with breast cancer: Results from a randomized controlled trial

Psycho-Oncology, EarlyView.


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The Impact of Dialect Density on the Growth of Language and Reading in African American Children

Purpose
The goal of the current study was to examine the impact of dialect density on the growth of oral language and reading skills in a sample of African American English (AAE)-speaking children reared in urban communities.
Method
Eight hundred thirty-five African American children in first through fifth grades participated. Using an accelerated cohort design, univariate and bivariate growth models were employed to examine dialect density, oral language and reading, and the relationships between these variables.
Results
For the univariate models, results indicated that (a) dialect density decreased over time by approximately 5% per year beyond first grade, (b) language skills improved approximately 0.5 SD per year, and (c) reading comprehension increased significantly from first to second grade and slowed 23% per year in second through fifth grades. Results from the bivariate models revealed that (a) dialect density and language ability are negatively associated, although dialect density did not affect change in language over time, and (b) higher dialect density is related to slower growth in reading.
Conclusions
Findings from this investigation provide converging evidence for accounts in the extant literature particularly supporting a negative relationship between dialect density and oral language and between dialect density and reading while also contributing novel longitudinal evidence that suggests that changes in dialect use over time may be driven by oral language skills and that reading and dialect have a reciprocal relationship.

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Effective Use of Auditory Bombardment as a Therapy Adjunct for Children With Developmental Language Disorders

Purpose
Modeling of grammatical forms has been used in conjunction with conversational recast treatment in various forms. This study tests the relative effect of providing bombardment prior to or after recast treatment.
Method
Twenty-eight children with developmental language disorder participated in daily conversational recast treatment for morpheme errors. This treatment was either preceded or followed by a brief period of intensive auditory bombardment. Generalization to untreated lexical contexts was measured throughout the treatment period to assess the degree of learning and how quickly the onset of measurable learning occurred.
Results
There were no significant differences in elicited use of morphemes for the groups of children who received auditory bombardment before or after enhanced conversational recast treatment. However, there was a difference in the number of children who could be considered treatment responders versus nonresponders, favoring those who received auditory bombardment after recast treatment.
Conclusion
A brief period of auditory bombardment is a relatively low cost addition to recast treatment methods, given how little time it takes. There is a small but measurable advantage to following recast treatment with a period of auditory bombardment.
Supplemental Material
https://doi.org/10.23641/asha.5960005

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Unique Contributors to the Curriculum: From Research to Practice for Speech-Language Pathologists in Schools

Purpose
This lead article of the Clinical Forum focuses on the research that supports why speech-language pathologists (SLPs) are an integral part of the overarching curriculum for all students in schools.
Method
Focus on education has shifted to student performance in our global world, specifically in college and career readiness standards. This article reviews recommendations on best practice from the American Speech-Language-Hearing Association on SLPs' roles in schools, as well as data on school-based services. Implementation of these practices as it is applicable to school initiatives will be explored. Methods of interventions available in schools, from general education to special education, will be discussed based on national guidelines for a Response to Intervention and Multi-Tiered System of Support. Research regarding teacher knowledge of the linguistic principles of reading instruction will be explored, as well as correlation between teacher knowledge and student performance.
Results
The implications for how SLPs as the linguistic experts offer unique roles in curriculum and the evidence available to support this role will be explored. Implications for future research needs will be discussed.
Conclusion
The demands of a highly rigorous curriculum allow SLPs a unique opportunity to apply their knowledge in linguistic principles to increase student performance and achievement. With the increased focus on student achievement, growth outcome measures, and value-added incentives, it is critical that SLPs become contributors to the curriculum for all students and that data to support this role are gathered through focused research initiatives.

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Evaluating English Morpheme Accuracy, Diversity, and Productivity Measures in Language Samples of Developing Bilinguals

Purpose
This work explores the clinical relevance of three measures of morpheme use for preschool-age Spanish–English bilingual children with varying language skills. The 3 measures reflect accuracy, diversity (the tense marker total), and productivity (the tense and agreement productivity score [TAP score]) of the English tense and agreement system.
Method
Measures were generated from language samples collected at the beginning and end of the participants' preschool year. Participants included 74 typically developing Spanish–English bilinguals and 19 peers with low language skills. The morpheme measures were evaluated with regard to their relationships with other language sample measures, their ability to reflect group differences, and their potential for capturing morphological development at group and individual levels.
Results
Across both groups, the tense marker total and TAP scores were associated with other language measures and demonstrated both group differences and growth over time. The accuracy measure met few of these benchmarks.
Conclusion
The tense marker total and TAP score, which were designed to capture emerging morphological abilities, contribute valuable information to a comprehensive language assessment of young bilinguals developing English. Case examples are provided to illustrate the clinical significance of including these measures in assessment.

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Laying a Firm Foundation: Embedding Evidence-Based Emergent Literacy Practices Into Early Intervention and Preschool Environments

Purpose
As part of this clinical forum on curriculum-based intervention, the goal of this tutorial is to share research about the importance of language and literacy foundations in natural environments during emergent literacy skill development, from infancy through preschool. Following an overview of intervention models in schools by Powell (2018), best practices at home, in child care, and in preschool settings are discussed. Speech-language pathologists in these settings will be provided a toolbox of best emergent literacy practices.
Method
A review of published literature in speech-language pathology, early intervention, early childhood education, and literacy was completed. Subsequently, an overview of the impact of early home and preschool literacy experiences are described. Research-based implementation of best practice is supported with examples of shared book reading and child-led literacy embedded in play within the coaching model of early intervention. Finally, various aspects of emergent literacy skill development in the preschool years are discussed. These include phonemic awareness, print/alphabet awareness, oral language skills, and embedded/explicit literacy.
Results
Research indicates that rich home literacy environments and exposure to rich oral language provide an important foundation for the more structured literacy environments of school. Furthermore, there is a wealth of evidence to support a variety of direct and indirect intervention practices in the home, child care, and preschool contexts to support and enhance all aspects of oral and written literacy.
Conclusions
Application of this "toolbox" of strategies should enable speech-language pathologists to address the prevention and intervention of literacy deficits within multiple environments during book and play activities. Additionally, clinicians will have techniques to share with parents, child care providers, and preschool teachers for evidence-based literacy instruction within all settings during typical daily activities.

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Curriculum-Based Language Interventions: What, Who, Why, Where, and How?

Purpose
School-based speech-language pathologists (SLPs) have been asked to be contributors to the educational curriculum (American Speech-Language-Hearing Association, 2010). The aim of this tutorial is to provide elementary school-based SLPs with a guide to explore curriculum-based language interventions (CBLIs) in their practices.
Method
In this tutorial, the authors (a) describe CBLI, (b) review the existing literature available to guide this type of practice in elementary school, (c) provide examples of how we have explored CBLIs, and (d) discuss the existing barriers for implementing CBLIs in schools.
Conclusion
SLPs have language and literacy expertise qualifying us to be well-suited for playing an important role in supporting CBLI. The information presented in this article provides school-based SLPs with support to implement CBLIs in early elementary school and illustrates the need for additional evidence to support CBLIs.

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Performance of Low-Income Dual Language Learners Attending English-Only Schools on the Clinical Evaluation of Language Fundamentals–Fourth Edition, Spanish

Purpose
The aim of this study was to examine the performance of a group of Spanish-speaking, dual language learners (DLLs) who were attending English-only schools and came from low-income and low-parental education backgrounds on the Clinical Evaluation of Language Fundamentals–Fourth Edition, Spanish (CELF-4S; Semel, Wiig, & Secord, 2006).
Method
Spanish-speaking DLLs (N = 656), ages 5;0 (years;months) to 7;11, were tested for language impairment (LI) using the core language score of the CELF-4S and the English Structured Photographic Expressive Language Test (Dawson, Stout, & Eyer, 2003). A subsample (n = 299) was additionally tested using a Spanish language sample analysis and a newly developed Spanish morphosyntactic measure, for identification of children with LI and to conduct a receiver operating characteristics curve analysis.
Results
Over 50% of the sample scored more than 1 SD below the mean on the core language score. In our subsample, the sensitivity of the CELF-4S was 94%, and specificity was 65%, using a cutoff score of 85 as suggested in the manual. Using an empirically derived cutoff score of 78, the sensitivity was 86%, and the specificity was 80%.
Conclusions
Results suggest that the CELF-4S overidentifies low-income Spanish–English DLLs attending English-only schools as presenting with LI. For this sample, 1 in every 3 Latino children from low socioeconomic status was incorrectly identified with LI. Clinicians should be cautious when using the CELF-4S to evaluate low-income Spanish–English DLLs and ensure that they have converging evidence before making diagnostic decisions.

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Facilitating Postsecondary Transition and Promoting Academic Success Through Language/Literacy-Based Self-Determination Strategies

Purpose
As noted by Powell (2018), speech-language pathologists (SLPs) are an integral part of the overarching curriculum for all students in schools, and this holds true for adolescents who require transition planning. The purpose of this tutorial is to focus on transition planning for secondary school students with a language-based learning disability (LLD) and provide a case illustration for how SLPs may use self-determination strategies to facilitate postsecondary transition while promoting academic success.
Method
As students with LLD enter secondary school, they are expected to write and think at more complex levels than ever before to meet post-graduation workforce demands, yet the provision of needed language–literacy intervention services drastically declines. Teaching students with LLD self-determination skills, such as awareness of their own strengths and limitations, self-advocacy strategies, and self-regulation, is found to be related to positive post-school outcomes and can be readily integrated into transition planning by the SLP.
Conclusion
SLPs may ideally support secondary school student language–literacy needs in transition planning by using self-determination strategies to help access the curriculum and experience postsecondary success.

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Introduction to the Clinical Forum: Exploring Curriculum-Based Language Assessment and Interventions

Purpose
The purpose of this article is to introduce the Clinical Forum: Exploring Curriculum-Based Language Assessment and Interventions, which investigates the current evidence supporting curriculum-based language intervention and assessment.
Method
This introduction highlights the need for speech-language pathologists to approach intervention with knowledge of the best evidence available and highlights the 6 articles presented in this clinical forum.
Conclusion
The articles in this clinical forum shed light on the current state of the evidence for curriculum-based language intervention and assessment across the educational continuum. Authors provide readers with access to techniques available to all school-based speech-language pathologists to advocate for, assess, and implement interventions within the classroom curriculum. This forum also establishes the need for more data to support current school-based models of assessment and intervention.

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Curriculum-Based Language Assessment With Culturally and Linguistically Diverse Students in the Context of Mathematics

Purpose
The purpose of this tutorial is to discuss the use of curriculum-based language assessment (CBLA) with students who are English language learners and students who speak nonmainstream varieties of English, such as African American English.
Method
The article begins with a discussion of the discourse of mathematics and the role of the speech-language pathologist (SLP), followed by a review of studies that includes those that examined the performance of English language learner and nonmainstream dialect-speaking students on word-based math items.
Results
The literature review highlights the linguistic and content biases associated with word-based math problems. Useful strategies that SLPs and educators can incorporate in culturally and linguistically appropriate assessments are discussed. The tutorial ends with a discussion of CBLA as a viable assessment approach to use with culturally and linguistically diverse students.
Conclusions
Tests used at national, state, and school levels to assess students' math abilities have associated linguistic bias and content bias often leading to an inaccurate depiction of culturally and linguistically diverse students' math skills. CBLA as an assessment method can be used by school-based SLPs to gather valid and useful information about culturally and linguistically diverse students' language for learning math. By using CBLA, SLPs can help modify curricular tasks in broader contexts in an effort to make math, including high-level math, "accessible and achievable for all" students (American Speech-Language-Hearing Association, 2017).

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A Multiyear Population-Based Study of Kindergarten Language Screening Failure Rates Using the Rice Wexler Test of Early Grammatical Impairment

Purpose
The purpose of this study was to evaluate, over 2 separate school years, the school-district-wide failure rate of kindergartners on a screener of grammatical tense marking—the Rice Wexler Test of Early Grammatical Impairment (TEGI) Screening Test (Rice & Wexler, 2001)—composed of past tense (PT) and third-person singular (3S) probes.
Method
In the fall of 2 consecutive school years, consented and eligible kindergartners (n = 148 in Year 1, n = 126 in Year 2) in a rural southern school district were administered the TEGI Screening Test. Children who failed the screening test or either of the individual probes (PT or 3S) were administered the Primary Test of Nonverbal Intelligence. All children also completed the Test of Articulation Performance–Screen (Bryant & Bryant, 1983) and, in Year 2, the Get Ready to Read! emergent literacy screener (Whitehurst & Lonigan, 2001).
Results
The screening tool outcome most closely and consistently aligned with the recommended failure rate of approximately 30% (Oetting, Gregory, & Rivière, 2016; based on Tomblin et al., 1997) was the TEGI PT probe. TEGI Screening Test and 3S probe failure rates fell below the recommended level. Most children who failed the PT probe demonstrated nonverbal intelligence skills within the average range. In addition, most children who failed the PT probe would not have been readily identified on the basis of only the results of their articulation or emergent literacy screenings.
Conclusions
The TEGI PT probe is an efficient and reliable screener that identifies children for monitoring or additional language assessment. Children with language vulnerabilities are not necessarily identified by articulation or emergent literacy screenings at entry to kindergarten. To identify children at risk for language impairment, it is therefore necessary to directly screen oral language.

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Improving Narrative Production in Children With Language Disorders: An Early-Stage Efficacy Study of a Narrative Intervention Program

Purpose
As noted in this forum, more research is needed to support the work of school-based speech-language pathologists who are designing and implementing interventions for students with language disorders. This article presents the findings of a multiple-baseline, single-subject study that was conducted to assess the outcomes of an intervention designed to improve narrative discourse proficiency for children with language disorders.
Method
Four school-age children with language disorders that included deficits in narration received an experimental version of a 3-phase narrative language intervention program called Supporting Knowledge in Language and Literacy (Gillam, Gillam, & Laing, 2014). Two additional children remained in baseline throughout the study and served as controls for history, testing, and maturation effects. Measures of story productivity (number of different words) and overall story complexity (Monitoring Indicators of Scholarly Language; Gillam, Gillam, Fargo, Olszewski, & Segura, 2016) were used to assess the children's self-generated narratives.
Results
After the onset of treatment, all 4 children who received the narrative intervention made moderate-to-large improvements in narrative productivity (number of different words). Three of the 4 children also made moderate-to-large improvements in narrative complexity (Monitoring Indicators of Scholarly Language). The narrative abilities of the 2 children who did not receive intervention did not change over the course of the study.
Conclusion
This study provides evidence for the feasibility of the Supporting Knowledge in Language and Literacy narrative instruction program for improving self-generated narratives by children with language disorders. Future research is needed to determine how gains in oral narration transfer to written narrative skills.

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Understanding Disorder Within Variation: Production of English Grammatical Forms by English Language Learners

Purpose
This study examines English performance on a set of 11 grammatical forms in Spanish–English bilingual, school-age children in order to understand how item difficulty of grammatical constructions helps correctly classify language impairment (LI) from expected variability in second language acquisition when taking into account linguistic experience and exposure.
Method
Three hundred seventy-eight children's scores on the Bilingual English–Spanish Assessment–Middle Extension (Peña, Bedore, Gutiérrez-Clellen, Iglesias, & Goldstein, 2008) morphosyntax cloze task were analyzed by bilingual experience groups (high Spanish experience, balanced English–Spanish experience, high English experience, ability (typically developing [TD] vs. LI), and grammatical form. Classification accuracy was calculated for the forms that best differentiated TD and LI groups.
Results
Children with LI scored lower than TD children across all bilingual experience groups. There were differences by grammatical form across bilingual experience and ability groups. Children from high English experience and balanced English–Spanish experience groups could be accurately classified on the basis of all the English grammatical forms tested except for prepositions. For bilinguals with high Spanish experience, it was possible to rule out LI on the basis of grammatical production but not rule in LI.
Conclusions
It is possible to accurately identify LI in English language learners once they use English 40% of the time or more. However, for children with high Spanish experience, more information about development and patterns of impairment is needed to positively identify LI.

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Prologue: Toward Accurate Identification of Developmental Language Disorder Within Linguistically Diverse Schools

Purpose
Although the 5 studies presented within this clinical forum include children who differ widely in locality, language learning profile, and age, all were motivated by a desire to improve the accuracy at which developmental language disorder is identified within linguistically diverse schools. The purpose of this prologue is to introduce the readers to a conceptual framework that unites the studies while also highlighting the approaches and methods each research team is pursuing to improve assessment outcomes within their respective linguistically diverse community.
Method
A disorder within diversity framework is presented to replace previous difference vs. disorder approaches. Then, the 5 studies within the forum are reviewed by clinical question, type of tool(s), and analytical approach.
Conclusion
Across studies of different linguistically diverse groups, research teams are seeking answers to similar questions about child language screening and diagnostic practices, using similar analytical approaches to answer their questions, and finding promising results with tools focused on morphosyntax. More studies that are modeled after or designed to extend those in this forum are needed to improve the accuracy at which developmental language disorder is identified.

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Communicative Function Use of Preschoolers and Mothers From Differing Racial and Socioeconomic Groups

Purpose
This study explores whether communicative function (CF: reasons for communicating) use differs by socioeconomic status (SES), race/ethnicity, or gender among preschoolers and their mothers.
Method
Mother–preschooler dyads (N = 95) from the National Center for Early Development and Learning's (2005) study of family and social environments were observed during 1 structured learning and free-play interaction. CFs were coded by trained independent raters.
Results
Children used all CFs at similar rates, but those from low SES homes produced fewer utterances and less reasoning, whereas boys used less self-maintaining and more predicting. African American mothers produced more directing and less responding than European American and Latino American mothers, and Latino American mothers produced more utterances than European American mothers. Mothers from low SES homes did more directing and less responding.
Conclusions
Mothers exhibited more sociocultural differences in CFs than children; this suggests that maternal demographic characteristics may influence CF production more than child demographics at school entry. Children from low SES homes talking less and boys producing less self-maintaining coincided with patterns previously detected in pragmatic literature. Overall, preschoolers from racial/ethnic minority and low SES homes were not less deft with CF usage, which may inform how their pragmatic skills are described.
Supplemental Material
https://doi.org/10.23641/asha.5890255

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Classification Accuracy of Teacher Ratings When Screening Nonmainstream English-Speaking Kindergartners for Language Impairment in the Rural South

Purpose
We compared teacher ratings as measured by the Teacher Rating of Oral Language and Literacy (TROLL; Dickinson, McCabe, & Sprague, 2001, 2003) and Children's Communication Checklist–Second Edition (CCC-2; Bishop, 2006) to 2 established screeners, the Part II of the Diagnostic Evaluation of Language Variation–Screening Test (DELV-ST-II; Seymour, Roeper, & de Villiers, 2003) and Dynamic Indicators of Basic Early Literacy Skills–Next (DIBELS; Good, Gruba, & Kaminski, 2009), and then examined whether teacher ratings alone or when combined with the DELV-ST-II or DIBELS accurately classify nonmainstream English-speaking kindergartners by their clinical status.
Method
Data came from 98 children who lived in the rural South; 47 spoke African American English, and 51 spoke Southern White English. Using the syntax subtest of the Diagnostic Evaluation of Language Variation–Norm Referenced (Seymour, Roeper, & de Villiers, 2005) as the reference standard, 43 were language impaired and 55 were typically developing. Analyses included analysis of variance, correlations, and discriminant function with sensitivity and specificity indices.
Results
The TROLL, CCC-2, DELV-ST-II, and DIBELS showed clinical status but not dialect effects, and they correlated with each other, the Diagnostic Evaluation of Language Variation–Norm Referenced, and other language measures. Classification accuracies of all 4 tools were too low for screening purposes; however, empirically derived cut scores improved the results, and a discriminant function selected the TROLL and DELV-ST-II as optimal for determining who should be referred for an evaluation, with the TROLL yielding the highest level of sensitivity (77%).
Conclusion
Findings support teacher ratings as measured by the TROLL when screening nonmainstream English-speaking kindergartners for language impairment in the rural South, while also calling for additional development and study of teacher rating tools and other screening instruments.
Supplemental Material
https://doi.org/10.23641/asha.6007712

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Masthead



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Enhanced Vascular Biocompatibility and Remodeling of Decellularized and Secured Xenogeneic/Allogeneic Matrices in a Porcine Model

Background/Purpose: Calcifications and absence of growth potential are the major drawbacks of glutaraldehyde-treated prosthesis. Decellularized and secured xeno-/allogeneic matrices were assessed in a preclinical porcine model for biocompatibility and vascular remodeling in comparison to glutaraldehyde-fixed bovine pericardium (GBP; control). Methods: Native human (fascia lata, pericardium) and porcine tissues (peritoneum) were used and treated. In vitro, biopsies were performed before and after treatment to assess decellularization (hematoxylin and eosin/DAPI). In vivo, each decellularized and control tissue sample was implanted subcutaneously in 4 mini-pigs. In addition, 9 mini-pigs received a patch or a tubularized prosthesis interposition on the carotid artery or abdominal aorta of decellularized (D) human fascia lata (DHFL; n = 4), human pericardium (DHP; n = 9), porcine peritoneum (DPPt; n = 7), and control tissue (GBP: n = 3). Arteries were harvested after 1 month and subcutaneous samples after 15–30 days. Tissues were processed for hematoxylin and eosin/von Kossa staining and immunohistochemistry for CD31, alpha-smooth muscle actin, CD3, and CD68. Histomorphometry was achieved by point counting. Results: A 95% decellularization was confirmed for DHP and DPPt, and to a lower degree for DHFL. In the subcutaneous protocol, CD3 infiltration was significantly higher at day 30 in GBP and DHFL, and CD68 infiltration was significantly higher for GBP (p #x3c; 0.05). In intravascular study, no deaths, aneurysms, or pseudoaneurysms were observed. Inflammatory reaction was significantly higher for DHFL and GBP (p #x3c; 0.05), while it was lower and comparable for DHP/DPPt. DHP and DPPt showed deeper recellularization, and a new arterial wall was characterized. Conclusions: In a preclinical model, DPPt and DHP offered better results than conventional commercialized GBP for biocompatibility and vascular remodeling.
Eur Surg Res 2018;59:58–71

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Feature Selection for the Classification of Traced Neurons

Publication date: Available online 5 April 2018
Source:Journal of Neuroscience Methods
Author(s): José D. López-Cabrera, Juan V. Lorenzo-Ginori
BackgroundThe great availability of computational tools to calculate the properties of traced neurons leads to the existence of many descriptors which allow the automated classification of neurons from these reconstructions. This situation determines the necessity to eliminate irrelevant features as well as making a selection of the most appropriate among them, in order to improve the quality of the classification obtained.MethodsThe dataset used contains a total of 318 traced neurons, classified by human experts in 192 GABAergic interneurons and 126 pyramidal cells. The features were extracted by means of the L-measure software, which is one of the most used computational tools in neuroinformatics to quantify traced neurons. We review some current feature selection techniques as filter, wrapper, embedded and ensemble methods. The stability of the feature selection methods was measured. For the ensemble methods, several aggregation methods based on different metrics were applied to combine the subsets obtained during the feature selection process.ResultsThe subsets obtained applying feature selection methods were evaluated using supervised classifiers, among which Random Forest, C4.5, SVM, Naïve Bayes, Knn, Decision Table and the Logistic classifier were used as classification algorithms.Comparison with Existing MethodsFeature selection methods of types filter, embedded, wrappers and ensembles were compared and the subsets returned were tested in classification tasks for different classification algorithms.ConclusionsL-measure features EucDistanceSD, PathDistanceSD, Branch_pathlengthAve, Branch_pathlengthSD and EucDistanceAve were present in more than 60% of the selected subsets which provides evidence about their importance in the classification of this neurons.



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Smaller, Sleeker, Smarter, but Special? A Look at the Latest Hearing Aid Technology

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Hearing Aids and Balance Improvement

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Symptoms: History of Ear Infection and Meningitis

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New Guide to Translate and Adapt Hearing-Related Questionnaires

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Improving Equitable Access to Hearing Care

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From Screen to Trial: Evidence-Based Decisions for Drug-Induced Hearing Loss

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Safe-in-Sound Award Recognizes Innovations in Hearing Loss Prevention

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Hearing Loss in Nursing Homes

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Advocate for Your Hearing Health

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Long After Chemotherapy, Cisplatin and Hearing Loss Remain

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Evaluating Neural Markers of Listening in Real-Life Conditions

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Rock On…with Caution: Hearing Loss Risk in Musicians

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Central Presbycusis Counseling

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MRI Noise and Hearing Loss

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Manufacturers News

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Benralizumab efficacy by atopy status and serum immunoglobulin E for patients with severe, uncontrolled asthma

Patients with severe asthma can have eosinophilic inflammation and/or allergen sensitization. Benralizumab is an anti-eosinophilic monoclonal antibody being developed for patients with severe, uncontrolled asthma with eosinophilic inflammation.

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Impact of a structured oculoplastic surgery rotation on specialist training in oral and maxillofacial surgery

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Publication date: Available online 5 April 2018
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): K. Payne, N. Barnard, P. Earl, K. McVeigh, J. Sen




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Preoperative assessment of the risk of postoperative death in patients with oral squamous cell carcinoma: a consideration beyond age, sex, and stage of cancer

Publication date: Available online 5 April 2018
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): A.K. Bartella, A.-K. Sander, M. Kamal, J. Steegmann, A. Kloss-Brandstätter, J. Teichmann, F. Hölzle, B. Lethaus
Despite improvements in the management of patients in critical care, about 3% patients who have an operation with curative intent for oral squamous cell carcinoma (SCC) do not survive their stay in hospital. Our aim was to assess the risk factors for postoperative death that were independent of the stage of the cancer, or the age and sex of the patients. We screened 4760 consecutive inpatients at a maxillofacial tertiary care centre from 2011 to 2016, and 34 of them had died within the first three months after operation. We matched them with a further 34 patients with the same TNM stage, age, and sex. General personal and clinical data and preoperative laboratory values were screened, and we applied a Charlson Comorbidity Score (for anaesthetic risk) for each group. Patients' mean (SD) age was 66 (12) years old. There was no significant difference in sex (p=1), age (p=0.718), or TNM classification. Those who died after operation had significantly more renal (p=0.027) and gastrointestinal (p=0.006) diseases, but cardiac diseases (p=0.468) and diabetes mellitus (p=1) were not significant risk factors in themselves. Patients who died postoperatively had significantly worse risk scores (p=0.001) overall. The most common causes of death were septic shock (n=10) and acute cardiac (n=9) or respiratory failure (n=7). Our findings suggested that general diseases were not intrinsically a contraindication for operation with curative intent. The Charlson Comorbidity Score helped to detect potentially fatal courses and could be useful in the preoperative assessment of patients whose general health is not good.



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Sexual Function, Self-image Improve After Clitoral Reconstruction

Clitoral reconstruction after female genital mutilation is associated with improved sexual function and genital self-image, clinicians from Spain report.
Reuters Health Information

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Height and Weight Estimation From Anthropometric Measurements Using Machine Learning Regressions

Height and weight are measurements explored to tracking nutritional diseases, energy expenditure, clinical conditions, drug dosages, and infusion rates. Many patients are not ambulant or may be unable to communicate, and a sequence of these factors may not allow accurate estimation or measurements; in those cases, it can be estimated approximately by anthropometric means. Different groups have proposed different linear or non-linear equations which coefficients are obtained by using single or multiple linear regressions. In this paper, we present a complete study of the application of different learning models to estimate height and weight from anthropometric measurements: support vector regression, Gaussian process, and artificial neural networks. The predicted values are significantly more accurate than that obtained with conventional linear regressions. In all the cases, the predictions are non-sensitive to ethnicity, and to gender, if more than two anthropometric parameters are analyzed. The learning model analysis creates new opportunities for anthropometric applications in industry, textile technology, security, and health care.

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Transcription and microRNA Profiling of Cultured Human Tympanic Membrane Epidermal Keratinocytes

Abstract

The human tympanic membrane (TM) has a thin outer epidermal layer which plays an important role in TM homeostasis and ear health. The specialised cells of the TM epidermis have a different physiology compared to normal skin epidermal keratinocytes, displaying a dynamic and constitutive migration that maintains a clear TM surface and assists in regeneration. Here, we characterise and compare molecular phenotypes in keratinocyte cultures from TM and normal skin. TM keratinocytes were isolated by enzymatic digestion and cultured in vitro. We compared global mRNA and microRNA expression of the cultured cells with that of human epidermal keratinocyte cultures. Genes with either relatively higher or lower expression were analysed further using the biostatistical tools g:Profiler and Ingenuity Pathway Analysis. Approximately 500 genes were found differentially expressed. Gene ontology enrichment and Ingenuity analyses identified cellular migration and closely related biological processes to be the most significant functions of the genes highly expressed in the TM keratinocytes. The genes of low expression showed a marked difference in homeobox (HOX) genes of clusters A and C, giving the TM keratinocytes a strikingly low HOX gene expression profile. An in vitro scratch wound assay showed a more individualised cell movement in cells from the tympanic membrane than normal epidermal keratinocytes. We identified 10 microRNAs with differential expression, several of which can also be linked to regulation of cell migration and expression of HOX genes. Our data provides clues to understanding the specific physiological properties of TM keratinocytes, including candidate genes for constitutive migration, and may thus help focus further research.



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Self-reported nocturnal sleep duration and glycosylated hemoglobin A in the Study of Cardiovascular Risks in Adolescents (ERICA)

At present, epidemiologic studies regarding the relationship between sleep duration and glucose metabolism in adolescents are scarce. The objective was to investigate the association between self-reported nocturnal sleep duration and glycosylated hemoglobin A in 12- to 17-year-old Brazilian adolescents.

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Relationship between obstructive sleep apnoea syndrome and essential hypertension: a dose–response meta-analysis

The objective of this study was to summarize the evidence regarding the relationship between obstructive sleep apnoea syndrome (OSAS) and the risk of essential hypertension.

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The associations among objectively estimated sleep and obesity indicators in elementary schoolchildren

A negative linear association between sleep duration and obesity in children has been reported, but this has been predominantly based on subjective estimates of sleep duration and one indicator of obesity. This cross-sectional study aimed to examine the relationships among objectively measured sleep parameters and a range of obesity indicators in schoolchildren.

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Kleine-Levin syndrome: the contribution of PET scan and hydrogen breath test for small intestinal bacterial overgrowth

A 13 year-old boy started to present recurrent episodes, lasting from 3 to 12 days, characterized by prolonged sleep time, megaphagia, derealization, mood depression, rudeness and hypersexual behaviour. Episodes occurred after infective diseases, moderate alcohol assumption or sleep deprivation, and were often heralded by terrifying visual hallucinations. Physical examination, blood tests, lumbar puncture, EEG, brain CT scan and MRI were normal. The patient arrived at our lab at the age of 15, during a relapse.

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Effect of Wheelchair Stroke Pattern on Upper Extremity Muscle Fatigue

Shoulder dysfunction is common in persons with spinal cord injury (SCI) with an incidence of up to 63%1. Dysfunction is a result of muscle imbalances, specifically denervated rotator cuff muscles that are repetitively used during manual wheelchair propulsion.

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The importance of lymph node ratio for patients with mandibular infiltration of oral squamous cell carcinoma

Lymph node ratio (LNR) essentially improves assessment of prognosis and therapeutic decision making for patients with oral squamous cell carcinoma, as it considers both the number of positive lymph nodes and the number of dissected lymph nodes. Mandibular infiltration by oral squamous cell carcinoma is a vital clinicopathological feature, significantly worsens prognosis. However, to the best of our knowledge, data on the influence of LNR on prognosis for patients with OSCC and mandibular infiltration are not available.

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Patient-specific pre-contouring of osteosynthesis plates for mandibular reconstruction: Using a three-dimensional key printed solution

In mandibular reconstructive surgery, the osteosynthesis plates require contouring according to the patients' individual anatomical situation. These plates are frequently contoured around a three-dimensional (3D) printed model. However, the translation to the actual patient can introduce inaccuracies and unwanted rotations in the condyles and mandibular ramus, due to malpositioning of the pre-contoured plate.

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The value of histological grading of biopsy and resection specimens in early stage oral squamous cell carcinomas

In oral squamous cell carcinoma (OSCC) the differentiation grade of the tumor is determined on the biopsy and the resection specimen. The relation between tumor grade, nodal metastasis and survival is debatable. The aims of this study were to determine the correlation between differentiation grade of the biopsy and the resection specimen. Furthermore, we wanted to correlate tumor differentiation grade with nodal stage and survival.

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Evaluation of nerve growth factor−treated mesenchymal stem cells for recovery in neurotmesis model of peripheral nerve injury

Peripheral nerve damages are a relatively common type of the nervous system injuries. Although peripheral nerves show some capacity of regeneration after injury, the extent of regeneration is not remarkable. The present study aimed to evaluate the effect of NGF treated mesenchymal stem cells on regeneration of transected sciatic nerve.

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sAssessment of Regional Asymmetry of the Face Before and After Surgical Correction of Unilateral Cleft Lip

This study was carried out on 26 unilateral cleft lip and palate (UCLP) cases with mean age 3.6 ± 0.7 months.3D facial images were captured for each infant 2–3 days before the repair of cleft lip and at 4 months following surgery at a mean age of 8.2 ± 1.8 months, using a stereophotogrammetry imaging system. An iterative closest point (ICP) algorithm was used to superimpose the 3D facial model to its mirror image using VRMesh software. After the superimposition, the face model was divided into seven anatomical regions.

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The value of histological grading of biopsy and resection specimens in early stage oral squamous cell carcinomas

Publication date: Available online 5 April 2018
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Eric A. Dik, Norbertus A. Ipenburg, Peter A. Kessler, Robert J.J. van Es, Stefan M. Willems
IntroductionIn oral squamous cell carcinoma (OSCC) the differentiation grade of the tumor is determined on the biopsy and the resection specimen. The relation between tumor grade, nodal metastasis and survival is debatable. The aims of this study were to determine the correlation between differentiation grade of the biopsy and the resection specimen. Furthermore, we wanted to correlate tumor differentiation grade with nodal stage and survival.Patients and methodsOne-hundred and forty-five patients with OSCC staged as T1-2, N0 of the tongue, floor of mouth or cheek with primary resection of the tumor were examined. Biopsy and resection specimen were histologically re-assessed with regard to differentiation grade, as well as infiltrative, peri-neural and vascular invasive growth.ResultsThis study showed a poor correlation between differentiation grade in the incisional biopsy and the resection specimen of the same tumor. No significant relation between differentiation grade of the resection specimen and nodal involvement, as well as overall and disease-specific survival was found.ConclusionIn early OSCC the differentiation grade determined by biopsy is of little predictive value for the grading of the resection specimen. Poor differentiation grade could not be related to the presence of nodal metastasis or survival and seems not to have any prognostic value concerning outcome. Treatment planning must be related to these findings.



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The importance of lymph node ratio for patients with mandibular infiltration of oral squamous cell carcinoma

Publication date: Available online 5 April 2018
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Ali-Farid Safi, Martin Kauke, Andrea Grandoch, Hans-Joachim Nickenig, Joachim Zöller, Matthias Kreppel
PurposeLymph node ratio (LNR) essentially improves assessment of prognosis and therapeutic decision making for patients with oral squamous cell carcinoma, as it considers both the number of positive lymph nodes and the number of dissected lymph nodes. Mandibular infiltration by oral squamous cell carcinoma is a vital clinicopathological feature, significantly worsens prognosis. However, to the best of our knowledge, data on the influence of LNR on prognosis for patients with OSCC and mandibular infiltration are not available.Materials and MethodsA retrospective chart review of 89 patients with treatment-naive oral squamous cell carcinoma and histopathologically proven mandibular infiltration (pT4a) was performed. Exclusion criteria were primarily curative intended surgery (radical tumor resection, neck dissection and segmental mandibulectomy) with negative resection margins. Exclusion criteria were neoadjuvant chemoradiotherapy, erosive infiltration of the mandible, T4b classification, perioperative death, unresectable disease, synchronous malignancy, follow-up < 3 months, and inadequate information to correctly determine clinicopathological characteristics.ResultsWe observed a significant correlation on univariate analysis between locoregional recurrence and pathologic N classification (p=0.004), perineural invasion (p=0.005) and lymph node ratio (p<0.001). On multivariate analysis, lymph node ratio (p=0.028) was shown to be an independent indicator for locoregional recurrence.ConclusionLNR predicted locoregional recurrence better than the conventional nodal staging system and therefore might serve as a more precise risk stratification tool. LNR > 7% led to a 11.419-fold higher risk for locoregional recurrence of patients with mandibular infiltration due to OSCC.



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