Assessment of the correlations of lacosamide concentrations in saliva and serum in patients with epilepsy

Summary

Therapeutic drug monitoring of antiepileptic drugs is based on patient serum samples. In this study, we evaluated the correlation between lacosamide (LCM) steady state concentrations in serum and saliva samples. Additionally, we investigated the relation with daily dose, and assessed the feasibility of saliva collection. This was an open-label, single center study including data from 25 patients at the Bethel Epilepsy Center treated with LCM (50-650 mg/d). Samples were collected in the morning (fasting values) and in selected cases at 50 minutes to 5 hours after the morning dose. Nonsignificant differences in the mean LCM morning (trough) concentration in serum and saliva were observed. Serum and saliva concentrations across all samples were highly correlated, (r = .874), with a slightly lower correlation when only fasting values were analyzed (r = .860). Higher correlation with daily dosages was observed in serum samples (r = .773) than in saliva samples (r = .604). Serum and saliva concentrations increased significantly after intake of the LCM morning dose (P < .001). The median absolute and percentage increase of LCM in serum were moderately lower than in saliva samples, with a few outliers in saliva samples. Consequently, saliva could offer great clinical potential to monitor drug concentrations and guide LCM treatment in epileptic patients.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oaL305

Efficacy and safety of eslicarbazepine acetate monotherapy in patients converting from carbamazepine

Summary

Objective

To evaluate the influence of prior use of carbamazepine (CBZ) and other antiepileptic drugs (AEDs) with a putatively similar mechanism of action (inhibition of voltage-gated sodium channels; VGSCs) on seizure outcomes and tolerability when converting to eslicarbazepine acetate (ESL), using data pooled from 2 controlled conversion-to-ESL monotherapy trials (studies: 093-045, 093-046).

Methods

Adults with treatment-resistant focal (partial-onset) seizures were randomized 2:1 to ESL 1600 or 1200 mg once daily. The primary efficacy endpoint was study exit (meeting predefined exit criteria related to worsening seizure control) versus an historical control group. Other endpoints included change in seizure frequency, responder rate, and tolerability. Endpoints were analyzed for subgroups of patients who received CBZ (or any VGSC inhibitor [VGSCi]) during baseline versus those who received other AEDs.

Results

Of 365 patients in the studies, 332 were evaluable for efficacy. The higher risk of study exit in the subgroups that received CBZ (or any VGSCi) during baseline, versus other AEDs, was not statistically significant (hazard ratios were 1.49 for +CBZ vs −CBZ [P = .10] and 1.27 for +VGSCi vs. −VGSCi [P = .33]). Reductions in seizure frequency and responder rates were lower in patients who converted from CBZ or other VGSCi compared with those who converted from other AEDs. There were no notable differences in overall tolerability between subgroups, but the incidence of some adverse events (eg, dizziness, somnolence, nausea) differed between subgroups and/or between treatment periods.

Significance

Baseline use of CBZ or other major putative VGSC inhibitors did not appear to significantly increase the risk of study exit due to worsening seizure control, or to increase the frequency of side effects when converting to ESL monotherapy. However, bigger improvements in efficacy may be possible in patients converting to ESL monotherapy from an AED regimen that does not include a VGSC inhibitor.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2EK0GGc

Optimizing the induction chemotherapy regimen for patients with locoregionally advanced nasopharyngeal Carcinoma: A big-data intelligence platform-based analysis

Publication date: April 2018
Source:Oral Oncology, Volume 79
Author(s): Hao Peng, Ling-Long Tang, Bin-Bin Chen, Lei Chen, Wen-Fei Li, Yan-Ping Mao, Xu Liu, Yuan Zhang, Li-Zhi Liu, Li Tian, Ying Guo, Ying Sun, Jun Ma
ObjectivesThis study aimed at identifying the optimal induction chemotherapy regimen for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy.Materials and methodsWe identified eligible patients with newly-diagnosed stage III-IVA NPC (excluding T3N0) between September 2009 and May 2015. Survival outcomes and grade 3–4 toxicities were compared between different IC regimen groups.ResultsIn total, 3738 patients were eligible for this study, with 1572 (42.1%), 1085 (29.0%) and 1081 (28.9%) receiving TPF, PF and TP, respectively. In the whole population, multivariate analysis found that TPF seems to be better than PF and TP. Howerver, subgroup analysis revealed TPF and TP had same effectiveness in patients receiving a cumulative cisplatin dose (CCD) ≥200mg/m² in concurrent chemotherapy, while TPF shows relatively better survival benefit in patients receiving CCD<200mg/m². Grade 3–4 toxicities were similar between TPF and TP groups, but were relatively higher than that in PF group.ConclusionsOur study concluded that induction TP regimen may be enough for patients receiving a CCD≥200mg/m², while TPF may be superior to TP and PF for patients receiving a CCD<200mg/m², although grade 3–4 toxic events were more common but tolerable. Further studies are needed to validate our findings.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2HkYJhJ

Social Factors in the Development of Chronic Rhinosinusitis: a Systematic Review

Abstract

Purpose of Review

In an era where prevention is paramount, understanding social factors for chronic rhinosinusitis (CRS) may facilitate preventive interventions that mitigate risk factors associated with the initiation or progression of the disease.

Recent Findings

Both passive and active smoking are clearly and unequivocally associated with both the incidence and the severity of rhinosinusitis, while there an increasing body of evidence linking social deprivation and low socioeconomic status with rhinosinusitis and its complications. However, overall, only a handful of studies were longitudinal, while the available studies suffer from lack of standardized definitions of rhinosinusitis.

Summary

In this systematic review, we assessed the available evidence linking CRS with social factors, such as socioeconomic status and class, educational status, family status, living and working location and conditions, and use of toxins or recreational drugs as well as exercise and diet. Thirty studies from 1995 onwards fulfilled our inclusion criteria and were used for this review. Social deprivation and low socioeconomic level seem to be directly associated with rhinosinusitis, as there are pollutants in living or working environment. A clear and direct association between smoking (both active and passive) and rhinosinusitis was also shown. However, the link between rhinosinusitis and education level, and exercise and diet, if any, seems to be more complex.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2C31LYX

Systematic Reviews and Meta-analysis in Rhinosinusitis: a Critical Review of the Reviews

Abstract

Purpose of Review

There has been an explosion in the number of published systematic reviews on chronic rhinosinusitis in the last decade.

Recent Findings

While the aim of these reviews in facilitating evidence-based practice is laudable, poor quality reviews may contain significant bias that can mislead a non-discerning reader.

Summary

Attention therefore must be given to review methodology before implanting findings. Organisations such as the Cochrane Collaboration promote high-quality reviews, but are limited in chronic sinus disease by heterogeneous outcomes and a paucity of randomised trials.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2sxmiAV

Modified Allergens for Immunotherapy

Abstract

Purpose of Review

During the past few decades, modified allergens have been developed for use in allergen-specific immunotherapy (AIT) with the aim to improve efficacy and reduce adverse effects. This review aims to provide an overview of the different types of modified allergens, their mechanism of action and their potential for improving AIT.

Recent Findings

In-depth research in the field of allergen modifications as well as the advance of recombinant DNA technology have paved the way for improved diagnosis and research on human allergic diseases. A wide range of structurally modified allergens has been generated including allergen peptides, chemically altered allergoids, adjuvant-coupled allergens, and nanoparticle-based allergy vaccines. These modified allergens show promise for the development of AIT regimens with improved safety and long-term efficacy. Certain modifications ensure reduced IgE reactivity and retained T cell reactivity, which facilities induction of immune tolerance to the allergen. To date, multiple clinical trials have been performed using modified allergens. Promising results were obtained for the modified cat, grass and birch pollen, and house dust mite allergens.

Summary

The use of modified allergens holds promise for improving AIT efficacy and safety. There is however a need for larger clinical studies to reliably assess the added benefit for the patient of using modified allergens for AIT.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2sAN1wc

Occupational Animal Allergy

Abstract

Purpose of Review

This review explores animal allergen exposure in research laboratories and other work settings, focusing on causes and prevention.

Recent Findings

(1) Consistent with the hygiene hypothesis, there is new evidence that early childhood exposure to pets produces changes in the gut microbiome that likely lead to a lower risk of allergy. (2) Anaphylaxis from laboratory animal bites occurs more frequently than suggested by prior literature. (3) Animal allergens represent an occupational hazard in a wide variety of work settings ranging from fields that work with animals to public settings like schools and public transportation where allergens are brought into or are present in the workplace.

Summary

Exposure to animal allergens can result in allergy, asthma, and anaphylaxis. Animal allergy has been most studied in the research laboratory setting, where exposure reduction can prevent the development of allergy. Similar prevention approaches need to be considered for other animal work environments and in all settings where animal allergens are present.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Hi4xbU

Cancers, Vol. 10, Pages 52: The Epithelial-to-Mesenchymal Transition in Cancer

Cancers, Vol. 10, Pages 52: The Epithelial-to-Mesenchymal Transition in Cancer

Cancers doi: 10.3390/cancers10020052

Authors: Joëlle Roche

The epithelial-to-mesenchymal transition (EMT) occurs during normal embryonic development, tissue regeneration, organ fibrosis, and wound healing.[...]

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2sxfhjz

Editorial Board

Publication date: March 2018
Source:Dental Materials, Volume 34, Issue 3





from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2C3245W

Features of fracture of prosthetic tooth-endocrown constructions by means of acoustic emission analysis

Publication date: March 2018
Source:Dental Materials, Volume 34, Issue 3
Author(s): Valentyn Skalskyi, Valentyn Makeev, Olena Stankevych, Roman Pavlychko
ObjectiveThe study aims at comparing the fracture resistance of different restorative materials used in dental endocrown restorations and respective endocrown restorations under a quasi-static compressive load using acoustic emission (AE) method.MethodsFive restorative materials were used in this study. The restorative materials were manufactured into discs 13mm in diameter and 5mm thick, which were then divided into 5 groups and included into Type 1: Group B: zirconium dioxide (Prettau zirconia); Group C: ceramics (IPS e.max Press); Group D: metal ceramics (GC Initial MC+Nicrallium N2 BCS); Group E: composite resin (Nano Q); Group F: luting cement (RelyX™ U200). Twenty-five extracted human molars were divided into 5 groups and included into Type 2: Group A: control, no restoration; Group BE: restored by zirconium dioxide endocrowns; Group CE: restored by ceramic endocrowns; Group DE: restored by metal ceramic endocrowns; Group EE: restored by composite resin endocrowns. An increasing load was applied to the center of the samples with a hard steel ball until a fracture occurred. The loading rate was 0.12mm/min. An AE system was used to monitor the fracture of the samples. The load corresponding to the first AE event and the final fracture load were used to evaluate the fracture resistance of the restored teeth. The data were analyzed using ANOVA and Tukey's post hot test (α=0.05).ResultsA lower threshold of 220μV was selected to exclude spurious background signals. For the initial fracture load of Type 1 samples, Group F (0.029kN)<Group E (0.039kN)<Group D (0.056kN)<Group C (0.253kN)<Group B (intact). The same trend was found for the final fracture load, i.e., Group F (1.289kN)<Group E (1.735kN)<Group D (3.362kN)<Group C (6.449kN)<Group B (intact). For the initial and final fracture load, statistically significant differences (p<0.05) were found between group C and the others groups. For the initial fracture load of Type 2 samples, Group EE (0.069kN)<Group DE (0.072kN)<Group CE (0.148kN)<Group BE (2.511kN). For the final fracture load, Group EE (1.533kN)<Group CE (2.726kN)<Group BE (3.082 kN)<Group DE (3.320kN). The initial fracture load of the ceramic samples is somewhat higher than that for the endocrown restorations with the endocrowns made of this material (0.253 and 0.148kN, respectively). At the same time, for the metal ceramic and composite resin samples, the initial fracture loads are somewhat lower than in case of compression of the endocrown restorations with the endocrowns made of these materials (0.056 and 0.072kN; 0.039 and 0.069kN, respectively). The final fracture load of all the samples of the dental materials exceeds the strength of the respective endocrown restorations. The final fracture loads of the endocrown restorations with zirconium dioxide and ceramic endocrowns (3.082 and 2.726kN, respectively) are significantly lower than the final fracture load of the respective endocrown materials (intact and 6.449kN, respectively).SignificanceDental restorations should be made of high-strength materials. Zirconia displayed the highest fracture strength, while composite resin had the lowest fracture strength out of the materials used for the endocrowns. For teeth restored with endocrowns, the use of metal ceramics as endocrown material may lower the risk of failure during clinical use.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BtTRql

Geriatric Traumatic Brain Injury: Epidemiology, Outcomes, Knowledge Gaps, and Future Directions

Journal of Neurotrauma , Vol. 0, No. 0.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GjsnCZ

Preoperative Clinical and Sonographic Predictors for Lateral Cervical Lymph Node Metastases in Sporadic Medullary Thyroid Carcinoma

Thyroid , Vol. 0, No. 0.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2F5qrOY

Renin angiotensin system and its role in biomarkers and treatment in gliomas

Abstract

Gliomas are the most common primary intrinsic tumor in the brain and are classified as low- or high-grade according to the World Health Organization (WHO). Patients with high-grade gliomas (HGG) who undergo surgical resection with adjuvant therapy have a mean overall survival of 15 months and 100% recurrence. The renin-angiotensin system (RAS), the primary regulator of cardiovascular circulation, exhibits local action and works as a paracrine system. In the context of this local regulation, the expression of RAS peptides and receptors has been detected in different kinds of tumors, including gliomas. The dysregulation of RAS components plays a significant role in the proliferation, angiogenesis, and invasion of these tumors, and therefore in their outcomes. The study and potential application of RAS peptides and receptors as biomarkers in gliomas could bring advantages against the limitations of current tumoral markers and should be considered in the future. The targeting of RAS components by RAS blockers has shown potential of being protective against cancer and improving immunotherapy. In gliomas, RAS blockers have shown a broad spectrum for beneficial effects and are being considered for use in treatment protocols. This review aims to summarize the background behind how RAS plays a role in gliomagenesis and explore the evidence that could lead to their use as biomarkers and treatment adjuvants.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2CpT6et

Transcriptional Regulation of the Warburg Effect in Cancer by SIX1

Publication date: Available online 15 February 2018
Source:Cancer Cell
Author(s): Ling Li, Yingchun Liang, Lei Kang, Yang Liu, Shan Gao, Siyu Chen, Ying Li, Wenye You, Qian Dong, Tian Hong, Zhifeng Yan, Shuai Jin, Tao Wang, Wei Zhao, Haixing Mai, Jun Huang, Xiao Han, Quanbo Ji, Qi Song, Chao Yang, Shixin Zhao, Xiaojie Xu, Qinong Ye
Aerobic glycolysis (the Warburg effect) facilitates tumor growth, and drugs targeting aerobic glycolysis are being developed. However, how the Warburg effect is directly regulated is largely unknown. Here we show that transcription factor SIX1 directly increases the expression of many glycolytic genes, promoting the Warburg effect and tumor growth in vitro and in vivo. SIX1 regulates glycolysis through HBO1 and AIB1 histone acetyltransferases. Cancer-related SIX1 mutation increases its ability to promote aerobic glycolysis and tumor growth. SIX1 glycolytic function is directly repressed by microRNA-548a-3p, which is downregulated, inversely correlates with SIX1, and is a good predictor of prognosis in breast cancer patients. Thus, the microRNA-548a-3p/SIX1 axis strongly links aerobic glycolysis to carcinogenesis and may become a promising cancer therapeutic target.

Graphical abstract

Teaser

Li et al. show that transcription factor SIX1 regulates aerobic glycolysis in cancer by binding promoters and recruiting HBO1 and AIB1 to induce the expression of glycolytic genes. SIX1 is negatively regulated by miR-548a-3p, and modulation of components of this pathway affects tumor metabolism and growth.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GhvriU

Fibroblast Heterogeneity and Immunosuppressive Environment in Human Breast Cancer

Publication date: Available online 15 February 2018
Source:Cancer Cell
Author(s): Ana Costa, Yann Kieffer, Alix Scholer-Dahirel, Floriane Pelon, Brigitte Bourachot, Melissa Cardon, Philemon Sirven, Ilaria Magagna, Laetitia Fuhrmann, Charles Bernard, Claire Bonneau, Maria Kondratova, Inna Kuperstein, Andrei Zinovyev, Anne-Marie Givel, Maria-Carla Parrini, Vassili Soumelis, Anne Vincent-Salomon, Fatima Mechta-Grigoriou
Carcinoma-associated fibroblasts (CAF) are key players in the tumor microenvironment. Here, we characterize four CAF subsets in breast cancer with distinct properties and levels of activation. Two myofibroblastic subsets (CAF-S1, CAF-S4) accumulate differentially in triple-negative breast cancers (TNBC). CAF-S1 fibroblasts promote an immunosuppressive environment through a multi-step mechanism. By secreting CXCL12, CAF-S1 attracts CD4⁺CD25⁺ T lymphocytes and retains them by OX40L, PD-L2, and JAM2. Moreover, CAF-S1 increases T lymphocyte survival and promotes their differentiation into CD25^HighFOXP3^High, through B7H3, CD73, and DPP4. Finally, in contrast to CAF-S4, CAF-S1 enhances the regulatory T cell capacity to inhibit T effector proliferation. These data are consistent with FOXP3+ T lymphocyte accumulation in CAF-S1-enriched TNBC and show how a CAF subset contributes to immunosuppression.

Graphical abstract

Teaser

Costa et al. identify four subsets of carcinoma-associated fibroblasts (CAF) in breast cancer. CAF-S1 promotes an immunosuppressive microenvironment by recruiting CD4⁺CD25⁺ T cells, via secreting CXCL12, and promoting their differentiation to Tregs and survival, via expressing T cell interacting proteins.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2HiLXR1

Enhancing decision-making about adjuvant chemotherapy in early breast cancer following EndoPredict testing

Abstract

Chemotherapy side-effects can be substantial. There is increasing recognition that some oestrogen receptor positive (ER+ve), human epidermal growth factor receptor 2 negative (HER2–ve) patients with breast cancer derive no benefit from chemotherapy and experience only iatrogenic harm. Gene expression profiling tests help refine recurrence risk and likely chemotherapy benefit. EndoPredict® is one such test, which classifies risks of distant recurrence as low or high in patients treated with surgery and adjuvant endocrine therapy alone. We compared treatment decisions pre and post test results, patients' anxiety, decisional conflict and oncologists' confidence about the decisions made.

Methods

14 oncologists in 7 UK hospitals saw 149 pts judged to have equivocal indications for chemotherapy. Provisional treatment decisions were recorded then reconsidered when EPClin results were available. Pre and post test results, patients completed State/Trait Anxiety Inventories (STAI) and the decisional conflict scale (DCS). Oncologists also recorded basic clinical details, their agreement with, and confidence about treatment decisions.

Results

67% patients initially prescribed endocrine alone with high risk result upgraded to endocrine+chemotherapy (E+C); 83% prescribed E+C and had low risk scores, downgraded to E. None of 46 patients initially favouring E alone, who were low risk changed decisions. Oncologists' confidence about decisions was significantly increased following the results (p=0.002). Patients with downgraded treatment decisions had significantly lower anxiety scores (p=0.045); those upgraded had increased scores (p=0.001). Overall decisional conflict and uncertainty fell significantly post-test (p<0.022).

Conclusions

EndoPredict scores increased oncologists' and patients' decision-making confidence, generally improving the matching of risk with therapy decisions.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2odBqxZ

Cancers, Vol. 10, Pages 51: Next Generation Immunotherapy for Pancreatic Cancer: DNA Vaccination is Seeking New Combo Partners

Cancers, Vol. 10, Pages 51: Next Generation Immunotherapy for Pancreatic Cancer: DNA Vaccination is Seeking New Combo Partners

Cancers doi: 10.3390/cancers10020051

Authors: Paola Cappello Claudia Curcio Giorgia Mandili Cecilia Roux Sara Bulfamante Francesco Novelli

Pancreatic Ductal Adenocarcinoma (PDA) is an almost incurable radio- and chemo-resistant tumor, and its microenvironment is characterized by a strong desmoplastic reaction associated with a significant infiltration of T regulatory lymphocytes and myeloid-derived suppressor cells (Tregs, MDSC). Investigating immunological targets has identified a number of metabolic and cytoskeletal related molecules, which are typically recognized by circulating antibodies. Among these molecules we have investigated alpha-enolase (ENO1), a glycolytic enzyme that also acts a plasminogen receptor. ENO1 is also recognized by T cells in PDA patients, so we developed a DNA vaccine that targets ENO1. This efficiently induces many immunological processes (antibody formation and complement-dependent cytotoxicity (CDC)-mediated tumor killing, infiltration of effector T cells, reduction of infiltration of myeloid and Treg suppressor cells), which significantly increase the survival of genetically engineered mice that spontaneously develop pancreatic cancer. Although promising, the ENO1 DNA vaccine does not completely eradicate the tumor, which, after an initial growth inhibition, returns to proliferate again, especially when Tregs and MDSC ensue in the tumor mass. This led us to develop possible strategies for combinatorial treatments aimed to broaden and sustain the antitumor immune response elicited by DNA vaccination. Based on the data we have obtained in recent years, this review will discuss the biological bases of possible combinatorial treatments (chemotherapy, PI3K inhibitors, tumor-associated macrophages, ENO1 inhibitors) that could be effective in amplifying the response induced by the immune vaccination in PDA.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BwnFT7

Reply to ‘Comment on ‘Prognostic biomarkers for oral tongue squamous cell carcinoma: a systematic review and meta-analysis”

Reply to 'Comment on 'Prognostic biomarkers for oral tongue squamous cell carcinoma: a systematic review and meta-analysis"

Reply to 'Comment on 'Prognostic biomarkers for oral tongue squamous cell carcinoma: a systematic review and meta-analysis", Published online: 15 February 2018; doi:10.1038/bjc.2017.491

Reply to 'Comment on 'Prognostic biomarkers for oral tongue squamous cell carcinoma: a systematic review and meta-analysis"

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Hitt32

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients, Published online: 15 February 2018; doi:10.1038/bjc.2017.492

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GiCJDc

The Improving Rural Cancer Outcomes Trial: a cluster-randomised controlled trial of a complex intervention to reduce time to diagnosis in rural cancer patients in Western Australia

The Improving Rural Cancer Outcomes Trial: a cluster-randomised controlled trial of a complex intervention to reduce time to diagnosis in rural cancer patients in Western Australia

The Improving Rural Cancer Outcomes Trial: a cluster-randomised controlled trial of a complex intervention to reduce time to diagnosis in rural cancer patients in Western Australia, Published online: 15 February 2018; doi:10.1038/bjc.2017.457

The Improving Rural Cancer Outcomes Trial: a cluster-randomised controlled trial of a complex intervention to reduce time to diagnosis in rural cancer patients in Western Australia

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2HfYy7D

Comment on ‘Prognostic biomarkers for oral tongue squamous cell carcinoma: a systematic review and meta-analysis’

Comment on 'Prognostic biomarkers for oral tongue squamous cell carcinoma: a systematic review and meta-analysis'

Comment on 'Prognostic biomarkers for oral tongue squamous cell carcinoma: a systematic review and meta-analysis', Published online: 15 February 2018; doi:10.1038/bjc.2017.482

Comment on 'Prognostic biomarkers for oral tongue squamous cell carcinoma: a systematic review and meta-analysis'

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GfUMJX

Single-cell transcriptome analyses reveal endothelial cell heterogeneity in tumors and changes following anti-angiogenic treatment

Angiogenesis involves dynamic interactions between specialized endothelial tip and stalk cells that are believed to be regulated in part by VEGF and Dll4-Notch signaling. However, our understanding of this process is hampered by limited knowledge of the heterogeneity of endothelial cells and the role of different signaling pathways in specifying endothelial phenotypes. Here we characterized by single cell transcriptomics the heterogeneity of mouse endothelial cells and other stromal cells during active angiogenesis in xenograft tumors as well as from adult normal heart, following pharmacologic inhibition of VEGF and Dll4-Notch signaling. We classified tumor endothelial cells into three subpopulations that appeared to correspond with tip-like, transition and stalk-like cells. Previously identified markers for tip and stalk cells were confirmed and several novel ones discovered. Blockade of VEGF rapidly inhibited cell cycle genes and strongly reduced the proportion of endothelial tip cells in tumors. In contrast, blockade of Dll4 promoted endothelial proliferation as well as tip cell markers; blockade of both pathways inhibited endothelial proliferation but preserved some tip cells. We also phenotypically classified other tumor stromal cells and found that tumor-associated fibroblasts (TAFs) responded to anti-angiogenic drug treatments by upregulating hypoxia-associated genes and producing secreted factors involved in angiogenesis. Overall, our findings better define the heterogeneity of tumor endothelial and other stromal cells and reveal the roles of VEGF and Dll4-Notch in specifying tumor endothelial phenotype, highlighting the response of stromal cells to anti-angiogenic therapies.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GfeTrW

Non-invasive vagus nerve stimulation reduces blood-brain barrier disruption in a rat model of ischemic stroke

Publication date: Available online 15 February 2018
Source:Brain Stimulation
Author(s): Yirong Yang, Lisa Y. Yang, Lilla Orban, Darnell Cuylear, Jeffrey Thompson, Bruce Simon, Yi Yang
BackgroundVagus nerve stimulation (VNS) significantly reduces infarct volume in rat models of cerebral ischemia, but the mechanism of this protective effect remains open.HypothesisThis study tested the hypothesis that non-invasive VNS (nVNS), during transient middle cerebral artery occlusion (MCAO), protects the blood-brain barrier (BBB), leading to reduced infarct size in ischemic brain.MethodsSpontaneous hypertensive rats (SHRs) were subjected to a 90 min MCAO. nVNS treated rats received 5 stimulations (duration: 2 min; every 10 min) on the skin overlying the cervical vagus nerve in the neck beginning 30 min after MCAO onset. Control rats received the same stimulations on the quadriceps femoris muscle. Twenty-four hours after MCAO onset, MRI and immunohistochemistry (IHC) were performed for analyses of infarct size and BBB leakage.ResultsCompared with the control group, anatomic MRI T2-weighted images showed significantly smaller infarct sizes in the nVNS group. Dynamic contrast-enhanced (DCE)-MRI showed a significantly decreased BBB transfer rate (Ki map) in the lesion area in the nVNS group, which was spatially correlated with the attenuation of the infarct size. Furthermore, significantly lower serum IgG leakage, visualized by IHC, was seen in the ischemic hemisphere in nVNS treated rats. nVNS also protected vascular tight junction proteins from disruption in microvessels, and reduced expression of matrix metalloproteinases-2/9 in reactive astrocytes surrounding the compromised vessels in the ischemic hemispheres.ConclusionOur data suggest that the neuroprotective role of a series of nVNS administrations during MCA occlusion, spatially correlates with protection of BBB integrity from damage and reduction of infarct extent induced by ischemic stroke.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Cpogml

The Effect of Unfocused Extracorporeal Shock Wave Therapy on Bone Defect Healing in Diabetics

Aim: The purpose of this study was to evaluate the effect of the unfocused extracorporeal shock wave therapy (ESWT) on healing of mandible ramus defects in diabetic rats. Material and method: Forty male Wistar albino rats were used in the experiment. All animals were randomly divided into 2 main groups, nondiabetic and diabetic. Critical-sized defects were created on ramus in all rats. ESWT was performed to half of rats in each group at 3 sessions after surgery. Animals were euthanized at either fourth or eighth week. Stereological and radiologic examination was performed. Data were statistically analyzed by one-way variance analysis and Tukey post-hoc test. Results: Hounsfield Unit (HU) values were higher in D−E+ group than D−E− group in both 8-week and 4-week groups (P > 0.05). In both 4-week and 8-week diabetic groups, higher value was observed when compared with nondiabetic groups (P > 0.05). According to stereological results, in 4-week groups, there was a higher NB, CT, and NV volume in D−E− group than D−E+ group and in D+E− group than D+E+ group. These results are similar for the 8-week groups except NV volume. Conclusion: It was found that ESWT application has no positive effect on the healing of critical-sized bone defects in nondiabetics whereas promising effects in diabetics were observed. Address correspondence and reprint requests to Enes Özkan, DDs, PhD, Bafra Oral and Dental Health Hospital, 55400, Samsun, Turkey; E-mail: drenesozkan@gmail.com Received 28 April, 2017 Accepted 10 November, 2017 This experimental study was supported by Project Management Office Coordinatorship of Ondokuz Mayis University with PYO.DIS.1904.12.006 project code. The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2o4lVZF

Alternatives to Autologous Bone Graft in Alveolar Cleft Reconstruction: The State of Alveolar Tissue Engineering

Alveolar cleft reconstruction has historically relied on autologous iliac crest bone grafting (ICBG), but donor site morbidity, pain, and prolonged hospitalization have prompted the search for bone graft substitutes. The authors evaluated bone graft substitutes with the highest levels of evidence, and highlight the products that show promise in alveolar cleft repair and in maxillary augmentation. This comprehensive review guides the craniofacial surgeon toward safe and informed utilization of biomaterials in the alveolar cleft. A literature search was performed to identify in vitro human studies that fulfilled the following criteria: Level I or Level II of evidence, ≥30 subjects, and a direct comparison between a autologous bone graft and a bone graft substitute. A second literature search was performed that captured all studies, regardless of level of evidence, which evaluated bone graft substitutes for alveolar cleft repair or alveolar augmentation for dental implants. Adverse events for each of these products were tabulated as well. Sixteen studies featuring 6 bone graft substitutes: hydroxyapatite, demineralized bone matrix (DBM), β-tricalcium phosphate (TCP), calcium phosphate, recombinant human bone morphogenic protein-2 (rhBMP-2), and rhBMP7 fit the inclusion criteria for the first search. Through our second search, the authors found that DBM, TCP, rhBMP-2, and rhBMP7 have been studied most extensively in the alveolar cleft literature, though frequently in studies using less rigorous methodology (Level III evidence or below). rhBMP-2 was the best studied and showed comparable efficacy to ICBG in terms of volume of bone regeneration, bone density, and capacity to accommodate tooth eruption within the graft site. Pricing for products ranged from $290 to $3110 per 5 mL. The balance between innovation and safety is a complex process requiring constant vigilance and evaluation. Here, the authors profile several bone graft substitutes that demonstrate the most promise in alveolar cleft reconstruction. Address correspondence and reprint requests to Fan Liang, MD, Division of Plastic Surgery, Keck School of Medicine of USC, 1510 San Pablo Street, Suite 415 Los Angeles, CA 90033; E-mail: fan.liang@med.usc.edu Received 16 January, 2017 Accepted 10 November, 2017 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2o9JD6h

Safety Outcomes in Endoscopic Versus Open Repair of Metopic Craniosynostosis

Background: Premature fusion of the metopic suture leads to a range of clinical presentations, with more severe patients presenting characteristically with trigonocephaly. Endoscopic-assisted correction of craniosynostosis is emerging as an alternative to the gold-standard open cranial vault remodeling. While there are several documented benefits of endoscopic correction, the management of craniosynostosis varies widely in the literature with little consensus as to the preferred timing and surgical technique for repair. The purpose of this study was to investigate the safety outcomes of endoscopic versus open surgery at our institution. Methods: This retrospective cohort study included all patients diagnosed with metopic craniosynostosis who underwent open or closed surgical management and received at least 6 months of follow-up. Data extraction was performed via chart review and included demographic information and safety outcome variables. Results: During the study period, 17 patients who met our inclusion criteria were treated by the multidisciplinary craniofacial team at our institution. Eight patients underwent endoscopic surgery and 9 underwent open surgery. The mean age at surgery was significantly higher in the open surgery group than the endoscopic surgery group (13.7 months versus 2.3 months, respectively). Estimated blood loss, percent estimated blood volume lost, transfusion volume, procedure length, hospital length of stay, and intensive care unit (ICU) length of stay were all significantly higher in the open surgery group compared with the endoscopic group. Conclusions: In our patient population, endoscopic surgery for metopic craniosynostosis had an improved safety profile versus open surgery based on reduced procedure length, estimated blood loss, volume of blood transfusion, and length of stay in the ICU and hospital. Address correspondence and reprint requests to Dr Laura A. Monson, MD, Baylor College of Medicine, 6701 Fannin Street, Suite 610, Houston, TX 77030; E-mail: Laura.Monson@bcm.edu). Received 18 September, 2017 Accepted 10 November, 2017 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2EHFQXY

Reevaluation of Mandibular Morphometry According to Age, Gender, and Side

Aim: This study aims to reevaluation the linear and angular measurements of mandibles with multidetector computed tomography (MDCT) that is a new method and used frequently in recent years. Materials and Methods: The archived MDCT images of 100 adult patients (age range, 15–74 years) without mandibular operation and trauma history were evaluated retrospectively. Mandibular ramus heights, maximal mandibular length, mandibular symphysis height, mandibular angles, and mandibular foramen distance measurements were performed on MDCT images. All measurement parameters were analyzed by gender, age groups, and sides. Results: Mandibular linear length measurements were higher in males than in females (P 

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2o9Jpfr

Facial Artery as a Recipient Vessel for Extensive Scalp Reconstruction With Free Omental Flap Without Vein Graft

Most patients with reconstruction for extensive scalp defects require the use of a free flap. The suitability of the recipient vessel has a major impact on the surgery and postoperative outcome. Flaps that can be used to reconstruct the total scalp with a single flap include the latissimus dorsi (LD) and omental flaps; the LD flap is generally preferred since the omental flap results in relatively larger donor site morbidity. The recipient vessel most commonly used for scalp defect reconstruction is the superficial temporal vessel. The authors report a patient with successful total scalp reconstruction using a free omental flap on a patient whose bilateral superficial temporal arteries could not be used and who did not have available LD on both sides due to previous LD free flap surgeries for recurrent scalp angiosarcoma. In this patient, direct anastomosis of the flap to the right facial artery was performed without pedicle lengthening, such as vein graft or arteriovenous loops, and favorable outcome was achieved in terms of facial contour after recovery. The free omental flap is useful for reconstruction of extensive scalp defects without additional complex surgical procedures when other flaps are not viable or when the recipient vessel is located at a far distance. Address correspondence and reprint requests to Han Koo Kim, MD, PhD, Department of Plastic and Reconstructive Surgery, Chung-Ang University Hospital, 102, Heuksuk-Ro, Dongjak-Gu, Seoul 06973, Korea; E-mail: hkkiim@cau.ac.kr Received 10 October, 2017 Accepted 11 November, 2017 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2o9JlMJ

A Standard Operating Procedure of Clean and Fast Craniotomy Without Application of Raney Clips

Clean and fast craniotomy and closure (CAC) is a fundamental part of modern microneurosurgery, and is an essential technique that young neurosurgeons shall master. The hemostatic instruments of CAC have evolved from forceps to raney clips. Thanks to the wide application of bipolar coagulation, local infiltration anesthesia combined with cauterization is become an effective method of hemostasis. The authors worked out a standard operating procedure (SOP) of CAC assisted by fishhooks without the application of raney clips. According to the authors' experience, the average time spent on CAC decreased from more than 1 hour to

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2EHG5SS

Crushed Cartilage: A Rescue Procedure in Rhinoplasty

While the use of crushed cartilage is now universally recognized as a valid procedure in rhinoplasty to mask irregularities and eliminate slight deficits, there is still no consensus as to the optimal degree of crushing and the rate of graft resorption over time. With a view to casting light on these 2 important aspects and providing some guidelines, the authors present a study of 123 patients subjected to grafts of cartilage with different degrees of crushing in the different areas of the nasal pyramid: upper third (45 patients), middle third (40), and lower third (38). The degree of crushing was medium for 95 patients and high for 28 who presented thinner and less elastic skin. Comparison of the performance over time of the cartilage grafts inserted in the same areas but with different degrees of crushing provides important indications as regard the best way of preparing the material. The results proved satisfactory with improvements for all of the 95 patients subjected to grafts of moderately crushed cartilage. The initial defect was instead still present, albeit with some partial improvement, at a distance of 12 months in 17 of the 28 patients where highly crushed cartilage was used. The study suggests that a moderate degree of crushing offers better results as regard flexibility and stability over time. Address correspondence and reprint requests to Tito M. Marianetti, MD, Viale delle Provincie 55/18, 00162 Rome, Italy; E-mail: titomatteo.marianetti@tin.it Received 3 May, 2017 Accepted 26 November, 2017 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2EHFC34

Parotid Mucoepidermoid Carcinoma Mimicking a Large Mucocele

Mucoepidermoid carcinoma is a malign tumor involving the parotid gland and minor salivary glands. Parotid pure cystic mucoepidermoid carcinoma can also masquerade mucocele, and hence, histopathological examination is crucial to distinguish the 2. Herein, the authors report a patient of mucoepidermoid carcinoma presenting as an asymptomatic mucocele-like cystic parotid mass. A 69-year-old female presented with cystic parotid mass; her examination findings and diagnostic imaging were consistent with that of mucocele. Histological examination revealed mucoepidermoid carcinoma. This case indicates that parotid mucocele-like cysts should be included in the differential diagnosis of malign salivary gland tumors. Address correspondence and reprint requests to Nurdoğan Ata, MD, Department of Otorhinolaryngology, Gaziantep 25 Aralik State Hospital, Sarigüllük Mah. Fevziçakmak bulvari PK: 27060 Şehitkamil, Gaziantep, Turkey; E-mail: nurdoganata@mynet.com Received 5 October, 2017 Accepted 24 November, 2017 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2o9Jb85

Modified Unilateral Pedicled V-Y Advancement Flap for Scalp Defect Repair

Reconstruction of scalp defects caused by tumor resection or trauma is very challenging. A majority of the surgeons prefer to use local flap rather than skin graft or free flap for scalp defects repair. The aim of this study is to investigate the technique of modified unilateral pedicled V-Y advancement flap for the reconstruction of scalp defect. A retrospective review was performed in a series of 18 patients who had a modified unilateral pedicled V-Y advancement flap to restore scalp defect from May 2013 to January 2017. Their mean age is 58 (24–78) years. These patients suffered from basal cell carcinoma, seborrhoeic keratosis, squamous cell carcinoma, or trauma on the scalp. All of them underwent preoperative Doppler scanning to identify the scalp arteries and then individually designed. The flap size ranged from 33 × 50 mm to 68 × 105 mm. Patients were followed for an average of 12 months postoperatively (ranged from 6 to 37 months). No major complications occurred, only 2 cases had a minor distal epidermal necrosis or obstruction of venous backflow observed for the first 3 days of the surgery, and they both healed well. Modified unilateral pedicled V-Y flap technique with fairly rapid recovery and acceptable reorientation of hair follicles leads to esthetical outcome and patient satisfaction. Most importantly, no tumor recurrence at the original site during the follow-up period was seen. The modified unilateral pedicled V-Y advancement flap is a simple but efficient technique, particularly suitable for the repair of small and medium size scalp defects with advantages including the safety of the procedure and overall esthetic results like hairline preservation and less scarring when compared to other local flap techniques. Address correspondence and reprint requests to Hua Shen, MD and Zhengdong Cai, MD, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No.100 Haining Road, Hongkou District, Shanghai 200080, People's Republic of China; E-mails: samwells@sina.com; caizdvip@163.com Received 20 October, 2017 Accepted 24 November, 2017 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2o2wwVa

Total Lower Lip Reconstruction With Functional Gracilis Free Muscle Flap

Free flaps based on static slings principles cannot provide esthetic and functional outcomes at a desired level in total or close to total lip loss. Therefore, dynamic methods have become a current issue in recent years and especially the idea of functional gracilis free muscle flap has been suggested. In this study, we present a case of a successful total lower lip repair with this flap. In a 78-year-old female patient who was diagnosed with squamous cell carcinoma involving the entire lower lip, bilateral modified radical neck dissection and full-thickness total resection with 1 cm surgical margin so as to include both commissures of the tumor were performed and then a free gracilis muscle flap was transferred from the same side. After microvascular anastomoses, the motor nerve of the flap was coapted to the marginal mandibular branch of the fascial nerve. The entire intra- and extraoral surfaces of the flap were covered with a partial-thickness skin graft which was taken from the right thigh. There was no any intra- or early postoperative complication. The skin graft and flap survived without any problem. In the controls of the patient who was followed-up for 8 postoperative months, it was observed that the gracilis muscle flap was well-adapted to its place, gained a very good tonus, its volume reduced over time and reached to ideal dimensions, and the overlying skin graft provided a good color and texture match with the surrounding tissues. The motor activity of the muscle was monitored with the Tinel's test. The speech and facial expressions of the patient were very clear. Despite the patient has an edentulous mandible and was not using prosthesis, her feeding with fluid and solid foods was free of problems, oral competence was highly sufficient, and there was no any drooling. Esthetic appearance was very good and intraoral vestibular depth was sufficient. The mouth opening was 3 cm. When comparing with upper orbicularis oculi muscle on the electroneuromyography (ENMG) ordered at the 8th month, a similar nerve conduction time (3.3 versus 3.8 ms) and contraction amplitude (0.5 versus 0.4 mV) values were obtained from the gracilis muscle. Follow-up of the patient is still continued with no tumor recurrence observed during this period. Being the real dynamic flap and its tonus of the functional gracillis free muscle flap in opposite to the static methods provides a significant superiority over the other options in terms of oral functions; moreover, the overlying skin graft presents a very good color and texture harmony aesthetically. This method is a candidate to be an exclusive surgical technique in the repair of total or close to total lip losses in the future. Address correspondence and reprint requests to Dr Mehmet Akif Cakmak, MD, Ataturk Universitesi Tip Fakultesi, Yakutiye Arastirma Hastanesi, Plastik Rekonstruktif ve Estetik Cerrahi A.D., 25240 Erzurum, Turkey; E-mail: makifcakmak@gmail.com Received 20 October, 2017 Accepted 26 November, 2017 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2o7HNCI

Hemodynamic Assessment with SPY-Indocyanine Green Angiography in Expansion Period: A Study for Expansion Capsule Pressure Optimization

Tissue expansion-related severe complication exists, and the poor blood supply is one of the causes. After decades of negative correlation between capsule pressure and blood flow was verified, the widely recognized expansion capsule pressure is still absent. A prospective randomized controlled trial was performed to explore the optimal expanding capsule pressure. Thirty subjects were randomly divided into 5 groups, received a weekly expanding on 60-, 70-, 80-, 90-, and 100-mm Hg capsule pressure, respectively. All patients achieved 8-week follow-up; hemodynamic assessment by SPY-indocyanine green (ICG) angiography was taken every 2 weeks. Standardized indexes from SPY-ICG angiography were used to assess the blood supply, in which the ratio of ingress rate and the ingress rate of normal skin (IR/NIR) reflects the arterial perfusion level, and the ratio of Engress Rate and IR (ER/IR) indicates the venous reflux level. The expansion-related adverse events during the trial were recorded. The IR/NIR and the ER/IR are both obviously negatively correlated to the capsule pressure of tissue expander (P ≤ 0.05, the ER/IR's correlation coefficient = −0.453; the IR/NIR's correlation coefficient = −0.482). The post-expansion IR/NIR increased significantly after 8 weeks of expansion (P ≤ 0.05) in 90-mm Hg group. And the post-expansion ER/IR was significantly elevated (P ≤ 0.05) in 80 and 90-mmHg groups. There were 2 expansion-related complications reported in 100-mm Hg group, whereas no complication occurred in 4 other lower groups. SPY-ICG angiography is an objective measurement for tissue expansion hemodynamic monitoring. The expanding capsule pressure of 80 to 90 mm Hg is a reasonable upper limit. Address correspondence and reprint requests to Tao Zan, MD, PhD, Department of Plastic and Reconstructive Surgery, the Ninth Hospital, Medical School of Shanghai Jiao Tong University, Shanghai 200011, People's Republic of China; E-mail: zantaodoctor@yahoo.com; zantaodoctor@gmail.com; QingFeng Li, MD, PhD, Department of Plastic and Reconstructive Surgery, the Ninth Hospital, Medical School of Shanghai Jiao Tong University, Shanghai 200011, People's Republic of China; E-mail: dr.liqingfeng@shsmu.edu.cn; dr.liqingfeng@yahoo.cn Received 2 June, 2017 Accepted 29 October, 2017 Q.L. and T.Z. contributed equally to the article, and Q.L. should be considered as the co-correspondent author. This work was supported by grants from the National Natural Science Foundation of China (81471857), Shanghai Pujiang Program (15PJD022). The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2o3Sffv

Performance on Auditory and Visual Tasks of Inhibition in English Monolingual and Spanish–English Bilingual Adults: Do Bilinguals Have a Cognitive Advantage?

Purpose

Bilingual individuals have been shown to be more proficient on visual tasks of inhibition compared with their monolingual counterparts. However, the bilingual advantage has not been evidenced in all studies, and very little is known regarding how bilingualism influences inhibitory control in the perception of auditory information. The purpose of the current study was to examine inhibition of irrelevant information using auditory and visual tasks in English monolingual and Spanish–English bilingual adults.

Method

Twenty English monolinguals and 19 early balanced Spanish–English bilinguals participated in this study. All participants were 18–30 years of age, had hearing thresholds < 25 dB HL from 250 to 8000 Hz, bilaterally (American National Standards Institute, 2003), and were right handed. Inhibition was measured using a forced-attention dichotic consonant–vowel listening task and the Simon task, a nonverbal visual test.

Results

Both groups of participants demonstrated a significant right ear advantage on the dichotic listening task; however, no significant differences in performance were evidenced between the monolingual and bilingual groups in any of the dichotic listening conditions. Both groups performed better on the congruent trial than on the incongruent trial of the Simon task and had significantly faster response times on the congruent trial than on the incongruent trial. However, there were no significant differences in performance between the monolingual and bilingual groups on the visual test of inhibition.

Conclusions

No significant differences in performance on auditory and visual tests of inhibition of irrelevant information were evidenced between the monolingual and bilingual participants in this study. These findings suggest that bilinguals may not exhibit an advantage in the inhibition of irrelevant information compared with monolinguals.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2EqRoMH

Mechanisms of Vowel Variation in African American English

Purpose

This research explored mechanisms of vowel variation in African American English by comparing 2 geographically distant groups of African American and White American English speakers for participation in the African American Shift and the Southern Vowel Shift.

Method

Thirty-two male (African American: n = 16, White American controls: n = 16) lifelong residents of cities in eastern and western North Carolina produced heed, hid, heyd, head, had, hod, hawed, whod, hood, hoed, hide, howed, hoyd, and heard 3 times each in random order. Formant frequency, duration, and acoustic analyses were completed for the vowels /i, ɪ, e, ɛ, æ, ɑ, ɔ, u, ʊ, o, aɪ, aʊ, oɪ, ɝ/ produced in the listed words.

Results

African American English speakers show vowel variation. In the west, the African American English speakers are participating in the Southern Vowel Shift and hod fronting of the African American Shift. In the east, neither the African American English speakers nor their White peers are participating in the Southern Vowel Shift. The African American English speakers show limited participation in the African American Shift.

Conclusion

The results provide evidence of regional and socio-ethnic variation in African American English in North Carolina.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2E5Rj39

Erratum

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Ea2esZ

Listeners Experience Linguistic Masking Release in Noise-Vocoded Speech-in-Speech Recognition

Purpose

The purpose of this study was to evaluate whether listeners with normal hearing perceiving noise-vocoded speech-in-speech demonstrate better intelligibility of target speech when the background speech was mismatched in language (linguistic release from masking [LRM]) and/or location (spatial release from masking [SRM]) relative to the target. We also assessed whether the spectral resolution of the noise-vocoded stimuli affected the presence of LRM and SRM under these conditions.

Method

In Experiment 1, a mixed factorial design was used to simultaneously manipulate the masker language (within-subject, English vs. Dutch), the simulated masker location (within-subject, right, center, left), and the spectral resolution (between-subjects, 6 vs. 12 channels) of noise-vocoded target–masker combinations presented at +25 dB signal-to-noise ratio (SNR). In Experiment 2, the study was repeated using a spectral resolution of 12 channels at +15 dB SNR.

Results

In both experiments, listeners' intelligibility of noise-vocoded targets was better when the background masker was Dutch, demonstrating reliable LRM in all conditions. The pattern of results in Experiment 1 was not reliably different across the 6- and 12-channel noise-vocoded speech. Finally, a reliable spatial benefit (SRM) was detected only in the more challenging SNR condition (Experiment 2).

Conclusion

The current study is the first to report a clear LRM benefit in noise-vocoded speech-in-speech recognition. Our results indicate that this benefit is available even under spectrally degraded conditions and that it may augment the benefit due to spatial separation of target speech and competing backgrounds.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2EA2u24

Lingual Pressure as a Clinical Indicator of Swallowing Function in Parkinson's Disease

Purpose

Swallowing impairment, or dysphagia, is a known contributor to reduced quality of life, pneumonia, and mortality in Parkinson's disease (PD). However, the contribution of tongue dysfunction, specifically inadequate pressure generation, to dysphagia in PD remains unclear. Our purpose was to determine whether lingual pressures in PD are (a) reduced, (b) reflect medication state, or are (c) consistent with self-reported diet and swallowing function.

Method

Twenty-eight persons with idiopathic PD (PwPD) and 28 age- and sex-matched controls completed lingual pressure tasks with the Iowa Oral Performance Instrument. PwPD were tested during practically defined ON and OFF dopaminergic medication states. Participants were also stratified into three sex- and age-matched cohorts (7 men, 5 women): (a) controls, (b) PwPD without self-reported dysphagia symptoms or diet restrictions, and (c) PwPD with self-reported dysphagia symptoms with or without diet restrictions.

Results

PwPD exhibited reduced tongue strength and used elevated proportions of tongue strength during swallowing compared with controls (p < .05) without an effect of medication state (p > .05). Reduced tongue strength distinguished PwPD with self-reported dysphagia symptoms from PwPD without reported symptoms or diet restrictions (p = .045) and controls (p = .002).

Conclusion

Tongue strength was significantly reduced in PwPD and did not differ by medication state. Tongue strength differentiated between PwPD with and without self-reported swallowing symptoms. Therefore, measures of tongue strength and swallowing pressures may serve as clinical indicators for further dysphagia evaluation and may promote early diagnosis and management of dysphagia in PD.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2DVaN7m

Voice, Articulation, and Prosody Contribute to Listener Perceptions of Speaker Gender: A Systematic Review and Meta-Analysis

Purpose

The aim of this study was to provide a systematic review of the aspects of verbal communication contributing to listener perceptions of speaker gender with a view to providing clinicians with guidance for the selection of the training goals when working with transsexual individuals.

Method

Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) guidelines were adopted in this systematic review. Studies evaluating the contribution of aspects of verbal communication to listener perceptions of speaker gender were rated against a new risk of bias assessment tool. Relevant data were extracted, and narrative synthesis was then conducted. Meta-analyses were conducted when appropriate data were available.

Results

Thirty-eight articles met the eligibility criteria. Meta-analysis showed speaking fundamental frequency contributing to 41.6% of the variance in gender perception. Auditory-perceptual and acoustic measures of pitch, resonance, loudness, articulation, and intonation were found to be associated with listeners' perceptions of speaker gender. Tempo and stress were not significantly associated. Mixed findings were found as to the contribution of a breathy voice quality to gender perception. Nonetheless, there exists significant risk of bias in this body of research.

Conclusions

Speech and language clinicians working with transsexual individuals may use the results of this review for goal setting. Further research is required to redress the significant risk of bias.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FEnvb7

Cognitive Profiles of Finnish Preschool Children With Expressive and Receptive Language Impairment

Purpose

The aim of this study was to compare the verbal and nonverbal cognitive profiles of children with specific language impairment (SLI) with problems predominantly in expressive (SLI-E) or receptive (SLI-R) language skills. These diagnostic subgroups have not been compared before in psychological studies.

Method

Participants were preschool-age Finnish-speaking children with SLI diagnosed by a multidisciplinary team. Cognitive profile differences between the diagnostic subgroups and the relationship between verbal and nonverbal reasoning skills were evaluated.

Results

Performance was worse for the SLI-R subgroup than for the SLI-E subgroup not only in verbal reasoning and short-term memory but also in nonverbal reasoning, and several nonverbal subtests correlated significantly with the composite verbal index. However, weaknesses and strengths in the cognitive profiles of the subgroups were parallel.

Conclusions

Poor verbal comprehension and reasoning skills seem to be associated with lower nonverbal performance in children with SLI. Performance index (Performance Intelligence Quotient) may not always represent the intact nonverbal capacity assumed in SLI diagnostics, and a broader assessment is recommended when a child fails any of the compulsory Performance Intelligence Quotient subtests. Differences between the SLI subgroups appear quantitative rather than qualitative, in line with the new Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM V) classification (American Psychiatric Association, 2013).

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Em2uVQ

Remote Microphone System Use at Home: Impact on Caregiver Talk

Purpose

The purpose of this study was to investigate the effects of home use of a remote microphone system (RMS) on the spoken language production of caregivers with young children who have hearing loss.

Method

Language Environment Analysis recorders were used with 10 families during 2 consecutive weekends (RMS weekend and No-RMS weekend). The amount of talk from a single caregiver that could be made accessible to children with hearing loss when using an RMS was estimated using Language Environment Analysis software. The total amount of caregiver talk (close and far talk) was also compared across both weekends. In addition, caregivers' perceptions of RMS use were gathered.

Results

Children, with the use of RMSs, could potentially have access to approximately 42% more words per day. In addition, although caregivers produced an equivalent number of words on both weekends, they tended to talk more from a distance when using the RMS than when not. Finally, caregivers reported positive perceived communication benefits of RMS use.

Conclusions

Findings from this investigation suggest that children with hearing loss have increased access to caregiver talk when using an RMS in the home environment. Clinical implications and future directions for research are discussed.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2EOV363

Well-Being and Resilience in Children With Speech and Language Disorders

Purpose

Children with speech and language disorders are at risk in relation to psychological and social well-being. The aim of this study was to understand the experiences of these children from their own perspectives focusing on risks to their well-being and protective indicators that may promote resilience.

Method

Eleven 9- to 12-year-old children (4 boys and 7 girls) were recruited using purposeful sampling. One participant presented with a speech sound disorder, 1 presented with both a speech and language disorder, and 9 with language disorders. All were receiving additional educational supports. Narrative inquiry, a qualitative design, was employed. Data were generated in home and school settings using multiple semi-structured interviews with each child over a 6-month period. A total of 59 interviews were conducted. The data were analyzed to identify themes in relation to potential risk factors to well-being and protective strategies.

Results

Potential risk factors in relation to well-being were communication impairment and disability, difficulties with relationships, and concern about academic achievement. Potential protective strategies were hope, agency, and positive relationships.

Conclusion

This study highlights the importance of listening to children's narratives so that those at risk in relation to well-being can be identified. Conceptualization of well-being and resilience within an ecological framework may enable identification of protective strategies at both individual and environmental levels that can be strengthened to mitigate negative experiences.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2DRHG8f

The Effect of Remote Masking on the Reception of Speech by Young School-Age Children

Purpose

Psychoacoustic data indicate that infants and children are less likely than adults to focus on a spectral region containing an anticipated signal and are more susceptible to remote masking of a signal. These detection tasks suggest that infants and children, unlike adults, do not listen selectively. However, less is known about children's ability to listen selectively during speech recognition. Accordingly, the current study examines remote masking during speech recognition in children and adults.

Method

Adults and 7- and 5-year-old children performed sentence recognition in the presence of various spectrally remote maskers. Intelligibility was determined for each remote-masker condition, and performance was compared across age groups.

Results

It was found that speech recognition for 5-year-olds was reduced in the presence of spectrally remote noise, whereas the maskers had no effect on the 7-year-olds or adults. Maskers of different bandwidth and remoteness had similar effects.

Conclusions

In accord with psychoacoustic data, young children do not appear to focus on a spectral region of interest and ignore other regions during speech recognition. This tendency may help account for their typically poorer speech perception in noise. This study also appears to capture an important developmental stage, during which a substantial refinement in spectral listening occurs.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Ey83xO

A Narrative Evaluation of Mandarin-Speaking Children With Language Impairment

Purpose

We aimed to study narrative skills in Mandarin-speaking children with language impairment (LI) to compare with children with LI speaking Indo-European languages.

Method

Eighteen Mandarin-speaking children with LI (mean age 6;2 [years;months]) and 18 typically developing (TD) age controls told 3 stories elicited using the Mandarin Expressive Narrative Test (de Villiers & Liu, 2014). We compared macrostructure-evaluating descriptions of characters, settings, initiating events, internal responses,plans, actions, and consequences. We also studied general microstructure, including productivity, lexical diversity, syntactic complexity, and grammaticality. In addition, we compared the use of 6 fine-grained microstructure elements that evaluate particular Mandarin linguistic features.

Results

Children with LI exhibited weaknesses in 5 macrostructure elements, lexical diversity, syntactic complexity, and 3 Mandarin-specific, fine-grained microstructure elements. Children with LI and TD controls demonstrated comparable performance on 2 macrostructure elements, productivity, grammaticality, and the remaining 3 fine-grained microstructure features.

Conclusions

Similarities and differences are noted in narrative profiles of children with LI who speak Mandarin versus those who speak Indo-European languages. The results are consistent with the view that profiles of linguistic deficits are shaped by the ambient language. Clinical implications are discussed.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FigjkE

Masthead

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2EvmFRY

Toxicological profile and safety pharmacology of a single dose of fibroblast activation protein-α-based doxorubicin prodrug: in-vitro and in-vivo evaluation

Fibroblast activation protein-α (FAPα) is a promising tumor-associated target expressed by reactive stromal fibroblasts in tumor tissue. FAPα has a postprolyl peptidase activity and can specifically cleave N-terminal benzyloxycarbonyl (Z)-blocked peptides, such as the substrate Z-Gly-Pro-AMC. Doxorubicin (DOX) is an effective antitumor drug, but its application is greatly limited by toxic adverse effects owing to poor tumor selectivity. Based on these facts, we previously designed a FAPα-targeting prodrug of doxorubicin (FTPD) which can be selectively hydrolyzed by FAPα. FTPD can retain potent antitumor efficacy and has favorable tumor targeting. The present study aimed to further evaluate the toxicological profile and the safety pharmacological property of FTPD in vitro and in vivo. The cytotoxicity assay showed that FTPD displayed markedly lower cytotoxicity to 3T3 cells and HEK-293 cells compared with DOX. In the short-term toxicity study, mice treated with 25 mg/kg of FTPD showed no obvious change in the appearance and general behavior, and no case of mortality was observed within 14 days. Unlike DOX, FTPD exhibited reduced toxicity to heart, liver, kidney, spleen as well as peripheral white blood cells in mice. Moreover, open file test and general pharmacology study were also conducted correspondingly in mice and beagle dogs. It was found that FTPD may not produce significant pharmacological effects on spontaneous locomotor activity and cardiovascular-respiratory system except for a transient decreasing in systolic blood pressure. Taken together, the results of this work suggest that FTPD has more favorable toxicological profile and better drug safety compared with its parent drug DOX.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GjV4zz

Antitumor effect of the Newcastle disease viral hemagglutinin–neuraminidase gene is expressed through an oncolytic adenovirus effect in osteosarcoma cells

Newcastle disease virus (NDV) can specifically kill cancer cells and has less toxicity to normal cells. The hemagglutinin–neuraminidase (HN) protein is an important structural protein in NDV pathogenesis and has been postulated as a promising candidate for antitumor therapy. The aim of this study was to investigate the anticancer potential of recombinant adenovirus Ad-HN-PEG3p-E1a. An MTS assay was performed to determine viral proliferation after viral infection, the data showed that the proliferation ability of osteosarcoma cells decreased, whereas there was no significant change in normal hepatic cells. DAPI and Annexin V experiments showed that osteosarcoma cells were killed because of apoptosis, active oxygen content, and augmented mitochondrial membrane potential loss. Caspase Activity Assay Kits were used to detect the caspase-3 activities of the treated OS-732 for increased expression. Western blot analysis showed that cytochrome C increased significantly and apoptosis of the virus was confirmed in tumor cells. In-vivo experiments show that NDV has an inhibitory effect on tumor growth. The recombinant adenovirus, which is composed of a HN protein and progressive increment promoter PEG3p, could inhibit the growth of OS-732 and promote the apoptosis of tumor cells. However, there was no clear relationship with normal cell (L02) apoptosis.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2HkEEYT

Sonic hedgehog and Wnt/β-catenin pathways mediate curcumin inhibition of breast cancer stem cells

Cancer stem cells (CSCs) play an essential role in the progression of many tumors. Sonic hedgehog (Shh) and Wnt/β-catenin pathways are crucial in maintaining the stemness of CSCs. Curcumin has been shown to possess anticancer activity. However, the interventional effect of curcumin on breast CSCs has not been elucidated. In the present study, we investigated the role of Shh and Wnt/β-catenin pathway in curcumin inhibition of breast CSCs. We showed that the levels of breast CSCs markers were significantly elevated in SUM159 and MCF7 sphere-forming cells. We further illustrated that curcumin effectively decreased breast CSCs activity by inhibiting tumor sphere formation, decreasing breast CSCs markers (CD44, ALDH1A1, Nanog, and Oct4), as well as inhibiting proliferation and inducing apoptosis. Moreover, we showed that downregulation of Shh and Wnt/β-catenin activity resulted in breast CSCs inhibition; curcumin exerted an inhibitory effect on breast CSCs by suppressing both Shh and Wnt/β-catenin pathways. Taken together, these results indicated curcumin inhibition of breast CSCs by downregulation of Shh and Wnt/β-catenin pathways. Findings from this study could provide new insights into the potential therapeutic application of curcumin in breast CSCs elimination and cancer intervention.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GhOOrU

Palbociclib has no clinically relevant effect on the QTc interval in patients with advanced breast cancer

The aim of this study was to assess the potential effects of palbociclib in combination with letrozole on QTc. PALOMA-2, a phase 3, randomized, double-blind, placebo-controlled trial, compared palbociclib plus letrozole with placebo plus letrozole in postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. The study included a QTc evaluation substudy carried out as a definitive QT interval prolongation assessment for palbociclib. Time-matched triplicate ECGs were performed at 0, 2, 4, 6, and 8 h at baseline (Day 0) and on Cycle 1 Day 14. Additional ECGs were collected from all patients for safety monitoring. The QT interval was corrected for heart rate using Fridericia's correction (QTcF), Bazett's correction (QTcB), and a study-specific correction factor (QTcS). In total, 666 patients were randomized 2 : 1 to palbociclib plus letrozole or placebo plus letrozole. Of these, 125 patients were enrolled in the QTc evaluation substudy. No patients in the palbociclib plus letrozole arm of the substudy (N=77) had a maximum postbaseline QTcS or QTcF value of ≥ 480 ms, or a maximum increase from clock time-matched baseline for QTcS or QTcF values of ≥ 60 ms. The upper bounds of the one-sided 95% confidence interval for the mean change from time-matched baseline for QTcS, QTcF, and QTcB at all time points and at steady-state Cmax following repeated administration of 125 mg palbociclib were less than 10 ms. Palbociclib, when administered with letrozole at the recommended therapeutic dosing regimen, did not prolong the QT interval to a clinically relevant extent.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2HkvPhO

FoxM1 promotes epithelial–mesenchymal transition, invasion, and migration of tongue squamous cell carcinoma cells through a c-Met/AKT-dependent positive feedback loop

Forkhead box protein M1 (FoxM1) has been associated with cancer progression and metastasis. However, the function of FoxM1 in tongue squamous cell carcinoma (TSCC) remains largely unknown. The purpose of this study was to determine the role of FoxM1 in regulation of epithelial–mesenchymal transition (EMT) and migration of TSCC cells. We found that FoxM1 induced EMT and increased invasion/migration capacity in SCC9 and SCC25 cells. FoxM1 stimulation increased c-Met, pAKT, and vimentin levels but decreased E-cadherin level. Chromatin immunoprecipitation assay established that FoxM1 is bound to the promoter of c-Met to activate its transcription. In turn, c-Met promoted the expression of FoxM1 and pAKT. Blocking AKT signaling attenuated the invasion and migration of SCC9 and SCC25 cells stimulated by FoxM1 or c-Met. These results indicate that a positive feedback loop controls the EMT and migration of TSCC cells induced by FoxM1 and c-Met through AKT. Furthermore, the expression levels of FoxM1, pAKT, and c-Met were found to significantly increase in TSCC tissues compared with normal tissues, and these three biomarkers were concomitantly expressed in TSCC tissues. Clinical association analyses indicated that the expression of FoxM1, c-Met, and pAKT was associated with clinicopathological characteristics of patients with TSCC including tumor stage, tumor size, and lymph node metastasis. Taken together, our findings suggest that FoxM1 promotes the EMT, invasion and migration of TSCC cells, and cross-talks with c-Met/AKT signaling to form a positive feedback loop to promote TSCC development.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Gj9sIt

Antileukemic effects of neurokinin-1 receptor inhibition on hematologic malignant cells: a novel therapeutic potential for aprepitant

Genetic and laboratory studies have remodeled the conventional understanding of cancer pathogenesis by identifying different molecular alterations. Intrigued by the contribution of neurokinin-1 receptor (NK1R) network in cancer pathogenesis, we investigated the antileukemic effects of aprepitant, a nonpeptide antagonist of NK1R, in a panel of hematological cell lines. In this study, we found that aprepitant decreased the survival of all the tested cells; however, as compared with NB4, viability of the other cell lines was inhibited at higher concentrations. By increasing both p21 and p73 along with suppressing c-Myc and hTERT, aprepitant probably disordered cell distribution in the cell cycle, decreased DNA replication rate, and, thereby, impeded the proliferative capability of NB4 cells. Moreover, exposing cells to this agent led to activation of the caspase-3-dependent apoptotic pathway through altering the expression of apoptosis-related genes. Noteworthy, aprepitant also sensitized NB4 cells to the cytotoxic effects of arsenic trioxide and vincristine. Overall, it seems that pharmaceutical targeting of NK1R using aprepitant, either as a single agent or in combination, possesses novel promising potential for leukemia treatment strategies.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2HkIqSg

Sodium butyrate increases P-gp expression in lung cancer by upregulation of STAT3 and mRNA stabilization of ABCB1

As a new type of anticancer drug, the effect of histone deacetylase inhibitors (HDACIs) in cancer clinical therapy is disappointing owing to drug resistance. P-glycoprotein (P-gp) is clearly recognized as a multidrug resistance protein. However, the relationship between P-gp and sodium butyrate (SB), a kind of HDACIs, has not been investigated. In this study, we found that SB increased mRNA and protein expression of P-gp in lung cancer cells and the underlying mechanisms were elucidated. We found that SB treatment enhanced the mRNA and protein expression of STAT3 rather than that of β-catenin, Foxo3a, PXR, or CAR, which were reported to directly regulate the transcription of ABCB1, a P-gp-encoding gene. Interestingly, inhibition of STAT3 expression obviously attenuated SB-increased P-gp expression in lung cancer cells, indicating that STAT3 played an important role in SB-mediated P-gp upregulation. Furthermore, we found that SB increased the mRNA stability of ABCB1. In summary, this study showed that SB increased P-gp expression by facilitating transcriptional activation and improving ABCB1 mRNA stability. This study indicated that we should pay more attention to HDACIs during cancer clinical therapy.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GheBkc

Antitumor effects of histone deacetylase inhibitor suberoylanilide hydroxamic acid in epidermal growth factor receptor-mutant non-small-cell lung cancer lines in vitro and in vivo

Histone acetylation is one of the most abundant post-translational modifications in eukaryotic cells; aberrant histone acetylation is related to a range of cancer types because of the dysregulation of histone deacetylases (HDACs). Inhibition of HDACs leads to suppression of tumor growth in multiple cancers, whereas the inhibitory effects of HDAC inhibitors remain incompletely understood in epidermal growth factor receptor (EGFR)-mutant lung cancers. In this study, the antitumor effects of HDACs inhibitor suberoylanilide hydroxamic acid (SAHA, vorinostat) were examined in EGFR-mutant lung cancer cell lines. The results of the present work showed that SAHA markedly inhibited cell viability and proliferation, induced cell apoptosis by arresting the cell cycle in the G2/M phase, and significantly reduced tumor growth in a xenograft model. Further study confirmed that the suppression function of SAHA might be mediated by regulating the ERK-dependent and/or the AKT-dependent pathway; meanwhile, angiogenesis abrogation induced by SAHA exerted effects on tumor regression in vivo. Taken together, our results identify the antitumor effects of HDACs inhibitor SAHA as an alternative therapeutic application for the epigenetic treatment of EGFR-mutant non-small-cell lung cancer.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Hh1DEe

Dioscin inhibits colon cancer cells’ growth by reactive oxygen species-mediated mitochondrial dysfunction and p38 and JNK pathways

Dioscin is a natural steroid saponin derived from several plants that shows potent anticancer effects against a variety of cancer cells. Here, we investigated the antitumor effect of dioscin against human colon cancer cells and evaluated the molecular mechanism involved in this process. The cell cytotoxicity was studied by the MTT assay and BrdU incorporation. The proapoptotic mechanism of dioscin was characterized by flow cytometry analysis. A western blot and an immunofluorescence staining were used to investigate how dioscin induces apoptosis in vitro. In our study, dioscin could significantly inhibit the growth of colon cancer cells in a time-dependent and dose-dependent manner. Dioscin induces apoptosis and reactive oxygen species (ROS) generation, promoting the disruption of mitochondrial membrane potential, Bax translocation to the mitochondria, cytochrome C release to cytosol, activations of caspase-9/3, PARP cleavage, and subsequent apoptosis. Dioscin-induced apoptosis was accompanied by sustained phosphorylation of JNK, p38-MAPK. N-acetyl-L-cysteine, a scavenger of ROS, significantly reversed dioscin-induced cell death and activation of JNK and p38. Collectively, the data indicate that the induction of apoptosis by dioscin is mediated through ROS proteins, which are critical upstream signals for JNK/p38-MAPK activation.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GfSsCM

Erlotinib for coexisting typical bronchial carcinoid and advanced lung adenocarcinoma: does the epidermal growth factor receptor mutation status matter?

Adenocarcinoma (AC) is the most common type of primary pulmonary malignancy. Lung carcinoid, however, is a rare neuroendocrine tumor. Their coexistence is extremely uncommon. We report the unique case of synchronous advanced lung AC of the right upper lobe (stage IIIB) and typical endobronchial carcinoid tumor in the contralateral lower lobe in a 49-year-old white female who had never smoked. PET-computed tomography scan revealed a fluorine-18-fluorodeoxyglucose-avid AC lesion, whereas the carcinoid tumor was fluorine-18-fluorodeoxyglucose occult. After two lines of platinum-based combination chemotherapies and radiotherapy, the AC progressed, and oral tyrosine kinase inhibitor therapy with erlotinib was initiated in third line. On erlotinib, the AC remained stable for 50 months until disease progression, whereas the carcinoid completely regressed. Molecular testing of the rebronchoscopied AC revealed an exon 19 deletion mutation in the epidermal growth factor receptor (EGFR) gene, whereas the carcinoid was retrospectively EGFR mutation negative. The patient eventually succumbed to ileus caused by intra-abdominal spread of disease, surviving a remarkable 80 months with good performance status throughout most of the follow-up period. To the best of our knowledge, this is the first reported case of synchronous primary lung cancers with different EGFR mutation status, describing an unexpected response of an EGFR-wild-type carcinoid to third-line erlotinib.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Hixbd1

Dysphagia and Pharyngeal Obstruction in a Nonsmoker

A man in his 60s presented with a 6-month history of dysphagia and a 3-month history of a 5-pound weight loss and a right neck mass; physical examination, including flexible nasolaryngoscopy, was notable for a large smooth nonulcerated right base of tongue mass. What is your diagnosis?

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AlOgmI

Granulomatosis With Polyangiitis

This Viewpoint examines the continued use of the name Wegner granulomatosis despite the 2011 consensus to change the name of the disease to granulomatosis with polyangiitis.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zKDBkJ

Addition to Funding/Support

In the Original Investigation titled "Association of Oral Cavity and Oropharyngeal Cancer Biomarkers in Surgical Drain Fluid With Patient Outcomes," published online April 13, 2017, and in the July 2017 print issue, a funding source and grant information were missing from the Funding/Support section. University of Minnesota Cancer Center (grant P30CA077598) was added. This article has been corrected online.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2kV00BP

Sensory Changes and the Hearing Loss–Cognition Link

The UK National Institute of Health and Care Excellence (NICE) and the US National Institutes of Health (NIH) identified peripheral age-related hearing loss (ARHL) and social isolation as potentially modifiable dementia risk factors. A growing body of evidence suggested that ARHL and cognition in older age are interrelated and that midlife ARHL may be a risk factor for the development of Alzheimer disease (AD) and dementia in older adults. In a recent meta-analysis of only 3 selected studies with follow-up periods of 9 to 17 years, Livingstone and colleagues found that peripheral ARHL was a significant risk factor for incident dementia, calculating a pooled risk ratio of 1.94. At early stage of ARHL, part of the hearing problems are not related to the peripheral deficit of the auditory system but also to the central auditory processing (CAP) dysfunction, with considerable difficulty in understanding speech in presence of a background noise. Both peripheral and central auditory dysfunctions are therefore relevant to assess a possible influence of ARHL on late-life cognitive disorders.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nEsvZj

Association of Hearing Loss and Otologic Outcomes With Fibrous Dysplasia

This study characterizes audiologic and otologic manifestations in a cohort of individuals with fibrous dysplasia and/or McCune-Albright syndrome and investigated potential mechanisms of hearing loss.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Bz3gKL

Hypercoagulability and Severe Obstructive Sleep Apnea

To the Editor I read with interest the study by Hong et al, which assessed the association between hypercoagulability and severe obstructive sleep apnea (OSA). The authors measured several coagulation tests, including platelet count, bleeding time, prothrombin time (PT) in seconds and as international normalized ratio, and activated partial thromboplastin time and their association with severity of OSA. They found that patients with moderate to severe OSA had elevated blood coagulability markers compared with healthy individuals.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2kXZ5AS

Association of Lymph Node Density With Survival in Papillary Thyroid Cancer

This cohort study assesses the association of lymph node density—the ratio of the number of positive lymph nodes to the total number of nodes excised—with survival in patients with papillary thyroid cancer.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2kd5ew5

Missing Acknowledgment

In the article titled "Asymptomatic Septal Mass," an acknowledgement that was omitted has been added to thank Jonathan B. McHugh, MD, for his consultation on the case presented. The article was corrected online.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2EH9xsm

Age-Related Hearing Loss, Cognitive Function, and Dementia

This meta-analysis examines the association between age-related hearing loss and cognitive function, cognitive impairment, and dementia in epidemiologic studies from 12 countries.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AlO7Qc

Prevalence of Laryngeal Cleft in Patients With Esophageal Atresia

This study uses data from the Esophageal and Airway Treatment Center at Boston Children's Hospital to assess the prevalence of laryngeal cleft in pediatric patients with esophageal atresia with or without tracheoesophageal fistula.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2kBG2g7

Association of Sudden Sensorineural Hearing Loss With Cardiocerebrovascular Disease

This cohort study uses Korea National Health Insurance Service data to investigate the association between sudden sensorineural hearing loss and cardiocerebrovascular disease.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2kUF8KU

Asymptomatic Septal Mass

A woman in her 40s presented with a 2-month history of an enlarging asymptomatic anterior septal mass; she denied a history of localized trauma, and examination revealed an 8-mm pink-red, soft fleshy growth posterior to the membranous septum near the nostril apex. What is your diagnosis?

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BzGhPG

Cerebrospinal Fluid Rhinorrhea and a Lytic-Appearing Lesion

A man with a recent history of meningitis presented with a 1-month history of intermittent clear drainage from his left naris during activity; temporal bone computed tomography demonstrated a lytic-appearing lesion of the posterior fossa and partial opacification of the mastoid air cells. What is your diagnosis?

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2j1XUzz

Association of GERD With Cancer of the Upper Aerodigestive Tract in Elderly Patients

This case-control study uses a database of population-based tumor registries to investigate the association of gastroesophageal reflux disease with the risk of malignancy in the upper aerodigestive tract in elderly patients.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2DqIcqT

Hypercoagulability and Severe Obstructive Sleep Apnea—Reply

In Reply We appreciate the interest of Dr Ghadami in our recently published study titled "Association Between Hypercoagulability and Severe Obstructive Sleep Apnea." The comments raised by the reader can be summarized as follows: The frequent arousals in sleep might be one of the reasons for elevated coagulability markers in patients with obstructive sleep apnea (OSA).

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2kCkHTI

Outcomes Following Cordotomy by Coblation for Bilateral Vocal Fold Immobility

This case series of 19 patients examines outcomes of coblation in cordotomy for treatment of patients with bilateral vocal fold immobility.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zdoI8X

Errors in Figures 1, 2, and 3

In the Original Investigation titled "Association of Age-Related Hearing Loss With Cognitive Function, Cognitive Impairment, and Dementia: A Systematic Review and Meta-analysis," published online December 7, 2017, in Figure 1, the total number of studies included in quantitative synthesis (meta-analysis) should have been 36 instead of 40; in Figure 2, the r value for reasoning should have been −0.18 instead of −0.17; and in Figure 3, the numbers of participants and events for all categories were incorrect. This article has been corrected online.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2DqyCqG

The Improving Rural Cancer Outcomes Trial: a cluster-randomised controlled trial of a complex intervention to reduce time to diagnosis in rural cancer patients in Western Australia

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2EHstae

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2EHsmeO

Comment on ‘Prognostic biomarkers for oral tongue squamous cell carcinoma: a systematic review and meta-analysis’

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Bwy01k

Next‐Generation Sequencing for Patients with Sarcoma: A Single Center Experience

AbstractBackground.Sarcomas comprise over 50 subtypes of mesenchymal cancers. For the majority of sarcomas, the driver mutations remain unknown. In this article, we describe our experience with a targeted next‐generation sequencing (NGS) platform in clinic patients.Materials and Methods.We retrospectively analyzed results of NGS using 133 tumor samples from patients diagnosed with a variety of sarcomas that were analyzed with targeted NGS covering over 400 cancer‐related genes (405 DNA, 265 RNA) on a commercially available platform.Results.An average of two gene alterations were identified per tumor sample (range 0–14), and a total of 342 DNA mutations were detected. Eight‐eight percent of samples had at least one detected mutation. The most common mutations were in the cell cycle, including TP53 (n = 35), CDKN2A/B (n = 23), and RB1 (n = 19). Twenty‐seven PI3‐kinase pathway alterations were observed, including PTEN (n = 14), PIK3Ca (n = 4), TSC1 (n = 1), TSC2 (n = 3), STK11 (n = 1), mTOR (n = 3), and RICTOR (n = 2). There were 75 mutations in genes that are targetable with existing drugs (excluding KIT in gastrointestinal stromal tumor) that would allow enrollment onto clinical trials. In general, the estimated tumor mutation burden was low, in particular for those with disease‐defining gene fusions or genetic alterations. Microsatellite instability (MSI) data were available for 50 patients, and all were MSI stable.Conclusion.Our study describes a single‐center experience with targeted NGS for patients with sarcoma. Mutations were readily detected and 75 (representing 40% of patients) were testable for therapeutic effect using existing drugs within the confines of a clinical trial. These data indicate that targeted NGS is a useful tool in potentially routing patients to mutation‐specific clinical trials. Further study will be required to determine if these mutations are clinically meaningful drug targets in sarcoma.Implications for Practice.The sarcomas are a heterogenous family of over 50 different mesenchymal tumors. Current practice for metastatic disease involves systemic chemotherapy or nonspecific kinase inhibitors such as pazopanib. Sarcomas typically lack the classic kinase alterations seen in many carcinomas. The role of next‐generation sequencing in sarcoma clinical practice remains undefined.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2szjS4r