Platelet-released growth factors inhibit proliferation of primary keratinocytes in vitro

Publication date: Available online 18 September 2017
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Andreas Bayer, Mersedeh Tohidnezhad, Rouven Berndt, Sebastian Lippross, Peter Behrendt, Tim Klüter, Thomas Pufe, Holger Jahr, Jochen Cremer, Franziska Rademacher, Maren Simanski, Regine Gläser, Jürgen Harder
Autologous thrombocyte concentrate lysates as platelet-released growth factors (PRGF) or Vivostat Platelet Rich Fibrin (PRF^®) represent important tools in modern wound therapy, especially in the treatment of chronic, hard-to-heal or infected wounds.Nevertheless, underlying cellular and molecular mechanisms of the beneficial clinical effects of a local wound therapy with autologous thrombocyte concentrate lysates are poorly understood. Recently, we have demonstrated that PRGF induces antimicrobial peptides in primary keratinocytes and accelerates keratinocytes' differentiation. In the present study we analyzed the influence of PRGF on primary human keratinocytes' proliferation.Using the molecular proliferation marker Ki-67 we observed a concentration- and time dependent inhibition of Ki-67 gene expression in PRGF treated primary keratinocytes. These effects were independent from the EGFR- and the IL-6-R pathway. Inhibition of primary keratinocytes' proliferation by PRGF treatment was confirmed in colorimetric cell proliferation assays.Together, these data indicate that the clinically observed positive effects of autologous thrombocytes concentrates in the treatment of chronic, hard-to-heal wounds are not based on an increased keratinocytes proliferation.



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Debates in Allergy Medicine: Allergy skin testing cannot be replaced by molecular diagnosis in the near future

Percutaneous skin prick tests (SPT) have been considered the preferred method for confirming IgE-mediated sensitization. This reliable and minimally invasive technique correlates with in vivo challenges, has g...

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Debates in allergy medicine: Molecular allergy diagnosis with ISAC will replace screenings by skin prick test in the future

In today's clinical practice patients' skin is used as screening organ for diagnosing type 1 allergy. According to European guidelines skin prick testing with a panel of 18 allergen extracts is recommended, in...

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Phase I/II Study of Hypofractionated Intensity-Modulated Radiotherapy for Prostate Cancer including Simultaneously Integrated Boost

Publication date: Available online 18 September 2017
Source:Practical Radiation Oncology
Author(s): Michael G. Chang, Nitai Mukhopadhyay, Diane Holdford, Vicki Skinner, Siddharth Saraiya, Drew Moghanaki, Mitchell S. Anscher
PurposeTo evaluate the safety and efficacy of moderately hypofractionated radiotherapy with simultaneous integrated boost (HSIB) IMRT that includes coverage of the seminal vesicles (SV) and pelvic lymph nodes (LN).MethodsMen with localized prostate cancer were prospectively enrolled in a phase I/II trial to receive HSIB-IMRT to the prostate, ±SV, ±pelvic LN using a risk-based method. Low-risk (LR) patients received 69.6Gy to only the prostate in 29 fractions. Intermediate- (IR) and high-risk (HR) patients received 30 fractions with 72Gy to the prostate, 54Gy to the SV, and 50.4Gy to the pelvic LN when risk of LN involvement exceeded 15% by the Roach formula. IR and HR patients received androgen deprivation therapy. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated with patient and physician reported surveys.ResultsFifty-five men were enrolled and 49 had at least one year of follow up with 19.2% LR, 40.4% IR, and 40.4% HR disease. The median age was 69years and median follow-up time was 36.9months. Twenty-six patients received pelvic nodal HSIB-IMRT. At 2years, the cumulative incidence of physician-reported late grade 2+ GU and GI toxicity were 32.6%, and 18.4% respectively. At 2-years, only 10.2% grade 2+ GU toxicities and 2.0% grade 2+ GI toxicities remained unresolved. At last follow up, the prevalence of unresolved physician-reported late grade 2+ GU and GI toxicity was 4.1% and 0%. The median patient-reported AUA-IPSS score fell from 10 at baseline to 7.5 at 2years. The 3-year biochemical relapse-free survival rate for the cohort was 96%.ConclusionsHSIB-IMRT with risk-based nodal coverage results in excellent biochemical control. While the cumulative incidence of physician-reported GU toxicity was higher than anticipated, late GI and GU toxicity was relatively transient.



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Pilot Study on the Impact of F18-Labeled Thymidine PET/CT on Gross Tumor Volume Identification and Definition for Pancreatic Cancer

Publication date: Available online 18 September 2017
Source:Practical Radiation Oncology
Author(s): Jennifer L. Pretz, Michael A. Blake, Joseph H. Killoran, Harvey J. Mamon, Jennifer Y. Wo, Andrew X. Zhu, Theodore S. Hong
PurposeAccurate target definition for radiotherapy planning in localized pancreatic cancer is critical, particularly when using strategies that omit elective coverage. Standard imaging modalities such as CT, MRI, and endoscopic ultrasound have limited concordance with pathologic evaluation. Biologic imaging with [F18]-fluorodeoxyglucose (FDG)-PET can also be difficult to interpret, as increased activity is indicative of increased glucose metabolism, rather than cellular proliferation. F18 – labeled thymidine (FLT) is a proliferative marker which exploits the expression of pyrimidine-metabolizing enzymes. We evaluate the impact of FLT-PET on pancreatic target definition for radiation planning.Methods and MaterialsPatients with biopsy proven, newly diagnosed, untreated pancreatic adenocarcinoma were enrolled on an IRB-approved prospective study. Patients were injected with FLT and scanned 20–30minutes later. Two physicians (referred to as observer 1 and observer 2) independently contoured the gross tumor volume (GTV) and involved nodes on CT scan only, and then again with the assistance of co-registered FLT-PET. Conformality index (CI), the ratio of the volumes of intersection and union, was used as the metric for volume comparison (where CI=0 represented no overlap and CI=1 represented perfect overlap).ResultsNine patients were enrolled on this study. FLT-avidity was discerned in 8 of 9 patients. Average CT-GTV volume for observers 1 and 2 was 38.1cc and 26.5cc respectively. Average FLT-GTV volume for observers 1 and 2 was 39.1cc and 25.0cc respectively. For the 8 patients with FLT-avid tumors, addition of FLT data improved concordance of GTV definition between physicians in 6 of 8 tumors. Average CI for inter-observer CT-GTV was 0.325. Addition of FLT-PET information improved average CI to 0.400.ConclusionFLT-PET improves inter-observer concordance in GTV definition. Further studies will focus on verification of these findings, pathologic verification of the FLT-PET signal, and optimization of the FLT-PET signal threshold for auto-segmentation.



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Proton Craniospinal Irradiation During the Third Trimester of Pregnancy

Publication date: Available online 18 September 2017
Source:Practical Radiation Oncology
Author(s): Anusha Kalbasi, Maura Kirk, Boon-Keng Kevin Teo, Eric Diffenderfer, Xuanfeng Ding, James McDonough, Erin Murphy, Christine Hill-Kayser




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Enterprise stent in recanalizing non-acute atherosclerotic intracranial internal carotid artery occlusion

Publication date: November 2017
Source:Clinical Neurology and Neurosurgery, Volume 162
Author(s): Xiaofei Wang, Zhigang Wang, Yong Ji, Xuan Ding, Yizheng Zang, Chengwei Wang
ObjectiveTo investigate the safety and effectiveness of recanalization in non-acute occlusion of intracranial internal carotid arteries using the flexible Enterprise self-expanding stent.Patients and methodsFrom June 2014 to June 2016, 12 consecutive patients with non-acute occlusion of intracranial internal carotid arteries received endovascular recanalization with Enterprise stenting. All patients received medication for anti-platelet aggregation therapy before and after the operation. The perioperative complications and recanalization efficacy were evaluated with the modified Rankin scoring system and digital subtraction angiography (DSA) follow-up, respectively.ResultsEndovascular recanalization was successfully performed in 10 out of 12 patients with Enterprise stenting. Stent implantation following balloon dilatation failed in one patient because the lumen diameter was too small. Another recanalization failed because the guide wire could not pass through the occlusion. No perioperative mortality was observed. One case of acute thrombosis and one case of intraoperative carotid spasm occurred, but these were resolved with thrombolytic therapy by microcatheter exposure treatment and antispasmodic medications, respectively. DSA follow-up in seven patients revealed no re-occlusion. One stroke event occurred in the 10 patients who completed the follow-up. A meaningful improvement in the modified Rankin score during follow-up was suggested by Wilcoxon signed-rank test results.ConclusionThe Enterprise stent was shown to be safe and efficient in recanalizing non-acute atherosclerotic intracranial internal carotid artery occlusion. However, the long-term outcomes need to be further investigated.



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Influence of obesity on experimental periodontitis in rats: histopathological, histometric and immunohistochemical study

Abstract

Objectives

This study assessed the influence of obesity on the progression of ligature-induced periodontitis in rats.

Materials and methods

Forty-eight adult Wistar rats were randomly divided into two groups: the HL group (n = 24) was fed high-fat animal food to induce obesity, and the NL group (n = 24) was fed normolipidic animal food. Obesity was induced within a period of 120 days, and the induction of experimental periodontitis (EP) was subsequently performed for 30 days. The animals were euthanized after 7, 15, and 30 days, and the jaws were removed for histopathological, histometric, and immunohistochemical analyses. Tartrate-resistant acid phosphatase (TRAP), receptor activator of nuclear factor kappa beta ligand (RANKL), and osteoprotegerin (OPG) were analyzed via immunolabeling.

Results

Histological findings indicated that the inflammation was more extensive and lasted longer in the HL⁄EP; however, advanced destruction also occurred in the NL/EP. Greater bone loss was verified in the HL/EP group (2.28 ± 0.35) in the period of 7 days than in the NL/EP group (1.2 ± 0.29). High immunolabeling was identified in the HL/EP group in the initial periods for RANKL and TRAP, whereas the NL⁄EP group presented with moderate immunolabeling for both factors. The HL/EP and NL/EP groups showed low immunolabeling for OPG.

Conclusions

Obesity induced by a high-fat diet influenced alveolar bone metabolism when associated with experimental periodontitis and caused a more severe local inflammatory response and alveolar bone loss.

Clinical relevance

Obesity is related to greater alveolar bone loss and an accentuated local inflammatory response, which may be reflected in the clinical severity of periodontitis and dental loss.

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Trends in active surveillance for very low-risk prostate cancer: do guidelines influence modern practice?

Abstract

As recommended by current NCCN guidelines, patients with very low-risk prostate cancer may be treated with active surveillance (AS), but this may be underutilized. Using the National Cancer Database (NCDB), we identified men (2010–2013) with biopsy-proven, very low-risk prostate cancer that met AS criteria as suggested by Epstein (stage ≤ T1c; Gleason score (GS) ≤ 6; PSA < 10; and ≤2 [or <33%] positive biopsy cores) and aged ≤76, and low comorbidity index (Charlson-Deyo score = 0). For those patients meeting this criteria, we performed generalized estimation equation (GEE) method with incorporation of correlation in patients clustered within facility to determine the likelihood of undergoing AS. Among the 448 773 patients in the NCDB with low-risk prostate cancer, 40 839 patients met the inclusion criteria. AS was utilized in 5798 patients (14.2%), while within the very low-risk patients receiving treatment, up to 52.2% received radical prostatectomy. In univariate analyses, AS utilization was associated with older age, uninsured status (compared to private insurance), farther distance from facility, academic/research institutions and particularly in the New England region (all P < 0.01). After adjustments of other predictors in multivariate analysis, patients preferentially received AS if they were older (all OR's > 1 compared to younger groups), uninsured (vs. any insurance type, OR's > 1); or treated at academic/research center (OR > 1). The overall use of AS increased from 11.6% (2010) to 27.3% (2013). We found a low, but rising rate of AS in a nationally representative group of very low-risk prostate cancer patients. Disparities in the use of AS may be targeted to improve adherence to national guidelines.

This article demonstrates one of the largest series examining the role of active surveillance in patients with very low-risk prostate cancer. Our results in disparities and trends in recommendations for active surveillance reveal an important aspect of cancer care in the management of this disease entity.

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Etiology, diagnosis, and demographic analysis of maxillofacial trauma in elderly persons: A 10-year investigation

The aim of this study was to investigate etiologies and diagnoses of maxillofacial trauma in emergency services in Brazil over a period of 10 years. Additionally, associations among sex, age, accident location, and dependent variables were analyzed. Understanding the epidemiology of trauma and the physiology of aging is important in maintaining health and bettering service for the elderly population.

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Surgical treatment of synkinesiss between smiling and eyelid closure

Synkinetics movements are common among patients with incomplete recovery from facial palsy, with reported rates ranging from 9.1% to almost 100%.The authors propose the separation of the neural stimulus of the orbicularis oculi from that of the zygomatic muscular complex to treat eyelid closure/smiling synkinesiss. This technique, associated with an anastomosis between the masseteric nerve and a central branch of the facial nerve, as well as with the use of a cross-facial nerve graft, resolves most of the spasms of the midface musculature, leading to a more relaxed tone when the mimic muscle is at rest and enhancing muscle excursion during voluntary and spontaneous smiling.

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Tongue movement during articulation in magnetic resonance imaging: Findings in 20 healthy volunteers and a patient with anterior floor of the mouth squamous cell carcinoma

Combined ablative and reconstructive oral maxillofacial surgery involves a multitude of anatomical and functional structures for speech and swallowing. Although there are a few methods to objectively examine swallowing function, this is not true for speech. We describe the development of an objective visualization and measurement tool for magnetic resonance imaging (MRI) to evaluate speech and its first application in a patient.

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Autonomous Bone Reposition around Anatomical Landmark for Robot-Assisted Orthognathic Surgery

The purpose of this study was to develop a new method for enabling a robot to assist a surgeon in repositioning a bone segment to accurately transfer a preoperative virtual plan into the intraoperative phase in orthognathic surgery. We developed a robot system consisting of an arm with six degrees of freedom, a robot motion-controller, and a PC. An end-effector at the end of the robot arm transferred the movements of the robot arm to the patient's jawbone. The registration between the robot and CT image spaces was performed completely preoperatively, and the intraoperative registration could be finished using only position changes of the tracking tools at the robot end-effector and the patient's splint.

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Nipple sparing mastectomy and microsurgical breast reconstruction: an approach for success

Surgical management of breast cancer has evolved to allow for nipple sparing mastectomy (NSM) in oncologically eligible patients. Successful reconstruction requires complication-free execution and overall aesthetic harmony of the reconstructed and unaffected breasts. Few articles have described technical considerations and challenges encountered while performing NSM reconstruction with autologous tissue. Herein, we report our algorithm for success.

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LDT classification and therapeutic strategy of congenital body wall defects

We shared the repairing methods, which were used in our 5 cases of congenital malformations, at "The Third World Congress for Plastic Surgeons of Chinese Descent" in 2012. The title of this conference paper was "Clinical Experiences on Repairing of Huge Body Wall Defects".

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Intrafamilial phenotypic heterogeneity in a Taiwanese family with a MAPT p.R5H mutation: a case report and literature review

Frontotemporal degeneration (FTD) is a clinically and genetically heterogeneous neurodegenerative disorder characterized by deficits in executive function that frequently overlaps with parkinsonism and motor n...

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Bolstering Skin Grafts With a Surgical Scrub Brush

How does the dry, sterile surgical scrub brush compare with other options for the bolstering of skin grafts?
ePlasty, Open Access Journal of Plastic Surgery

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Evaluation of Nitrogen Concentration in Final Effluent of Advanced Nitrogen-Removal Onsite Wastewater Treatment Systems (OWTS)

Abstract

Advanced nitrogen (N)-removal onsite wastewater treatment systems (OWTS) are installed in coastal areas throughout the USA to reduce N loading to groundwater and marine waters. However, final effluent total nitrogen (TN) concentration from these systems is not always routinely monitored, making it difficult to determine the extent to which they contribute to N loads. We monitored the final effluent TN concentration of 42 advanced N-removal OWTS within the Greater Narragansett Bay Watershed, Rhode Island between March 2015 and August 2016. The compliance rate with the State of Rhode Island final effluent standard (TN ≤ 19 mg N/L) was 64.3, 70.6, and 75.0% for FAST, Advantex, and SeptiTech systems, respectively. The median (range) final effluent TN concentration (mg N/L) was 11.3 (0.1–41.6) for SeptiTech, 14.9 (0.6–61.6) for Advantex, and 17.1 (0.6–104.9) for FAST systems. Variation in final effluent TN concentration was not driven by temperature; TN concentrations plotted against effluent temperature values resulted in R ² values of 0.001 for FAST, 0.007 for Advantex, and 0.040 for SeptiTech systems. The median effluent TN concentration for all the systems in our study (16.7 mg N/L) was greater than reported for Barnstable County, MA systems (13.3 mg N/L), which are monitored quarterly. Depending on technology type, ammonium (NH₄⁺), nitrate (NO₃⁻), alkalinity, forward flow, biochemical oxygen demand (BOD), and effluent temperature best predicted effluent TN concentrations. Service providers made adjustments to seven underperforming systems, but TN was reduced to 19 mg N/L in only two of the seven systems. Advanced N-removal OWTS can reduce TN to meet regulations, and monitoring of these systems can enable service providers to proactively manage systems. However, improvement of performance may require recursive adjustments and long-term monitoring.

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Marital status as a predictor of survival in patients with human papilloma virus-positive oropharyngeal cancer

Determine whether marital status is a significant predictor of survival in human papillomavirus-positive oropharyngeal cancer.

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Comparison of radiation doses imparted during 128-multislice CT-scanners and cone beam computed tomography for intra- and perioperative cochlear implant assessment

To examine radiation-doses imparted during multislice (MSCT) and cone-beam computed-tomography (CBCT) for perioperative examination of cochlear-implant insertion.

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The folded postauricular flap: A novel approach to reconstruction of large full thickness defects of the conchal bowl

Extensive subtotal full-thickness auriculectomy defects pose a challenge for the reconstructive surgeon. The posterior island flap (PIF), based on the posterior auricular artery, has been described as a reconstructive option for auricular defects, with reports describing a "pull-through" or "revolving door" technique to reconstruct subtotal partial thickness and full thickness auricular defects. These techniques may result in posterior "pinning" of the auricle. This patient is an 87-year-old male who presented after Mohs excision of squamous cell carcinoma of the conchal bowl, which resulted in a 4x4cm subtotal auriculectomy defect.

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Influence of cerebrovascular disease on brain networks in prodromal and clinical Alzheimer’s disease

Abstract

Network-sensitive neuroimaging methods have been used to characterize large-scale brain network degeneration in Alzheimer's disease and its prodrome. However, few studies have investigated the combined effect of Alzheimer's disease and cerebrovascular disease on brain network degeneration. Our study sought to examine the intrinsic functional connectivity and structural covariance network changes in 235 prodromal and clinical Alzheimer's disease patients with and without cerebrovascular disease. We focused particularly on two higher-order cognitive networks—the default mode network and the executive control network. We found divergent functional connectivity and structural covariance patterns in Alzheimer's disease patients with and without cerebrovascular disease. Alzheimer's disease patients without cerebrovascular disease, but not Alzheimer's disease patients with cerebrovascular disease, showed reductions in posterior default mode network functional connectivity. By comparison, while both groups exhibited parietal reductions in executive control network functional connectivity, only Alzheimer's disease patients with cerebrovascular disease showed increases in frontal executive control network connectivity. Importantly, these distinct executive control network changes were recapitulated in prodromal Alzheimer's disease patients with and without cerebrovascular disease. Across Alzheimer's disease patients with and without cerebrovascular disease, higher default mode network functional connectivity z-scores correlated with greater hippocampal volumes while higher executive control network functional connectivity z-scores correlated with greater white matter changes. In parallel, only Alzheimer's disease patients without cerebrovascular disease showed increased default mode network structural covariance, while only Alzheimer's disease patients with cerebrovascular disease showed increased executive control network structural covariance compared to controls. Our findings demonstrate the differential neural network structural and functional changes in Alzheimer's disease with and without cerebrovascular disease, suggesting that the underlying pathology of Alzheimer's disease patients with cerebrovascular disease might differ from those without cerebrovascular disease and reflect a combination of more severe cerebrovascular disease and less severe Alzheimer's disease network degeneration phenotype.

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Cancers, Vol. 9, Pages 126: The Impact of DNA Repair Pathways in Cancer Biology and Therapy

Cancers, Vol. 9, Pages 126: The Impact of DNA Repair Pathways in Cancer Biology and Therapy

Cancers doi: 10.3390/cancers9090126

Authors: Anatoly Nikolaev Eddy Yang

Genomic instability is one of the key hallmarks of cancer progression [1].[...]

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Treatment outcomes of sialendoscopy for submandibular gland sialolithiasis: The minor axis of the sialolith is a regulative factor for the removal of sialoliths in the hilum of the submandibular gland using sialendoscopy alone

To assess the general guidelines for the removal of sialoliths for submandibular gland sialolithiasis using sialendoscopy alone.

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Personal use of hair dyes and risk of leukemia: a systematic literature review and meta-analysis

Abstract

The objective of this study was to examine the association between personal use of hair dyes and the risk of leukemia. We conducted a systematic literature review of epidemiology studies reporting leukemia-specific cancer risks among hair dye users, and estimated the meta-relative risk (meta-RR) and corresponding 95% confidence interval (95% CI) of leukemia, comparing hair dye users to nonusers. When data from all 20 studies that met the inclusion criteria were combined, ever use of hair dye was associated with a nonstatistically significant increased risk of leukemia, meta-RR = 1.09 (95% CI: 0.97–1.22). When restricted to studies that adjusted for smoking, ever use of hair dye was not associated with leukemia, meta-RR = 0.99 (95% CI: 0.76–1.29). A statistically significant increased risk of leukemia was associated with permanent hair dye use (meta-RR = 1.19 [95% CI: 1.07–1.33]), dark hair dye use (meta-RR = 1.29 [95% CI: 1.11–1.50]), hair dye use among males (meta-RR = 1.42 [95% CI: 1.01–2.00]), hair dye use pre-1980 (meta-RR = 1.49 [95% CI: 1.21–1.83]), and hair dye use for ≥15 years (meta-RR = 1.35 [95% CI: 1.13–1.62]). Overall, findings suggest that ever use of hair dye is not a significant risk factor for leukemia. Certain hair dye use characteristics were associated with a statistically significant increased risk, but further research is required to determine whether these associations truly reflect a risk of leukemia due to methodological limitations in the underlying studies.

The purpose of this study was to synthesize and examine the evidence on the relative risk of leukemia among hair dye users under various exposure scenarios. Findings suggest that personal hair dye use is not a significant risk factor for leukemia when data from all studies were combined. Upon stratification, permanent hair dye use, dark hair dye use, hair dye use pre-1980, hair dye use among males, and hair dye use for ≥15 years were associated with a statistically significant increased risk of leukemia. Further research is required to determine whether these associations truly reflect a risk of leukemia due to methodological limitations in the underlying studies.

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Relationship of tumor PD-L1 (CD274) expression with lower mortality in lung high-grade neuroendocrine tumor

Abstract

Programmed death-ligand 1 (PD-L1) promotes immunosuppression by binding to PD-1 on T lymphocytes. Although tumor PD-L1 expression is a potential predictive marker of clinical response to anti-PD-1/PD-L1 therapy, little is known about its association with clinicopathological features, including prognosis, in high-grade neuroendocrine tumors (HGNETs), including small-cell lung carcinoma (SCLC) and large-cell neuroendocrine carcinoma (LCNEC), of the lung. We immunohistochemically examined the membranous of expression of PD-L1 in 115 consecutive surgical cases of lung HGNET (74 SCLC cases and 41 LCNEC cases). We examined the prognostic association of tumor PD-L1 positivity using the log-rank test as well as Cox proportional hazards regression models to calculate the hazard ratio (HR) for mortality. Programmed death-ligand 1 immunostaining (at least 5% tumor cells) was observed in 25 (21%) of the 115 HGNET cases. In a univariable analysis, PD-L1 positivity was associated with lower lung cancer-specific (univariable HR = 0.23; 95% confidence interval [CI] = 0.056–0.64; P = 0.0028) and overall (univariable HR = 0.28; 95% CI = 0.11–0.60; P = 0.0005) mortality. Additionally, in a multivariable analysis, PD-L1 positivity was independently associated with lower lung cancer-specific (multivariable HR = 0.24; 95% CI = 0.058–0.67; P = 0.0039) and overall (multivariable HR = 0.29; 95% CI = 0.11–0.61; P = 0.0006) mortality. Our study demonstrated the prevalence of PD-L1 positivity in lung HGNET cases, and the independent association of tumor PD-L1 positivity with lower mortality in lung HGNET cases. Further studies are needed to confirm our findings.

High-grade neuroendocrine tumor (HGNET) (small cell lung carcinoma and large cell neuroendocrine carcinoma) is the most aggressive histological subtype of lung cancer, and immunotherapies, including anti-PD-1/Programmed death-ligand 1 (PD-L1) therapy, are emerging and promising. The prevalence of PD-L1 positivity in lung HGNET is shown. PD-L1 positivity is associated with lower mortality in lung HGNET.

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Clinical predictive factors of long-term survival after curative resection of pancreatic cancer: a retrospective study

Abstract

Pancreatic ductal adenocarcinoma (PDAC) continues to have the poorest prognosis of all gastrointestinal malignancies, even after the tumor has been completely resected. However, only a proportion of patients achieve 5-year survival after resection. The factors predictive of achieving 5-year survival remain unclear. The aim of this study was to investigate the pre- and postoperative clinicopathological characteristics of PDAC patients with a >5-year survival after curative resection. We retrospectively reviewed patients who underwent pancreatectomy for PDAC between January 1995 and December 2011. Logistic regression analysis was performed to determine the predictive factors for 5-year survival. One hundred and fifty-one patients were enrolled, including 38 patients with 5-year survival (actual 5-year survival rate, 25.2%). The independent preoperative factors predictive of achieving 5-year survival included serum albumin levels (odds ratio [OR]: 5.06, 95.0% confidence interval [CI]: 1.49–17.19; P = 0.009) and neoadjuvant chemoradiotherapy (OR: 3.02, 95.0% CI: 1.00–9.08; P = 0.049). Venous infiltration (OR: 2.99, 95.0% CI: 1.09–8.25; P = 0.034), liver recurrence (OR: 0.17, 95.0% CI: 0.04–0.69; P = 0.013), and perioperative portal vein infusion chemotherapy (OR: 3.06, 95.0% CI: 1.09–8.25; P = 0.028) were found to be independent postoperative predictive factors for achieving 5-year survival. Serum albumin levels could be a biomarker for predicting the prognosis of PDAC patients after curative resection. Liver recurrence and perioperative portal vein infusion chemotherapy were independent postoperative factors, suggesting that perioperative portal vein infusion chemotherapy could be promising for improving the survival rate of PDAC patients after curative resection.

Relationship between neoadjuvant chemoradiotherapy (NACRT) and (A) postoperative disease-free survival (DFS) and (B) postoperative overall survival (OS) and relationship between perioperative adjuvant portal vein infusion (PVI) chemotherapy and (C) postoperative DFS and (D) postoperative OS.

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Erratum to “Craniofacial and extracraniofacial anomalies in craniofacial macrosomia: A multicenter study of 755 patients” [J Craniomaxillofac Surg vol. 45(8) (August 2017), 1302–1310]

The publisher regrets an error in the above title. The correct title for this article is as follows: Craniofacial and extracraniofacial anomalies in craniofacial microsomia: A multicenter study of 755 patients.

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Evaluation of stopping-power prediction by dual- and single-energy computed tomography in an anthropomorphic ground-truth phantom

Publication date: Available online 17 September 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Patrick Wohlfahrt, Christian Möhler, Christian Richter, Steffen Greilich
PurposeTo determine the accuracy of particle range prediction for proton and heavier ion radiotherapy based on dual-energy computed tomography (DECT) in a realistic inhomogeneous geometry and to compare it to the state-of-the-art clinical approach.Methods and MaterialsA 3D ground-truth map of stopping-power ratios (SPRs) was created for an anthropomorphic head phantom by assigning measured SPR values to segmented structures in a high-resolution CT scan. This reference map was validated independently comparing proton transmission measurements to Monte Carlo transport simulations.Two DECT-based methods for direct SPR prediction via the Bethe formula (DirectSPR) and two established approaches based on Hounsfield look-up tables (HLUTs) were chosen for evaluation. SPR predictions from the four investigated methods were compared to the reference, employing material-specific voxel statistics and 2D gamma analysis. Furthermore, range deviations were analyzed in an exemplary proton treatment plan.ResultsThe established reference SPR map was successfully validated for the discrimination of SPR and range differences well below 0.3% and 1 mm respectively, even in complex inhomogeneous settings. For the phantom materials of larger volume (mainly brain, soft tissue), the investigated methods were overall able to predict SPR within 1% median deviation. The DirectSPR methods generally performed better than the HLUT approaches. For smaller phantom parts (such as cortical bone, air cavities), all methods were affected by image smoothing, leading to considerable SPR under- or overestimation. This effect was superimposed on the general SPR prediction accuracy in the exemplary treatment plan.ConclusionsDirectSPR predictions proved to be more robust with high accuracy in particular for larger volumes. In contrast, HLUT approaches exhibited a fortuitous component. The evaluation of accuracy in a realistic phantom with validated ground-truth SPR represents a crucial step towards possible clinical application of DECT-based SPR prediction methods.



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A Population-Based Study of Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy for Vestibular Schwannoma: Long-Term Outcomes and Toxicities

Publication date: Available online 17 September 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Andrea Lo, Gareth Ayre, Roy Ma, Fred Hsu, Ryojo Akagami, Michael McKenzie, Boris Valev, Ermias Gete, Isabelle Vallieres, Alan Nichol
PurposeThe purpose of the study is to examine long-term local control of vestibular schwannoma (VS) and side effects in patients treated with stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) in XX-region.Methods and MaterialsFrom August 1998 to May 2009, 207 patients were treated with radiation therapy (RT) at XX-center; 136 (66%) received SRS and 71 (34%) received SRT. Dose prescriptions were 50Gy/25 for SRT and 12Gy/1 for SRS. Our multidisciplinary provincial neuro-stereotactic conference recommended SRT for tumors >3cm and for patients with serviceable hearing (Gardner-Robertson Class I & II).ResultsMedian follow-up was 7.7 years to the last MRI and 6.4 years to the last clinical assessment. Local control for SRS vs. SRT was 94% vs. 87% at 5 years and 90% vs. 85% at 10 years (P=0.2). Five- and 10-year actuarial rates of RT-induced trigeminal nerve dysfunction (TND) were 25% and 25% after SRS, compared to 7% and 12% after SRT (P=0.01). Five- and 10-year actuarial rates of RT-induced facial nerve dysfunction were 15% and 15% after SRS, vs. 13% and 15% after SRT (P=0.93). In the 49 patients with serviceable hearing at baseline who were treated with SRT, hearing preservation was 55% at 3 years, 37% at 5 years, and 29% at 7 years. In multivariable analysis, better pre-treatment ipsilateral pure tone average was significantly associated with hearing preservation (HR 1.03; 95% CI 1.00-1.07; P=0.04).ConclusionsBoth SRS and SRT provided excellent long-term local control of VS. SRS was associated with higher rates of trigeminal nerve dysfunction. Even with a fractionated course, hearing preservation declined steadily with long-term audiometric follow-up.



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The Economic Burden of Urinary Tract Infection and Pressure Ulceration in Acute Traumatic Spinal Cord Injury Admissions: Evidence for Comparative Economics and Decision Analytics from a Matched Case-Control Study

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


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Mechanisms Influencing Older Adolescents’ Bedtimes during Videogaming: The Roles of Game Difficulty and Flow

Publication date: Available online 18 September 2017
Source:Sleep Medicine
Author(s): Lisa J. Smith, Daniel L. King, Cele Richardson, Brandy M. Roane, Michael Gradisar
A relationship between evening technology use and sleep has been established, and models suggest various mechanisms to explain this relationship. Recent updates to these models also suggest the influence of individual difference factors, such that the relationship between technology and sleep varies between young people. Flow is an experience of immersion and time distortion that could vary between adolescents when using technology. The aim of the present study was to investigate the effects of flow on the self-selected bedtimes of adolescents when videogaming. 17 older adolescent, experienced videogamers (age=15.9±0.83 yrs) played a new videogame on two school-night evenings in a sleep laboratory. Game difficulty was set to 'hard' one evening (flow condition), and the other set to 'easy' (disrupted flow). Measures of trait and state flow were taken, along with heart rate during videogaming, and bedtime measured objectively with real-time cameras. An interaction effect for heart rate indicated an elevated heart rate in the easy condition after 150-min of gaming (p<.02). No significant differences were found in bedtimes between the easy and hard conditions (p=.77). Adolescents high on trait flow played for longer and selected significantly later bedtimes than their low trait flow peers, but only for the hard (flow) condition (12:22 A.M vs 10:53 P.M, p=.004). Likewise, adolescents with high state flow went to bed significantly later than those low on state flow (12:24 PM vs 10:52 PM, p=.001), again, only in the hard condition. These findings suggest that individual and situational characteristics may amplify the effects of technology use on the 'sleep' of adolescents, and provides support for the displacement of bedtime hypothesis.



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Decreases in self-reported sleep duration among U.S. adolescents 2009-2015 and links to new media screen time

Publication date: Available online 18 September 2017
Source:Sleep Medicine
Author(s): Jean M. Twenge, Zlatan Krizan, Garrett Hisler
Study ObjectivesInsufficient sleep among adolescents carries significant health risks, making it important to determine social factors that change sleep duration. We sought to determine whether the self-reported sleep duration of U.S. adolescents changed between 2009 and 2015 and to examine whether new media screen time (relative to other factors) might be responsible for changes in sleep.MethodsWe drew from yearly, nationally representative surveys of sleep duration and time use among adolescents conducted since 1991 (Monitoring the Future) and 2007 (Youth Risk Behavior Surveillance System of the Centers for Disease Control; total N = 369,595).ResultsCompared to 2009, adolescents in 2015 were 16% to 17% more likely to report sleeping less than 7 hours a night on most nights, with an increase in short sleep duration after 2011-2013. New media screen time (electronic device use, social media, and reading news online) increased over this time period and was associated with increased odds of short sleep duration, with a clear exposure-response relationship for electronic devices after 2 or more hours a day of use. Other activities linked to short sleep duration, such as homework time, working for pay, and TV watching, were relatively stable or decreased over this time period, making it unlikely they caused the sudden increase in short sleep duration.ConclusionsIncreased new media screen time may be involved in the recent increases (from 35% to 41% and from 37% to 43%) in short sleep among adolescents. Public health interventions should consider electronic device use as a target of intervention to improve adolescent health.



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Overweight and obesity adds to behavioral problems in children with sleep disordered breathing

Publication date: Available online 17 September 2017
Source:Sleep Medicine
Author(s): Sarah N. Biggs, Knarik Tamanyan, Lisa M. Walter, Aidan J. Weichard, Margot J. Davey, Gillian M. Nixon, Rosemary SC. Horne
ObjectiveThis study aimed to determine whether overweight and obesity increased the detrimental effects of pediatric sleep disordered breathing (SDB) on cognition, behavior, mood and quality of life.MethodsChildren and adolescents (8-16y) with clinically diagnosed SDB were categorized into two groups: healthy weight (BMI z-score <1.04, N=11) and overweight/obese (BMI z-score ≥ 1.04, N=10). Age-matched healthy weight, non-snoring Controls (N=25) were recruited from the community. All participants underwent overnight laboratory polysomnography (PSG). Cognitive, behavioral, and quality of life assessments were conducted in the home following the PSG. ANCOVA assessed group differences in cognitive outcomes, controlling for socio-economic status. Kruskal-Wallis ANOVA determined group differences in behavior and quality of life. Where group differences were found, hierarchical linear regressions determined the effect of weight on outcomes.ResultsChildren with SDB had significantly poorer behavior and quality of life than Controls, with overweight/obese children with SDB having the greatest dysfunction. No group differences were found in cognitive outcomes. The obstructive apnea hypopnea index (OAHI) was a significant predictor of withdrawn behavior (R²=0.42), inattention (R²=0.43) and aggressive behavior (R²=0.30). BMI z-score added significantly to aggressive behavior (R²=0.22) and was an independent predictor of externalizing behaviors (R²=0.26). OAHI predicted school functioning (R²=0.30). BMI z-score predicted social functioning (R²=0.38) and significantly added to physical functioning over OAHI (OAHI R²=30; BMI z-score R²=0.37).ConclusionsOverweight and obesity comorbid with SDB increases the risk of externalizing behaviors such as aggression, but does not affect other behavioral associates of SDB such as inattention and school functioning.



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Serum lipid profile, sleep-disordered breathing and blood pressure in the elderly: a 10-year follow-up of the PROOF-SYNAPSE cohort

Publication date: Available online 17 September 2017
Source:Sleep Medicine
Author(s): Denis Monneret, Jean-Claude Barthélémy, David Hupin, Delphine Maudoux, Sébastien Celle, Emilia Sforza, Frédéric Roche
ObjectivesDyslipidemia, sleep-disordered breathing (SDB) and hypertension are comorbid factors evidenced in adults, but poorly studied in old people. This study aimed to examine the long-term evolution of the serum lipid profile, and its relationships with SDB and blood pressure (BP) in the elderly.MethodsA 10-year follow-up of the prospective Prognostic Indicator of Cardiovascular and Cerebrovascular Events (PROOF) and the Autonomic Nervous System Activity, Aging and Sleep Apnea/Hypopnea (SYNAPSE) cohort, which initially included 1011 elderly subjects from the general population, and who were untreated by continuous positive airway pressure (CPAP). Serum lipid profile, respiratory polygraphy for SDB and ambulatory blood pressure monitoring were performed.ResultsA total of 266 subjects (male/female 150/116; age 66.2±0.8 years) were reassessed after 9.6±0.7 years (age 75.8±1.2 years). The prevalence of high-risk dyslipidemia decreased from 61.3 to 44.4%, and hypertension from 57.9 to 27.4%. The nocturnal oxygen desaturation index increased (mean +2.3±6.7 events/hour; p<0.001), while the mean SaO2 and minimal SaO2 decreased. These variations (Δ) of oxygen desaturation worsened whether or not elderly subjects took anti-hypertensive and lipid-lowering treatments, and were not associated with serum lipid variations. The decrease in diurnal diastolic BP was independently associated with aging, and with the lowering of the waist/hip ratio (ΔW/H) and low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio, while the decrease in diurnal systolic BP only depended on aging and ΔW/H.ConclusionsThe results suggested that the observed worsening of nocturnal oxygen desaturation after 10 years in the elderly was independent of the change in circulating lipids, and not influenced by lipid-lowering treatments. However, the variation in blood pressure remained associated with aging, waist/hip and LDL-C/HDL-C ratios.Trial registryNCT00759304 and NCT00766584 at clinicaltrials.gov.



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Vocal Aspects of Brazilian Evangelical Pastors

Investigate the vocal and laryngopharyngeal symptoms, vocal quality, Voice Activity and Participation Profile (VAPP), and vocal acoustic and auditory-perceptual characteristics from evangelical pastors comparing with the same aspects of nonprofessional voice men.

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Office-Based Procedures for the Diagnosis and Treatment of Laryngeal Pathology

Since the development of distal chip endoscopes with a working channel, diagnostic and therapeutic possibilities in the outpatient clinic in the management of laryngeal pathology have increased. Which of these office-based procedures are currently available, and their clinical indications and possible advantages, remains unclear.

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Establishment and Analysis of False Vocal Folds Hypertrophy Model in Excised Canine Larynges

This study aimed to investigate the role of false vocal folds (FVFs) medialization in phonation and the acoustic impact of ventricular hypertrophy by establishing an FVF hypertrophy model.

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In silico modeling of immunotherapy and stroma-targeting therapies in human colorectal cancer

Despite the fact that the local immunological microenvironment shapes the prognosis of colorectal cancer, immunotherapy has shown no benefit for the vast majority of colorectal cancer patients. A better understanding of the complex immunological interplay within the microenvironment is required. In this study, we utilized wet lab migration experiments and quantitative histological data of human colorectal cancer tissue samples (n=20) including tumor cells, lymphocytes, stroma and necrosis to generate a multi-agent spatial model. The resulting data accurately reflected a wide range of situations of successful and failed immune surveillance. Validation of simulated tissue outcomes on an independent set of human colorectal cancer specimens (n=37) revealed the model recapitulated the spatial layout typically found in human tumors. Stroma slowed down tumor growth in a lymphocyte-deprived environment but promoted immune escape in a lymphocyte-enriched environment. A subgroup of tumors with less stroma and high numbers of immune cells showed high rates of tumor control. These findings were validated using data from colorectal cancer patients (n=261). Low-density stroma and high lymphocyte levels showed increased overall survival (hazard ratio 0.322, p=0.0219) as compared with high stroma and low lymphocyte levels. To guide immunotherapy in colorectal cancer, simulation of immunotherapy in pre-established tumors showed that a complex landscape with optimal stroma permeabilization and immune cell activation is able to markedly increase therapy response in silico. These results can help guide the rational design of complex therapeutic interventions which target the colorectal cancer microenvironment.

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MCT1 inhibitor AZD3965 increases mitochondrial metabolism, facilitating combination therapy and non-invasive magnetic resonance spectroscopy

Monocarboxylate transporters (MCT) modulate tumor cell metabolism and offer promising therapeutic targets for cancer treatment. Understanding the impact of MCT blockade on tumor cell metabolism may help develop combination strategies or identify pharmacodynamic biomarkers to support the clinical development of MCT inhibitors now in clinical trials. In this study, we assessed the impact of the MCT1 inhibitor AZD3965 on cancer cell metabolism in vitro and in vivo. Exposing human lymphoma and colon carcinoma cells to AZD3965 increased MCT4-dependent accumulation of intracellular lactate, inhibiting monocarboxylate influx and efflux. AZD3965 also increased the levels of TCA cycle-related metabolites and 13C-glucose mitochondrial metabolism, enhancing oxidative pyruvate dehydrogenase and anaplerotic pyruvate carboxylase fluxes. Increased mitochondrial metabolism was necessary to maintain cell survival under drug stress. These effects were counteracted by co-administration of the mitochondrial complex I inhibitor metformin and the mitochondrial pyruvate carrier inhibitor UK5099. Improved bioenergetics were confirmed in vivo after dosing AZD3965 in mouse xenograft models of human lymphoma. Our results reveal new metabolic consequences of MCT1 inhibition that might be exploited for therapeutic and pharmacodynamic purposes. 

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Upregulation of Cystathionine-{beta}-synthase in Colonic Epithelia Reprograms Metabolism and Promotes Carcinogenesis

The transsulfuration enzyme cystathionine-β-synthase (CBS) and its product hydrogen sulfide (H2S) are aberrantly upregulated in colorectal cancers, where they contribute to tumor growth and progression by both autocrine and paracrine mechanisms. However, it is unknown whether the CBS/H2S axis plays a role in colorectal carcinogenesis. Here, we report upregulation of CBS in human biopsies of precancerous adenomatous polyps and show that forced upregulation of CBS in an adenoma-like colonic epithelial cell line is sufficient to induce metabolic and gene expression profiles characteristic of colorectal cancer cells. Differentially expressed metabolites (65 increased and 20 decreased) clustered into the glycolytic pathway, nucleotide sugars, intermediates of the pentose phosphate pathway, and lipogenesis, including primarily phospholipids, sphingolipids, and bile acids. CBS upregulation induced broad changes in the NCM356 cell transcriptome with over 350 differentially expressed genes. These genes overlapped significantly with gene sets related to glycolysis, hypoxia, and a colon cancer cell phenotype, including genes regulated by NF-kappaB, KRAS, p53, and Wnt signaling, genes downregulated after E-cadherin knockdown, and genes related to increased extracellular matrix, cell adhesion, and epithelial-to-mesenchymal transition. The CBS-induced switch to an anabolic metabolism was associated with increased NCM356 cell bioenergetics, proliferation, invasion through Matrigel, resistance to anoikis, and CBS-dependent tumorigenesis in immune compromised mice. Genetic ablation of CBS in CBS heterozygous mice (CBS+/-) reduced the number of mutagen-induced aberrant colonic crypt foci. Taken together, these results establish that activation of the CBS/H2S axis promotes colon carcinogenesis.

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MetaLnc9 facilitates lung cancer metastasis via a PGK1-activated AKT/mTOR pathway

Long non-coding RNAs participate in carcinogenesis and tumor progression in lung cancer. Here we report the identification of a lncRNA signature associated with metastasis of non-small cell lung cancer (NSCLC). In particular, elevated expression of LINC00963 (MetaLnc9) in human NSCLC specimens correlated with poor prognosis, promoted migration and invasion of NSCLC cells in vitro, and enhanced lung metastasis formation in vivo. Mechanistic investigations showed that MetaLnc9 interacted with the glycolytic kinase PGK1 and prevented its ubiquitination in NSCLC cells, leading to activation of the oncogenic AKT/mTOR signaling pathway. MetaLnc9 also interacted with P54nrb/NonO (NONO) to help mediate the activity of CRTC, a co-activator for the transcription factor CREB, reinforcing a positive feedback loop for metastasis. Taken together, our results establish MetaLnc9 as a driver of metastasis and a candidate therapeutic target for treating advanced NSCLC.

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Mitosis-mediated intravasation in a tissue-engineered tumor-microvessel platform

Intravasation involves the migration of tumor cells across the local endothelium and escape into vessel flow. While tumor cell invasiveness has been correlated to increased intravasation, the details of transendothelial migration and detachment into circulation are still unclear. Here we analyzed the intravasation of invasive human breast cancer cells within a tissue-engineered microvessel model of the tumor microenvironment. Using live-cell fluorescence microscopy, we captured 2,330 hours of tumor cell interactions with functional microvessels and provide evidence for a mitosis-mediated mechanism where tumor cells located along the vessel periphery are able to disrupt the vessel endothelium through cell division and detach into circulation. This model provides a framework for understanding the physical and biological parameters of the tumor microenvironment that mediate intravasation of tumor cells across an intact endothelium.

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Anti-CD137 suppresses tumor growth by blocking reverse signaling by CD137 ligand

CD137 (4-1BB) is a T cell co-stimulatory molecule and agonstic CD137 antibodies are currently being evaluated in clinic as cancer immunotherapy. Recently, it was found that CD137-/- mice or mice injected with agonistic anti-CD137 antibodies exhibit heightened antitumor responses, contrary to expectations based on other knowledge of CD137 function. Here we report findings related to reverse signaling by CD137 ligand (CD137L) in antigen-presenting dendritic cells (DC) in tumors that address these paradoxical results. Specifically, CD137L suppressed intratumoral differentiation of IL-12-producing CD103+ DC and type 1 tumor-associated macrophages (TAM). Differentiation of these cell types is important because they are required to generate IFN-γ-producing CD8+ cytotoxic T lymphocytes (Tc1). Notably, CD137L blockade increased levels of IL-12 and IFN-γ which promoted intratumoral differentiation of IFN-γ-producing Tc1, IL-12-producing CD103+ DC, and type 1 TAM within tumors. Our results offer an explanation for the paradoxical effects of CD137 blockade, based on differential immunomodulatory effects of CD137 signaling and reverse signaling in T cells and DC, respectively. Further, they show how CD137L blockade can seed a forward feedback loop for activation of CD103+ DC/type 1 TAM and Tc1 that can create a self-perpetuating cycle of highly effective immunosurveillance.

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Genomic activation of PPARG reveals a candidate therapeutic axis in bladder cancer

The PPARG gene encoding the nuclear receptor PPAR-gamma is activated in bladder cancer, either directly by gene amplification or mutation, or indirectly by mutation of the RXRA gene which encodes the heterodimeric partner of PPAR-gamma. Here we show that activating alterations of PPARG or RXRA lead to a specific gene expression signature in bladder cancers. Reducing PPARG activity, whether by pharmacologic inhibition or genetic ablation, inhibited proliferation of PPARG-activated bladder cancer cells. Our results offer a preclinical proof of concept for PPARG as a candidate therapeutic target in bladder cancer.

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Caveolae-Mediated Endocytosis is Critical for Albumin Cellular Uptake and Response to Albumin-Bound Chemotherapy

Nab-paclitaxel, a nanoparticle conjugate of paclitaxel to human albumin, exhibits efficacy in pancreatic cancer, non-small cell lung cancer and breast cancer. However, there is a lack of predictive biomarkers to identify patients who might benefit most from its administration. This study addresses this gap in knowledge by identifying that caveolin-1 (Cav-1) is a candidate mechanism-based biomarker. Caveolae are small membrane invaginations important for trans-endothelial albumin uptake. Cav-1, the principal structural component of caveolae, is overexpressed in the cancers noted above which respond to nab-paclitaxel. Thus, we hypothesized that Cav-1 may be critical for albumin uptake in tumors and perhaps determine their response to this drug. Cav-1 protein levels correlated positively with nab-paclitaxel sensitivity. RNAi-mediated attenuation of Cav-1 expression reduced uptake of albumin and nab-paclitaxel in cancer cells and rendered them resistant to nab-paclitaxel-induced apoptosis. Conversely, Cav-1 overexpression enhanced sensitivity to nab-paclitaxel. Selection for cellular resistance to nab-paclitaxel in cell culture correlated with a loss of Cav-1 expression. In mouse xenograft models, cancer cells where Cav-1 was attenuated exhibited resistance to the antitumor effects of nab-paclitaxel therapy. Overall, our findings suggest Cav-1 as a predictive biomarker for the response to nab-paclitaxel and other albumin-based cancer therapeutic drugs.

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Adaptation to TKI treatment reactivates ERK signaling in tyrosine kinase-driven leukemias and other malignancies

FLT3 tyrosine kinase inhibitors (TKI) have been tested extensively to limited benefit in acute myeloid leukemia. We hypothesized that FLT3/ITD leukemia cells exhibit mechanisms of intrinsic signaling adaptation to TKI treatment that are associated with an incomplete response. Here we identified reactivation of ERK signaling within hours following treatment of FLT3/ITD AML cells with selective inhibitors of FLT3. When these cells were treated with inhibitors of both FLT3 and MEK in combination, ERK reactivation was abrogated and anti-leukemia effects were more pronounced compared to either drug alone. ERK reactivation was also observed following inhibition of other tyrosine kinase-driven cancer cells, including EGFR-mutant lung cancer, HER2-amplified breast cancer and BCR-ABL leukemia. These studies reveal an adaptive feedback mechanism in tyrosine kinase-driven cancers associated with reactivation of ERK signaling in response to targeted inhibition.

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TET-mediated sequestration of miR-26 drives EZH2 expression and gastric carcinogenesis

DNA demethylases of the TET family function as tumor suppressors in various human cancers but their pathogenic contributions and mechanisms of action in gastric carcinogenesis and progression remain unclear. Here we report that TET is transcriptionally upregulated in gastric cancer (GC) where it correlates with poor prognosis. Mechanistic investigations revealed that TET facilitated gastric carcinogenesis through a non-coding function of the 3'UTR which interacted with miR-26. This interaction resulted in sequestration of miR-26 from its target EZH2, which released the suppression on EZH2, and thereby leaded to EZH2 overexpression in gastric cancer. Our findings uncover a novel non-coding function for TET family proteins in facilitating gastric carcinogenesis.

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Salivary duct cyst of accessory parotid gland in contact with the temporomandibular joint

Publication date: Available online 17 September 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Atsushi-Doksa Lee, Takashi Mima, Yasunari Morimoto, Yoko Takigawa
A 60-year-old woman presented with a painless swelling in the right preauricular region. Physical examination revealed a soft, non-tender, oval-shaped lump in this location. Computed tomography scanning indicated an anterolateral cystic lesion that was attached to the condyle of the mandible and to the accessory parotid gland. Differential diagnoses included ganglion cyst, synovial cyst of the TMJ, and accessory parotid gland cyst. Surgical removal of the cyst was performed under general anesthesia. The specimen was 18 × 20 × 18 mm in size; it contained fluid that was clear, slightly yellow, and amylase-positive. Hematoxylin and eosin staining revealed that a bilayer cuboidal epithelium lined the cyst wall. Immunohistochemical analyses of the cyst wall showed strong expression of cytokeratin and weak expression of vimentin. The final diagnosis was a salivary duct cyst. The postoperative course was uneventful except for a transient facial motor paresis.



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Texture and art with deep neural networks

Publication date: October 2017
Source:Current Opinion in Neurobiology, Volume 46
Author(s): Leon A .Gatys, Alexander S Ecker, Matthias Bethge
Although the study of biological vision and computer vision attempt to understand powerful visual information processing from different angles, they have a long history of informing each other. Recent advances in texture synthesis that were motivated by visual neuroscience have led to a substantial advance in image synthesis and manipulation in computer vision using convolutional neural networks (CNNs). Here, we review these recent advances and discuss how they can in turn inspire new research in visual perception and computational neuroscience.



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Effects of Lexical Variables on Silent Reading Comprehension in Individuals With Aphasia: Evidence From Eye Tracking

Purpose

Previous eye-tracking research has suggested that individuals with aphasia (IWA) do not assign syntactic structure on their first pass through a sentence during silent reading comprehension. The purpose of the present study was to investigate the time course with which lexical variables affect silent reading comprehension in IWA. Three lexical variables were investigated: word frequency, word class, and word length.

Methods

IWA and control participants without brain damage participated in the experiment. Participants read sentences while a camera tracked their eye movements.

Results

IWA showed effects of word class, word length, and word frequency that were similar to or greater than those observed in controls.

Conclusions

IWA showed sensitivity to lexical variables on the first pass through the sentence. The results are consistent with the view that IWA focus on lexical access on their first pass through a sentence and then work to build syntactic structure on subsequent passes. In addition, IWA showed very long rereading times and low skipping rates overall, which may contribute to some of the group differences in reading comprehension.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/60/9/2589/2653404/Effects-of-Lexical-Variables-on-Silent-Reading

Automatic Speech Recognition Predicts Speech Intelligibility and Comprehension for Listeners With Simulated Age-Related Hearing Loss

Purpose

The purpose of this article is to assess speech processing for listeners with simulated age-related hearing loss (ARHL) and to investigate whether the observed performance can be replicated using an automatic speech recognition (ASR) system. The long-term goal of this research is to develop a system that will assist audiologists/hearing-aid dispensers in the fine-tuning of hearing aids.

Method

Sixty young participants with normal hearing listened to speech materials mimicking the perceptual consequences of ARHL at different levels of severity. Two intelligibility tests (repetition of words and sentences) and 1 comprehension test (responding to oral commands by moving virtual objects) were administered. Several language models were developed and used by the ASR system in order to fit human performances.

Results

Strong significant positive correlations were observed between human and ASR scores, with coefficients up to .99. However, the spectral smearing used to simulate losses in frequency selectivity caused larger declines in ASR performance than in human performance.

Conclusion

Both intelligibility and comprehension scores for listeners with simulated ARHL are highly correlated with the performances of an ASR-based system. In the future, it needs to be determined if the ASR system is similarly successful in predicting speech processing in noise and by older people with ARHL.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/60/9/2394/2648888/Automatic-Speech-Recognition-Predicts-Speech

Visual Cues Contribute Differentially to Audiovisual Perception of Consonants and Vowels in Improving Recognition and Reducing Cognitive Demands in Listeners With Hearing Impairment Using Hearing Aids

Purpose

We sought to examine the contribution of visual cues in audiovisual identification of consonants and vowels—in terms of isolation points (the shortest time required for correct identification of a speech stimulus), accuracy, and cognitive demands—in listeners with hearing impairment using hearing aids.

Method

The study comprised 199 participants with hearing impairment (mean age = 61.1 years) with bilateral, symmetrical, mild-to-severe sensorineural hearing loss. Gated Swedish consonants and vowels were presented aurally and audiovisually to participants. Linear amplification was adjusted for each participant to assure audibility. The reading span test was used to measure participants' working memory capacity.

Results

Audiovisual presentation resulted in shortened isolation points and improved accuracy for consonants and vowels relative to auditory-only presentation. This benefit was more evident for consonants than vowels. In addition, correlations and subsequent analyses revealed that listeners with higher scores on the reading span test identified both consonants and vowels earlier in auditory-only presentation, but only vowels (not consonants) in audiovisual presentation.

Conclusion

Consonants and vowels differed in terms of the benefits afforded from their associative visual cues, as indicated by the degree of audiovisual benefit and reduction in cognitive demands linked to the identification of consonants and vowels presented audiovisually.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/60/9/2687/2635215/Visual-Cues-Contribute-Differentially-to

Inner Speech's Relationship With Overt Speech in Poststroke Aphasia

Purpose

Relatively preserved inner speech alongside poor overt speech has been documented in some persons with aphasia (PWA), but the relationship of overt speech with inner speech is still largely unclear, as few studies have directly investigated these factors. The present study investigates the relationship of relatively preserved inner speech in aphasia with selected measures of language and cognition.

Method

Thirty-eight persons with chronic aphasia (27 men, 11 women; average age 64.53 ± 13.29 years, time since stroke 8–111 months) were classified as having relatively preserved inner and overt speech (n = 21), relatively preserved inner speech with poor overt speech (n = 8), or not classified due to insufficient measurements of inner and/or overt speech (n = 9). Inner speech scores (by group) were correlated with selected measures of language and cognition from the Comprehensive Aphasia Test (Swinburn, Porter, & Al, 2004).

Results

The group with poor overt speech showed a significant relationship of inner speech with overt naming (r = .95, p < .01) and with mean length of utterance produced during a written picture description (r = .96, p < .01). Correlations between inner speech and language and cognition factors were not significant for the group with relatively good overt speech.

Conclusions

As in previous research, we show that relatively preserved inner speech is found alongside otherwise severe production deficits in PWA. PWA with poor overt speech may rely more on preserved inner speech for overt picture naming (perhaps due to shared resources with verbal working memory) and for written picture description (perhaps due to reliance on inner speech due to perceived task difficulty). Assessments of inner speech may be useful as a standard component of aphasia screening, and therapy focused on improving and using inner speech may prove clinically worthwhile.

Supplemental Materials

http://ift.tt/2xiwlv4

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/60/9/2406/2653957/Inner-Speechs-Relationship-With-Overt-Speech-in

Training Peer Partners to Use a Speech-Generating Device With Classmates With Autism Spectrum Disorder: Exploring Communication Outcomes Across Preschool Contexts

Purpose

This study examined effects of a peer-mediated intervention that provided training on the use of a speech-generating device for preschoolers with severe autism spectrum disorder (ASD) and peer partners.

Method

Effects were examined using a multiple probe design across 3 children with ASD and limited to no verbal skills. Three peers without disabilities were taught to Stay, Play, and Talk using a GoTalk 4+ (Attainment Company) and were then paired up with a classmate with ASD in classroom social activities. Measures included rates of communication acts, communication mode and function, reciprocity, and engagement with peers.

Results

Following peer training, intervention effects were replicated across 3 peers, who all demonstrated an increased level and upward trend in communication acts to their classmates with ASD. Outcomes also revealed moderate intervention effects and increased levels of peer-directed communication for 3 children with ASD in classroom centers. Additional analyses revealed higher rates of communication in the added context of preferred toys and snack. The children with ASD also demonstrated improved communication reciprocity and peer engagement.

Conclusions

Results provide preliminary evidence on the benefits of combining peer-mediated and speech-generating device interventions to improve children's communication. Furthermore, it appears that preferred contexts are likely to facilitate greater communication and social engagement with peers.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/60/9/2648/2653179/Training-Peer-Partners-to-Use-a-SpeechGenerating

Indicators of Dysphagia in Aged Care Facilities

Purpose

The current cross-sectional study aimed to investigate risk factors for dysphagia in elderly individuals in aged care facilities.

Method

A total of 878 individuals from 42 aged care facilities were recruited for this study. The dependent outcome was speech therapist-determined swallowing function. Independent factors were Eating Assessment Tool score, oral motor assessment score, Mini-Mental State Examination, medical history, and various functional status ratings. Binomial logistic regression was used to identify independent variables associated with dysphagia in this cohort.

Results

Two statistical models were constructed. Model 1 used variables from case files without the need for hands-on assessment, and Model 2 used variables that could be obtained from hands-on assessment. Variables positively associated with dysphagia identified in Model 1 were male gender, total dependence for activities of daily living, need for feeding assistance, mobility, requiring assistance walking or using a wheelchair, and history of pneumonia. Variables positively associated with dysphagia identified in Model 2 were Mini-Mental State Examination score, edentulousness, and oral motor assessments score.

Conclusions

Cognitive function, dentition, and oral motor function are significant indicators associated with the presence of swallowing in the elderly. When assessing the frail elderly, case file information can help clinicians identify frail elderly individuals who may be suffering from dysphagia.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/60/9/2416/2649235/Indicators-of-Dysphagia-in-Aged-Care-Facilities

Speech Recognition and Cognitive Skills in Bimodal Cochlear Implant Users

Purpose

To examine the relation between speech recognition and cognitive skills in bimodal cochlear implant (CI) and hearing aid users.

Method

Seventeen bimodal CI users (28–74 years) were recruited to the study. Speech recognition tests were carried out in quiet and in noise. The cognitive tests employed included the Reading Span Test and the Trail Making Test (Daneman & Carpenter, 1980; Reitan, 1958, 1992), measuring working memory capacity and processing speed and executive functioning, respectively. Data were analyzed using paired-sample t tests, Pearson correlations, and partial correlations controlling for age.

Results

The results indicate that performance on some cognitive tests predicts speech recognition and that bimodal listening generates a significant improvement in speech in quiet compared to unilateral CI listening. However, the current results also suggest that bimodal listening requires different cognitive skills than does unimodal CI listening. This is likely to relate to the relative difficulty of having to integrate 2 different signals and then map the integrated signal to representations stored in the long-term memory.

Conclusions

Even though participants obtained speech recognition benefit from bimodal listening, the results suggest that processing bimodal stimuli involves different cognitive skills than does unimodal conditions in quiet. Thus, clinically, it is important to consider this when assessing treatment outcomes.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/60/9/2752/2653958/Speech-Recognition-and-Cognitive-Skills-in-Bimodal

Alveolar and Postalveolar Voiceless Fricative and Affricate Productions of Spanish–English Bilingual Children With Cochlear Implants

Purpose

This study investigates the production of voiceless alveolar and postalveolar fricatives and affricates by bilingual and monolingual children with hearing loss who use cochlear implants (CIs) and their peers with normal hearing (NH).

Method

Fifty-four children participated in our study, including 12 Spanish–English bilingual CI users (M = 6;0 [years;months]), 12 monolingual English-speaking children with CIs (M = 6;1), 20 bilingual children with NH (M = 6;5), and 10 monolingual English-speaking children with NH (M = 5;10). Picture elicitation targeting /s/, /tʃ/, and /ʃ/ was administered. Repeated-measures analyses of variance comparing group means for frication duration, rise time, and centroid frequency were conducted for the effects of CI use and bilingualism.

Results

All groups distinguished the target sounds in the 3 acoustic parameters examined. Regarding frication duration and rise time, the Spanish productions of bilingual children with CIs differed from their bilingual peers with NH. English frication duration patterns for bilingual versus monolingual CI users also differed. Centroid frequency was a stronger place cue for children with NH than for children with CIs.

Conclusion

Patterns of fricative and affricate production display effects of bilingualism and diminished signal, yielding unique patterns for bilingual and monolingual CI users.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/60/9/2427/2648980/Alveolar-and-Postalveolar-Voiceless-Fricative-and

Input Subject Diversity Accelerates the Growth of Tense and Agreement: Indirect Benefits From a Parent-Implemented Intervention

Purpose

This follow-up study examined whether a parent intervention that increased the diversity of lexical noun phrase subjects in parent input and accelerated children's sentence diversity (Hadley et al., 2017) had indirect benefits on tense/agreement (T/A) morphemes in parent input and children's spontaneous speech.

Method

Differences in input variables related to T/A marking were compared for parents who received toy talk instruction and a quasi-control group: input informativeness and full is declaratives. Language growth on tense agreement productivity (TAP) was modeled for 38 children from language samples obtained at 21, 24, 27, and 30 months. Parent input properties following instruction and children's growth in lexical diversity and sentence diversity were examined as predictors of TAP growth.

Results

Instruction increased parent use of full is declaratives (η_p² ≥ .25) but not input informativeness. Children's sentence diversity was also a significant time-varying predictor of TAP growth. Two input variables, lexical noun phrase subject diversity and full is declaratives, were also significant predictors, even after controlling for children's sentence diversity.

Conclusions

These findings establish a link between children's sentence diversity and the development of T/A morphemes and provide evidence about characteristics of input that facilitate growth in this grammatical system.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/60/9/2619/2654122/Input-Subject-Diversity-Accelerates-the-Growth-of

Swallowing Mechanics Associated With Artificial Airways, Bolus Properties, and Penetration–Aspiration Status in Trauma Patients

Purpose

Artificial airway procedures such as intubation and tracheotomy are common in the treatment of traumatic injuries, and bolus modifications may be implemented to help manage swallowing disorders. This study assessed artificial airway status, bolus properties (volume and viscosity), and the occurrence of laryngeal penetration and/or aspiration in relation to mechanical features of swallowing.

Method

Coordinates of anatomical landmarks were extracted at minimum and maximum hyolaryngeal excursion from 228 videofluoroscopic swallowing studies representing 69 traumatically injured U.S. military service members with dysphagia. Morphometric canonical variate and regression analyses examined associations between swallowing mechanics and bolus properties based on artificial airway and penetration–aspiration status.

Results

Significant differences in swallowing mechanics were detected between extubated versus tracheotomized (D = 1.32, p < .0001), extubated versus decannulated (D = 1.74, p < .0001), and decannulated versus tracheotomized (D = 1.24, p < .0001) groups per post hoc discriminant function analysis. Tracheotomy-in-situ and decannulated subgroups exhibited increased head/neck extension and posterior relocation of the larynx. Swallowing mechanics associated with (a) penetration–aspiration status and (b) bolus properties were moderately related for extubated and decannulated subgroups, but not the tracheotomized subgroup, per morphometric regression analysis.

Conclusion

Specific differences in swallowing mechanics associated with artificial airway status and certain bolus properties may guide therapeutic intervention in trauma-based dysphagia.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/60/9/2442/2649304/Swallowing-Mechanics-Associated-With-Artificial

Applying Item Response Theory to the Development of a Screening Adaptation of the Goldman-Fristoe Test of Articulation–Second Edition

Purpose

Item response theory (IRT) is a psychometric approach to measurement that uses latent trait abilities (e.g., speech sound production skills) to model performance on individual items that vary by difficulty and discrimination. An IRT analysis was applied to preschoolers' productions of the words on the Goldman-Fristoe Test of Articulation–Second Edition (GFTA-2) to identify candidates for a screening measure of speech sound production skills.

Method

The phoneme accuracies from 154 preschoolers, with speech skills on the GFTA-2 ranging from the 1st to above the 90th percentile, were analyzed with a 2-parameter logistic model.

Results

A total of 108 of the 232 phonemes from stimuli in the sounds-in-words subtest fit the IRT model. These phonemes, and subgroups of the most difficult of these phonemes, correlated significantly with the children's overall percentile scores on the GFTA-2. Regression equations calculated for the 5 and 10 most difficult phonemes predicted overall percentile score at levels commensurate with other screening measures.

Conclusions

These results suggest that speech production accuracy can be screened effectively with a small number of sounds. They motivate further research toward the development of a screening measure of children's speech sound production skills whose stimuli consist of a limited number of difficult phonemes.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/60/9/2672/2653405/Applying-Item-Response-Theory-to-the-Development

Modeling the Pathophysiology of Phonotraumatic Vocal Hyperfunction With a Triangular Glottal Model of the Vocal Folds

Purpose

Our goal was to test prevailing assumptions about the underlying biomechanical and aeroacoustic mechanisms associated with phonotraumatic lesions of the vocal folds using a numerical lumped-element model of voice production.

Method

A numerical model with a triangular glottis, posterior glottal opening, and arytenoid posturing is proposed. Normal voice is altered by introducing various prephonatory configurations. Potential compensatory mechanisms (increased subglottal pressure, muscle activation, and supraglottal constriction) are adjusted to restore an acoustic target output through a control loop that mimics a simplified version of auditory feedback.

Results

The degree of incomplete glottal closure in both the membranous and posterior portions of the folds consistently leads to a reduction in sound pressure level, fundamental frequency, harmonic richness, and harmonics-to-noise ratio. The compensatory mechanisms lead to significantly increased vocal-fold collision forces, maximum flow-declination rate, and amplitude of unsteady flow, without significantly altering the acoustic output.

Conclusion

Modeling provided potentially important insights into the pathophysiology of phonotraumatic vocal hyperfunction by demonstrating that compensatory mechanisms can counteract deterioration in the voice acoustic signal due to incomplete glottal closure, but this also leads to high vocal-fold collision forces (reflected in aerodynamic measures), which significantly increases the risk of developing phonotrauma.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/60/9/2452/2652562/Modeling-the-Pathophysiology-of-Phonotraumatic

The Effect of Dynamic Pitch on Speech Recognition in Temporally Modulated Noise

Purpose

This study investigated the effect of dynamic pitch in target speech on older and younger listeners' speech recognition in temporally modulated noise. First, we examined whether the benefit from dynamic-pitch cues depends on the temporal modulation of noise. Second, we tested whether older listeners can benefit from dynamic-pitch cues for speech recognition in noise. Last, we explored the individual factors that predict the amount of dynamic-pitch benefit for speech recognition in noise.

Method

Younger listeners with normal hearing and older listeners with varying levels of hearing sensitivity participated in the study, in which speech reception thresholds were measured with sentences in nonspeech noise.

Results

The younger listeners benefited more from dynamic pitch for speech recognition in temporally modulated noise than unmodulated noise. Older listeners were able to benefit from the dynamic-pitch cues but received less benefit from noise modulation than the younger listeners. For those older listeners with hearing loss, the amount of hearing loss strongly predicted the dynamic-pitch benefit for speech recognition in noise.

Conclusions

Dynamic-pitch cues aid speech recognition in noise, particularly when noise has temporal modulation. Hearing loss negatively affects the dynamic-pitch benefit to older listeners with significant hearing loss.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/60/9/2725/2648979/The-Effect-of-Dynamic-Pitch-on-Speech-Recognition

Trans Male Voice in the First Year of Testosterone Therapy: Make No Assumptions

Purpose

The purpose of this study was to prospectively examine changes in gender-related voice domain of pitch measured by fundamental frequency, function-related domains of vocal quality, range, and habitual pitch level and the self-perceptions of transmasculine people during their first year of testosterone treatment.

Method

Seven trans men received 2 voice assessments at baseline and 1 assessment at 3, 6, 9, and 12 months after starting treatment.

Results

Vocal quality measures varied between and within participants but were generally within normal limits throughout the year. Mean fundamental frequency (MF0) during reading decreased, although to variable extents and rates. Phonation frequency range shifted down the scale, although it increased in some participants and decreased in others. Considering MF0 and phonation frequency range together in a measure of habitual pitch level revealed that the majority of participants spoke using an MF0 that was low within their range compared with cisgender norms. Although the trans men generally self-reported voice masculinization, it was not correlated with MF0, frequency range, or habitual pitch level at any time point or with MF0 note change from baseline to 1 year of testosterone treatment, but correlations should be interpreted with caution due to the heterogeneous responses of the 7 participants.

Conclusion

In trans men, consideration of voice deepening in the context of objective and subjective measures of voice can reveal unique profiles and inform patient care.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/60/9/2472/2654123/Trans-Male-Voice-in-the-First-Year-of-Testosterone

Relevance of the Implementation of Teeth in Three-Dimensional Vocal Tract Models

Purpose

Recently, efforts have been made to investigate the vocal tract using magnetic resonance imaging (MRI). Due to technical limitations, teeth were omitted in many previous studies on vocal tract acoustics. However, the knowledge of how teeth influence vocal tract acoustics might be important in order to estimate the necessity of implementing teeth in vocal tract models. The aim of this study was therefore to estimate the effect of teeth on vocal tract acoustics.

Method

The acoustic properties of 18 solid (3-dimensional printed) vocal tract models without teeth were compared to the same 18 models including teeth in terms of resonance frequencies (f _Rn). The f _Rn were obtained from the transfer functions of these models excited by white noise at the glottis level. The models were derived from MRI data of 2 trained singers performing 3 different vowel conditions (/i/, /a/, and /u/) in speech and low-pitched and high-pitched singing.

Results

Depending on the oral configuration, models exhibiting side cavities or side branches were characterized by major changes in the transfer function when teeth were implemented via the introduction of pole-zero pairs.

Conclusions

To avoid errors in modeling, teeth should be included in 3-dimensional vocal tract models for acoustic evaluation.

Supplemental Material

http://ift.tt/2wnkzL9

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/60/9/2379/2654188/Relevance-of-the-Implementation-of-Teeth-in

How Stuttering Develops: The Multifactorial Dynamic Pathways Theory

Purpose

We advanced a multifactorial, dynamic account of the complex, nonlinear interactions of motor, linguistic, and emotional factors contributing to the development of stuttering. Our purpose here is to update our account as the multifactorial dynamic pathways theory.

Method

We review evidence related to how stuttering develops, including genetic/epigenetic factors; motor, linguistic, and emotional features; and advances in neuroimaging studies. We update evidence for our earlier claim: Although stuttering ultimately reflects impairment in speech sensorimotor processes, its course over the life span is strongly conditioned by linguistic and emotional factors.

Results

Our current account places primary emphasis on the dynamic developmental context in which stuttering emerges and follows its course during the preschool years. Rapid changes in many neurobehavioral systems are ongoing, and critical interactions among these systems likely play a major role in determining persistence of or recovery from stuttering.

Conclusion

Stuttering, or childhood onset fluency disorder (Diagnostic and Statistical Manual of Mental Disorders, 5th edition; American Psychiatric Association [APA], 2013), is a neurodevelopmental disorder that begins when neural networks supporting speech, language, and emotional functions are rapidly developing. The multifactorial dynamic pathways theory motivates experimental and clinical work to determine the specific factors that contribute to each child's pathway to the diagnosis of stuttering and those most likely to promote recovery.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/60/9/2483/2652602/How-Stuttering-Develops-The-Multifactorial-Dynamic

“Whatdunit?” Sentence Comprehension Abilities of Children With SLI: Sensitivity to Word Order in Canonical and Noncanonical Structures

Purpose

With Aim 1, we compared the comprehension of and sensitivity to canonical and noncanonical word order structures in school-age children with specific language impairment (SLI) and same-age typically developing (TD) children. Aim 2 centered on the developmental improvement of sentence comprehension in the groups. With Aim 3, we compared the comprehension error patterns of the groups.

Method

Using a "Whatdunit" agent selection task, 117 children with SLI and 117 TD children (ages 7:0–11:11, years:months) propensity matched on age, gender, mother's education, and family income pointed to the picture that best represented the agent in semantically implausible canonical structures (subject–verb–object, subject relative) and noncanonical structures (passive, object relative).

Results

The SLI group performed worse than the TD group across sentence types. TD children demonstrated developmental improvement across each sentence type, but children with SLI showed improvement only for canonical sentences. Both groups chose the object noun as agent significantly more often than the noun appearing in a prepositional phrase.

Conclusions

In the absence of semantic–pragmatic cues, comprehension of canonical and noncanonical sentences by children with SLI is limited, with noncanonical sentence comprehension being disproportionately limited. The children's ability to make proper semantic role assignments to the noun arguments in sentences, especially noncanonical, is significantly hindered.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/60/9/2603/2652493/Whatdunit-Sentence-Comprehension-Abilities-of

A Cross-Language Study of Acoustic Predictors of Speech Intelligibility in Individuals With Parkinson's Disease

Purpose

The present study aimed to compare acoustic models of speech intelligibility in individuals with the same disease (Parkinson's disease [PD]) and presumably similar underlying neuropathologies but with different native languages (American English [AE] and Korean).

Method

A total of 48 speakers from the 4 speaker groups (AE speakers with PD, Korean speakers with PD, healthy English speakers, and healthy Korean speakers) were asked to read a paragraph in their native languages. Four acoustic variables were analyzed: acoustic vowel space, voice onset time contrast scores, normalized pairwise variability index, and articulation rate. Speech intelligibility scores were obtained from scaled estimates of sentences extracted from the paragraph.

Results

The findings indicated that the multiple regression models of speech intelligibility were different in Korean and AE, even with the same set of predictor variables and with speakers matched on speech intelligibility across languages. Analysis of the descriptive data for the acoustic variables showed the expected compression of the vowel space in speakers with PD in both languages, lower normalized pairwise variability index scores in Korean compared with AE, and no differences within or across language in articulation rate.

Conclusions

The results indicate that the basis of an intelligibility deficit in dysarthria is likely to depend on the native language of the speaker and listener. Additional research is required to explore other potential predictor variables, as well as additional language comparisons to pursue cross-linguistic considerations in classification and diagnosis of dysarthria types.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/60/9/2506/2650812/A-CrossLanguage-Study-of-Acoustic-Predictors-of

Distributed Training Enhances Implicit Sequence Acquisition in Children With Specific Language Impairment

Purpose

This study explored the effects of 2 different training structures on the implicit acquisition of a sequence in a serial reaction time (SRT) task in children with and without specific language impairment (SLI).

Method

All of the children underwent 3 training sessions, followed by a retention session 2 weeks after the last session. In the massed-training condition, the 3 training sessions were in immediate succession on 1 day, whereas in the distributed-training condition, the 3 training sessions were spread over a 1-week period in an expanding schedule format.

Results

Statistical analyses showed that the children with normal language were unaffected by the training conditions, performing the SRT task similarly in both training conditions. The children with SLI, however, were affected by the training structure, performing the SRT task better when the training sessions were spaced over time rather than clustered on 1 day.

Conclusion

This study demonstrated that although intensive training does not increase learning in children with SLI, distributing training sessions over time does increase learning. The implications of these results on the learning abilities of children with SLI are discussed, as are the mechanisms involved in massed versus distributed learning.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/60/9/2636/2653205/Distributed-Training-Enhances-Implicit-Sequence

Short-Term Effect of Two Semi-Occluded Vocal Tract Training Programs on the Vocal Quality of Future Occupational Voice Users: “Resonant Voice Training Using Nasal Consonants” Versus “Straw Phonation”

Purpose

The purpose of this study was to determine the short-term effect of 2 semi-occluded vocal tract training programs, "resonant voice training using nasal consonants" versus "straw phonation," on the vocal quality of vocally healthy future occupational voice users.

Method

A multigroup pretest–posttest randomized control group design was used. Thirty healthy speech-language pathology students with a mean age of 19 years (range: 17–22 years) were randomly assigned into a resonant voice training group (practicing resonant exercises across 6 weeks, n = 10), a straw phonation group (practicing straw phonation across 6 weeks, n = 10), or a control group (receiving no voice training, n = 10). A voice assessment protocol consisting of both subjective (questionnaire, participant's self-report, auditory–perceptual evaluation) and objective (maximum performance task, aerodynamic assessment, voice range profile, acoustic analysis, acoustic voice quality index, dysphonia severity index) measurements and determinations was used to evaluate the participants' voice pre- and posttraining. Groups were compared over time using linear mixed models and generalized linear mixed models. Within-group effects of time were determined using post hoc pairwise comparisons.

Results

No significant time × group interactions were found for any of the outcome measures, indicating no differences in evolution over time among the 3 groups. Within-group effects of time showed a significant improvement in dysphonia severity index in the resonant voice training group, and a significant improvement in the intensity range in the straw phonation group.

Conclusions

Results suggest that the semi-occluded vocal tract training programs using resonant voice training and straw phonation may have a positive impact on the vocal quality and vocal capacities of future occupational voice users. The resonant voice training caused an improved dysphonia severity index, and the straw phonation training caused an expansion of the intensity range in this population.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/60/9/2519/2652563/ShortTerm-Effect-of-Two-SemiOccluded-Vocal-Tract

Structural investigation of nucleophosmin interaction with the tumor suppressor Fbw7γ

Structural investigation of nucleophosmin interaction with the tumor suppressor Fbw7γ

Oncogenesis 6, e379 (September 2017). doi:10.1038/oncsis.2017.78

Authors: A Di Matteo, M Franceschini, A Paiardini, A Grottesi, S Chiarella, S Rocchio, C Di Natale, D Marasco, L Vitagliano, C Travaglini-Allocatelli & L Federici

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2f5HRih

Targeting tumor multicellular aggregation through IGPR-1 inhibits colon cancer growth and improves chemotherapy

Targeting tumor multicellular aggregation through IGPR-1 inhibits colon cancer growth and improves chemotherapy

Oncogenesis 6, e378 (September 2017). doi:10.1038/oncsis.2017.77

Authors: N Woolf, B E Pearson, P A Bondzie, R D Meyer, M Lavaei, A C Belkina, V Chitalia & N Rahimi

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2f5HPa9

Effect of Linguistic and Musical Experience on Distributional Learning of Nonnative Lexical Tones

Purpose

Evidence suggests that extensive experience with lexical tones or musical training provides an advantage in perceiving nonnative lexical tones. This investigation concerns whether such an advantage is evident in learning nonnative lexical tones based on the distributional structure of the input.

Method

Using an established protocol, distributional learning of lexical tones was investigated with tone language (Mandarin) listeners with no musical training (Experiment 1) and nontone language (Australian English) listeners with musical training (Experiment 2). Within each experiment, participants were trained on a bimodal (2-peak) or a unimodal (single peak) distribution along a continuum spanning a Thai lexical tone minimal pair. Discrimination performance on the target minimal pair was assessed before and after training.

Results

Mandarin nonmusicians exhibited clear distributional learning (listeners in the bimodal, but not those in the unimodal condition, improved significantly as a function of training), whereas Australian English musicians did not (listeners in both the bimodal and unimodal conditions improved as a function of training).

Conclusions

Our findings suggest that veridical perception of lexical tones is not sufficient for distributional learning of nonnative lexical tones to occur. Rather, distributional learning appears to be modulated by domain-specific pitch experience and is constrained possibly by top-down interference.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/doi/10.1044/2016_JSLHR-S-16-0080/2610303/Effect-of-Linguistic-and-Musical-Experience-on