Αρχειοθήκη ιστολογίου

Πέμπτη 8 Μαρτίου 2018

Development of Foundational Movement Skills: A Conceptual Model for Physical Activity Across the Lifespan

Abstract

Evidence supports a positive association between competence in fundamental movement skills (e.g., kicking, jumping) and physical activity in young people. Whilst important, fundamental movement skills do not reflect the broad diversity of skills utilized in physical activity pursuits across the lifespan. Debate surrounds the question of what are the most salient skills to be learned which facilitate physical activity participation across the lifespan. In this paper, it is proposed that the term 'fundamental movement skills' be replaced with 'foundational movement skills'. The term 'foundational movement skills' better reflects the broad range of movement forms that increase in complexity and specificity and can be applied in a variety of settings. Thus, 'foundational movement skills' includes both traditionally conceptualized 'fundamental' movement skills and other skills (e.g., bodyweight squat, cycling, swimming strokes) that support physical activity engagement across the lifespan. A proposed conceptual model outlines how foundational movement skill competency can provide a direct or indirect pathway, via specialized movement skills, to a lifetime of physical activity. Foundational movement skill development is hypothesized to vary according to culture and/or geographical location. Further, skill development may be hindered or enhanced by physical (i.e., fitness, weight status) and psychological (i.e., perceived competence, self-efficacy) attributes. This conceptual model may advance the application of motor development principles within the public health domain. Additionally, it promotes the continued development of human movement in the context of how it leads to skillful performance and how movement skill development supports and maintains a lifetime of physical activity engagement.



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Upfront surgery versus definitive chemoradiotherapy in patients with human Papillomavirus-associated oropharyngeal squamous cell cancer

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Publication date: April 2018
Source:Oral Oncology, Volume 79
Author(s): Jacqueline R. Kelly, Henry S. Park, Yi An, Wendell G. Yarbrough, Joseph N. Contessa, Roy Decker, Saral Mehra, Benjamin L. Judson, Barbara Burtness, Zain Husain
ObjectivesCurrently, human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV-A OPC) is managed with either primary surgery or definitive chemoradiotherapy (CRT), despite the lack of supporting randomized prospective data. We therefore assessed the outcomes of each treatment strategy using the National Cancer Database (NCDB).MethodsThe NCDB was used to identify patients diagnosed with cT1 N2a-2b or cT2 N1-2b HPV-A OPC from 2010 to 2013 who underwent treatment with primary surgery or CRT. Demographic and clinicopathologic predictors of treatment were analyzed by the chi-square test and logistic regression. Overall survival (OS) was evaluated using multivariable Cox proportional hazard regression, Kaplan-Meier, log-rank test, and propensity score-matched analysis.ResultsWe identified 3063 patients; 1576 (51.5%) received CRT and 1487 (48.5%) underwent primary surgery. Median follow up was 32 months. 972 (65.4%) surgical patients received adjuvant CRT. On multivariable Cox regression, 3-year OS was comparable between surgery and CRT (hazard ratio [HR] 1.08, 95% confidence interval [CI] 0.83–1.41, P = 0.58). Inferior OS was significantly associated with increasing clinical T and N stage, older age, and non-private insurance. Propensity score-matching yielded a 2526 patient cohort and redemonstrated similar OS (HR, 1.09; 95% CI 0.81–1.47; P = 0.55). Comparable outcomes persisted in a subset analysis of patients with margin-negative resection, with 3-year OS 90.8% in CRT patients vs. 93.6% in surgery patients (log-rank P = 0.27).ConclusionsUpfront surgery and CRT yielded comparable 3-year OS outcomes in this cohort. In this national sample, 65.4% of surgical patients received trimodal therapy with adjuvant CRT, highlighting the need for improved patient selection for primary surgery.



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Chemoradiotherapy using retrograde superselective intra-arterial infusion for tongue cancer: Analysis of therapeutic results in 118 cases

Publication date: April 2018
Source:Oral Oncology, Volume 79
Author(s): Kenji Mitsudo, Yuichiro Hayashi, Shuhei Minamiyama, Nobuhide Ohashi, Masaki Iida, Toshinori Iwai, Senri Oguri, Toshiyuki Koizumi, Mitomu Kioi, Makoto Hirota, Izumi Koike, Masaharu Hata, Iwai Tohnai
ObjectivesTo evaluate the therapeutic results and rate of organ preservation in patients with squamous cell carcinoma of the tongue treated with retrograde superselective intra-arterial chemoradiotherapy.Materials and methodsBetween June 2006 and June 2015, 118 patients with tongue cancer were treated with intra-arterial chemoradiotherapy. Treatment consisted of radiotherapy (total 50–70 Gy) and daily concurrent intra-arterial chemotherapy (docetaxel, total 50–70 mg/m2; cisplatin, total 125–175 mg/m2) for 5–7 weeks. Locoregional control and overall survival rates were calculated by the Kaplan-Meier method. Cox's proportional hazards model was used for both univariate and multivariate analyses.ResultsThe median follow-up for all patients was 38.5 months (range, 3–129 months). After intra-arterial chemoradiotherapy, primary site complete response was achieved in 113 (95.8%) of 118 cases. Three-year locoregional control and overall survival rates were 80.3% and 81.5%, respectively. Grade 3 or 4 toxicities included neutropenia in 16.1% and mucositis in 87.3%. Grade 3 toxicities included anemia in 12.7%, thrombocytopenia in 3.4%, nausea/vomiting in 3.4%, dermatitis in 45.7%, dysphagia in 74.6%, and fever in 2.5% of patients. Late toxicity consisting of grade 3 osteoradionecrosis of the jaw occurred in 4.2% of patients. On univariate analysis, T stage and overall stage were significantly associated with locoregional control, and N stage and overall stage were significantly associated with overall survival. On multivariate analysis, the only significant predictor of overall survival was overall stage classification.ConclusionRetrograde superselective intra-arterial chemoradiotherapy for tongue cancer provided good overall survival and locoregional control.



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Systematic review: Disease-specific instruments to assess gastrointestinal symptoms in functional dyspepsia

Abstract

Background

Functional dyspepsia (FD) is a common functional gastrointestinal disorder with incompletely understood pathophysiology and heterogeneous symptom presentation. Assessment of treatment efficacy in FD is a methodological challenge as response to treatment must be assessed primarily by measuring subjective symptoms. Therefore, the use of patient-reported outcome measures (PROMs) is recommended by regulatory authorities to assess gastrointestinal symptoms in clinical trials for FD. In the last decades, a multitude of outcome measures has been developed. However, currently no PROM has been approved by the regulatory authorities, and no consensus has been reached with regard to the most relevant outcome measure in FD.

Purpose

This systematic review discusses the available disease-specific outcome measures for assessment of FD symptoms with psychometric validation properties, strengths, and limitations. Moreover, recommendations for use of current available outcome measures are provided, and potential areas of future research are discussed.

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Multiple different questionnaires are currently used in clinical trials to assess gastrointestinal symptoms in patients with functional dyspepsia. Although current available questionnaires do not fulfill all criteria for psychometric validation, the Leuven Postprandial Distress Scale and Functional Dyspepsia Symptom Diary seem most promising.



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Diabetes-induced colonic slow transit mediated by the up-regulation of PDGFRα+ cells/SK3 in streptozotocin-induced diabetic mice

Abstract

Background

A major complication related to gastrointestinal (GI) symptoms in diabetic patients is chronic constipation. Constipation has serious negative impacts on quality of life; however, without a comprehensive understanding of the disease, currently available treatments cannot provide a cure. Platelet-derived growth factor receptor alpha-positive cells (PDGFRα+ cells), which form the SIP syncytium with interstitial cells of Cajal and smooth muscle cells, play important roles in GI motility. In the present study, the contributions of PDGFRα+ cells to diabetes-induced colonic slow transit were investigated in streptozotocin (STZ)-induced diabetic mice.

Methods

Western blotting, quantitative PCR, contractile experiments, and intracellular recording were used in the present study.

Key Results

The results demonstrated that the colon length was increased in STZ-treated mice. The colonic transit of artificial fecal pellets in vitro was significantly delayed in STZ-treated mice. The mRNA and protein expression of PDGFRα, small-conductance Ca2+-activated K channels (SK3), and P2Y1 receptors were increased in the colons of STZ-treated mice. In contractile experiments, the colonic smooth muscles were more sensitive to the SK3 agonist and antagonist (CyPPA and apamin) and the P2Y1 agonist and antagonist (MRS2365 and MRS2500) in STZ-treated mice. Intracellular recordings showed the responses of membrane potentials in colonic smooth muscle cells to CyPPA, apamin, MRS2365, and MRS2500 were more sensitive in STZ-treated mice. The electric field stimulation-induced P2Y1/SK3-dependent fast inhibitory junctional potentials (fIJPs) of colonic smooth muscles were more significantly hyperpolarized in STZ-treated mice.

Conclusions and Inferences

These results suggest that the purinergic neurotransmitters/P2Y1/SK3 signaling pathway is up-regulated in the diabetic colons, thereby mediating diabetes-induced colonic slow transit.

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This article investigates the contributions of PDGFRα+ cells to diabetes-induced colonic slow transit in streptozotocin-induced diabetic mice. The colonic smooth muscles were more sensitive to apamin (the SK3 antagonist) in STZ-treated mice, indicating that the functionally up-regulated SK3 channels exerted more inhibitory effects on the colonic motility.



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Enteric motor dysfunctions in experimental chronic pancreatitis: Alterations of myenteric neurons regulating colonic motility in rats

Abstract

Background

The mechanism underlying gastrointestinal (GI) dysmotility associated with chronic pancreatitis (CP) has not been fully elucidated, and enteric nervous system (ENS) has an important regulatory role in gastrointestinal motor function. The aim of this study is to investigate the effect of ENS in the colonic hypomotility induced by trinitrobenzene sulfonic acid (TNBS) infusion which mimics CP.

Methods

Male Sprague-Dawley rats were submitted to CP which was induced by pancreatic infusion of 2% TNBS, or sham group with treatment of equal saline. Three weeks after induction of CP, we pathologically examined the inflammation of pancreas and counted the number of withdrawal events stimulated by Von Frey filaments to evaluate hyperalgesia. The gastrointestinal transit rate was measured using Carbon inkl driving test, and the contraction activities of colonic muscle strip were studied in an organ bath system. The expression of choline acetyltransferase (ChAT) and nitric oxide synthase (NOS) in colonic myenteric plexus (MP) of ENS were investigated by Western blotting and double immunofluorescence staining.

Key Results

In TNBS-treated group, rats had the signs of chronic pancreatitis 3 weeks after intraductal infusion and had increased sensitivity to mechanical stimulation of the abdomen. For rats with CP, the gastrointestinal transit rate was reduced; in addition, the contractile activities of longitudinal muscle (LM) and circular muscle (CM) strips of distal colon in TNBS group were lower than those in sham group. Immunofluorescence demonstrated that the percentage of ChAT-immunoreactive (IR) neurons in the MP was decreased, but the proportion of NOS-IR neurons in the MP was increased when compared with sham-operated group. Western blotting proved that TNBS infusion down-regulated ChAT but up-regulated NOS expression in the colon MP.

Conclusions & Inferences

Decreased ChAT-IR neurons and increased NOS-IR in the MP of colon ENS may contribute to the pathogenesis of colonic dysmotility in CP.

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Chronic pancreatitis (CP) is regarded to be an irreversible progressive chronic inflammatory disorder, which is complicated by gastrointestinal dysmotility in some cases. Decreased ChAT-IR neurons and increased NOS-IR in the MP of colon ENS may contribute to the pathogenesis of colonic dysmotility in CP.



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An internally validated prognostic model for success in revision stapes surgery for otosclerosis

Objectives/Hypothesis

To develop a prediction model that can accurately predict the chance of success following revision stapes surgery in patients with recurrent or persistent otosclerosis at 2- to 6-months follow-up and to validate this model internally.

Study Design

A retrospective cohort study of prospectively gathered data in a tertiary referral center.

Methods

The associations of 11 prognostic factors with treatment success were tested in 705 cases using multivariable logistic regression analysis with backward selection. Success was defined as a mean air-bone gap closure to 10 dB or less. The most relevant predictors were used to derive a clinical prediction rule to determine the probability of success. Internal validation by means of bootstrapping was performed. Model performance indices, including the Hosmer-Lemeshow test, the area under the receiver operating characteristics curve (AUC), and the explained variance were calculated.

Results

Success was achieved in 57.7% of cases at 2- to 6-months follow-up. Certain previous surgical techniques, primary causes of failure leading up to revision stapes surgery, and positions of the prosthesis placed during revision surgery were associated with higher success percentages. The clinical prediction rule performed moderately well in the original dataset (Hosmer-Lemeshow P = .78; AUC = 0.73; explained variance = 22%), which slightly decreased following internal validation by means of bootstrapping (AUC = 0.69; explained variance = 13%).

Conclusions

Our study established the importance of previous surgical technique, primary cause of failure, and type of the prosthesis placed during the revision surgery in predicting the probability of success following stapes surgery at 2- to 6-months follow-up.

Level of Evidence

2b. Laryngoscope, 2018



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A novel method to visualise the three-dimensional organisation of the human cerebral cortical vasculature

Abstract

Current tissue-clearing protocols for imaging in three dimensions (3D) are typically applied to optimally fixed, small-volume rodent brain tissue – which is not representative of the tissue found in diagnostic neuropathology laboratories. We present a method to visualise the cerebral cortical vasculature in 3D in human post-mortem brain tissue which had been preserved in formalin for many years. Tissue blocks of cerebral cortex from two control cases, two Alzheimer's brains and two cases from Alzheimer's patients immunised against Aβ42 were stained with fluorescent Lycopersicon esculentum agglutinin (Tomato lectin), dehydrated and cleared using an adapted three-dimensional imaging of solvent cleared organs (3DISCO) protocol to visualise the vascular endothelium. Tissue was imaged using light sheet and confocal microscopy and reconstructed in 3D using amira software. The method permits visualisation of the arrangement of the parallel penetrating cortical vasculature in the human brain. The presence of four vascular features including anastomosis, U-shaped vessels, spiralling and loops were revealed. In summary, we present a low cost and simple method to visualise the human cerebral vasculature in 3D compatible with prolonged fixation times (years), allowing study of vascular involvement in a range of normative and pathological states.



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Relationship among perceived stress, xerostomia, and salivary flow rate in patients visiting a saliva clinic

Abstract

Objective

This aimed to assess the potential role of chronic stress in saliva secretion, xerostomia, and oral health in a population attending a saliva clinic.

Materials and methods

Data of 114 patients who met the inclusion criteria and completed all questionnaires were analyzed in this study. Participants completed several validated questionnaires, including the Perceived Stress Scale, the Oral Health Impact Profile (OHIP-14), Xerostomia Inventory (XI), and Bother xerostomia Index (BI). Subsequently, the unstimulated, chewing-stimulated, and citric acid-stimulated saliva secretion rates were determined gravimetrically. Data were evaluated using Spearman's correlation analysis and the Mann–Whitney U test.

Results

A significant correlation was observed between perceived stress and XI score (r = 0.312, p = 0.001), as well as between perceived stress and BI score (r = 0.334, p = 0.001). Stress levels also were significantly associated with OHIP-14 scores (r = 0.420, p < 0.001), but an association between experienced stress and salivary flow rate could not be established.

Conclusion

In this population, perceived chronic stress seems to be related to several aspects of dry mouth, including the perception of dry mouth, suffering from dry mouth, and the impact on quality of life. These effects were independent of the use of psychotropic medication. No actual reduction in salivary flow was found. Further studies to explore the causal linkage of stress with xerostomia seem warranted.

Clinical relevance

Perceived chronic stress seems to be related with several aspects of dry mouth. This finding might be relevant in future prevention and treatment of xerostomia.



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Exercise Professionals with Advanced Clinical Training Should be Afforded Greater Responsibility in Pre-Participation Exercise Screening: A New Collaborative Model between Exercise Professionals and Physicians

Abstract

Regular exercise improves health but can also induce adverse responses. Although such episodes are rare, many guidelines for pre-participation exercise screening have historically had a low threshold for recommending medical clearance prior to the commencement of exercise, placing the responsibility for decision making about exercise participation on physicians. The 'clearance to exercise' model still occurs widely in practice, but creates cost burdens and barriers to the uptake of exercise. Moreover, many physicians are not provided the training, nor time in a standard consultation, to be able to effectively perform this role. We present a model for pre-participation exercise screening and the initial assessment of clients wishing to commence an exercise programme. It is designed to guide professional practice for the referral, assessment and prescription of exercise for people across the health spectrum, from individuals who are apparently healthy, through to clients with pre-existing or occult chronic conditions. The model removes the request that physicians provide a 'clearance' for patients to engage in exercise programmes. Instead the role of physicians is identified as providing relevant clinical guidance to suitably qualified exercise professionals to allow them to use their knowledge, skills and expertise in exercise prescription to assess and manage any risks related to the prescription and delivery of appropriate exercise programmes. It is anticipated that removing unjustified barriers to exercise participation, such as mandated medical review, will improve the uptake of exercise by the unacceptably high proportion of the population who do not undertake sufficient physical activity for health benefit.



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Foreign body giant cell reaction to a Proplast/Teflon interpositional implant: a case report and literature review

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Publication date: Available online 8 March 2018
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Kevin C. Lee, Sidney B. Eisig, Michael A. Perrino




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Isolated light chain amyloidosis involving the parotid gland: A case report

Publication date: Available online 8 March 2018
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Barzi Gareb, Michael Perry, Paul Joseph Tadrous
Amyloidosis in the parotid gland is rare and is usually associated with systemic amyloidosis. Localized amyloidosis in the parotid gland is extremely rare. The authors present a case of localized light chain amyloidosis of the parotid gland without systemic involvement. A 70-year-old woman with an asymptomatic presented with a swelling of the right parotid region. Physical examination, hematological and biochemical investigations, imaging, and cytology were non-conclusive. The patient underwent an extracapsular dissection of the right parotid gland. Histology showed that the tissue of the right parotid gland mostly consisted of amyloid depositions. The amyloid stained with antibodies to lambda light chains. Additional investigations showed no systemic involvement. The patient is asymptomatic 5 months after surgery. Clinicians should be aware of the possibility of localized AL amyloidosis in the parotid gland, especially if MRI, CT-imaging, and ultrasound are non-conclusive, and should recognize, evaluate, and treat it accordingly.



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Fluorescence tumor imaging by i.v. administered indocyanine green in a mouse model of colitis-associated colon cancer

Summary

Fluorescence tumor imaging using exogenous fluorescent tumor-targeting agents has potential to improve early tumor detection. The fluorescent contrast agent indocyanine green (ICG) is used in medical diagnostics. The aim of the present study is to investigate the tumor imaging capability and the imaging mechanism of i.v. administered ICG in a mouse model of colitis-associated colon cancer. To do this, an azoxymethane/dextran sodium sulfate-induced colon cancer mouse model was used. Ex vivo imaging experiments were performed 1 hour after i.v. injection of ICG. ICG fluorescence was observed in the colon tumor tissues, with sufficient tumor to normal tissue ratio, correlating with tumor malignancy. In the tumor tissues, ICG fluorescence was localized in the vascular interstitial tissue. Immunofluorescence microscopy revealed that tumor cells formed tight junctions normally, suggesting an inability of tumor cellular uptake of ICG. In contrast, tumor tissues increased the CD31-immunoreactive endothelial cell area, and accumulated stromal cells immunoreactive for cyclooxygenase-2 (COX-2) and tumor cell population immunoreactive for inducible nitric oxide synthase (iNOS). vivo vascular permeability assay revealed that prostaglandin E2 promoted the endothelial cell permeability of ICG. In conclusion, our data demonstrated that fluorescence contrast-enhanced imaging following i.v. administered ICG can be applied to the detection of colon tumors in a mouse colitis-associated colon cancer model. The tumor tissue preference of ICG in the present model can be attributed to the enhanced vascular leakage of ICG involving inflammatory mediators, such as COX-2 and iNOS, in conjunction with increased tumor vascularity.

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CD169-positive sinus macrophages in the lymph nodes determine bladder cancer prognosis

Summary

CD169+ macrophages are suggested to play a pivotal role in establishing anti-tumor immunity. They capture dead tumor cell-associated antigens and transfer their information to lymphocytes including CD8+ T cells, which is important for successful tumor suppression. This study aimed to determine the prognostic significance of CD169+ macrophages residing in the tumor-draining lymph nodes from cases of bladder cancer. In this retrospective study, 44 bladder cancer patients who received radical cystectomy were examined. The abundance of CD169+ macrophages in the regional lymph nodes and the number of CD8+ T cells in the primary tumor were investigated by immunohistochemistry. A CD169 score was calculated based on the intensity of CD169 staining and the proportion of CD169+ macrophages, and the scores were compared to the patients' clinicopathological parameters. A high CD169 score was significantly associated with low T stage and with a high number of CD8+ T cells infiltrating into the tumor. The group with high CD169 expression had significantly longer cancer-specific survival than the group with low CD169 expression (5-year cancer-specific survival rate: 83.3% versus 31.3%). In a multivariate analysis, the CD169 score was identified as the strongest and independent favorable prognostic factor for cancer-specific survival. Our findings suggest that CD169+ macrophages in the lymph nodes enhance anti-tumor immunity by expanding CD8+ T cells in bladder cancer. The CD169 score may serve as a novel marker for the evaluation of bladder cancer prognosis.

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A novel method for DNA methylation analysis using high-performance liquid chromatography and its clinical application

Summary

The aim of this study was to develop a new methodology that is suitable for DNA methylation diagnostics and to demonstrate its clinical applicability. We developed a new anion-exchange column for high-performance liquid chromatography (HPLC) with electrostatic and hydrophobic properties. Both cytosine and thymine, corresponding to methylated and unmethylated cytosine after bisulfite modification, respectively, are captured by electrostatic interaction and then discriminated from each other by their hydrophobic interactions. The DNA methylation levels of synthetic DNAs were quantified accurately and reproducibly within 10 minutes without time-consuming pretreatment of PCR products, and the measured values were unaffected by the distribution of methylated CpGs within the synthetic DNA fragments. When the DNA methylation status of the FAM150A gene, a marker of the CpG island methylator phenotype specific to clear cell renal cell carcinoma (ccRCC), was examined in 98 patients with ccRCCs, bulk specimens of tumorous tissue including cancer cells showing DNA methylation of the FAM150A gene were easily identifiable by simply viewing the differentiated chromatograms, even when the cancer cell content was low. Sixteen ccRCCs showing DNA methylation more frequently exhibited clinicopathological parameters reflecting tumor aggressiveness, i.e. a larger diameter, higher histological grade, vascular involvement, renal vein tumor thrombi, infiltrating growth, tumor necrosis, renal pelvis invasion and higher pathological Tumor-Node-Metastasis stage, and had significantly lower recurrence-free and overall survival rates. These data indicate that HPLC analysis using this newly developed anion-exchange column can be a powerful tool for DNA methylation diagnostics, including prognostication of patients with cancers, in a clinical setting.

This article is protected by copyright. All rights reserved.



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The role of primary lymph node sites in survival and mortality prediction in Hodgkin lymphoma: a SEER population-based retrospective study

Abstract

As diagnostic and therapeutic modalities for Hodgkin's Lymphoma (HL) continue to improve, patient-related factors affecting survival become more difficult to identify. Very little is known about the relationship between the primary site of lymph node (LN) involvement and survival of HL patients. We retrospectively analyzed the United States Surveillance, Epidemiology and End Results (SEER) database for 12,658 HL patients reported between 1973 and 2010 using survival analysis and time-interval multiple logistic regression (MLR) to disclose that relationship. The effect of all primary LN sites on the survival of HL patients was supported. The intra-abdominal (IAB) primary LN site was significantly associated with the worst survival. The pelvic (P) LN sites were significantly and independently associated with nearly 2 times and 2.5 times the probability of having 1-year overall mortality (OM) and 1-year cancer-specific mortality (CSM), respectively. Head, face and neck (HFN) primary LN sites were significant and independent predictors of better overall and HL-specific survival. A worse survival with the intra-abdominal primary LN site was probably related to their association with higher age, or advanced stages of HL. The biological basis behind the aggressiveness of intra-abdominal and pelvic LN sites is yet to be investigated.

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Little is known about the role of primary lymph node sites in survival in Hodgkin lymphoma (HL). This study uses a huge population-based cohort using the SEER database. It was found that intra-abdominal LN sites predict the worst survival in HL patients and that pelvic LN sites were the most aggressive in predicting HL-specific 1-year mortality, and hence, we recommend that primary LN sites be added to future international prognostic scores for HL.



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Cross cultural comparison of constipation profiles at tertiary care centers between India and USA

Abstract

Background

Despite potential differences in patient perception of chronic constipation (CC) in geographically and culturally distinct regions, head-to-head studies comparing the clinical profile, constipation severity, impact on quality of life (QOL) and economic impact are lacking.

Methods

We conducted a cross-sectional cohort study of patients presenting with CC to tertiary care centers in the USA and India. Standardized instruments were used to assess constipation subtype, disease severity, disease-specific QOL, somatization, and psychiatric comorbidities. We used multivariable linear regression to determine the predictors of QOL and number of healthcare visits.

Key Results

Sixty-six and 98 patients with CC were enrolled in the USA and India, respectively. Indian patients with CC had significantly more frequent bowel movements/week compared to their USA counterparts (Median 5 vs 3, P < .0001). The proportion of patients with Bristol stool form scale type 1 and 2 was significantly higher in the USA compared to India (65.5% vs 48%, P = .04). Higher depression score (P = .001), more severe constipation symptoms (P = .001) and site of the study being USA (P = .008) independently predicted worse QOL. Indian patients (P < .001) and worse QOL (P = .02) were independent predictors of number of healthcare visits in the last 12 months.

Conclusions and Inferences

Indian patients with CC have more frequent and softer bowel movements compared to those in the USA suggesting significant differences in perception of CC in different geographic and cultural settings. QOL and economic impact related to constipation varies with geographic/cultural setting irrespective of other clinical and psychosomatic features.

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Ours is the first study with head-to-head comparison of clinical profile, psychosomatic burden, constipation-related symptoms severity, constipation specific quality of life and economic impact of chronic constipation between Indian and US patients presenting to tertiary care centres with chronic constipation. We found that Indian patients had significantly higher stool frequency and softer stool consistency (consistent with faster colonic transit) compared to US counterparts. We also showed that constipation-related quality of life not only depends on symptom severity, psychiatric burden but also site of study (Site of study being USA was independent predictor of inferior quality of life). Nevertheless, after adjusting for other covariates, Indian patients had higher direct and indirect healthcare expenditures with increased work absenteeism due to constipation-related symptoms and higher number of healthcare visits for constipation compared to their US counterparts.



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Pediatric versus adult meningioma: comparison of epidemiology, treatments, and outcomes using the Surveillance, Epidemiology, and End Results database

Abstract

Pediatric meningiomas, which account for < 1% of all meningiomas, are thought to have unique features, including being more aggressive than their adult counterparts. The goal of this investigation was to compare pediatric and adult meningiomas in a large head-to-head comparison. We used the Surveillance, Epidemiology, and End Result (SEER) datasets to compare meningioma demographics, first treatments, and outcomes among children/adolescents (0–21 years), young adults (22–45 years), and older adults (> 45 years). During 2004–2012, SEER contained 59148 patients age 0–107 years diagnosed with meningioma, with children/adolescents accounting for 381 (0.64%) patients. Unlike older and young adults, children/adolescents with meningioma did not demonstrate female predominance, and had an equal 1:1 male-to-female ratio. Children/adolescents also had almost three-times as many spinal tumors (13.1%) than young adults (4.2%) and older adults (4.4%). Both children/adolescents and young adults had undergone more gross total resections (both 43%) versus older adults (25%), and were treated more with radiation (14.6%, and 12.0% respectively) than their older counterparts (8.5%). In addition, both children/adolescents and young adults had significantly lower all-cause mortality (4.5% in both) than older adults (24.6%), during median 35-month follow-up. Inherent limitations of the SEER datasets restrict our ability to answer important questions regarding comparisons of tumor grading, histological diagnosis, cause-specific mortality, and neurofibromatosis status. Pediatric meningiomas appear distinct from their adult counterparts as they do not display the typical female predominance and include more clinically relevant spinal tumors. More extensive surgeries, greater use of radiation therapy, and lower all-cause mortality were seen in both children/adolescents and young adults, which raises questions regarding the perceived uniquely aggressive nature of pediatric meningiomas. However, due to the significant limitations of the SEER datasets, our results must be interpreted cautiously and stand only to foster novel questions, which would be better answered in well-designed, prospective studies.



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Effect of Chemical Disinfectants on the Color Stability of Maxillofacial Silicones: An In Vitro Study

Abstract

Purpose

To evaluate the effect of chemical disinfection on the color stability of room temperature vulcanizing (RTV) maxillofacial silicone elastomer with and without pigment addition.

Materials and Methods

Sixty specimens were obtained from a RTV maxillofacial silicone. The specimens were randomly divided into 6 groups according to pigments and disinfectant to be used (n = 10). NP-DW-nonpigmented silicone specimens to be immersed in distilled water (control). NP-S- nonpigmented silicone specimens to be rubbed with an anti-bacterial soap. NP-CHX-nonpigmented silicone specimens to be immersed in chlorhexidine gluconate solution (2%). P-DW-pigmented silicone specimens to be immersed in distilled water (control). P-S-pigmented silicone specimens to be rubbed with antibacterial soap. P-CHX-pigmented silicone specimens to be immersed in chlorhexidine gluconate solution (2%). Disinfection was conducted 6 times a day for 60 days simulating 1 year of usage. Color was evaluated after 60 days (disinfection period) using a reflectance spectrophotometer. Color alterations were calculated by the CIE Lab system. Data were analyzed by t-test, one-way ANOVA, and Tukey test (α = 0.05).

Results

NP-S and P-S exhibited the highest color alterations, whereas NP-DW and P-DW the lowest color alterations.

Conclusion

Disinfection procedures affect the color stability of maxillofacial silicone. Chlorhexidine gluconate solution (2%) can be effectively used as a chemical disinfectant for maxillofacial prostheses. Antibacterial soap produced clinically unacceptable color changes in the silicone, hence is not advisable as a disinfectant.



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Restless Legs Syndrome is associated with major comorbidities in a population of Danish blood donors

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Publication date: Available online 8 March 2018
Source:Sleep Medicine
Author(s): Maria Didriksen, Richard P. Allen, Brendan J. Burchell, Lise W. Thørner, Andreas S. Rigas, Emanuele Di Angelantonio, Maria H. Nielsen, Poul J. Jennum, Thomas Werge, Christian Erikstrup, Ole B. Pedersen, Kaspar Nielsen, Mie T. Bruun, Kristoffer S. Burgdorf, Erik Sørensen, Henrik Ullum
BackgroundRestless Legs Syndrome (RLS) is characterized by uncomfortable nocturnal sensations in the legs making sedentary activities and sleep difficult, and thus is linked with psychosocial distress. Due to the symptomatology and neurobiology of RLS (disrupting brain iron and dopamine) it is likely that RLS associates with poorer health-related quality of life (HRQL) and depressive disorder. The objective of this study was to investigate the RLS-HRQL and the RLS-depressive disorder links in a generally healthy population that is not biased by medications.MethodsComplete data, including the Cambridge-Hopkins RLS questionnaire, the 12-item short-form standardized health survey (SF-12), the Major Depression Inventory (MDI), body mass index, smoking status, alcohol consumption, and education were available for 24,707 participants enrolled in the Danish Blood Donor Study from May 1, 2015 to February 1, 2017. Information on quality of sleep was available for all RLS cases. T-tests and multivariable logistic regression models were applied to examine the associations of RLS and MDI scores, and the physical and mental component scores (PCS and MCS) of SF-12, respectively. Analyses were conducted separately for men and women.ResultsRLS associated with poorer MCS and poorer PCS. Moreover, Participants with RLS were more likely to classify with depressive disorder. Poor quality of sleep was associated with depressive disorder and poorer MCS among RLS cases, and with poorer PCS in female RLS cases.ConclusionThus, we demonstrated that RLS is associated with a significantly lower HRQL and a higher prevalence of depressive disorder among otherwise healthy individuals.



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Maintenance of Wakefulness Test, real and simulated driving in narcolepsy/hypersomnia patients

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Publication date: Available online 8 March 2018
Source:Sleep Medicine
Author(s): Patricia Sagaspe, Jean-Arthur Micoulaud-Franchi, Olivier Coste, Damien Léger, Stéphane Espié, Damien Davenne, Régis Lopez, Yves Dauvilliers, Pierre Philip
Study ObjectivesTo assess the relationship between real and simulated driving performance and the objective level of alertness as measured by the Maintenance of Wakefulness Test (MWT) in patients suffering from narcolepsy or idiopathic hypersomnia.Methods27 patients (10 patients with narcolepsy, type 1 (n=7) and type 2 (n=3), and 17 patients with idiopathic hypersomnia, mean age=33.8 ± 11.1 years, range=18-65 y; 4 males) were recruited in a randomized, crossover, double-blind placebo-controlled trial and compared to 27 matched healthy controls. Patients were randomly assigned to receive modafinil (400 mg) or placebo before the driving test (2 hours of real and 2 hours of simulated highway driving for each patient). Standard Deviation of Lateral Position (SDLP) of the vehicle in real and simulated driving and mean sleep latency in a 4 x 40min MWT were assessed.ResultsUntreated patients presented shorter sleep latencies on the MWT (20.8 (IQ range 16.1-32.9) vs. 34.9 min (IQ range 28.1-40.0)) and worse simulated driving performance (P<0.001) than treated patients. Nevertheless, treated patients still exhibited shorter mean sleep latencies on the MWT than controls (34.9 (IQ range 28.1-40.0) vs. 40 min (IQ range 37.1-40.0), P<0.05) but driving performance was identical in both groups. The SDLP of the vehicle in real driving conditions and the MWT score correlated with the SDLP in simulated driving (respectively, r=0.34, P<0.05 and r=-0.56, P<0.001).ConclusionsIn patients with narcolepsy/idiopathic hypersomnia, simulated driving and MWT explore different dimensions of fitness-to-drive and could be used complementarily to better evaluate sleep-related driving impairment.



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Impaired short-term plasticity in Restless Legs Syndrome: a pilot rTMS study

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Publication date: Available online 8 March 2018
Source:Sleep Medicine
Author(s): Giuseppe Lanza, Bartolo Lanuzza, Debora Aricò, Mariagiovanna Cantone, Filomena Irene Ilaria Cosentino, Rita Bella, Giovanni Pennisi, Raffaele Ferri, Manuela Pennisi
BackgroundPrevious studies showed an impairment of the LTP-like plasticity to TMS in Restless Legs Syndrome (RLS). Clinically, repetitive TMS (rTMS) was effective in alleviating the sensory-motor complaints of patients, although the effects induced by low-frequency (inhibitory) rTMS have not been investigated yet. An impaired LTD-like mechanism of cortical plasticity has been hypothesized, which we have directly assessed in this pilot study.MethodsMotor evoked potentials (MEPs) from the right first dorsal interosseus muscle were recorded at the stimulus intensity of 110% of the resting motor threshold (rMT) from 13 right-handed patients and 10 age-matched right-handed healthy controls. Median peak-to-peak amplitudes were calculated in all participants at baseline (T0), after the first train of a single evening session of low-frequency (1 Hz) rTMS over the left primary motor cortex (T1), and after the whole rTMS procedure (T2), which consists of 20 trains with 50 stimuli per train and intertrain interval of 30 s (1,000 stimuli in total).ResultsNo differences were found for rMT and MEPs size between the two groups at T0. Smaller MEPs amplitudes both at T1 and T2 were observed in all subjects, although this was significantly more pronounced in controls than in patients.Conclusionscompared to normal individuals, patients exhibited an impairment of the LTD-like mechanisms induced by inhibitory rTMS, adding support to the involvement of GABA in RLS pathophysiology. Although future studies with a larger population are needed, TMS is confirmed to be effetive in non-invasively probing of the neurophysiology and neurochemistry of RLS.



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Prevalence and risk factors of type 2 diabetes in insomnia sufferers: A study on 1311 individuals referred for sleep examinations

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Publication date: Available online 8 March 2018
Source:Sleep Medicine
Author(s): Matthieu Hein, Jean-Pol Lanquart, Gwénolé Loas, Philippe Hubain, Paul Linkowski
BackgroundSeveral studies have investigated the particular relationship between insomnia and type 2 diabetes. However, few studies have investigated the prevalence and risk factors for type 2 diabetes in insomnia sufferers. The aim of this study was to examine the prevalence and risk factors of type 2 diabetes in a large sample of insomnia sufferers.MethodsData from 1311 insomnia sufferers recruited from the research database of the Erasme Hospital sleep laboratory were analysed. Only individuals with a diagnosis of type 2 diabetes according to the diagnostic criteria of the American Diabetes Association at admission were included in the diabetes group. Logistic regression analyses were conducted to examine clinical and demographic risk factors of type 2 diabetes in insomnia sufferers.ResultsThe prevalence of type 2 diabetes in insomnia sufferers is 21.13%. Multivariate logistic regression analysis revealed that significant risk factors of type 2 diabetes in insomnia sufferers were as follows: being male, Z-drugs use, high blood pressure, hypertriglyceridemia, alcohol consumption of ≥4 units/day, BMI ≥25 & <30 kg/m2, BMI ≥30 kg/m2, age ≥50 years, C-reactive protein ≥4.5 mg/L, a sleep duration of <6.5 hours, apnea-hypopnea index ≥15/hour, periodic limb movements index ≥26/hour, and severe complaints of early morning awakening.ConclusionType 2 diabetes is a common pathology in insomnia sufferers. In this subpopulation, most of the risk factors for type 2 diabetes are reversible, which justifies better prevention and management of this pathology in order to avoid its negative consequences.



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Stability of matrix metalloproteinase-9 as biological marker in colorectal cancer

Abstract

Matrix metalloproteinases (MMPs) are believed to be of importance in the growth and spread of colorectal cancer (CRC). MMP-9 level has been suggested as a biological predictor of prognosis in CRC as well as in other types of cancer such as breast and cervical cancer. The purpose of this study was to investigate the stability over time of MMP-9 in cryopreserved plasma, colorectal tumor tissue extract and macroscopically tumor-free colon mucosa tissue extract samples. Plasma and tissue samples were taken from patients at primary CRC surgery and analyzed for MMP-9. Aliquots of samples from the same patients were stored at – 80 °C pending analysis. These aliquots were analyzed using identical methods after storage periods of nine (plasma) and twelve (tissue) years. No significant difference in plasma MMP-9 concentration was seen between baseline samples and those after 9 years of cryopreservation (median values 9.9 and 9.7 ng/mL, respectively; p > 0.05). MMP-9 levels in the tumor-free tissue extracts had increased to baseline (median values 7.1 and 8.1 ng/mL, respectively; p < 0.01). MMP-9 levels in the tumor tissue extracts had also increased significantly (median values 89.9 and 133.5 ng/mL, respectively; p < 0.01). We have demonstrated that MMP-9 levels in frozen citrated plasma are stable if stored at − 80 °C, whereas MMP-9 levels in extracts from tumor tissue and tumor-free intestinal mucosa appear to increase with time. We conclude that MMP-9 levels in cryopreserved plasma may be considered stable over time and are thus suitable for comparison purposes in consecutive series.



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Phylogenetic patterns and correlation of key structures for jumping: bone crests and cross-sectional areas of muscles in Leptodactylus (Anura, Leptodactylidae)

Abstract

Anurans are characterized by their saltatory mode of locomotion, which is associated with a specific morphology. The coordinated action of the muscles and bones of the pelvic girdle is key to the transmission of the force of the hindlimbs to the axial skeleton during jumping. Two features are critical for optimal locomotory performance: the cross-sectional area of muscle and the bone crest attachment sites. The first character is a proxy of the force exerted by the muscle, whereas the crests are muscle attachments sites related to muscle force. The provisory relationship between these features has previously been identified and bone crest size can be used to infer the magnitude and, therefore, muscle force in fossils records. In this work, we explore the correlation between the cross-sectional area of essential muscles to the jumping mechanism (longissimus dorsi, extensor iliotibialis B, tenuissimus, puboischiofemoralis internus B, coccygeo-sacralis and coccygeo-iliacus) and the bone crests where these muscles are inserted (dorsal tubercle, dorsal crest and urostylar crest) in species of the genus Leptodactylus. This genus, along with other leptodactylids, exhibits a diversity of locomotor modes, including jumping, hopping, swimming and burrowing. We therefore analyzed the morphometric variation in the two features, cross-sectional area and bone crest area, expecting a correlation with different locomotor types. Our results showed: (i) a correlation between the urostylar crest and the cross-sectional area of the related muscles; (ii) that the bone crest surface area of urostyle and ilium and the cross-sectional area of the corresponding muscles can be utilized to infer locomotor faculties in leptodactylid frogs; and (iii) that the evolution of both characters demonstrates a general tendency from lower values in leptodactylid ancestors to higher values in the Leptodactylus genus. The results attest to the importance of the comparison of current ecological and phylogenetic analogues as they allow us to infer functionality and behavior in fossil and extant groups based on skeletal evidence. Phylogenetic patterns in character evolution and their correlation with locomotory types could imply that functional restrictions are also inherited in leptodactylid.



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Interpreting the three-dimensional orientation of vascular canals and cross-sectional geometry of cortical bone in birds and bats

Abstract

Cortical bone porosity and specifically the orientation of vascular canals is an area of growing interest in biomedical research and comparative/paleontological anatomy. The potential to explain microstructural adaptation is of great interest. However, the determinants of the development of canal orientation remain unclear. Previous studies of birds have shown higher proportions of circumferential canals (called laminarity) in flight bones than in hindlimb bones, and interpreted this as a sign that circumferential canals are a feature for resistance to the torsional loading created by flight. We defined the laminarity index as the percentage of circumferential canal length out of the total canal length. In this study we examined the vascular canal network in the humerus and femur of a sample of 31 bird and 24 bat species using synchrotron micro-computed tomography (micro-CT) to look for a connection between canal orientation and functional loading. The use of micro-CT provides a full three-dimensional (3D) map of the vascular canal network and provides measurements of the 3D orientation of each canal in the whole cross-section of the bone cortex. We measured several cross-sectional geometric parameters and strength indices including principal and polar area moments of inertia, principal and polar section moduli, circularity, buckling ratio, and a weighted cortical thickness index. We found that bat cortices are relatively thicker and poorly vascularized, whereas those of birds are thinner and more highly vascularized, and that according to our cross-sectional geometric parameters, bird bones have a greater resistance to torsional stress than the bats; in particular, the humerus in birds is more adapted to resist torsional stresses than the femur. Our results show that birds have a significantly (P = 0.031) higher laminarity index than bats, with birds having a mean laminarity index of 0.183 in the humerus and 0.232 in the femur, and bats having a mean laminarity index of 0.118 in the humerus and 0.119 in the femur. Counter to our expectation, the birds had a significantly higher laminarity index in the femur than in the humerus (P = 0.035). To evaluate whether this discrepancy was a consequence of methodology we conducted a comparison between our 3D method and an analogue to two-dimensional (2D) histological measurements. This comparison revealed that 2D methods significantly underestimate (P < 0.001) the amount of longitudinal canals by an average of 20% and significantly overestimate (P < 0.001) the laminarity index by an average of 7.7%, systematically mis-estimating indices of vascular canal orientations. In comparison with our 3D results, our approximated 2D measurement had the same results for comparisons between the birds and bats but found significant differences only in the longitudinal index between the humerus and the femur for both groups. The differences between our 3D and pseudo-2D results indicate that differences between our findings and the literature may be partially based in methodology. Overall, our results do not support the hypothesis that the bones of flight are more laminar, suggesting a complex relation between functional loading and microstructural adaptation.



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Valoración de la reacción emocional provocada por la prueba vestibular calórica mediante monitorización de variables fisiológicas

Publication date: Available online 8 March 2018
Source:Acta Otorrinolaringológica Española
Author(s): Rafael Barona-de-Guzmán, Claudio Krstulovic-Roa, Elena Donderis-Malea, Luz Barona-Lleó
Introducción y objetivosLa valoración emocional que provoca el vértigo se realiza mediante la historia clínica y diversos cuestionarios subjetivos. El objetivo del presente trabajo es valorar la respuesta emocional de forma objetiva, en sujetos normales, durante la crisis de vértigo inducida.Material y métodoSe realizó la prueba vestibular calórica con agua fría en 30 sujetos sanos. Durante los 60s previos a la estimulación y los 60s posteriores a la misma se monitorizaron las siguientes variables fisiológicas: Conductabilidad cutánea, Volumen de pulso periférico, Temperatura corporal, Contracción muscular, Frecuencia cardiaca y Frecuencia respiratoria. Se valoró la velocidad angular máxima de la fase lenta del nistagmo provocado en cada estimulación.ResultadosDurante las crisis de vértigo, la conductabilidad cutánea presentó un aumento estadísticamente significativo con relación al periodo previo a las mismas, mientras que el volumen de pulso periférico presentó una disminución estadísticamente significativa. No hubo relación entre la velocidad angular de la fase lenta del nistagmo provocado y los cambios de la conductabilidad y el volumen de pulso periférico. La disminución provocada en el volumen de pulso periférico fue significativamente mayor en la segunda crisis de vértigo.ConclusionesLa conductabilidad cutánea y el volumen de pulso periférico cambiaron de forma significativa durante las crisis de vértigo. No Hubo relación entre la intensidad de la crisis vertiginosa provocada y los cambios producidos en estas variables. El estrés generado por la estimulación calórica es mayor en la segunda crisis, cuando el sujeto tiene experiencia del vértigo que provoca la estimulación.Introduction and objectivesThe emotional evaluation of the causes of vertigo is made using the clinical records and several subjective questionnaires. The aim of the present study is to evaluate the emotional response objectively, in normal subjects, during an induced vertigo crisis.Material and methodA caloric vestibular test with cold water was performed on 30 healthy subjects. The following physiological parameters were monitored during the 60seconds prior to and the 60seconds after the stimulation: Skin Conductivity, Peripheral Pulse Volume, Body Temperature, Muscle Contraction, Heart Rate, and Respiratory Rate. The maximum angular speed of the nystagmus slow phase at each stimulation was assessed.ResultsSkin conductance presented a statistically significant increase during the vertigo crisis in relation to the prior period while the peripheral pulse volume presented a statistically significant decrease. There was no relationship between the slow phase of the provoked nystagmus angular speed and skin conductance and peripheral pulse volume changes. The decrease in peripheral pulse volume was significantly higher in the second vertigo crisis.ConclusionsSkin conductance and peripheral pulse volume changed significantly during a vertigo crisis. There was no relation between the provoked vertiginous crisis intensity and the changes produced in those variables. The stress generated by the caloric stimulation is higher in the second crisis, when the subject has experience of the vertigo caused by the stimulation.



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Audiological Assessment of Word Recognition Skills in Persons With Aphasia

Purpose
The purpose of this study was to evaluate the ability of persons with aphasia, with and without hearing loss, to complete a commonly used open-set word recognition test that requires a verbal response. Furthermore, phonotactic probabilities and neighborhood densities of word recognition errors were assessed to explore potential underlying linguistic complexities that might differentially influence performance among groups.
Method
Four groups of adult participants were tested: participants with no brain injury with normal hearing, participants with no brain injury with hearing loss, participants with brain injury with aphasia and normal hearing, and participants with brain injury with aphasia and hearing loss. The Northwestern University Auditory Test No. 6 (NU-6; Tillman & Carhart, 1966) was administered. Those participants who were unable to respond orally (repeating words as heard) were assessed with the Picture Identification Task (Wilson & Antablin, 1980), permitting a picture-pointing response instead. Error patterns from the NU-6 were assessed to determine whether phonotactic probability influenced performance.
Results
All participants with no brain injury and 72.7% of the participants with aphasia (24 out of 33) completed the NU-6. Furthermore, all participants who were unable to complete the NU-6 were able to complete the Picture Identification Task. There were significant group differences on NU-6 performance. The 2 groups with normal hearing had significantly higher scores than the 2 groups with hearing loss, but the 2 groups with normal hearing and the 2 groups with hearing loss did not differ from one another, implying that their performance was largely determined by hearing loss rather than by brain injury or aphasia. The neighborhood density, but not phonotactic probabilities, of the participants' errors differed across groups with and without aphasia.
Conclusions
Because the vast majority of the participants with aphasia examined could be tested readily using an instrument such as the NU-6, clinicians should not be reticent to use this test if patients are able to repeat single words, but routine use of alternative tests is encouraged for populations of people with brain injuries.

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Synchronisation in the prefrontal-striatal circuit tracks behavioural choice in a go no-go task in rats

Abstract

Rodent striatum is involved in sensory-motor transformations and reward-related learning. Lesion studies suggest dorsolateral striatum, dorsomedial striatum, and nucleus accumbens underlie stimulus-response transformations, goal-directed behaviour and reward expectation respectively. In addition, prefrontal inputs likely control these functions. Here we set out to study how reward-driven behaviour is mediated by the coordinated activity of these structures in the intact brain. We implemented a discrimination task requiring rats to either respond or suppress responding on a lever after the presentation of auditory cues in order to obtain rewards. Single unit activity in the striatal subregions and prelimbic cortex was recorded using tetrode arrays. Striatal units showed strong onset responses to auditory cues paired with an opportunity to obtain reward. Cue onset responses in both striatum and cortex were significantly modulated by previous errors suggesting a role of these structures in maintaining appropriate motivation or action selection during ongoing behaviour. Furthermore, failure to respond to the reward-paired tones was associated with higher pre-trial coherence among striatal subregions and between cortex and striatum suggesting a task-negative corticostriatal network whose activity may be suppressed to enable processing of reward-predictive cues. Our findings highlight that coordinated activity in a distributed network including both prelimbic cortex and multiple striatal regions underlies reward-related decisions.

This article is protected by copyright. All rights reserved.



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Investigating the Knowledge, Skills, and Tasks Required for Hearing Aid Management: Perspectives of Clinicians and Hearing Aid Owners

Purpose
The purpose of this study is to identify hearing aid owners' and clinicians' opinions of the knowledge, skills, and tasks required for hearing aid management and the importance of each of these to overall success with hearing aids.
Method
Concept mapping techniques were used to identify key themes, wherein participants generated, sorted, and rated the importance of statements in response to the question "What must hearing aid owners do in order to use, handle, manage, maintain, and care for their hearing aids?" Twenty-four hearing aid owners (56 to 91 years of age; 54.2% men, 45.8% women) and 22 clinicians (32 to 69 years of age; 9.1% men, 90.9% women) participated.
Result
Participants identified 111 unique items describing hearing aid management within 6 concepts: (a) "Daily Hearing Aid Use," (b) "Hearing Aid Maintenance and Repairs," (c) "Learning to Come to Terms with Hearing Aids," (d) "Communication Strategies," (e) "Working With Your Clinician," and (f) "Advanced Hearing Aid Knowledge." Clinicians' opinions of the importance of each statement varied only slightly from the opinions of the hearing aid owner group. Hearing aid owners indicated that all 6 concepts were of similar importance, whereas clinicians indicated that the concept "Advanced Hearing Aid Knowledge" was significantly less important than the other 5 concepts.
Conclusion
The results highlight the magnitude of information and skill required to optimally manage hearing aids. Clinical recommendations are made to improve hearing aid handling education and skill acquisition.

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Reevaluating Order Effects in the Binaural Bithermal Caloric Test

Purpose
The purpose of this study was to determine whether a significant order effect exists in the binaural bithermal caloric test.
Method
Fifteen volunteers (mean age = 24.3 years, range = 18–38 years) with no history of vestibular disorder, hearing loss, concussion, or neurological disease underwent caloric testing on 3 occasions. Irrigations were randomized using 8 possible order combinations. The parameters of interest included unilateral weakness, directional preponderance, total response from the right ear, and total response from the left ear.
Results
Order effects were analyzed using 2 methods. The first analysis was done looking at the 8 possible orders. We also had an a priori established hypothesis that the first irrigation tested would influence the calculation of unilateral weakness more than the other 3 irrigations. To test this hypothesis, the 8 orders were condensed into 4 order conditions based on the first irrigation. The effect of order was determined using analysis of variance tests. Although the first irrigation tended to be the largest, no significant effects were observed.
Conclusions
This experiment demonstrated that while there is great inter-individual and intra-individual variability in caloric test results, the order of irrigations had no significant effect in the test. Future studies may explore the effects of nonphysiological factors on test results.

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Clinicians' Guide to Obtaining a Valid Auditory Brainstem Response to Determine Hearing Status: Signal, Noise, and Cross-Checks

Purpose
The auditory brainstem response (ABR) is a powerful tool for making clinical decisions about the presence, degree, and type of hearing loss in individuals in whom behavioral hearing thresholds cannot be obtained or are not reliable. Although the test is objective, interpretation of the results is subjective.
Method
This review provides information about evidence-based criteria, suggested by the 2013 Newborn Hearing Screening Program guidelines, and the use of cross-check methods for making valid interpretations about hearing status from ABR recordings.
Results
The use of an appropriate display scale setting, templates of expected response properties, and objective criteria to estimate the residual noise, signal level, and signal-to-noise ratio will provide quality data for determining ABR thresholds. Cross-checks (e.g., immittance measures, otoacoustic emissions testing, functional indications of a child's hearing) are also needed to accurately interpret the ABR.
Conclusions
Using evidence-based ABR signal detection criteria and considering the results within the context of other physiologic tests and assessments of hearing function will improve the clinician's accuracy for detecting hearing loss and, when present, the degree of hearing loss. Diagnostic accuracy will ensure that appropriate remediation is initiated and that children or infants with normal hearing are not subjected to unnecessary intervention.

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Effects of Bilateral Hearing Aid Use on Balance in Experienced Adult Hearing Aid Users

Purpose
The purpose of this study was to evaluate the balance of experienced adult hearing aid users with and without their hearing aids via computerized posturography.
Method
Computerized posturography was accomplished by employing the Sensory Organization Test (SOT) on the NeuroCom Balance Master (Natus Medical Incorporated). The SOT assessed each participant's balance and the strategy used to maintain balance in 6 progressively challenging conditions. Twenty-two adults using bilateral at-the-ear hearing aids participated in the study. All participants completed all SOT protocols with and without their hearing aids.
Results
No statistically significant differences in participants' balance were identified regardless of the presence or absence of their hearing aids during the SOT.
Conclusions
These results failed to support previous research, which indicated that amplification of auditory input could benefit balance in individuals with hearing and balance disorders. Further research utilizing randomized controlled trials is needed to resolve the disparity between the current results and those of previous studies.

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Improving Hearing Aid Self-Efficacy and Utility Through Revising a Hearing Aid User Guide: A Pilot Study

Purpose
This pilot study aimed to investigate whether revising a hearing aid user guide (HAUG) is associated with improved hearing aid self-efficacy and utility performance.
Method
In Part 1, an HAUG was evaluated using the Suitability Assessment of Material (SAM) and readability formulas (Flesch Reading Ease [Flesch, 1943], Flesch-Kincaid Readability Formula [Kincaid, Fishburne, Rogers, & Chissom, 1957], and Simple Measure of Gobbledygook [McLaughlin, 1969]). The HAUG was revised using results from the SAM and best practice guidelines. The revision included generating a video. In Part 2, 30 adults with hearing impairment were randomly assigned to use either the original guide (N = 15) or the revised guide and video (N = 15) to perform a utility task. Participants' self-efficacy was measured using the Basic and Advanced Handling subscales of the Measure of Audiologic Rehabilitation Self-Efficacy for Hearing Aids questionnaire. SAM and readability were compared between the original and revised guides (Doak, Doak, & Root, 1996).
Results
SAM and readability were improved following the revision. Participants in the revised guide group performed significantly better on the utility task and on the Measure of Audiologic Rehabilitation Self-Efficacy for Hearing Aids subscales than participants in the original guide group.
Conclusions
These results are encouraging as they indicate that there is scope to influence self-efficacy and utility performance through the use of appropriate HAUGs.

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Self-Stigma and Age-Related Hearing Loss: A Qualitative Study of Stigma Formation and Dimensions

Purpose
This study explored experiences of self-stigma among older persons with age-related hearing loss (ARHL) using Corrigan's conceptualization of self-stigma process formation and the attribution model as its theoretical framework.
Method
In-depth semistructured interviews were conducted with 11 older persons (mean age = 81 years) with ARHL.
Results
Self-stigma was present in the lives of the participants. Analysis revealed the existence of 3 stages of self-stigma in which the 3 core dimensions of stigma (cognitive attributions: being old, stupid, and crippled; emotional reactions: shame, pity, and feeling ridiculed; and behavioral reactions: concealment, distancing, and adapting to hearing aids) were observed. Hearing devices emerged as having a significant influence on stigmatic experiences in all stages and dimensions of self-stigma.
Conclusion
The study contributes to the theoretical and practical understanding of self-stigma regarding ARHL as well as to the understanding of the role of hearing devices in the development of this stigma.

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The Effects of Varying Directional Bandwidth in Hearing Aid Users' Preference and Speech-in-Noise Performance

Purpose
Directional microphone systems are typically used to improve hearing aid users' understanding of speech in noise. However, directional microphones also increase internal hearing aid noise. The purpose of this study was to investigate how varying directional microphone bandwidth affected listening preference and speech-in-noise performance.
Method
Ten participants with normal hearing and 10 participants with hearing impairment compared internal noise levels between hearing aid memories with 4 different microphone modes: omnidirectional, full directional, high-frequency directionality with directional processing above 900 Hz, and high-frequency directionality with directional processing above 2000 Hz. Speech-in-noise performance was measured with each memory for the participants with hearing impairment.
Results
Participants with normal hearing preferred memories with less directional bandwidth. Participants with hearing impairment also tended to prefer the memories with less directional bandwidth. However, the majority of participants with hearing impairment did not indicate a preference between omnidirectional and directional above 2000 Hz memories. Average hearing-in-noise performance improved with increasing directional bandwidth.
Conclusions
Most participants preferred memories with less directional bandwidth in quiet. Participants with hearing impairment indicated no difference in preference between directional above 2000 Hz and the omnidirectional memories. Speech recognition in noise performance improved with increasing directional bandwidth.

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Management of Recurrent Vestibular Neuritis in a Patient Treated for Rheumatoid Arthritis

Purpose
This clinical report is presented to describe how results of vestibular function testing were considered along with other medical history to develop a management plan that was ultimately successful.
Method
The patient underwent audio-vestibular assessment including comprehensive audiogram, videonystagmography, cervical vestibular evoked myogenic potential, and postural stability testing.
Results
Results from initial testing were most consistent with uncompensated peripheral vestibular dysfunction affecting the right superior vestibular nerve. These results, considered along with history and symptoms, supported vestibular neuritis. After a second vertigo event, we became concerned about the potential temporal association between the patient's rheumatoid arthritis treatment and symptom onset. It is established that treatment for rheumatoid arthritis can exacerbate latent viral issues, but this has not specifically been reported for vestibular neuritis. There are reports in the literature in which patients successfully used viral suppressant medication to decrease viral activity while they were able to continue benefiting from immunosuppressive therapy. We hypothesized that, if the current patient's vestibular neuritis events were related to her treatment for rheumatoid arthritis, she may also benefit from use of viral suppressant medication while continuing her otherwise successful immunosuppressive intervention.
Conclusions
Patients treated with biologic disease-modifying antirheumatic drugs are more susceptible to viral issues, and this may include vestibular neuritis. For the current case, identifying this possibility and recommending viral suppressant medication allowed her to continue with successful treatment of rheumatoid arthritis while avoiding additional vertigo events.

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A Cross-Sectional Study on the Hearing Threshold Levels Among People in Qinling, Qinghai, and Nanjing, China

Purpose
This study aimed to investigate the hearing threshold among different age groups, genders, and geographic areas in China to provide some insight into the appropriate clinical interventions for hearing loss.
Method
Using a systematic random sampling technique, 562 participants from Qinling, Qinghai, and Nanjing were included. Participants in the same area were divided into 3 groups according to their age. Pure-tone audiometric thresholds were measured at octave and interoctave frequencies of 0.125–16 kHz for each subject.
Results
There were significant differences in auditory thresholds at nearly all frequencies among young, middle-aged, and elderly people, and hearing thresholds increased with increasing age. People generally had the best hearing ability in Nanjing, better hearing ability in Qinghai, and the worst hearing ability in Qinling. Significant differences in hearing thresholds were found between males and females at several frequencies in Qinling.
Conclusion
People living in the rural area of Qinling in China had higher hearing threshold levels, particularly males, and hearing thresholds increased with age.

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Validation of the Chinese Sound Test: Auditory Performance of Hearing Aid Users

Purpose
The Chinese Sound Test (Hung, Lin, Tsai, & Lee, 2016) has been recently developed as a modified version of the Ling Six-Sound Test (Ling, 2012). By incorporating Chinese speech sounds, this test should be able to estimate whether the listener can hear across the Chinese speech spectrum. To establish the clinical validity of the test, this study examined the relationship between the aided audiometric thresholds and the distance thresholds.
Method
Sixty children with bilateral hearing aids were recruited. The aided sound-field thresholds at 250, 500, 1000, 2000, 4000, and 6000 Hz were compared with the distance thresholds of six sounds, /u, ə, a, i, tɕʰ, and s/, which encompass the entire Chinese speech frequency range from low to high.
Results
Partial correlation and stepwise regression analyses revealed that the Chinese testing sounds are frequency specific and that the audibility of each sound could be predicted by a specific frequency threshold.
Conclusions
The results confirm the validity of the Chinese Sound Test, indicating that the testing sounds can be reliably used to assess the perception of frequency-specific information. Crucially, these data also demonstrate that the Chinese Sound Test is a useful tool to identify red flags of poor auditory access in daily environment to monitor device malfunctions and possible hearing fluctuations.

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Structured Review of Dichotic Tests of Binaural Integration: Clinical Performance in Children

Purpose
The aim of the study was to evaluate the evidence of clinical utility for dichotic speech tests of binaural integration used to assess auditory processing in English-speaking children 6–14 years old.
Method
Dichotic speech test recordings and pertinent research studies were identified from iterative searches of the Internet and bibliographic databases, as well as communication with colleagues and test publishers. Test documentation and peer-reviewed literature were evaluated for evidence of reliability, accuracy, usefulness, and value.
Results
Eleven dichotic tests of binaural integration were identified for children. Evidence of test–retest reliability was found for 5 tests and demonstrated moderate to good correlation between results on repeated administration (r = .59–.92). Evidence of accuracy was identified for 5 tests but was either inconsistent with accurate performance or was not generalizable due to significant limitations in study design. No evidence was found to either support or dispute claims of usefulness or value.
Conclusions
A medical diagnostic framework is useful for evaluating dichotic tests. Although dichotic procedures show moderate reliability, the absence of a widely accepted gold standard reference test limits our ability to assess their value. Overall, the data available at the time of this review do not support the routine use of dichotic tests of binaural integration for clinical evaluation of children.

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Newborn Screening of Genetic Mutations in Common Deafness Genes With Bloodspot-Based Gene Chip Array

Purpose
This study screens for deafness gene mutations in newborns in the Northwest China population.
Method
The 9 sites of 4 common deafness genes (GJB2, GJB3, SLC26A 4, and mt 12S rRNA) were detected by bloodspot-based gene chip array in 2,500 newborns.
Results
We detected mutations of the 4 genes in 101 (4.04%) newborns; particularly, 0.20% detected the double mutations. In the Hui population, 4.58% of the newborns tested positive for mutations, whereas 4.01% of Han newborns tested positive for mutations. The detective rates are as follows: 1.44% for GJB2 235delC, 1.08% for SLC26A4 IVS7-2A>G, 0.48% for GJB2 299_300delAT, 0.28% for SLC26A4 2168A>G, 0.2% for mt 12S rRNA 1555A>G, and 0.16% for GJB3 538C>T. The 31.25% (5/16) of infants with GJB2 235delC, 50% (3/6) with GJB2 299_300delAT, and 25% (3/12) with SLC26A4 IVS7-2A>G showed abnormal hearing when tested; only 1 double mutation case received the hearing test, and this infant showed abnormality in both ears on the hearing test.
Conclusions
High mutation rates in the common deafness genes were detected in newborns in Northwest China. Our study is helpful in understanding the deafness genomic epidemiology and also provides evidence for prenatal and postnatal care as well as policy making on population health in the region.

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Comment on Hall et al. (2017), “How to Choose Between Measures of Tinnitus Loudness for Clinical Research? A Report on the Reliability and Validity of an Investigator-Administered Test and a Patient-Reported Measure Using Baseline Data Collected in a Phase IIa Drug Trial”

Purpose
The purpose of this letter, in response to Hall, Mehta, and Fackrell (2017), is to provide important knowledge about methodology and statistical issues in assessing the reliability and validity of an audiologist-administered tinnitus loudness matching test and a patient-reported tinnitus loudness rating.
Method
The author uses reference textbooks and published articles regarding scientific assessment of the validity and reliability of a clinical test to discuss the statistical test and the methodological approach in assessing validity and reliability in clinical research.
Results
Depending on the type of the variable (qualitative or quantitative), well-known statistical tests can be applied to assess reliability and validity. The qualitative variables of sensitivity, specificity, positive predictive value, negative predictive value, false positive and false negative rates, likelihood ratio positive and likelihood ratio negative, as well as odds ratio (i.e., ratio of true to false results), are the most appropriate estimates to evaluate validity of a test compared to a gold standard. In the case of quantitative variables, depending on distribution of the variable, Pearson r or Spearman rho can be applied.
Conclusion
Diagnostic accuracy (validity) and diagnostic precision (reliability or agreement) are two completely different methodological issues. Depending on the type of the variable (qualitative or quantitative), well-known statistical tests can be applied to assess validity.

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Binaural Speech Understanding With Bilateral Cochlear Implants in Reverberation

Purpose
The purpose of this study was to investigate whether bilateral cochlear implant (CI) listeners who are fitted with clinical processors are able to benefit from binaural advantages under reverberant conditions. Another aim of this contribution was to determine whether the magnitude of each binaural advantage observed inside a highly reverberant environment differs significantly from the magnitude measured in a near-anechoic environment.
Method
Ten adults with postlingual deafness who are bilateral CI users fitted with either Nucleus 5 or Nucleus 6 clinical sound processors (Cochlear Corporation) participated in this study. Speech reception thresholds were measured in sound field and 2 different reverberation conditions (0.06 and 0.6 s) as a function of the listening condition (left, right, both) and the noise spatial location (left, front, right).
Results
The presence of the binaural effects of head-shadow, squelch, summation, and spatial release from masking in the 2 different reverberation conditions tested was determined using nonparametric statistical analysis. In the bilateral population tested, when the ambient reverberation time was equal to 0.6 s, results indicated strong positive effects of head-shadow and a weaker spatial release from masking advantage, whereas binaural squelch and summation contributed no statistically significant benefit to bilateral performance under this acoustic condition. These findings are consistent with those of previous studies, which have demonstrated that head-shadow yields the most pronounced advantage in noise. The finding that spatial release from masking produced little to almost no benefit in bilateral listeners is consistent with the hypothesis that additive reverberation degrades spatial cues and negatively affects binaural performance.
Conclusions
The magnitude of 4 different binaural advantages was measured on the same group of bilateral CI subjects fitted with clinical processors in 2 different reverberation conditions. The results of this work demonstrate the impeding properties of reverberation on binaural speech understanding. In addition, results indicate that CI recipients who struggle in everyday listening environments are also more likely to benefit less in highly reverberant environments from their bilateral processors.

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The effect of neoadjuvant androgen deprivation therapy on tumour hypoxia in high-grade prostate cancer: a 18F-MISO PET/MRI imaging study.

Publication date: Available online 8 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Ismini C. Mainta, Thomas Zilli, Jean-Christophe Tille, Thomas De Perrot, Jean-Paul Vallée, Franz Buchegger, Valentina Garibotto, Raymond Miralbell
PurposeTumour hypoxia is associated with radio-resistance and poor prognosis after radiotherapy (RT) for prostate cancer (PCa). In this prospective pilot study we assessed the ability of 18F-misonidazole (18F-MISO) PET/MRI to detect hypoxia in high-grade PCa patients candidates for curative RT and we evaluated 18F-MISO PET/MRI modulation after 3 months of neoadjuvant androgen-deprivation therapy (nADT).MethodsEleven PCa patients with Gleason score (GS) ≥8 underwent 18F-Choline (18F-FCH) PET/CT at diagnosis and two 18F-MISO hybrid PET/MRI before and after 3 months of nADT, respectively. Immunohistochemistry (IHC) for tissue hypoxia and proliferation-related biomarkers (Glut1, CA-IX, VEGF-A, Ki67, HIF-1-alpha, EGFR) was performed in lesions bearing the highest GS. We used non-parametric tests to assess: 1. the presence of 18F-MISO positive regions (Tumour-to-Background ratios - TBR ≥ 1.4) at baseline; 2. The correlation between imaging parameters (PET tracers uptake, Prostate Imaging Reporting and Data System (PIRADS) scores, dynamic contrast enhancement perfusion markers) at baseline; 3. The difference in IHC staining between 18F-MISO positive and 18F-MISO negative lesions; 4. The changes in 18F-MISO PET/MRI imaging after nADT.Results18F-MISO uptake was significant in 7 patients, 5 of them being coincidental with the highest GS region. A significant correlation was found at baseline between GS and 18F-MISO TBR, between 18F-MISO TBR and MRI perfusion markers, between GS and 18F-FCH SUVmax, between GS and PIRADS and between 18F-FCH SUVmax and PIRADS. No difference was found between 18F-MISO positive and negative biopsies with respect to tissue biomarkers. 18F-MISO TBR diminished significantly after nADT only in high-grade lesions and in regions with a significant uptake at baseline.Conclusions18F-MISO PET imaging showed variable uptake in PCa, associated with a higher GS, lowering significantly after 3 months of nADT in high grade lesions. These results suggest the existence of a hypoxic microenvironment in PCa and a re-oxygenation effect of nADT.

Teaser

Tumour hypoxia is associated to treatment resistance. In this prospective study of 11 patients, we evaluated the occurrence of hypoxia in high-grade prostate cancer by multiparametric integrated18F-MISO PET/MRI before and after 3 months of androgen deprivation. Our results show the presence of hypoxic conditions in prostate carcinoma, correlated with tumour grade and responding to androgen ablation, thus supporting the re-oxygenation role of a neoadjuvant androgen deprivation therapy phase in combination with curative radiotherapy.


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Hypopituitarism after Single-Fraction Pituitary Adenoma Radiosurgery: Dosimetric Analysis based on Patients treated Using Contemporary Techniques

Publication date: Available online 8 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Christopher S. Graffeo, Michael J. Link, Paul D. Brown, William F. Young, Bruce E. Pollock
PurposeHypopituitarism is the most frequent complication after pituitary adenoma radiosurgery (SRS). The dosimetric factors associated with pituitary insufficiency remain unclear despite more than 30 years of clinical usage.Methods and MaterialsRetrospective review of 97 patients having single-fraction SRS from 2007 until 2014. Eligible patients had no history of prior radiation, normal age- and gender-specific pituitary function before SRS, and at least 24 months of endocrine follow-up. Forty patients (41%) had hormone secreting tumors; 57 patients had non-secreting tumors (59%). The median prescription isodose volume was 2.8 cm3 (IQR, 1.3-4.7); the median tumor margin dose was 20 Gy (IQR, 15-25).ResultsThe median follow-up after SRS was 48 months (IQR, 34-68). Twenty-seven patients (28%) developed pituitary insufficiency at a median of 22 months (IQR, 12-36) after SRS. The rate of new endocrine deficits was 17% at 2-years (95% CI 10%-25%) and 31% at 5-years (95% CI 20%-42%). Male sex (HR=2.38, 95% CI 1.05-5.26, P=0.04), smaller pituitary gland volume (HR=0.99, 95% CI 0.99-0.99, P=0.01), and higher mean pituitary gland dose (HR=1.31, 95% CI 1.16-1.47, P<0.001) were associated with post-SRS hypopituitarism in multivariable analysis. The rate of hypopituitarism for patients with a mean gland dose <11.0 Gy at 2-years was 2% (95% CI 0%-4%) and 5-years was 5% (95% CI 0%-11%) whereas rate of hypopituitarism for patients with a mean gland dose ≥11.0 Gy at 2-years was 31% (95% CI 17%-43%) and at 5-years was 51% (95% CI 34%-65%).ConclusionsHypopituitarism after pituitary adenoma SRS increases in a time- and dose-dependent manner. Reducing the radiation exposure to the identifiable gland to a mean dose <11.0 Gy whenever feasible may lower the incidence of new hormonal deficits after pituitary adenoma SRS.



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Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project

Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project

Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project, Published online: 09 March 2018; doi:10.1038/s41416-018-0007-z

Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project

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Physical activity, sedentary behaviour and colorectal cancer risk in the UK Biobank

Physical activity, sedentary behaviour and colorectal cancer risk in the UK Biobank

Physical activity, sedentary behaviour and colorectal cancer risk in the UK Biobank, Published online: 08 March 2018; doi:10.1038/bjc.2017.496

Physical activity, sedentary behaviour and colorectal cancer risk in the UK Biobank

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Intraword Variability in Children With Cochlear Implants: The Long-Term Development up to 5 Years of Age and a Comparison With Children With Normal Hearing

Purpose
This study evaluates intraword or token-to-token variability in the spontaneous speech of Dutch-speaking children with cochlear implants (CIs) longitudinally up to 5 years of age in comparison with intraword variability in age-matched peers with normal hearing (NH).
Method
Spontaneous speech samples of 9 children with CI were collected longitudinally up to age 5. The data of the NH control group consisted of cross-sectional recordings. Children's word productions were categorized into 4 response types of the variability score (consistent correct, consistent incorrect, variable with hits, variable with no hits), and the proportion of whole-word variation (PWV) was calculated.
Results
PWV was high in both groups of children but decreased with age. All response types of the variability score appeared in both groups. Children with CI were significantly more variable than their peers with NH up to age 4, but this difference has disappeared by age 5. Longer words had a higher PWV and were more often consistent incorrect and variable.
Conclusions
Intraword variability was characteristic of children with CI's spontaneous speech productions as it was in children with NH, and a similar factor (word length) affected variability in production. Group comparisons showed higher rates of intraword variability in children with CI, but they seemed to catch up with their peers with NH by age 5.

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Sentence Diversity in Early Language Development: Recommendations for Target Selection and Progress Monitoring

Purpose
This clinical focus article describes how to assess and when to target diverse, simple sentences as part of early language intervention.
Method
The theoretical foundations and clinical motivations for assessing sentence diversity based on unique combinations of subjects and verbs are explained, followed by a description of how to compute the measure. Sentence diversity is then related to familiar developmental measures of lexical diversity, utterance length, and grammatical complexity in a sample of 40 typically developing toddlers at 30 months of age. Descriptive and correlational analyses are used to demonstrate how sentences become more diverse as utterances also become longer and more complex.
Conclusions
The ability to produce simple sentences with diverse subject–verb combinations is proposed as a general developmental expectation for toddlers at 30 months of age. All 40 children produced at least 10 different subject–verb combinations in 30 min of parent–toddler conversation. Sentence diversity is also associated with familiar developmental measures. Recommendations are provided for using the measure of sentence diversity to inform treatment planning and monitor progress for young children with language disorders.
Supplemental Material
https://doi.org/10.23641/asha.5895976

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Artificial limb representation in amputees

Abstract
The human brain contains multiple hand-selective areas, in both the sensorimotor and visual systems. Could our brain repurpose neural resources, originally developed for supporting hand function, to represent and control artificial limbs? We studied individuals with congenital or acquired hand-loss (hereafter one-handers) using functional MRI. We show that the more one-handers use an artificial limb (prosthesis) in their everyday life, the stronger visual hand-selective areas in the lateral occipitotemporal cortex respond to prosthesis images. This was found even when one-handers were presented with images of active prostheses that share the functionality of the hand but not necessarily its visual features (e.g. a 'hook' prosthesis). Further, we show that daily prosthesis usage determines large-scale inter-network communication across hand-selective areas. This was demonstrated by increased resting state functional connectivity between visual and sensorimotor hand-selective areas, proportional to the intensiveness of everyday prosthesis usage. Further analysis revealed a 3-fold coupling between prosthesis activity, visuomotor connectivity and usage, suggesting a possible role for the motor system in shaping use-dependent representation in visual hand-selective areas, and/or vice versa. Moreover, able-bodied control participants who routinely observe prosthesis usage (albeit less intensively than the prosthesis users) showed significantly weaker associations between degree of prosthesis observation and visual cortex activity or connectivity. Together, our findings suggest that altered daily motor behaviour facilitates prosthesis-related visual processing and shapes communication across hand-selective areas. This neurophysiological substrate for prosthesis embodiment may inspire rehabilitation approaches to improve usage of existing substitutionary devices and aid implementation of future assistive and augmentative technologies.

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A phase I trial of escalating doses of cixutumumab (IMC-A12) and sorafenib in the treatment of advanced hepatocellular carcinoma

Abstract

Purpose

The insulin-like growth factor (IGF) pathway is activated in hepatocarcinogenesis. Cixutumumab is a monoclonal antibody against human insulin-like growth factor-1 receptor (IGF-1R). Given the cross-talk between the IGF and VEGF pathways, we performed a phase I study of the combination of cixutumumab and sorafenib in hepatocellular cancer (HCC).

Methods

Eligible patients with no prior systemic therapy for advanced HCC and Child–Pugh A to B7 were treated with sorafenib 400 mg BID and escalating doses of cixutumumab (2, 4, or 6 mg/kg IV weekly) in a 3 + 3 design. Dose limiting toxicity (DLT) was defined as treatment-related grade 3 or 4 non-hematologic toxicity (except for a subset of manageable toxicities) or any grade 4 hematologic toxicities.

Results

In 21 patients enrolled, there were 3 DLTs; grade 3 hyperglycemia, grade 3 hypophosphatemia, and grade 5 peritonitis. The maximum tolerated dose of cixutumumab was 4 mg/kg IV weekly with standard dose sorafenib. Eighteen of 21 (86%) patients had grade 3 or above toxicities attributed to treatment. One patient also experienced grade 4 colonic perforation and grade 5 peritonitis. The median number of cycles completed was 4 (0–26). Of 16 patients evaluable for response, 81% achieved stable disease. The median progression free survival was 6.0 months (95% CI 3.6–undefined) and the median overall survival was 10.5 months (95% CI 7.1–undefined).

Conclusions

While the combination of cixutumumab and sorafenib had a toxicity profile similar to that of sorafenib monotherapy, it manifested limited clinical efficacy in unselected patients with HCC.



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