Τετάρτη 7 Ιουνίου 2017

Derivation and validation of the prediabetes self-assessment screening score after acute pancreatitis (PERSEUS)

Approximately 40% of patients develop abnormal glucose metabolism after a single episode of acute pancreatitis. This study aimed to develop and validate a prediabetes self-assessment screening score for patients after acute pancreatitis.

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ERCP and Laparoscopic cholecystectomy in a patient with situs inversus totalis



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Economic burden of diverticular disease: an observational analysis based on real world data from an italian region

Diverticular disease (DD), a herniation of the colonic mucosa through the muscle layer, covers a wide variety of conditions associated with the presence of diverticula in the colon. The most serious form is an acute episode of diverticulitis, which can lead to hospitalization and surgery with various types of consequences. The main aim of this study is to evaluate the economic burden of hospitalizations arising from acute episodes of diverticulitis using data from the administrative databases used in the Marche region in Italy and, as a secondary objective of this real-world data analysis, to study patient outcome variables following initial hospitalization for diverticulitis.

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Pupil size as a measure of within-task learning

Abstract

Pupillometry is commonly used in research to determine how much mental effort an individual is exerting while completing tasks. Traditionally, larger pupils are associated with increased mental effort when completing more difficult tasks. However, little research has investigated how pupils change as individuals learn a new task. In theory, as one repeatedly completes a task, the task demands should reduce, reliance on working memory should decrease, and the task should become more automatic. This should translate to faster completion times and smaller peak pupil dilations. We tested this hypothesis by having participants complete multiple trials of a cognitive task that requires individuals to orient themselves in space relative to a target. We found that trial completion times and maximum pupil size significantly reduced across trials. These data suggest that measuring changes in pupil dilation may help researchers determine whether individuals have shifted from a learned procedure to an automatic processing of information when learning a new task.



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A Case Report and Review of Postural Orthostatic Syndrome in an Adolescent

Because there are many young women between the ages of 12 and 25 years who have been diagnosed with postural orthostatic syndrome (POTS), with the time to the diagnosis of about 5 years, it is important for health care providers to have an understanding of the clinical presentation of POTS to manage the diagnosis appropriately. The purpose of this article is to present a case study review of an adolescent woman who experienced POTS syndrome at age 16 years and to provide a clinical overview of POTS in the adolescent population.

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Editorial Board



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Contents



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Contrasting results of tests of peripheral vestibular function in patients with bilateral large vestibular aqueduct syndrome



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Analysis of ictal magnetoencephalography using gradient magnetic-field topography (GMFT) in patients with neocortical epilepsy



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Three-dimensional translations following posterior three-column spinal osteotomies for the correction of severe and stiff kyphoscoliosis

Posterior three-column spinal osteotomies were shown to be effective to treat severe and stiff kyphoscoliosis. Translations at the site of osteotomy after deformity correction were commonly seen intraoperatively, which might cause potential neurologic deficits. However, this phenomenon was not thoroughly discussed in the current literature.

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Interactive pediatric emergency checklists to the palm of your hand - How the Pedi Crisis App traveled around the world

Summary

BACKGROUND

Cognitive aids help clinicians manage critical events and have been shown to improve outcomes by providing critical information at the point of care. Critical event guidelines, such as the Society of Pediatric Anesthesia's Critical Events Checklists described in this article, can be distributed globally via interactive smartphone apps. From October 1, 2013 to January 1, 2014, we performed an observational study to determine the global distribution and utilization patterns of the Pedi Crisis cognitive aid app that the Society for Pediatric Anesthesia developed. We analyzed distribution and utilization metrics of individuals using Pedi Crisis on iOS (Apple Inc., Cupertino, CA) devices worldwide. We used Google Analytics software (Google Inc., Mountain View, CA) to monitor users' app activity (eg, screen views, user sessions).

Methods

The primary outcome measurement was the number of user-sessions and geographic locations of Pedi Crisis user sessions. Each user was defined by the use of a unique Apple ID on an iOS device.

Results

Google Analytics correlates session activity with geographic location based on local Internet service provider logs. Pedi Crisis had 1 252 active users (both new and returning) and 4 140 sessions across 108 countries during the 3-month study period. Returning users used the app longer and viewed significantly more screens that new users (mean screen views: new users 1.3 [standard deviation +/−1.09, 95% confidence interval 1.22-1.55]; returning users 7.6 [standard deviation +/−4.19, 95% confidence interval 6.73—8.39]P<.01)

Conclusions

Pedi Crisis was used worldwide within days of its release and sustained utilization beyond initial publication. The proliferation of handheld electronic devices provides a unique opportunity for professional societies to improve the worldwide dissemination of guidelines and evidence-based cognitive aids.



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Derivation and validation of the prediabetes self-assessment screening score after acute pancreatitis (PERSEUS)

Approximately 40% of patients develop abnormal glucose metabolism after a single episode of acute pancreatitis. This study aimed to develop and validate a prediabetes self-assessment screening score for patients after acute pancreatitis.

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ERCP and Laparoscopic cholecystectomy in a patient with situs inversus totalis



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Economic burden of diverticular disease: an observational analysis based on real world data from an italian region

Diverticular disease (DD), a herniation of the colonic mucosa through the muscle layer, covers a wide variety of conditions associated with the presence of diverticula in the colon. The most serious form is an acute episode of diverticulitis, which can lead to hospitalization and surgery with various types of consequences. The main aim of this study is to evaluate the economic burden of hospitalizations arising from acute episodes of diverticulitis using data from the administrative databases used in the Marche region in Italy and, as a secondary objective of this real-world data analysis, to study patient outcome variables following initial hospitalization for diverticulitis.

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Next steps in Ewing sarcoma (epi-)genomics

Future Oncology Ahead of Print.


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Targeting ALK-rearranged non-small-cell lung cancer: an update

Future Oncology Ahead of Print.


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Variation in genital human papillomavirus infection prevalence and vaccination coverage among men and women in the USA

Future Oncology Ahead of Print.


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A review of binimetinib for the treatment of mutant cutaneous melanoma

Future Oncology Ahead of Print.


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Incidence and mortality of pancreatic cancer on a rapid rise in Taiwan, 1999–2012

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Publication date: August 2017
Source:Cancer Epidemiology, Volume 49
Author(s): Chao-Ming Tseng, Shih-Pei Huang, Wei-Chih Liao, Chun-Ju Chiang, Ya-Wen Yang, Chi-Yang Chang, Yao-Chun Hsu, Hui-Chi Chen, Han-Sun Chiang, Jaw-Town Lin
BackgroundAccumulating data has revealed a rapidly rising incidence of pancreatic cancer in Western countries, but convincing evidence from the East remains sparse. We aimed to quantify how the incidence and mortality rates of pancreatic malignancy changed over time in Taiwan, and to develop future projection for the next decade.MethodsThis nationwide population-based study analyzed the Taiwan National Cancer Registry and the National Cause of Death Registry to calculate the annual incidence and mortality rates of pancreatic malignancy from 1999 to 2012 in this country. The secular trend of the incidence was also examined by data from the National Health Insurance Research Database.ResultsA total of 21,986 incident cases of pancreatic cancer and 20,720 related deaths occurred during the study period. The age-standardized incidence rate increased from 3.7 per 100,000 in 1999 to 5.0 per 100,000 in 2012, with a significant rising trend (P<0.01). The increase was nationwide, consistently across subgroups stratified by age, gender, geographic region, and urbanization. Data from the National Health Insurance Research Database corroborated the rise of incident pancreatic cancer. Mortality also increased with time, with the age-standardized rate rising from 3.5 per 100,000 in 1999 to 4.1 per 100,000 in 2012 (P<0.01). In accordance with the incidence, the mortality trend was consistent in all subgroups. Both the incidence and mortality were projected to further increase by approximately 20% from 2012 to 2027.ConclusionThe incidence and mortality of pancreatic cancer have been rapidly rising and presumably will continue to rise in Taiwan.



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The completeness and timeliness of cancer registration and the implications for measuring cancer burden

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Publication date: August 2017
Source:Cancer Epidemiology, Volume 49
Author(s): Conan Donnelly, Victoria Cairnduff, Jingwen Jessica Chen, Therese Kearney, Deirdre Fitzpatrick, Colin Fox, Anna Gavin
BackgroundPopulation based cancer registration provides a critical role in disease surveillance in terms of incidence, survival, cancer cluster investigations and prevalence trends, and therefore high levels of completeness and timeliness are required. This study estimates completeness and variation between early and late registrations in the N. Ireland Cancer Registry (NICR) and assesses the implications for reporting cancer incidence and for registry-based research.MethodsTwo main approaches assessed completeness. For the period 2010–2012, incidence reported in the first year of data publication was compared to incidence reported in subsequent years until 2015. Demographic characteristics and survival of incident cases ascertained before the first publication year were compared to those ascertained in subsequent years. The flow method approach was used to estimate completeness annually after the incident year.ResultsOverall incidence for all cancers increased between the first year of data publication and subsequent years up to 2015, irrespective of year of diagnosis. Late registrations had poorer survival. The flow method approach estimated the completeness of case ascertainment of NICR data to be 96% complete at five years for all cancers combined.ConclusionThe estimated completeness levels for the NICR are comparable to other high quality cancer registries internationally. While data timeliness has little impact on incidence estimates, delays in registration may have implications for specific research studies into incidence and survival. This means that improvements in the timeliness of reporting should be a target for all registries but not at the expense of completeness.



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Management of advanced ovarian cancer in South West Wales − a comparison between primary debulking surgery and primary chemotherapy treatment strategies in an unselected, consecutive patient cohort

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Publication date: August 2017
Source:Cancer Epidemiology, Volume 49
Author(s): F. Drews, G. Bertelli, K. Lutchman-Singh
ObjectivesThis study represents the first reported outcomes for patients with advanced ovarian cancer (AOC) in South-West Wales undergoing treatment with primary debulking surgery or primary chemotherapy respectively.MethodsThis is a retrospective study of consecutive, unselected patients with advanced ovarian, fallopian tube or primary peritoneal cancer (FIGO III/IV) presenting to a regional cancer centre between October 2007 and October 2014. Patients were identified from Welsh Cancer Services records and relevant data was extracted from electronic National Health Service (NHS) databases. Main outcome measures were median overall survival (OS), progression free survival (PFS) and perioperative adverse events. Hazard ratio estimation was carried out with Cox Regression analysis and survival determined by Kaplan-Meier plots.ResultsOf 220 women with AOC, 32.3% underwent primary debulking surgery (PDS) and 67.7% primary chemotherapy and interval debulking (PCT-IDS). Patients were often elderly (median age 67 years) with a poor performance status (26.5% PS >1). Complete cytoreduction (0cm residual) was achieved in 32.4% of patients in the PDS group and in 50.0% of patients undergoing IDS. Median OS for all patients was 21.9 months (PDS: 27.0 and PCT-IDS: 19.2 months; p >0.05) and median PFS was 13.1 months (PDS: 14.3 months and PCT-IDS: 13.0 months; p >0.05). Median overall and progression free survival for patients achieving complete cytoreduction were 48.0 and 23.2 months respectively in the PDS group and 35.4 months and 18.6 months in the IDS group (p >0.05).ConclusionThis retrospective study of an unselected, consecutive cohort of women with AOC in South West Wales shows comparable survival outcomes with recently published trials, despite the relatively advanced age and poor performance status of our patient cohort. Over the seven-year study period, our data also demonstrated a non-significant trend towards improved survival following primary surgery in patients who achieved maximal cytoreduction. Our future aim therefore is to examine and develop the role of extended surgery in these patients.



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Cancer care in lesbian, gay, bisexual, transgender and queer populations

Future Oncology Ahead of Print.


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An update on genomic-guided therapies for pediatric solid tumors

Future Oncology Ahead of Print.


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Potential prognostic value of clinical characteristics, hormone status and major depressive disorder in breast cancer

Future Oncology Ahead of Print.


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Opportunities to significantly reduce expenditure associated with cancer drugs

Future Oncology Ahead of Print.


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Prognostic value of Ki-67 expression in patients with extensive-stage small cell lung cancer

Future Oncology Ahead of Print.


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Report from European Association for the Study of the Liver: HCC Summit, Geneva, Switzerland, 2–5 February 2017

Future Oncology Ahead of Print.


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The emerging role of professional social media use in oncology

Future Oncology Ahead of Print.


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Imatinib mesylate in desmoplastic small round cell tumors

Future Oncology Ahead of Print.


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Leukemic transformation in patients with myeloproliferative neoplasms: a population-based retrospective study

Future Oncology Ahead of Print.


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Next steps in Ewing sarcoma (epi-)genomics

Future Oncology Ahead of Print.


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Targeting ALK-rearranged non-small-cell lung cancer: an update

Future Oncology Ahead of Print.


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Variation in genital human papillomavirus infection prevalence and vaccination coverage among men and women in the USA

Future Oncology Ahead of Print.


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A review of binimetinib for the treatment of mutant cutaneous melanoma

Future Oncology Ahead of Print.


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Single-fiber electromyography in the orbicularis oculi muscle in patients with ocular myasthenia gravis symptoms: does abnormal jitter predict response to treatment?

Seronegative ocular myasthenia gravis (OMG) is diagnosed by ocular symptoms with supporting SFEMG, typically of frontalis or extensor digitorum muscles. We aimed to determine the sensitivity and specificity of...

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BMI May Be the Risk Factor for Arytenoid Dislocation Caused by Endotracheal Intubation: A Retrospective Case-Control Study

This study aimed to investigate the risk factors for postoperative arytenoid dislocation caused by endotracheal intubation.

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De novo exonic duplication of ATP1A2 in Italian patient with hemiplegic migraine: a case report

Sporadic Hemiplegic Migraine is a rare form of migraine headache. Mutations in three different genes, two ion-channel genes and one encoding an ATP exchanger, CACNA1A, ATP1A2 and SCN1A are all responsible for the...

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Farmakoekonomiczne aspekty zastosowania immunoterapii alergenowej w leczeniu alergicznego nieżytu nosa i astmy

Publication date: Available online 7 June 2017
Source:Alergologia Polska - Polish Journal of Allergology
Author(s): Radosław Gawlik, Grzegorz Zagórny, Andrzej Bożek
Allergic rhinitis is a most common allergic disease affecting 40% of the population. The impact of AR on health-related quality of life (QoL) and productivity results in a significant economic burden. Allergen immunotherapy is the only causative treatment of allergic rhinitis and asthma. However, it is still unclear whether AIT is more cost-effective than the other treatments of AR without long-term cost-effectiveness studies. There is a need for further economic evaluations comparing different ways of immunotherapy and immunotherapy with pharmacotherapy.



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New Frontiers in Surgical Innovation

It is an exciting time for head and neck surgical innovation with numerous advances in the perioperative planning and intraoperative management of patients with cancer, trauma patients, and individuals with congenital defects. The broad and rapidly changing realm of head and neck surgical innovation precludes a comprehensive summary. This article highlights some of the most important innovations from surgical planning with sentinel node biopsy and three-dimensional, stereolithic modeling to intraoperative innovations, such as transoral robotic surgery and intraoperative navigation. Future surgical innovations, such as intraoperative optical imaging of surgical margins, are also highlighted.

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Lithium Chloride Facilitates Autophagy Following Spinal Cord Injury via ERK-dependent Pathway

Abstract

Spinal cord injury (SCI) is one major cause of death and results in long-term disability even in the most productive periods of human lives with few efficacious drugs. Autophagy is a potential therapeutic target for SCI. In the present study, we examined the role of lithium in functional recovery in the rat model of SCI and explored the related mechanism. Locomotion tests were employed to assess the functional recovery after SCI, Western blotting and RT-PCT to determine the level of p-ERK and LC3-II as well as p62, immunofluorescence imaging to localize LC3 and p62. Here, we found that both the expression of LC3-II and p62 were increased after SCI. However, lithium chloride enhanced the level of LC3-II while abrogated the abundance of p62. Furthermore, lithium treatment facilitated ERK activation in vivo, and inhibition of MEK/ERK signaling pathway suppressed lithium-evoked autophagy flux. Taken together, our results illustrated that lithium facilitated functional recovery by enhancing autophagy flux.



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Whole Genome Resequencing Identifies the Molecular Genetic Cause for the Absence of a Gy5 Glycinin Protein in Soybean PI 603408

During ongoing proteomic analysis of the soybean (Glycine max (L.) Merr) germplasm collection, PI 603408 was identified as a landrace whose seeds lack accumulation of one of the major seed storage glycinin protein subunits. Whole genomic resequencing was used to identify a two-base deletion affecting glycinin 5. The newly discovered deletion was confirmed causative through immunological, genetic and proteomic analysis, and no significant differences in total seed protein content were found to be due to the glycinin 5 loss-of-function mutation per se. In addition to focused studies on this one specific glycinin subunit-encoding gene, a total of 1,858,185 nucleotide variants were identified, of which 39,344 were predicted to affect protein coding regions. In order to semi-automate analysis of a large number of soybean gene variants, a new SIFT 4G database was designed to predict the impact of non-synonymous single nucleotide soybean gene variants, potentially enabling more rapid analysis of soybean resequencing data in the future.



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Comparative Mapping of Seed Dormancy Loci Between Tropical and Temperate Ecotypes of Weedy Rice (Oryza sativa L.)

Genotypic variation at multiple loci for seed dormancy (SD) contributes to plant adaptation to diverse ecosystems. Weedy rice (Oryza sativa) was used as a model to address the similarity of SD genes between distinct ecotypes. A total of 12 quantitative trait loci for SD were identified in a primary and two advanced backcross populations derived from a temperate ecotype of weedy rice (34.3°N Lat.). Nine (75%) of the 12 loci were mapped to the same positions as those identified from a tropical ecotype of weedy rice (7.1°N Lat.). The high similarity suggested that a majority of SD genes were conserved during the ecotype differentiation. These common loci are largely those collocated/linked with the awn, hull color, pericarp color or plant height loci. Phenotypic correlations observed in the populations support that indirect selections for the wild-type morphological characters, together with direct selections for germination time, were major factors influencing allelic distributions of SD genes across ecotypes. Indirect selections for crop-mimic traits (e.g. plant height and flowering time) could also alter allelic frequencies for some SD genes in agroecosystems. In addition, three of the 12 loci were collocated with segregation distortion loci, indicating that some gametophyte development genes could also influence genetic equilibria of SD loci in hybrid populations. The SD genes with a major effect on germination across ecotypes could be used as silencing targets to develop transgene mitigation strategies to reduce the risk of gene flow from genetically modified crops into weed/wild relatives.



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Duplication and Loss of Function of Genes Encoding RNA Polymerase III Subunit C4 Causes Hybrid Incompatibility in Rice

Reproductive barriers are commonly observed in both animals and plants, in which they maintain species integrity and contribute to speciation. This report shows that a combination of loss-of-function alleles at two duplicated loci, DUPLICATED GAMETOPHYTIC STERILITY 1 (DGS1) on chromosome 4 and DGS2 on chromosome 7, causes pollen sterility in hybrid progeny derived from an interspecific cross between cultivated rice, Oryza sativa, and an Asian annual wild rice, Oryza nivara. Male gametes carrying the DGS1 allele from O. nivara (DGS1-nivaras) and the DGS2 allele from O. sativa (DGS2-T65s) were sterile, but female gametes carrying the same genotype were fertile. We isolated the causal gene, which encodes a protein homologous to DNA-dependent RNA polymerase III subunit C4 (RPC4). RPC4 facilitates the transcription of 5S rRNAs and tRNAs. The loss-of-function alleles at DGS1-nivaras and DGS2-T65s were caused by weak or non-expression of RPC4 and absence of RPC4, respectively. Phylogenetic analysis demonstrated that gene duplication of RPC4 at DGS1 and DGS2 was a recent event that occurred after divergence of the ancestral population of Oryza from other Poaceae or during diversification of AA-genome species.



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Genetic Dissection of Morphometric Traits Reveals that Phytochrome B Affects Nucleus Size and Heterochromatin Organization in Arabidopsis thaliana

Microscopically visible chromatin is partitioned into two major components in Arabidopsis thaliana nuclei. Chromocenters on one hand are conspicuous foci of highly condensed 'heterochromatic' domains that contain mostly repeated sequences. On the other hand, less condensed and gene-rich 'euchromatin' emanates from these chromocenters. This differentiation, together with the dynamic nature of chromatin compaction in response to developmental and environmental stimuli, makes Arabidopsis a powerful system for studying chromatin organization and dynamics. Heterochromatin dynamics can be monitored by measuring the Heterochromatin Index, i.e. the proportion of nuclei displaying well-defined chromocenters, or the DNA fraction of chromocenters (Relative Heterochromatin Fraction). Both measures are composite traits, thus their values represent the sum of effects of various underlying morphometric properties. We exploited genetic variation between natural occurring accessions to determine the genetic basis of individual nucleus and chromocenter morphometric parameters; Area, Perimeter, Density, Roundness and Heterogeneity, that together determine chromatin compaction. Our novel reductionistic genetic approach revealed Quantitative Trait Loci (QTLs) for all measured traits. Genomic co-localization among QTLs was limited, which suggests a complex genetic regulation of chromatin compaction. Yet, genomic intervals of QTLs for nucleus size (Area and Perimeter) both overlap with a known QTL for heterochromatin compaction that is explained by natural polymorphism in the red/far-red light and temperature receptor Phytochrome B. Mutant analyses and genetic complementation assays show that Phytochrome B is a negative regulator of nucleus size, unveiling that perception of climatic conditions by a phytochrome-mediated hub is a major determinant for coordinating nucleus size and heterochromatin compaction.



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Erratum to: Compartmental tongue resection with submental island flap reconstruction for large carcinoma of the oral tongue



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Erratum to: Compartmental tongue resection with submental island flap reconstruction for large carcinoma of the oral tongue



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Erratum to: Compartmental tongue resection with submental island flap reconstruction for large carcinoma of the oral tongue



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Morbidity and mortality of middle-aged and elderly narcoleptics

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Publication date: August 2017
Source:Sleep Medicine, Volume 36
Author(s): Poul Jennum, Eva Wiberg Thorstensen, Line Pickering, Rikke Ibsen, Jakob Kjellberg
ObjectivesThe objective of the study was to evaluate the morbidities and mortality in a national group of middle-aged and elderly narcolepsy patients before and after the first diagnosis of the condition.MethodsFrom the Danish National Patient Registry (NPR), 1174 patients (45.1% males) aged 20–59 years and 339 patients (44.8% males) aged 60+ who received a diagnosis of narcolepsy between 1998 and 2014 were compared, respectively, with 4716 and 1353 control citizens matched for age, gender and geography, who were randomly chosen from the Danish Civil Registration System Statistics. In the NPR, all morbidities are grouped into major WHO classes.ResultsMiddle-aged and elderly patients had more health contacts before and after their narcolepsy diagnosis with respect to several disease domains: infections, neoplasm, endocrine/metabolic diseases/diabetes, mental/psychiatric, neurological (including epilepsy), eye, cardiovascular (hypertension, ischemic heart disease), respiratory (upper-airway infections, sleep apnea), gastrointestinal, musculoskeletal (including discopathies) and skin diseases. Narcolepsy patients had lower reproductive rates. Furthermore, patients showed significantly more health contacts due to the evaluation and control contacts for disease and symptoms. Patients suffered from significantly more multiple diseases than did controls.The 17-year hazard ratio mortality rates were 1.35 (95% CI, 0.94–1.95, p = 0.106) among 20–59 year-olds, and 1.38 (1.12–1.69, p = 0.002) among those aged 60+ years.ConclusionThere are higher rates of morbidity in several disease domains before and after a diagnosis of narcolepsy. Elderly narcolepsy patients have higher mortality rates.



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Mother–father agreement and one-year stability of children's sleep functioning

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Publication date: August 2017
Source:Sleep Medicine, Volume 36
Author(s): Stephen P. Becker, Paul A. Isaacson, Mateu Servera, Belén Sáez, G. Leonard Burns
ObjectivesTo (1) evaluate mother–father agreement of total sleep problems and specific sleep problem domains and (2) examine the one-year stability of children's sleep functioning, including cross-rater stability.MethodsA community-based sample of 519 children (51% boys) in Spain was assessed in third grade and again 1 year later. At each time-point, both mothers and fathers provided ratings of sleep functioning using the Children's Sleep Habits Questionnaire (CSHQ).ResultsSleep scores did not differ between mothers' and fathers' ratings. Cross-sectionally (at both time-points) and longitudinally (from grade 3 to grade 4), strong agreement was found between mothers' and fathers' ratings of total sleep problems, sleep habits, night wakings, and parasomnias. Lower agreement was found for daytime sleepiness and sleep onset delay. There was large effect size stability for both mothers' and fathers' ratings over the one-year period on the total sleep disturbance scale and most sleep subscales.ConclusionsThis study provides the first evidence of strong mother–father agreement on subjective ratings of children's sleep functioning, both concurrently and over a one-year period, for overall sleep problems and certain sleep domains. However, agreement was far from identical, and further studies are needed to evaluate reasons for discrepancy and whether mother–father discrepancy in sleep functioning predicts children's functioning. More studies are needed that systematically include both mothers' and fathers' perspectives regarding children's sleep.



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Adaptation modulates correlated subthreshold response variability in visual cortex

Cortical sensory responses are highly variable across stimulus presentations. This variability can be correlated across neurons (due to some combination of dense intracortical connectivity, cortical activity level, and cortical state), with fundamental implications for population coding. Yet the interpretation of correlated response variability (or "noise correlation") has remained fraught with difficulty, in part because of the restriction to extracellular neuronal spike recordings. Here, we measured response variability and its correlation at the most microscopic level of electrical neural activity, the membrane potential, by obtaining dual whole-cell recordings from pairs of cortical pyramidal neurons during visual processing in the turtle whole-brain ex vivo preparation. We found that during visual stimulation, correlated variability adapts towards an intermediate level and that this correlation dynamic is likely mediated by intracortical mechanisms. A model network with external inputs, synaptic depression, and structure reproduced the observed dynamics of correlated variability. These results suggest that intracortical adaptation self-organizes cortical circuits towards a balanced regime at which correlated variability is maintained at an intermediate level.



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Robotic navigation to sub-cortical neural tissue for intracellular electrophysiology in vivo

In vivo studies of neurophysiology using the whole-cell patch clamp technique enable exquisite access to both intracellular dynamics and cytosol of cells in the living brain but are underrepresented in deep subcortical nuclei due to fouling of the sensitive electrode tip. We have developed an autonomous method to navigate electrodes around obstacles such as blood vessels, after identifying them as a source of contamination during regional pipette localization (RPL) in vivo. In mice, robotic navigation prevented fouling of the electrode tip, increasing RPL success probability 3 mm below the pial surface to 82% (n=72/88) over traditional, linear localization (25%, n=24/95) and resulted in high quality thalamic whole-cell recordings with average access resistance (32.0 M), and resting membrane potential (-62.9 mV) similar to cortical recordings in isoflurane-anesthetized mice. Whole-cell yield improved from 1% (n=1/95) to 10% (n=9/88) when robotic navigation was used during RPL. This method opens the door to whole-cell studies in deep subcortical nuclei, including multimodal cell typing and studies of long range circuits.



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Control of the strength of visual-motor transmission as the mechanism of rapid adaptation of priors for Bayesian inference in smooth pursuit eye movements

Bayesian inference provides a cogent account of how the brain combines sensory information with "priors" based on past experience to guide many behaviors, including smooth pursuit eye movements. We now demonstrate very rapid adaptation of the pursuit system's priors for target direction and speed. We go on to leverage that adaptation to outline possible neural mechanisms that could cause pursuit to show features consistent with Bayesian inference. Adaptation of the prior causes changes in the eye speed and direction at the initiation of pursuit. The adaptation appears after a single trial, and accumulates over repeated exposure to a given history of target speeds and directions. The influence of the priors depends on the reliability of visual motion signals: priors are more effective against the visual motion signals provided by low-contrast versus high-contrast targets. Adaptation of the direction prior generalizes to eye speed, and vice versa, suggesting that both priors could be controlled by a single neural mechanism. We conclude that the pursuit system can learn the statistics of visual motion rapidly and use those statistics to guide future behavior. Further, a model that adjusts the gain of visual-motor transmission predicts the effects of recent experience on pursuit direction and speed, as well as the specifics of the generalization between the priors for speed and direction. We suggest that Bayesian inference in pursuit behavior is implemented by distinctly non-Bayesian internal mechanisms that use the smooth eye movement region of the frontal eye fields to control of the gain of visual-motor transmission.



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Efferent inhibition strength is a Physiological Correlate of Hyperacusis in Children with Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a developmental disability that is poorly understood. ASD can influence communication, social interaction, and behavior. Children with ASD often have sensory hypersensitivities, including auditory hypersensitivity (hyperacusis). In adults with hyperacusis who are otherwise neurotypical, the medial olivocochlear (MOC) efferent reflex is stronger than usual. In children with ASD the MOC reflex has been measured, but without also assessing hyperacusis. We assessed the MOC reflex in children with ASD by measuring the strength of MOC-induced inhibition of transient-evoked otoacoustic emissions (TEOAEs), a non-invasive, physiological measure that reflects cochlear amplification. MOC activity was evoked by contralateral noise. Hyperacusis was assessed subjectively based on the children's symptoms. We found a strong correlation between hyperacusis scores and MOC strength in children with ASD. When children were divided into ASD-with-severe-hyperacusis (ASDs), ASD-with-not-severe-hyperacusis (ASDns) and neurotypical (NT) groups, the last two groups had similar hyperacusis and MOC reflexes while the ASDs group, on average, had hyperacusis and MOC reflexes that were approximately twice as strong. The MOC inhibition of TEOAEs averaged larger at all frequencies in the ASDs compared to ASDns and NT groups. The results suggest that the MOC reflex can be used to estimate hyperacusis in children with ASD and might be used to validate future questionnaires to assess hyperacusis. Our results also provide evidence that strong MOC reflexes in children with ASD are associated with hyperacusis and that hyperacusis is a comorbid condition as opposed to being an integral part of the abnormal neural processing associated with ASD.



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Validation of Electrical Stimulation Models: Intracellular Calcium Measurement in 3-Dimensional Scaffolds

Peripheral nerve injury can be disabling. Regeneration is limited by the rate of axonal extension, and proximal injury to peripheral nerves can take over a year to reach target organs. Electrical stimulation (ES) has been shown to increase the rate of neurite growth, though the mechanism is not yet well understood. In our prior manuscript, we developed a computational model that demonstrates how ES can functionally elevate intracellular calcium ([Ca2+]i) based on ES intensity and duration. Here, we validate the computation model for the intracellular [Ca2+]i changes in neuron soma. Embryonic chicken dorsal root ganglion cells were suspended in 3-dimensional collagen scaffolds. Fura-2 was used to measure the concentration of [Ca2+]i in response to biphasic ES pulses ranging from 70 V/m to 60,000 V/m in intensity, and 10 µs to 100 ms in duration. The computational model most closely matched the experimental data of the neurons with the highest [Ca2+]i elevation for ES pulses 100 µs or greater in duration. Nickel (200 µM) and cadmium (200 µM) blocked 98-99% of the [Ca2+]i rise, indicating that the rise in [Ca2+]i in response to ES is via voltage dependent calcium channels. The average [Ca2+]i rise in response to ES was about one tenth of the peak rise. Therefore, the computational model is validated for elevating [Ca2+]i of neurons and can be used as a tool for designing efficacious ES protocols for improving neuronal regeneration.



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Trajectory curvature in saccade sequences: spatiotopic influences vs residual motor activity.

When decisions drive saccadic eye movements, traces of the decision process can be inferred from the movement trajectories. For example, saccades can curve away from distractor stimuli, which was thought to reflect cortical inhibition biasing activity in the Superior Colliculus. Recent neurophysiological work does not support this theory, and two recent models have replaced top-down inhibition with lateral interactions in the Superior Colliculus or neural fatigue in the brainstem Saccadic Burst Generator. All current models operate in retinotopic coordinates and are based on single saccade paradigms. In order to extend these models to sequences of saccades, we assessed whether and how saccade curvature depends on previously fixated locations and the direction of previous saccades. With a two-saccade paradigm, we first demonstrated that second saccades curved away from the initial fixation stimulus. Furthermore, by varying the time from fixation offset and the intersaccadic duration, we distinguished the extent of curvature originating from the spatiotopic representation of the previous fixation location or residual motor activity of the previous saccade. Results suggest that both factors drive curvature, and we discuss how these effects could be implemented in current models. In particular, we propose that the collicular retinotopic maps receive an excitatory spatiotopic update from the Lateral Interparial region (LIP).



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Dynamics of human subthalamic neuron phase-locking to motor and sensory cortical oscillations during movement

Coupled oscillatory activity recorded between sensorimotor regions of the basal ganglia-thalamocortical loop is thought to reflect information transfer relevant to movement. A neuronal firing-rate model of basal ganglia-thalamocortical circuitry, however, has dominated thinking about basal ganglia function for the past three decades, without knowledge of the relationship between basal ganglia single neuron firing and cortical population activity during movement itself. We recorded activity from 34 subthalamic nucleus (STN) neurons, simultaneously with cortical local field potentials and motor output, in eleven subjects with Parkinson's disease (PD) undergoing awake deep brain stimulator lead placement. STN firing demonstrated phase synchronization to both low and high beta frequency cortical oscillations, and to the amplitude envelope of gamma oscillations, in motor cortex. We found that during movement, the magnitude of this synchronization was dynamically modulated in a phase-frequency-specific manner. Importantly, we found that phase synchronization was not correlated with changes in neuronal firing rate. Furthermore, we found that these relationships were not exclusive to motor cortex, as STN firing also demonstrated phase synchronization to both pre-motor and sensory cortex. The data indicate that models of basal ganglia function ultimately will need to account for the activity of populations of subthalamic nucleus neurons that are bound in distinct functional networks with both motor and sensory cortices and code for movement parameters independent of changes in firing rate.



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Adaptation modulates correlated subthreshold response variability in visual cortex

Cortical sensory responses are highly variable across stimulus presentations. This variability can be correlated across neurons (due to some combination of dense intracortical connectivity, cortical activity level, and cortical state), with fundamental implications for population coding. Yet the interpretation of correlated response variability (or "noise correlation") has remained fraught with difficulty, in part because of the restriction to extracellular neuronal spike recordings. Here, we measured response variability and its correlation at the most microscopic level of electrical neural activity, the membrane potential, by obtaining dual whole-cell recordings from pairs of cortical pyramidal neurons during visual processing in the turtle whole-brain ex vivo preparation. We found that during visual stimulation, correlated variability adapts towards an intermediate level and that this correlation dynamic is likely mediated by intracortical mechanisms. A model network with external inputs, synaptic depression, and structure reproduced the observed dynamics of correlated variability. These results suggest that intracortical adaptation self-organizes cortical circuits towards a balanced regime at which correlated variability is maintained at an intermediate level.



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Robotic navigation to sub-cortical neural tissue for intracellular electrophysiology in vivo

In vivo studies of neurophysiology using the whole-cell patch clamp technique enable exquisite access to both intracellular dynamics and cytosol of cells in the living brain but are underrepresented in deep subcortical nuclei due to fouling of the sensitive electrode tip. We have developed an autonomous method to navigate electrodes around obstacles such as blood vessels, after identifying them as a source of contamination during regional pipette localization (RPL) in vivo. In mice, robotic navigation prevented fouling of the electrode tip, increasing RPL success probability 3 mm below the pial surface to 82% (n=72/88) over traditional, linear localization (25%, n=24/95) and resulted in high quality thalamic whole-cell recordings with average access resistance (32.0 M), and resting membrane potential (-62.9 mV) similar to cortical recordings in isoflurane-anesthetized mice. Whole-cell yield improved from 1% (n=1/95) to 10% (n=9/88) when robotic navigation was used during RPL. This method opens the door to whole-cell studies in deep subcortical nuclei, including multimodal cell typing and studies of long range circuits.



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Control of the strength of visual-motor transmission as the mechanism of rapid adaptation of priors for Bayesian inference in smooth pursuit eye movements

Bayesian inference provides a cogent account of how the brain combines sensory information with "priors" based on past experience to guide many behaviors, including smooth pursuit eye movements. We now demonstrate very rapid adaptation of the pursuit system's priors for target direction and speed. We go on to leverage that adaptation to outline possible neural mechanisms that could cause pursuit to show features consistent with Bayesian inference. Adaptation of the prior causes changes in the eye speed and direction at the initiation of pursuit. The adaptation appears after a single trial, and accumulates over repeated exposure to a given history of target speeds and directions. The influence of the priors depends on the reliability of visual motion signals: priors are more effective against the visual motion signals provided by low-contrast versus high-contrast targets. Adaptation of the direction prior generalizes to eye speed, and vice versa, suggesting that both priors could be controlled by a single neural mechanism. We conclude that the pursuit system can learn the statistics of visual motion rapidly and use those statistics to guide future behavior. Further, a model that adjusts the gain of visual-motor transmission predicts the effects of recent experience on pursuit direction and speed, as well as the specifics of the generalization between the priors for speed and direction. We suggest that Bayesian inference in pursuit behavior is implemented by distinctly non-Bayesian internal mechanisms that use the smooth eye movement region of the frontal eye fields to control of the gain of visual-motor transmission.



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Efferent inhibition strength is a Physiological Correlate of Hyperacusis in Children with Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a developmental disability that is poorly understood. ASD can influence communication, social interaction, and behavior. Children with ASD often have sensory hypersensitivities, including auditory hypersensitivity (hyperacusis). In adults with hyperacusis who are otherwise neurotypical, the medial olivocochlear (MOC) efferent reflex is stronger than usual. In children with ASD the MOC reflex has been measured, but without also assessing hyperacusis. We assessed the MOC reflex in children with ASD by measuring the strength of MOC-induced inhibition of transient-evoked otoacoustic emissions (TEOAEs), a non-invasive, physiological measure that reflects cochlear amplification. MOC activity was evoked by contralateral noise. Hyperacusis was assessed subjectively based on the children's symptoms. We found a strong correlation between hyperacusis scores and MOC strength in children with ASD. When children were divided into ASD-with-severe-hyperacusis (ASDs), ASD-with-not-severe-hyperacusis (ASDns) and neurotypical (NT) groups, the last two groups had similar hyperacusis and MOC reflexes while the ASDs group, on average, had hyperacusis and MOC reflexes that were approximately twice as strong. The MOC inhibition of TEOAEs averaged larger at all frequencies in the ASDs compared to ASDns and NT groups. The results suggest that the MOC reflex can be used to estimate hyperacusis in children with ASD and might be used to validate future questionnaires to assess hyperacusis. Our results also provide evidence that strong MOC reflexes in children with ASD are associated with hyperacusis and that hyperacusis is a comorbid condition as opposed to being an integral part of the abnormal neural processing associated with ASD.



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Validation of Electrical Stimulation Models: Intracellular Calcium Measurement in 3-Dimensional Scaffolds

Peripheral nerve injury can be disabling. Regeneration is limited by the rate of axonal extension, and proximal injury to peripheral nerves can take over a year to reach target organs. Electrical stimulation (ES) has been shown to increase the rate of neurite growth, though the mechanism is not yet well understood. In our prior manuscript, we developed a computational model that demonstrates how ES can functionally elevate intracellular calcium ([Ca2+]i) based on ES intensity and duration. Here, we validate the computation model for the intracellular [Ca2+]i changes in neuron soma. Embryonic chicken dorsal root ganglion cells were suspended in 3-dimensional collagen scaffolds. Fura-2 was used to measure the concentration of [Ca2+]i in response to biphasic ES pulses ranging from 70 V/m to 60,000 V/m in intensity, and 10 µs to 100 ms in duration. The computational model most closely matched the experimental data of the neurons with the highest [Ca2+]i elevation for ES pulses 100 µs or greater in duration. Nickel (200 µM) and cadmium (200 µM) blocked 98-99% of the [Ca2+]i rise, indicating that the rise in [Ca2+]i in response to ES is via voltage dependent calcium channels. The average [Ca2+]i rise in response to ES was about one tenth of the peak rise. Therefore, the computational model is validated for elevating [Ca2+]i of neurons and can be used as a tool for designing efficacious ES protocols for improving neuronal regeneration.



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Trajectory curvature in saccade sequences: spatiotopic influences vs residual motor activity.

When decisions drive saccadic eye movements, traces of the decision process can be inferred from the movement trajectories. For example, saccades can curve away from distractor stimuli, which was thought to reflect cortical inhibition biasing activity in the Superior Colliculus. Recent neurophysiological work does not support this theory, and two recent models have replaced top-down inhibition with lateral interactions in the Superior Colliculus or neural fatigue in the brainstem Saccadic Burst Generator. All current models operate in retinotopic coordinates and are based on single saccade paradigms. In order to extend these models to sequences of saccades, we assessed whether and how saccade curvature depends on previously fixated locations and the direction of previous saccades. With a two-saccade paradigm, we first demonstrated that second saccades curved away from the initial fixation stimulus. Furthermore, by varying the time from fixation offset and the intersaccadic duration, we distinguished the extent of curvature originating from the spatiotopic representation of the previous fixation location or residual motor activity of the previous saccade. Results suggest that both factors drive curvature, and we discuss how these effects could be implemented in current models. In particular, we propose that the collicular retinotopic maps receive an excitatory spatiotopic update from the Lateral Interparial region (LIP).



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Dynamics of human subthalamic neuron phase-locking to motor and sensory cortical oscillations during movement

Coupled oscillatory activity recorded between sensorimotor regions of the basal ganglia-thalamocortical loop is thought to reflect information transfer relevant to movement. A neuronal firing-rate model of basal ganglia-thalamocortical circuitry, however, has dominated thinking about basal ganglia function for the past three decades, without knowledge of the relationship between basal ganglia single neuron firing and cortical population activity during movement itself. We recorded activity from 34 subthalamic nucleus (STN) neurons, simultaneously with cortical local field potentials and motor output, in eleven subjects with Parkinson's disease (PD) undergoing awake deep brain stimulator lead placement. STN firing demonstrated phase synchronization to both low and high beta frequency cortical oscillations, and to the amplitude envelope of gamma oscillations, in motor cortex. We found that during movement, the magnitude of this synchronization was dynamically modulated in a phase-frequency-specific manner. Importantly, we found that phase synchronization was not correlated with changes in neuronal firing rate. Furthermore, we found that these relationships were not exclusive to motor cortex, as STN firing also demonstrated phase synchronization to both pre-motor and sensory cortex. The data indicate that models of basal ganglia function ultimately will need to account for the activity of populations of subthalamic nucleus neurons that are bound in distinct functional networks with both motor and sensory cortices and code for movement parameters independent of changes in firing rate.



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Immunological effect of local ablation combined with immunotherapy on solid malignancies

Recent comprehensive investigations clarified that immune microenvironment surrounding tumor cells are deeply involved in tumor progression, metastasis, and response to treatment. Furthermore, several immunoth...

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Influence of Sewered Versus Septic Systems on Watershed Exports of E . coli

Abstract

Elevated bacteria concentrations have led to the impairment (e.g., closures of shellfisheries and recreational beaches) of coastal waters. Although many previous studies have suggested that wastewater inputs can lead to elevated fecal indicator bacteria (FIB) concentrations in surface waters, few studies have quantified wastewater-associated FIB exports at the watershed scale. The goal of this study was to estimate bacterial exports at the watershed scale based on wastewater management approach (septic vs. sewer). Six watersheds (three exclusively on septic and three exclusively served by a sewer system) were selected for water quality assessment and comparison. Streams were monitored approximately monthly from August 2011 to June 2012 during baseflow conditions. Additionally, three storms were monitored. Samples were collected in sterile 100-mL bottles and analyzed for Escherichia coli concentrations. Discharge from streams was measured and bacterial exports were estimated by multiplying discharge by E. coli concentration. The results revealed that (1) during baseflow conditions, septic watersheds contained elevated stream discharge and E. coli concentrations and exports as compared to sewer watersheds; (2) warmer months had elevated E. coli watershed exports compared to colder months in both septic and sewer watersheds; and (3) storms significantly increased watershed E. coli exports in both septic and sewer watersheds. Storms significantly increased watershed E. coli exports in both septic and sewered watersheds, but E. coli counts in sewered watersheds were considerably greater likely due to greater impervious surface coverage and or leaky sewer infrastructure. These findings in conjunction with previous studies suggest that septic systems may play a pivotal role in the delivery of FIB to receiving waters, particularly during baseflow conditions.



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Evaluation of the Combined Process of Coagulation/Flocculation and Microfiltration of Cassava Starch Wastewater: Removal Efficiency and Membrane Fouling

Abstract

In this study, cassava starch wastewater was subjected to coagulation/flocculation (C/F) combined with microfiltration (MF) to improve the final quality of treated water. In the C/F tests of the effluent, the best concentration of the natural coagulant (Tanfloc POP) was determined from a statistical analysis of color removal and turbidity data. The supernatant produced in the C/F step was subjected to MF while varying the transmembrane pressure to evaluate the permeate fluxes, fouling mechanism, and permeate quality. The mathematical model that best represented the filtration process was the fouling mechanism of partial membrane pore blockage. The best experimental conditions for coagulant dosage, settling time, and MF pressure in the combined C/F-MF process were 320 mg L−1, 15 min, and 1.4 bar, respectively. The highest overall removal efficiency rates achieved were 99% color, 91% cyanide, 75% total organic carbon, and 100% turbidity, demonstrating the promising potential of the combined C/F-MF process in the treatment of cassava starch wastewater.



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The effects of 10 days of separate heat and hypoxic exposure on heat acclimation and temperate exercise performance

Adaptations to heat and hypoxia are typically studied in isolation, but are often encountered in combination. Whether the adaptive response to multiple stressors affords the same response as when examined in isolation is unclear. We examined: i) the influence of overnight moderate normobaric hypoxia on the time course and magnitude of adaption to daily heat exposure; ii) whether heat acclimation (HA) was ergogenic and if this was influenced by an additional hypoxic-stimulus. Eight males (VO2max=58.5[8.3] mL·kg-1·min-1) undertook two 11-day HA programmes (balanced-crossover design), once with overnight normobaric hypoxia (8[1] h per night; 10 nights; FIO2=0.156; SpO2=91[2]% [HAHyp]) and once without (HACon). Days 1, 6, 11 were exercise-heat stress tests (HST [40°C, 50% RH]); days 2-5 and 7-10 were isothermal-strain (target rectal temperature [Tre] ~38.5°C), exercise-heat sessions. A graded exercise test and 30-minute cycle trial were undertaken pre, post and 14-days after HA in temperate-normoxia (22°C, 55% RH; FIO2=0.209). HA was evident on day 6 (e.g. reduced Tre, mean skin temperature [Tsk], heart rate, sweat [Na+], P<0.05) with additional adaptations on day 11 (further reduced Tsk, heart rate). HA increased plasma volume (+5.9[7.3]%) and erythropoietin concentration (+1.8[2.4] mIU/mL); tHbmass was unchanged. Peak power output (+12[20] W), lactate threshold (+15[18] W) and work done (+12[20] kJ) increased following HA. The additional hypoxic-stressor did not affect these adaptations. In conclusion, a separate moderate overnight normobaric hypoxic-stimulus does not affect the time-course or magnitude of HA. Performance may be improved in temperate-normoxia following HA, but this is unaffected by an additional hypoxic stressor.



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Localized and systemic variations in central motor drive at different local skin and muscle temperatures

This study investigated the ability to sustain quadriceps central motor drive while subjected to localized heat and metaboreceptive feedback from the contralateral leg. Eight active males each completed two counter-balanced trials, in which muscle temperature (Tm) of a single-leg (TEMP-LEG) was altered to 29.4 (COOL) or 37.6°C (WARM), while the contralateral leg (CL-LEG) remained thermoneutral; 35.3 and 35.2°C Tm in COOL and WARM respectively. To activate metaboreceptive feedback, participants first performed one 120-s isometric maximal voluntary contraction (MVC) of the knee extensors in the TEMP-LEG, immediately followed by post-exercise muscle ischemia (PEMI) via femoral blood flow occlusion. To assess central motor drive of a remote muscle group immediately following PEMI, another 120-s MVC was subsequently performed in the CL-LEG. Voluntary muscle activation (VA) was assessed using the twitch interpolation method. Perceived mental effort and limb discomfort were also recorded. In a cooled muscle, a significant increase in mean force output and mean VA (force, p<0.001; VA, p<0.05) as well as a significant decrease in limb discomfort (p<0.05) occurred during the sustained MVC in the TEMP-LEG. However, no differences between Tm were observed in mean force output, mean VA or limb discomfort during the sustained MVC in the CL-LEG (Force, p=0.33; VA, p>0.68, limb discomfort, p=0.73). The present findings suggest that elevated local Tsk and Tm can increase limb discomfort and decrease central motor drive, but this does not limit systemic motor activation of a thermoneutral muscle group.



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Heads you gain, tails you lose: Editorial Focus for R-00351-2016

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Eye Movements Are Correctly Timed During Walking Despite Bilateral Vestibular Hypofunction

Abstract

Individuals with bilateral vestibular hypofunction (BVH) often report symptoms of oscillopsia (the perception that the world is bouncing or unstable) during walking. Efference copy/proprioception contributes to locomotion gaze stability in animals, sometimes inhibiting the vestibulo-ocular reflex (VOR). Gaze stability requires both adequate eye velocity and appropriate timing of eye movements. It is unknown whether eye velocity (VOR gain), timing (phase), or both are impaired for individuals with BVH during walking. Identifying the specific mechanism of impaired gaze stability can better inform rehabilitation options. Gaze stability was measured for eight individuals with severe BVH and eight healthy age- and gender-matched controls while performing a gaze fixation task during treadmill walking. Frequency response functions (FRF) were calculated from pitch eye and head velocity. A one-way ANOVA was conducted to determine group differences for each frequency bin of the FRF. Pearson correlation coefficients were calculated to determine the relationship between the real and imaginary parts of the FRF and the Oscillopsia Visual Analog Scale (oVAS) scores. Individuals with BVH demonstrated significantly lower gains than healthy controls above 0.5 Hz, but their phase was ideally compensatory for frequencies below 3 Hz. Higher oVAS scores were correlated with lower gain. Individuals with BVH demonstrated ideal timing for vertical eye movements while walking despite slower than ideal eye velocity when compared to healthy controls. Rehabilitation interventions focusing on enhancing VOR gain during walking should be developed to take advantage of the intact timing reported here. Specifically, training VOR gain while walking may reduce oscillopsia severity and improve quality of life.



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Translation, Cultural Adaptation, and Preliminary Evaluation of the Spanish Version of the Transgender Voice Questionnaire for Male-to-Female Transsexuals (TVQ MtF)

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Publication date: Available online 7 June 2017
Source:Journal of Voice
Author(s): Elena Mora, Alvaro Carrillo, Ana Giribet, Antonio Becerra, M Jesús Lucio, Ignacio Cobeta
ObjectiveThis study aimed to perform translation, cross-cultural adaptation, and validation of the Spanish version of the Transsexual Voice Questionnaire for Male-to-Female Transsexuals (TVQ MtF).Study DesignThis is a prospective study.SettingThe study was conducted by the Gender Identity Unit and the Voice Unit of a tertiary hospital referral center for surgical feminization of the voice.Subjects and MethodsThe study had two parts: translation and adaptation of the TVQ MtF with the following actions: translation (with authorization and consensus of the authors of the original questionnaire), back-translation, pretesting, and final version; and preliminary study of the psychometric properties (feasibility, internal consistency, test-retest reliability, construct validity, discriminant validity, and ceiling and floor effects). Thirty male-to-female transsexual women filled out the questionnaire, and 18 of the 30 filled out the questionnaire approximately 2 weeks after filling it out for the first time.ResultsFeasibility was 100%. Cronbach α was 0.976. The intraclass correlation coefficient was 0.885. The Spearman correlation coefficient between TVQ MtF and the physical component of SF-12 v2 was 0.102 (P value = 0.592) and between TVQ MtF and the mental component was −0.263 (P value = 0.161). A ceiling effect was not found. A floor effect was found in two questionnaires (6.7%).ConclusionFeasibility, internal consistency, and reliability outcomes in our study support the validity of the authorized Spanish version of the TVQ MtF.



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Vocal Tract Discomfort and Voice-Related Quality of Life in Wind Instrumentalists

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Publication date: Available online 7 June 2017
Source:Journal of Voice
Author(s): Juliane Cappellaro, Bárbara Costa Beber
ObjectiveThis study aimed to investigate vocal tract discomfort and quality of life in the voice of wind instrumentalists.MethodIt is a cross-sectional study. The sample was composed of 37 musicians of the orchestra of Caxias do Sul city, RS, Brazil. The participants answered a nonstandard questionnaire about demographic and professional information, the Voice-Related Quality of Life (V-RQOL), the Vocal Tract Discomfort (VTD) scale, and additional items about fatigue after playing the instrument and pain in the cervical muscles. Correlation analyses were performed using Spearman correlation test.ResultsThe most frequent symptoms mentioned by musicians in the VTD, for both frequency and intensity of occurrence, were dryness, ache, irritability, and cervical muscle pain, in addition to the frequency of occurrence of fatigue after playing. The musicians showed high scores in the V-RQOL survey. Several symptoms evaluated by the VTD had a negative correlation with the musicians' years of orchestra membership and with V-RQOL scores.ConclusionSymptoms of vocal tract discomfort are present in wind instrumentalists in low frequency and intensity of occurrence. However, these symptoms affect the musicians' voice-related quality of life, and they occur more in musicians with fewer years of orchestra membership.



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Utility of Laryngeal High-speed Videoendoscopy in Clinical Voice Assessment

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Publication date: Available online 7 June 2017
Source:Journal of Voice
Author(s): Stephanie R.C. Zacharias, Dimitar D. Deliyski, Terri Treman Gerlach
ObjectiveThis study aimed to assess the utility of laryngeal high-speed videoendoscopy (HSV) as a clinical tool.DesignThis is a prospective study of 151 patients.MethodsA total of 151 adult patients (52 male, 99 female) underwent both videoendoscopy with stroboscopy (videostroboscopy) and HSV examination as part of a routine clinical voice assessment. At the time of the examination, ratings for videostroboscopy were reported in the clinical report. Next, the clinicians reviewed the HSV examination and indicated the changes in ratings of HSV relative to videostroboscopy. Finally, the clinical reports were reviewed by a clinician not involved in data collection or clinical care of the patients and noted differences between videostroboscopy and HSV clinical ratings, and resulting diagnoses were identified and grouped.ResultsRatings of all vibratory features showed change between videostroboscopy and HSV. Mucosal wave and amplitude of vibration showed the largest percentage change, respectively, in 74% and 53% of the reports. They were followed by the features of glottal closure (36%), phase closure (32%), glottal edge (25%), and phase symmetry (21%). Ratings of supraglottic compression and vocal fold vertical level showed the least change between videostroboscopy and HSV. Changes in initial diagnosis owing to the inclusion of HSV were indicated in 7% of the cases.ConclusionsHSV may be an important laryngeal imaging technique for functional assessment of the pathophysiology of certain voice disorders. HSV could enable important refinements in the diagnosis and management of vocal fold pathology.



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A Training Model for Improving Journalists' Voice

S08921997.gif

Publication date: Available online 7 June 2017
Source:Journal of Voice
Author(s): Emma Rodero, Celia Diaz-Rodriguez, Olatz Larrea
Voice education is a crucial aspect for professionals (journalists, teachers, politicians, actors, etc.) who use their voices as a working tool. The main concerns about such education are that, first, there is little awareness of the importance of voice education, and second there is little research devoted to it. The consequences of this lack of training are indeed visible in professionals who suffer voice pathologies or work with little effectiveness. This study seeks to overcome this deficiency by proposing a training model tested with a control group and a pilot study. Speech samples from a group of experimental participants—journalism students—were collected before and after a training course designed to improve their main vocal and prosodic features. These samples were contrasted with a control group without training. Results indicated significant differences in all tested voice elements (breathing, articulation, loudness, pitch, jitter, speech rate, pauses, and stress) except for shimmer and harmonics. The participants were able to enhance their main vocal and prosodic elements, and therefore their expressiveness maintaining optimal vocal hygiene.



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Aerodynamic Patterns in Patients With Voice Disorders: A Retrospective Study

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Publication date: Available online 7 June 2017
Source:Journal of Voice
Author(s): Marina Gilman, Brian Petty, Carissa Maira, Madeleine Pethan, Lijia Wang, Edie R. Hapner, Michael M. Johns
ObjectiveA recently published retrospective chart review of aerodynamic profiles of women with primary muscle tension dysphonia by Gillespie et al (2013) identified various relationships between mean airflow rate (MFR) and estimated subglottal pressure (est-Psub). The current retrospective study expanded the diagnostic categories to include all voice disorders referred for voice therapy. Three research questions were proposed: (1) Are there differences in the MFR and the est-Psub compared with the normal control group? (2) Within the disordered population, are there different variations in the pairing of MFR and est-Psub? (3) If these variations exist, are they diagnosis specific?MethodsA retrospective chart review of patients seen for acoustic and aerodynamic voice assessment at the Emory Voice Center between January 1, 2013 and December 31, 2014, were examined for aerodynamic measures of est-Psub and MFR; of these, 192 met the inclusion criteria. Simple t test, two-step cluster analysis, and analysis of variance, as well as Tukey multiple comparisons, were performed using R and SPSS.ResultsMean est-Psub was significantly greater in the group with voice disorder than in the control group (P value < 0.001). However, no statistical significance was found when comparing the MFR with the control group (P value <0.59). Nine possible pairings of MFR and est-Psub were found. Sufficient evidence was not found to detect significant differences in these pairings across diagnostic groups.ConclusionWith regard to the rate and interrelationships of MFR and est-Psub, the findings of this study are similar to those of Gillespie et al, that is, MFR and est-Psub are not determinate of diagnosis.



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Effects of Vertical Glottal Duct Length on Intraglottal Pressures and Phonation Threshold Pressure in the Uniform Glottis

S08921997.gif

Publication date: Available online 7 June 2017
Source:Journal of Voice
Author(s): Sheng Li, Ronald C. Scherer, Lewis P. Fulcher, Xianbo Wang, Lijun Qiu, Mingxi Wan, Supin Wang
According to Titze's 1988 derivations for phonation threshold pressure (PTP), there are a number of important variables that PTP depends upon. A primary one is the vertical glottal duct length T: PTP decreases if T is increased. Changing the length of T, however, may have a significant effect on other variables that PTP depends upon. This study examined the effects of lengthening the vertical uniform glottal duct on the transglottal and intraglottal pressures, and the derived transglottal pressure coefficients, for five glottal diameters (0.01, 0.02, 0.04, 0.08, and 0.16 cm) and three transglottal pressures (500, 1000, and 1500 Pa) for the uniform glottis by using the computational fluid dynamics code Fluent (for laminar, incompressible, two-dimensional flow). The results suggest the following: A longer vertical glottal duct length increases the intraglottal and transglottal pressures, and more so for smaller glottal diameters, and increases the transglottal pressure coefficient. In addition, unlike the transglottal pressure coefficient, the glottal entrance pressure coefficient is highly dependent on the vertical glottal duct length only for lower flows and Reynolds numbers, but is relatively independent of duct length, glottal diameter, and transglottal pressure above a flow value of approximately 50 cm3/s, suggesting that the entrance pressure coefficient is a relatively local phenomenon. These results suggest that the vertical glottal duct length and its effects need to be taken into consideration for vocal fold modeling, aeroacoustics purposes, and the estimation of PTP.



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Eye Movements Are Correctly Timed During Walking Despite Bilateral Vestibular Hypofunction

Abstract

Individuals with bilateral vestibular hypofunction (BVH) often report symptoms of oscillopsia (the perception that the world is bouncing or unstable) during walking. Efference copy/proprioception contributes to locomotion gaze stability in animals, sometimes inhibiting the vestibulo-ocular reflex (VOR). Gaze stability requires both adequate eye velocity and appropriate timing of eye movements. It is unknown whether eye velocity (VOR gain), timing (phase), or both are impaired for individuals with BVH during walking. Identifying the specific mechanism of impaired gaze stability can better inform rehabilitation options. Gaze stability was measured for eight individuals with severe BVH and eight healthy age- and gender-matched controls while performing a gaze fixation task during treadmill walking. Frequency response functions (FRF) were calculated from pitch eye and head velocity. A one-way ANOVA was conducted to determine group differences for each frequency bin of the FRF. Pearson correlation coefficients were calculated to determine the relationship between the real and imaginary parts of the FRF and the Oscillopsia Visual Analog Scale (oVAS) scores. Individuals with BVH demonstrated significantly lower gains than healthy controls above 0.5 Hz, but their phase was ideally compensatory for frequencies below 3 Hz. Higher oVAS scores were correlated with lower gain. Individuals with BVH demonstrated ideal timing for vertical eye movements while walking despite slower than ideal eye velocity when compared to healthy controls. Rehabilitation interventions focusing on enhancing VOR gain during walking should be developed to take advantage of the intact timing reported here. Specifically, training VOR gain while walking may reduce oscillopsia severity and improve quality of life.



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A new treatment of hypertrophic and keloid scars with combined triamcinolone and verapamil: a retrospective study

Abstract

Background

Since the management of keloid and hypertrophic scars still remains a difficult clinical problem, there is need for adequate, effective therapy. In this study, we explored for the first time the efficacy and the potential synergetic effect of combined triamcinolone and verapamil for the treatment of hypertrophic and keloid scars. The objective was to assess the efficacy of combined intralesional triamcinolone and verapamil therapy for hypertrophic and keloid scars.

Methods

Fifty-eight patients with hypertrophic scars (n = 31) and keloid scars (n = 27) were included. A specific injection therapy scheme was applied. Five follow-up moments were chosen, with a maximum follow-up of nearly 2 years. The effects of combination therapy on scar pliability, thickness, relief, vascularization, surface area, pain, and pruritus were examined by means of the Patient and Observer Scar Assessment Scale (POSAS).

Results

Our results reveal a fast and abiding improvement of both keloid and hypertrophic scars after treatment with the combination therapy. All POSAS components showed a reduction in scar score, while scar relief, pain, itchiness, and surface area improved significantly (P < 0.05) in keloids. Significant improvement in hypertrophic scars was found in scar pigmentation, vascularization, pliability, thickness, pain, and surface area. Overall POSAS scores revealed statistically significant decreases between baseline and 3–4 months, 4–6 months, and >12 months after start of therapy in both keloids and hypertrophic scars.

Conclusions

This study reveals that combined therapy of triamcinolone and verapamil results in overall significant scar improvement with a long-term stable result.

Level of evidence: Level IV, therapeutic study.



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Rater Reliability of the Hardy Classification for Pituitary Adenomas in the Magnetic Resonance Imaging Era

J Neurol Surg B
DOI: 10.1055/s-0037-1603649

Objectives The Hardy classification is used to classify pituitary tumors for clinical and research purposes. The scale was developed using lateral skull radiographs and encephalograms, and its reliability has not been evaluated in the magnetic resonance imaging (MRI) era. Design Fifty preoperative MRI scans of biopsy-proven pituitary adenomas using the sellar invasion and suprasellar extension components of the Hardy scale were reviewed. Setting This study was a cohort study set at a single institution. Participants There were six independent raters. Main Outcome Measures The main outcome measures of this study were interrater reliability, intrarater reliability, and percent agreement. Results Overall interrater reliability of both Hardy subscales on MRI was strong. However, reliability of the intermediate scores was weak, and percent agreement among raters was poor (12–16%) using the full scales. Dichotomizing the scale into clinically useful groups maintained strong interrater reliability for the sellar invasion scale and increased the percent agreement for both scales. Conclusion This study raises important questions about the reliability of the original Hardy classification. Editing the measure to a clinically relevant dichotomous scale simplifies the rating process and may be useful for preoperative tumor characterization in the MRI era. Future research studies should use the dichotomized Hardy scale (sellar invasion Grades 0–III versus Grade IV, suprasellar extension Types 0–C versus Type D).
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



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Biosorption of Lead(II) from Aqueous Solution by Sodium Hydroxide Modified Auricularia auricular Spent Substrate: Isotherms, Kinetics, and Mechanisms

Abstract

In this study, Auricularia auricular spent substrate (AASS) was modified by sodium hydroxide and prepared as biosorbents to remove lead(II) from aqueous solution. The batch experiments showed that the biosorption capacity and biosorption percentage reached 36.35 mg g−1 and 72.7% at initial concentration of 50 mg L−1, pH 5, contact time of 200 min, and biosorbent dosage of 1 g L−1. The biosorption of lead(II) onto modified AASS well fitted with the Langmuir isotherm model and the pseudo-second-order kinetic model with the maximum adsorption capacity(q max) of 49.53 mg L−1. The biosorption was an endothermic reaction and a spontaneous process based on positive value of ΔH 0 and negative value of ΔG 0. Fourier transform infrared (FTIR) analysis illuminated that amino and hydroxyl groups could bind lead(II) on biosorbent surface. Sodium hydroxide modification might enhance physical adsorption by enlarging surface area and pore volume as well as chemical adsorption by increasing ion exchange and forming crystalline species demonstrated by microscopy (SEM-EDX) and X-ray diffraction (XRD) analysis. After four regeneration cycles, the biosorption capacity of modified AASS still kept at 17.35 mg g−1.



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Translation, Cultural Adaptation, and Preliminary Evaluation of the Spanish Version of the Transgender Voice Questionnaire for Male-to-Female Transsexuals (TVQ MtF)

Publication date: Available online 7 June 2017
Source:Journal of Voice
Author(s): Elena Mora, Alvaro Carrillo, Ana Giribet, Antonio Becerra, M Jesús Lucio, Ignacio Cobeta
ObjectiveThis study aimed to perform translation, cross-cultural adaptation, and validation of the Spanish version of the Transsexual Voice Questionnaire for Male-to-Female Transsexuals (TVQ MtF).Study DesignThis is a prospective study.SettingThe study was conducted by the Gender Identity Unit and the Voice Unit of a tertiary hospital referral center for surgical feminization of the voice.Subjects and MethodsThe study had two parts: translation and adaptation of the TVQ MtF with the following actions: translation (with authorization and consensus of the authors of the original questionnaire), back-translation, pretesting, and final version; and preliminary study of the psychometric properties (feasibility, internal consistency, test-retest reliability, construct validity, discriminant validity, and ceiling and floor effects). Thirty male-to-female transsexual women filled out the questionnaire, and 18 of the 30 filled out the questionnaire approximately 2 weeks after filling it out for the first time.ResultsFeasibility was 100%. Cronbach α was 0.976. The intraclass correlation coefficient was 0.885. The Spearman correlation coefficient between TVQ MtF and the physical component of SF-12 v2 was 0.102 (P value = 0.592) and between TVQ MtF and the mental component was −0.263 (P value = 0.161). A ceiling effect was not found. A floor effect was found in two questionnaires (6.7%).ConclusionFeasibility, internal consistency, and reliability outcomes in our study support the validity of the authorized Spanish version of the TVQ MtF.



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Vocal Tract Discomfort and Voice-Related Quality of Life in Wind Instrumentalists

Publication date: Available online 7 June 2017
Source:Journal of Voice
Author(s): Juliane Cappellaro, Bárbara Costa Beber
ObjectiveThis study aimed to investigate vocal tract discomfort and quality of life in the voice of wind instrumentalists.MethodIt is a cross-sectional study. The sample was composed of 37 musicians of the orchestra of Caxias do Sul city, RS, Brazil. The participants answered a nonstandard questionnaire about demographic and professional information, the Voice-Related Quality of Life (V-RQOL), the Vocal Tract Discomfort (VTD) scale, and additional items about fatigue after playing the instrument and pain in the cervical muscles. Correlation analyses were performed using Spearman correlation test.ResultsThe most frequent symptoms mentioned by musicians in the VTD, for both frequency and intensity of occurrence, were dryness, ache, irritability, and cervical muscle pain, in addition to the frequency of occurrence of fatigue after playing. The musicians showed high scores in the V-RQOL survey. Several symptoms evaluated by the VTD had a negative correlation with the musicians' years of orchestra membership and with V-RQOL scores.ConclusionSymptoms of vocal tract discomfort are present in wind instrumentalists in low frequency and intensity of occurrence. However, these symptoms affect the musicians' voice-related quality of life, and they occur more in musicians with fewer years of orchestra membership.



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Utility of Laryngeal High-speed Videoendoscopy in Clinical Voice Assessment

Publication date: Available online 7 June 2017
Source:Journal of Voice
Author(s): Stephanie R.C. Zacharias, Dimitar D. Deliyski, Terri Treman Gerlach
ObjectiveThis study aimed to assess the utility of laryngeal high-speed videoendoscopy (HSV) as a clinical tool.DesignThis is a prospective study of 151 patients.MethodsA total of 151 adult patients (52 male, 99 female) underwent both videoendoscopy with stroboscopy (videostroboscopy) and HSV examination as part of a routine clinical voice assessment. At the time of the examination, ratings for videostroboscopy were reported in the clinical report. Next, the clinicians reviewed the HSV examination and indicated the changes in ratings of HSV relative to videostroboscopy. Finally, the clinical reports were reviewed by a clinician not involved in data collection or clinical care of the patients and noted differences between videostroboscopy and HSV clinical ratings, and resulting diagnoses were identified and grouped.ResultsRatings of all vibratory features showed change between videostroboscopy and HSV. Mucosal wave and amplitude of vibration showed the largest percentage change, respectively, in 74% and 53% of the reports. They were followed by the features of glottal closure (36%), phase closure (32%), glottal edge (25%), and phase symmetry (21%). Ratings of supraglottic compression and vocal fold vertical level showed the least change between videostroboscopy and HSV. Changes in initial diagnosis owing to the inclusion of HSV were indicated in 7% of the cases.ConclusionsHSV may be an important laryngeal imaging technique for functional assessment of the pathophysiology of certain voice disorders. HSV could enable important refinements in the diagnosis and management of vocal fold pathology.



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A Training Model for Improving Journalists' Voice

Publication date: Available online 7 June 2017
Source:Journal of Voice
Author(s): Emma Rodero, Celia Diaz-Rodriguez, Olatz Larrea
Voice education is a crucial aspect for professionals (journalists, teachers, politicians, actors, etc.) who use their voices as a working tool. The main concerns about such education are that, first, there is little awareness of the importance of voice education, and second there is little research devoted to it. The consequences of this lack of training are indeed visible in professionals who suffer voice pathologies or work with little effectiveness. This study seeks to overcome this deficiency by proposing a training model tested with a control group and a pilot study. Speech samples from a group of experimental participants—journalism students—were collected before and after a training course designed to improve their main vocal and prosodic features. These samples were contrasted with a control group without training. Results indicated significant differences in all tested voice elements (breathing, articulation, loudness, pitch, jitter, speech rate, pauses, and stress) except for shimmer and harmonics. The participants were able to enhance their main vocal and prosodic elements, and therefore their expressiveness maintaining optimal vocal hygiene.



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Aerodynamic Patterns in Patients With Voice Disorders: A Retrospective Study

Publication date: Available online 7 June 2017
Source:Journal of Voice
Author(s): Marina Gilman, Brian Petty, Carissa Maira, Madeleine Pethan, Lijia Wang, Edie R. Hapner, Michael M. Johns
ObjectiveA recently published retrospective chart review of aerodynamic profiles of women with primary muscle tension dysphonia by Gillespie et al (2013) identified various relationships between mean airflow rate (MFR) and estimated subglottal pressure (est-Psub). The current retrospective study expanded the diagnostic categories to include all voice disorders referred for voice therapy. Three research questions were proposed: (1) Are there differences in the MFR and the est-Psub compared with the normal control group? (2) Within the disordered population, are there different variations in the pairing of MFR and est-Psub? (3) If these variations exist, are they diagnosis specific?MethodsA retrospective chart review of patients seen for acoustic and aerodynamic voice assessment at the Emory Voice Center between January 1, 2013 and December 31, 2014, were examined for aerodynamic measures of est-Psub and MFR; of these, 192 met the inclusion criteria. Simple t test, two-step cluster analysis, and analysis of variance, as well as Tukey multiple comparisons, were performed using R and SPSS.ResultsMean est-Psub was significantly greater in the group with voice disorder than in the control group (P value < 0.001). However, no statistical significance was found when comparing the MFR with the control group (P value <0.59). Nine possible pairings of MFR and est-Psub were found. Sufficient evidence was not found to detect significant differences in these pairings across diagnostic groups.ConclusionWith regard to the rate and interrelationships of MFR and est-Psub, the findings of this study are similar to those of Gillespie et al, that is, MFR and est-Psub are not determinate of diagnosis.



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Effects of Vertical Glottal Duct Length on Intraglottal Pressures and Phonation Threshold Pressure in the Uniform Glottis

Publication date: Available online 7 June 2017
Source:Journal of Voice
Author(s): Sheng Li, Ronald C. Scherer, Lewis P. Fulcher, Xianbo Wang, Lijun Qiu, Mingxi Wan, Supin Wang
According to Titze's 1988 derivations for phonation threshold pressure (PTP), there are a number of important variables that PTP depends upon. A primary one is the vertical glottal duct length T: PTP decreases if T is increased. Changing the length of T, however, may have a significant effect on other variables that PTP depends upon. This study examined the effects of lengthening the vertical uniform glottal duct on the transglottal and intraglottal pressures, and the derived transglottal pressure coefficients, for five glottal diameters (0.01, 0.02, 0.04, 0.08, and 0.16 cm) and three transglottal pressures (500, 1000, and 1500 Pa) for the uniform glottis by using the computational fluid dynamics code Fluent (for laminar, incompressible, two-dimensional flow). The results suggest the following: A longer vertical glottal duct length increases the intraglottal and transglottal pressures, and more so for smaller glottal diameters, and increases the transglottal pressure coefficient. In addition, unlike the transglottal pressure coefficient, the glottal entrance pressure coefficient is highly dependent on the vertical glottal duct length only for lower flows and Reynolds numbers, but is relatively independent of duct length, glottal diameter, and transglottal pressure above a flow value of approximately 50 cm3/s, suggesting that the entrance pressure coefficient is a relatively local phenomenon. These results suggest that the vertical glottal duct length and its effects need to be taken into consideration for vocal fold modeling, aeroacoustics purposes, and the estimation of PTP.



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Geographic Tongue: assessment of Peripheral Nerve Status, Langerhans cell and HLA-DR Expression

Publication date: Available online 7 June 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): M.R. Darling, N. Su, S. Masen, P. Kwon, D. Fortino, T.R. McKerlie, M. Grushka
ObjectivesThe objectives of this study were to determine whether geographic tongue is an antigen-driven condition by assessing Langerhans cell numbers, and HLA-DP, -DQ and -DR expression in the epithelium of geographic tongue cases, and to assess peripheral nerve status for any possible damage/injury association by quantifying neurite area in the connective tissue of geographic tongue cases.Study DesignRandomly selected cases of geographic tongue were examined using routine immunoperoxidase staining methods to S100 protein, Neurofilament, CD1a and HLA class II. Student’s t-tests and Mann-Whitney U tests were used to assess statistical significance.ResultsLangerhans cell numbers were increased in geographic tongue. HLA expression was also seen in Langerhans cells, inflammatory cells, and, in two cases of geographic tongue, in the spinous layer and parabasal epithelial cells. Total nerve tissue, based on area measurements, was not significantly different in geographic tongue and controls.ConclusionsThe increase in Langerhans cells suggests that geographic tongue is an antigen-driven condition, probably by an unknown external antigen. Peripheral nerve damage was not apparent, suggesting that this is not a mechanism whereby patients become symptomatic in geographic tongue.



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Prognostic Significance of hMSH2, hMSH3 and hMSH6 Expression in Ameloblastoma

Publication date: Available online 7 June 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Gleyson Kleber do Amaral-Silva, Celeste Sánchez-Romero, Vivian Petersen Wagner, Manoela Domingues Martins, Hélder Antônio Rebelo Pontes, Eduardo Rodrigues Fregnani, Fernando Augusto Soares, Oslei Paes de Almeida, André Caroli Rocha, Alan Roger Santos-Silva, Felipe Paiva Fonseca, Pablo Agustin Vargas
AimsTo investigate hMutS proteins in human dental germ, ameloblastomas and ameloblastic carcinoma, and to determine whether the expression of these proteins has any prognostic potential.Methods and resultsTen cases of human dental germs, 39 ameloblastomas and 2 ameloblastic carcinomas were used to determine the distribution of the proteins during the carcinogenesis process. Simultaneously, another sample of 73 ameloblastomas was arranged in tissue microarray and their clinical, microscopic and radiographic features, treatment outcome, presence of BRAF-V600E mutation and follow-up data, were assessed to determine the prognostic relevance of the proteins. Immunohistochemistry was performed using antibodies against hMutS (hMSH2, hMSH3, hMSH6) and Ki67. hMSH2 and hMSH6 were significantly down-expressed in ameloblastomas (p=0.0059) than in human dental germs (p<0.0001). hMSH2, hMSH3 and the protein combinations were significantly associated with BRAF-V600E mutation (p<0.05). Simultaneous over-expression of hMutS was associated with recurrences (p=0.035); however, the proteins did not predict the disease-free survival of patients (p>0.05).ConclusionshMutS proteins are down-regulated in ameloblastoma; moreover, simultaneous over-expression of these proteins in ameloblastoma was associated with recurrence, but did not predict disease-free survival.



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Analysis of archived newborn dried blood spots (DBS) identifies congenital cytomegalovirus as a major cause of unexplained pediatric sensorineural hearing loss

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Publication date: Available online 7 June 2017
Source:American Journal of Otolaryngology
Author(s): Lucy Meyer, Bazak Sharon, Tina C. Huang, Abby C. Meyer, Kristin E. Gravel, Lisa A. Schimmenti, Elizabeth C. Swanson, Hannah E. Herd, Nelmary Hernandez-Alvarado, Kirsten R. Coverstone, Mark McCann, Mark R. Schleiss
PurposeCongenital cytomegalovirus (cCMV) infection is the most common non-genetic cause of sensorineural hearing loss (SNHL). However, accurate diagnosis of cCMV as the etiology of SNHL is problematic beyond the neonatal period. This study therefore examined whether cCMV infection could be identified retrospectively in children presenting with unexplained SNHL to a multidisciplinary diagnostic outpatient otolaryngology clinic at an academic medical center in Minnesota.MethodsOver a 4-year period, 57 patients age 3months to 10years of age with unexplained SNHL were recruited to participate in this study. Informed consent was obtained to test the archived dried blood spots (DBS) of these patients for cCMV infection by real-time PCR, targeting a highly conserved region of the CMV UL83 gene. Results were normalized to recovery of an NRAS gene control. Chart review was conducted to identify subjects who underwent genetic testing and/or neurodiagnostic imaging to investigate possible genetic, syndromic, or anatomical causes of SNHL.ResultsIn total, 15 of the 57 children with unexplained SNHL tested positive for CMV DNA in their DBS (26%). A mean viral load of 8.3×104 (±4.1×104) [range, 1×103–6×105] copies/μg DNA was observed in subjects retrospectively diagnosed with cCMV. No statistically significant correlation was found between viral load and SNHL severity.ConclusionsA retrospective DBS analysis demonstrated 26% of patients presenting with unexplained SNHL in childhood had cCMV. DBS testing is useful in the retrospective diagnosis of cCMV, and may provide definitive diagnostic information about the etiology of SNHL.



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