Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

Αρχειοθήκη ιστολογίου

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Δευτέρα 1 Φεβρουαρίου 2016

Sensors, Vol. 16, Pages 180: A Personal, Distributed Exposimeter: Procedure for Design, Calibration, Validation, and Application

This paper describes, for the first time, the procedure for the full design, calibration, uncertainty analysis, and practical application of a personal, distributed exposimeter (PDE) for the detection of personal exposure in the Global System for Mobile Communications (GSM) downlink (DL) band around 900 MHz (GSM 900 DL). The PDE is a sensor that consists of several body-worn antennas. The on-body location of these antennas is investigated using numerical simulations and calibration measurements in an anechoic chamber. The calibration measurements and the simulations result in a design (or on-body setup) of the PDE. This is used for validation measurements and indoor radio frequency (RF) exposure measurements in Ghent, Belgium. The main achievements of this paper are: first, the demonstration, using both measurements and simulations, that a PDE consisting of multiple on-body textile antennas will have a lower measurement uncertainty for personal RF exposure than existing on-body sensors; second, a validation of the PDE, which proves that the device correctly estimates the incident power densities; and third, a demonstration of the usability of the PDE for real exposure assessment measurements. To this aim, the validated PDE is used for indoor measurements in a residential building in Ghent, Belgium, which yield an average incident power density of 0.018 mW/m².

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Aerospace, Vol. 3, Pages 5: Target Tracking in 3-D Using Estimation Based Nonlinear Control Laws for UAVs

This paper presents an estimation based backstepping like control law design for an Unmanned Aerial Vehicle (UAV) to track a moving target in 3-D space. A ground-based sensor or an onboard seeker antenna provides range, azimuth angle, and elevation angle measurements to a chaser UAV that implements an extended Kalman filter (EKF) to estimate the full state of the target. A nonlinear controller then utilizes this estimated target state and the chaser's state to provide speed, flight path, and course/heading angle commands to the chaser UAV. Tracking performance with respect to measurement uncertainty is evaluated for three cases: (1) stationary white noise; (2) stationary colored noise and (3) non-stationary (range correlated) white noise. Furthermore, in an effort to improve tracking performance, the measurement model is made more realistic by taking into consideration range-dependent uncertainties in the measurements, i.e., as the chaser closes in on the target, measurement uncertainties are reduced in the EKF, thus providing the UAV with more accurate control commands. Simulation results for these cases are shown to illustrate target state estimation and trajectory tracking performance.

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Gels, Vol. 2, Pages 7: Supramolecular Assembly of pH-Sensitive Triphenylene Derived π-Gelators and Their Application as Molecular Template for the Preparation of Silica Nanotubes

The gelation properties and mode of self-assembly of six asymmetrical hexaether triphenylene derivatives mono-functionalized with carboxylic and primary amine groups were investigated. The presence of a carboxylic and amine group attached to the triphenylene core generated stable, thermo- and pH-sensitive supramolecular π-organogels with a reversible response to both stimuli. In order to understand the gelation process, we studied the effect of the spacer length and found a different gelation scope for the acid and basic derivatives that accounts for a different supramolecular self-assembly. The presence of the basic group on the amino derivatives was used to guide and catalyze the templated in situ sol-gel polymerization of TEOS and allowed us, under controlled hydrolytic conditions, to prepare an entangled fibrillar network of silica nanotubes.

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Diagnostics, Vol. 6, Pages 8: Interobserver and Intraobserver Reproducibility with Volume Dynamic Contrast Enhanced Computed Tomography (DCE-CT) in Gastroesophageal Junction Cancer

The purpose of this study was to assess inter- and intra-observer reproducibility of three different analytic methods to evaluate quantitative dynamic contrast-enhanced computed tomography (DCE-CT) measures from gastroesophageal junctional cancer. Twenty-five DCE-CT studies with gastroesophageal junction cancer were selected from a previous longitudinal study. Three radiologists independently reviewed all scans, and one repeated the analysis eight months later for intraobserver analysis. Review of the scans consisted of three analysis methods: (I) Four, fixed small sized regions of interest (2-dimensional (2D) fixed ROIs) placed in the tumor periphery, (II) 2-dimensional regions of interest (2D-ROI) along the tumor border in the tumor center, and (III) 3-dimensional volumes of interest (3D-VOI) containing the entire tumor volume. Arterial flow, blood volume and permeability (ktrans) were recorded for each observation. Inter- and intra-observer variability were assessed by Intraclass Correlation Coefficient (ICC) and Bland-Altman statistics. Interobserver ICC was excellent for arterial flow (0.88), for blood volume (0.89) and for permeability (0.91) with 3D-VOI analysis. The 95% limits of agreement were narrower for 3D analysis compared to 2D analysis. Three-dimensional volume DCE-CT analysis of gastroesophageal junction cancer provides higher inter- and intra-observer reproducibility with narrower limits of agreement between readers compared to 2D analysis.

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Polymers, Vol. 8, Pages 38: Comb-Type Grafted Hydrogels of PNIPAM and PDMAEMA with Reversed Network-Graft Architectures from Controlled Radical Polymerizations

Dual thermo- and pH-responsive comb-type grafted hydrogels of poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) and poly(N-isopropylacrylamide) (PNIPAM) with reversed network-graft architectures were synthesized by the combination of atom transfer radical polymerization (ATRP), reversible addition-fragmentation chain transfer (RAFT) polymerization and click chemistry. Two kinds of macro-cross-linkers with two azido groups at one chain-end and different chain length [PNIPAM–(N3)2 and PDMAEMA–(N3)2] were prepared with N,N-di(β-azidoethyl) 2-halocarboxylamide as the ATRP initiator. Through RAFT copolymerization of DMAEMA or NIPAM with propargyl acrylate (ProA) using dibenzyltrithiocarbonate as a chain transfer agent, two network precursors with different content of alkynyl side-groups [P(DMAEMA-co-ProA) and P(NIPAM-co-ProA)] were obtained. The subsequent azido-alkynyl click reaction of macro-cross-linkers and network precursors led to the formation of the network-graft hydrogels. These dual stimulus-sensitive hydrogels exhibited rapid response, high swelling ratio and reproducible swelling/de-swelling cycles under different temperatures and pH values. The influences of cross-linkage density and network-graft architecture on the properties of the hydrogels were investigated. The release of ceftriaxone sodium from these hydrogels showed both thermal- and pH-dependence, suggesting the feasibility of these hydrogels as thermo- and pH-dependent drug release devices.

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Microfluidic devices with templated regular macroporous structures for HIV viral capture

GA?id=C5AN02282G

Analyst, 2016, Advance Article
DOI: 10.1039/C5AN02282G, Paper
Krissada Surawathanawises, Kathryn Kundrod, Xuanhong Cheng
Microfluidic devices with embedded macroporous matrices significantly improve the capture yield of HIV viruses through affinity binding.
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
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Neonatal hyperbilirubinaemia

Paediatrics and Child Health

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Daclatasvir, sofosbuvir, and ribavirin for hepatitis C virus genotype 3 and advanced liver disease: A randomized phase III study (ALLY-3+)

Hepatology

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Significant intratumoral heterogeneity of HER2 status in gastric cancer: A comparative study among IHC, FISH, and DISH

Cancer Science

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Celiac disease in a large cohort of children and adolescents with recurrent headache: A retrospective study

Digestive and Liver Diseases

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Application of Deuteporfin in the Metastatic Lymph Node Mapping of Pancreatic Cancer: An in vivo Study

Abstract

For most cancer patients, the presence of metastatic lymph nodes usually indicates regional recurrence and poor prognosis. Therefore, lymph node mapping is a requisite for disease staging, prognosis prediction, and decision making in the treatment of cancer. Deuteporfin, a second-generation photosensitizer, has a maximum excitation wavelength that can reach the near infrared (NIR) region (650-700 nm). We aimed to take advantage of these aspects of deuteporfin and use it as a fluorescent probe for metastatic lymph node mapping in vivo using NIR fluorescent imaging. In our study, we further investigated whether a photosensitizer could be used as a tracer for metastatic lymph node mapping of pancreatic cancer based on previous reports. Compared to normal tissues, tumor tissues including primary tumors and metastatic lymph nodes had a higher uptake ability of deuteporfin (p<0.05). Our research confirmed this targeting property of deuteporfin using in vivo fluorescent imaging. Consistent with observations from in vivo imaging experiments, frozen sections of metastatic lymph nodes intuitively displayed significantly higher and wider distributions of deuteporfin than normal sections.

This article is protected by copyright. All rights reserved.



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Macular pigmentation of uncertain aetiology revisited: two case reports and a proposed algorithm for clinical classification

Abstract

Ashy dermatosis, erythema dyschromicum perstans, lichen planus pigmentosus and idiopathic eruptive macular pigmentation are various types of acquired macular hyperpigmentation disorders of the skin described in literature. However, a global consensus on the definitions of these entities is lacking. We report two cases of acquired macular (hyper)pigmentation of uncertain aetiology diagnosed as ashy dermatosis and attempt to clarify the various confusing nosologies based on existing literature. We infer that acquired small and large macular pigmentation of uncertain aetiology should be considered separate from that associated with lichen planus. We also propose a diagnostic algorithm for patients with acquired macular hyperpigmentation.



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Lip cancer

Publication date: Available online 30 January 2016
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Éder Ricardo Biasoli, Vitor Bonetti Valente, Bruna Mantovan, Francisco Urbano Collado, Sebastião Conrado Neto, Maria Lúcia Marçal Mazza Sundefeld, Glauco Issamu Miyahara, Daniel Galera Bernabé
PurposeThere are few clinical studies focusing on the lip cancer treatment outcomes. This study aims to investigate the clinicopathological variables profile of a large sample of lip squamous cell carcinoma (LSCC) patients treated in a head and neck cancer reference center for the last 25 years, and to analyze the influence of these variables on the treatment outcomes.Materials and MethodsIn this retrospective cohort study, we reviewed the clinical records of LSCC patients. The epidemiological data were age, gender, ethnicity, type of occupation, tobacco smoking, alcohol consumption, comorbid conditions and family cancer history. Clinicopathological features included the lip location of the tumor, TNM classification, clinical staging, histopathological grade, surgical margin analysis and treatment modality. Local recurrence, second primary tumor and survival were the outcome variables. Statistics was performed by Chi-square, Fisher exact test and Binary Logistic Regression. Survival analysis was assessed through the Kaplan and Meier curve. Level of statistical significance was set at p<0.05 for all tests.ResultsA total of 144 LSCC patients were studied. There were 117 men (81.25%) and 27 women (18.75%), with mean age of 60.21 years. One hundred thirty-four patients (93.05%) were considered of white ethnicity and in 57 cases (39.58%) the patients presented an occupation that was related to chronic solar exposure. Most cancers had initial clinical staging of I/II (84.02%). Microscopically, lesions were predominantly well- (43.05%) and moderately- (40.96%) differentiated tumors. The clinical staging was related to a specific higher survival rate (p=0.0049). One hundred twelve cases (77.78%) were submitted to surgical treatment and only six patients (4.80%) had local recurrence, which was directly associated with compromised surgical margins (p=0.0320).ConclusionA high success rate in LSCC treatment was observed in this study. Compromised surgical margin was associated to tumor recurrence and is a critical event in lip cancer treatment.


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Efficacy and safety of catheter-based rheolytic and aspiration thrombectomy in children

Background

Vascular thromboses are a significant cause of morbidity and mortality in children. Data in children regarding catheter-based rheolytic and aspiration thrombectomy systems are limited. We sought to review the safety and efficacy of catheter-based rheolytic and aspiration thrombectomy systems in children. Methods: Data of all children having undergone thrombectomy using specialized rheolytic or aspiration systems were reviewed. Results: Thrombectomy was performed in 50 vessels in 21 patients, median age 1.9 months (8 days–18 yrs), median weight 4.3 (1.1–67.9) kg. Thrombectomy was performed using AngioJet in 16, Helix Clot Buster in 5, Fetch catheter in 8, Pronto catheter in 1, and a combination of other systems in 20 vessels (with AngioJet in 16). Thrombectomy was successful in 47/50 (94%) vessels in 18/21 (86%) patients with additional balloon/stent therapy or tPA administration performed in 16/18 (89%) of these patients. There were 2 (9.5%) major complications (both with AngioJet) consisting of asystole when thrombectomy was performed using activation times of >5 sec. At a median follow-up of 10 months (2 weeks–7 years), all 47 successfully treated vessels are patent, with 8/18 (44%) patients requiring reintervention with angioplasty/stent placement or repeat thrombectomy. Conclusions: Catheter-based thrombectomy systems are an important adjunctive tool in the treatment of children with thrombotic vessel occlusions. Significant hemodynamic compromise seen when using AngioJet may be minimized by using activation times of ≤5 sec. © 2016 Wiley Periodicals, Inc.

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Carlino to the rescue: Use of intralesion contrast injection for bailout antegrade and retrograde crossing of complex chronic total occlusions

Percutaneous coronary intervention (PCI) of coronary chronic total occlusions (CTO) can be challenging. Although several crossing techniques are available, in some cases their application fails to cross the occlusion. Carlino et al. have pioneered the technique of hydraulic microdissection by contrast injection through a microcatheter inserted into the lesion. We report two CTO PCI cases in which the use of the Carlino technique enabled success after other crossing strategies failed to cross the occlusion. © 2016 Wiley Periodicals, Inc.

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Prognostic impact of the residual SYNTAX score on in-hospital outcomes in patients undergoing primary percutaneous coronary intervention

Objectives

This study sought to assess the impact of residual coronary artery disease (CAD), using the residual SYNTAX score (rSS), on in-hospital outcomes after primary percutaneous intervention (PPCI). The study also aimed to determine independent predictors for high rSS. Residual CAD has been associated with worsened prognosis in patients undergoing PCI for non-ST acute coronary syndromes. The rSS is a systematic angiographic score that measures the extent and complexity of residual CAD after PCI.

Materials and Methods

Data from 243 consecutive patients undergoing PPCI for ST-elevation myocardial infarction (STEMI) were analyzed. The rSS was derived from post-PPCI angiography. Patients were dichotomized into low (<8) and high rSS (≥8) groups and outcomes were compared between groups. The primary outcome of net adverse cardiovascular events (NACE) consisted of a composite of in-hospital death, congestive heart failure (CHF), recurrent MI and bleeding.

Results

The mean rSS was 4.7 (±7.2). A high rSS was associated with the primary outcome (P < 0.0001), in-hospital death (P = 0.0026), periprocedural death (P < 0.0001), CHF (P < 0.0004) and acute kidney injury (P < 0.0019). A high rSS was also an independent predictor of the primary outcome with an OR of 3.82. Independent predictors of a high rSS included a history of diabetes (OR 2.8), previous MI (OR 5.75), 2-vessel disease (VD) (OR 15.48, vs. 1-VD) and 3-VD (OR 57.06, vs. 1-VD).

Conclusions

Residual CAD, as assessed by the rSS, confers a worsened prognosis in patients undergoing PPCI. Diabetes, previous MI and multi-vessel disease were independent predictors of a high rSS. © 2016 Wiley Periodicals, Inc.

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Drikk kaffe med god samvittighet

Kaffe er ikke assosiert med høyere risiko for død hos ikke-røykere.

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Erratum

Future Oncology Ahead of Print.


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Early changes in condylar position after mandibular advancement

Early changes in condylar position after mandibular advancement: a three-dimensional analysis: The aim of this study was to perform a three-dimensional (3D) assessment of positional changes of the mandibular condyle after bilateral sagittal split osteotomy (BSSO). A prospective evaluation of 22 skeletal class II patients who underwent a BSSO for mandibular advancement was performed. Pre- and postoperative cone beam computed tomography scans were taken. Using the cranial base as a stable reference, the pre- and postoperative 3D skull models were superimposed virtually. Positional changes of the condyles were assessed with a 3D colour mapping system (SimPlant O&O).




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Ιnferior alveolar nerve lateralization and atrophied mandibles

Implant survival and complications in cases of inferior alveolar nerve lateralization and atrophied mandibles with 5-year follow-up: The objectives of this study were to evaluate the survival after 5 years of implants placed using inferior alveolar nerve (IAN) lateralization in cases of mandibular atrophy and to determine the incidence of complications. Twenty-seven patients received 74 implants by means of the IAN lateralization technique. Implant survival after 5 years of loading was 98.6%. Eighteen months after surgery, the recovery of sensitivity was complete in 26 cases. Implant placement with IAN lateralization was seen to be a satisfactory and predictable technique.




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Stylo-mandibular fusion complicating recurrent bilateral temporomandibular joint ankylosis

Stylo-mandibular fusion complicating recurrent bilateral temporomandibular joint ankylosis




Abstract

Ankylosis of the temporomandibular joint (TMJ) is debilitating, and difficult to manage because it recurs. Recurrent bilateral ankylosis is further complicated by the fusion of the styloid process and the mandible. We report such a case, and to our knowledge no similar case has been reported previously.


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Tumour seeding after fine-needle aspiration and core biopsy of the head and neck - a systematic review

Tumour seeding after fine-needle aspiration and core biopsy of the head and neck - a systematic review: Although fine-needle aspiration cytology (FNAC) and core needle biopsy are essential diagnostic investigations of lumps in the head and neck, seeding along the needle track has long been a concern, and various factors have been implicated. We therefore searched the Medline database for relevant English language papers published between 1970 and 2014, excluding those on the thyroid and parathyroid, and systematically reviewed them to assess the risk. In the 610 articles reviewed we found only 7 reports of seeding (5 after FNAC and 2 after core needle biopsy).




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Perceptual and Brain Response to Odors Is Associated with Body Mass Index and Postprandial Total Ghrelin Reactivity to a Meal

Perceptual and Brain Response to Odors Is Associated with Body Mass Index and Postprandial Total Ghrelin Reactivity to a Meal:

Animal studies have shown that olfactory sensitivity is greater when fasted than when fed. However, human research has generated inconsistent results. One possible explanation for these conflicting findings is metabolic health. Many metabolic peptides, including ghrelin, are moderated by adiposity and influence olfaction and olfactory-guided behaviors. We tested whether the effect of a meal on the perceived intensity of suprathreshold chemosensory stimuli is influenced by body mass index and/or metabolic response to a meal. We found that overweight or obese (n = 13), but not healthy weight (n = 20) subjects perceived odors, but not flavored solutions, as more intense when hungry than when sated. This effect was correlated with reduced postprandial total ghrelin suppression (n = 23) and differential brain response to odors in the cerebellum, as measured with functional magnetic resonance imaging. In contrast, it was unrelated to circulating leptin, glucose, insulin, triglycerides, or free fatty acids; or to odor pleasantness or sniffing (n = 24). These findings demonstrate that the effect of a meal on suprathreshold odor intensity perception is associated with metabolic measures such as body weight and total ghrelin reactivity, supporting endocrine influences on olfactory perception.



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Perceptual and Brain Response to Odors Is Associated with Body Mass Index and Postprandial Total Ghrelin Reactivity to a Meal.

Perceptual and Brain Response to Odors Is Associated with Body Mass Index and Postprandial Total Ghrelin Reactivity to a Meal

Chem Senses. 2016 Jan 28;

Authors: Sun X, Veldhuizen MG, Babbs AE, Sinha R, Small DM

Abstract

Animal studies have shown that olfactory sensitivity is greater when fasted than when fed. However, human research has generated inconsistent results. One possible explanation for these conflicting findings is metabolic health. Many metabolic peptides, including ghrelin, are moderated by adiposity and influence olfaction and olfactory-guided behaviors. We tested whether the effect of a meal on the perceived intensity of suprathreshold chemosensory stimuli is influenced by body mass index and/or metabolic response to a meal. We found that overweight or obese (n = 13), but not healthy weight (n = 20) subjects perceived odors, but not flavored solutions, as more intense when hungry than when sated. This effect was correlated with reduced postprandial total ghrelin suppression (n = 23) and differential brain response to odors in the cerebellum, as measured with functional magnetic resonance imaging. In contrast, it was unrelated to circulating leptin, glucose, insulin, triglycerides, or free fatty acids; or to odor pleasantness or sniffing (n = 24). These findings demonstrate that the effect of a meal on suprathreshold odor intensity perception is associated with metabolic measures such as body weight and total ghrelin reactivity, supporting endocrine influences on olfactory perception.

PMID: 26826114 [PubMed - as supplied by publisher]



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Moral Fixations: The Role of Moral Integrity and Social Anxiety in the Selective Avoidance of Social Threat

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Publication date: Available online 1 February 2016
Source:Biological Psychology
Author(s): Lotte F. Van Dillen, Dorien Enter, Leonie P.M. Peters, Wilco W. van Dijk, Mark Rotteveel
People derive their sense of belonging from perceptions of being a moral person. Research moreover suggests that social cues of rejection rapidly influence visual scanning, and result in avoidant gaze behavior, especially in socially anxious individuals. With the current eye-tracking experiment, we therefore examined whether moral integrity threats and affirmations influence selective avoidance of social threat, and how this varies with individual differences in social anxiety. Fifty-nine participants retrieved a memory of a past immoral, moral, or neutral act. Next, participants passively viewed angry, happy, and neutral faces, while we recorded how often they first fixated on the eyes. In addition, we administered the Liebowitz Social Anxiety Scale (1987). Participants first fixated less on angry eyes compared to happy or neutral eyes when their moral integrity was threatened, and this selective avoidance was enhanced with increasing social anxiety. Following a moral affirmation, however, participants no longer selectively avoided the eyes of angry faces, regardless of individual differences in social anxiety. The results thus suggest that both low and high socially anxious people adjust their social gaze behavior in response to threats and affirmations of their moral integrity, pointing to the importance of the social context when considering affective processing biases.



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Phylogenetic and morphologic evidence confirm the presence of a new montane cloud forest associated bird species in Mexico, the Mountain Elaenia (Elaenia frantzii; Aves: Passeriformes: Tyrannidae)

Here we provide evidence to support an extension of the recognized distributional range of the Mountain Elaenia (Elaenia frantzii) to include southern Mexico. We collected two specimens in breeding condition in northwestern Sierra Norte de Chiapas, Mexico. Morphologic and genetic evidence support their identity as Elaenia frantzii. We compared environmental parameters of records across the entire geographic range of the species to those at the northern Chiapas survey site and found no climatic differences among localities.

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Unequal contribution of native South African phylogeographic lineages to the invasion of the African clawed frog, Xenopus laevis, in Europe

Due to both deliberate and accidental introductions, invasive African Clawed Frog (Xenopus laevis) populations have become established worldwide. In this study, we investigate the geographic origins of invasive X. laevis populations in France and Portugal using the phylogeographic structure of X. laevis in its native South African range. In total, 80 individuals from the whole area known to be invaded in France and Portugal were analysed for two mitochondrial and three nuclear genes, allowing a comparison with 185 specimens from the native range. Our results show that native phylogeographic lineages have contributed differently to invasive European X. laevis populations. In Portugal, genetic and historical data suggest a single colonization event involving a small number of individuals from the south-western Cape region in South Africa. In contrast, French invasive X. laevis encompass two distinct native phylogeographic lineages, i.e., one from the south-western Cape region and one from the northern regions of South Africa. The French X. laevis population is the first example of a X. laevis invasion involving multiple lineages. Moreover, the lack of population structure based on nuclear DNA suggests a potential role for admixture within the invasive French population.

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Feasibility of self-administered sleep assessment in older women

Feasibility of self-administered sleep assessment in older women in the Women's Health Initiative (WHI):

Abstract



Purpose

Laboratory-based polysomnography (PSG) is the gold standard assessment of sleep disordered breathing (SDB). In large cohort studies and clinical trials, however, these overnight procedures can be expensive and burdensome to participants, especially older adults. In preparation for a large observational study, we determined the feasibility of self-administering two devices mailed to participants' homes that estimate indices of SDB.




Methods

In two separate studies, older women enrolled in the Women's Health Initiative (WHI) Memory Study extension aged mean (SD) 85.77 (2.98) years who were not using supplemental oxygen and consented to being in the feasibility study completed either an in-home, self-administered overnight sleep assessment using a multi-sensor device that measured oximetry, nasal pressure, chest effort, and snoring (ApneaLinkTM) (N = 58), or a wrist-worn oximeter (NoninWristOx2TM) (N = 33). A follow-up questionnaire assessed the devices' acceptability and important sleep-related exposures.




Results

Although the multi-sensor device was assessed only in older women with no cognitive impairment, the proportion of completed interpretable sleep studies was low (54 %) and participants reported needing help to administer the device successfully. In contrast, the wrist-worn device was used in women with either no or mild cognitive impairment (MCI), completion rates were higher (100 %), and women reported being able to administer the device independently.




Conclusions

These studies demonstrated that home-based self-administered assessments of SDB are feasible in older adults with and without cognitive impairment using wrist-worn oximetry. These data support the feasibility of using simple oximetry measurements to provide indices of overnight intermittent hypoxemia in large observational studies and clinical trials.



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Craniofacial and upper airway morphology in adult obstructive sleep apnea

Craniofacial and upper airway morphology in adult obstructive sleep apnea patients: a systematic review and meta-analysis of cephalometric studies: Obstructive sleep apnea (OSA) is one of the common sleep disordered breathings in adults, characterised by frequent episodes of upper airway collapse during sleep. Craniofacial disharmony is an important risk factor for OSA. Overnight polysomnography (PSG) study is considered to be the most reliable confirmatory investigation for OSA diagnosis, whereas the precise localization of site of obstruction to the airflow cannot be detected. Identifying the cause of OSA in a particular ethnic population/individual subject helps to understand the etiological factors and effective management of OSA.




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Comprehensive Sleep Bruxism Therapy as related to Sleep Disordered Breathing

Comprehensive Sleep Bruxism Therapy as related to Sleep Disordered Breathing:

Sleep Bruxism is a condition that is receiving a tremendous amount of attention of late in the news. Perhaps as a result of the number of dentists who are providing high level diagnostics using a medical grade sleep bruxism monitor  to collect surface EMG data. This kind of objective data has opened the opportunity to improve speed to treat for patient with jaw symptoms. Patients who clench and grind do not all generate pain or present with a jaw pain complaint in fact they may be unaware that they suffer from sleep bruxism. Often this underlying disease is associated with sleep disordered breathing and should be objectively evaluated and measured to better evaluate the severity of the condition and to rule out obstructive sleep apnea and related sleep disordered breathing.-ed

BRUXISM THERAPY AND OBSTRUCTIVE SLEEP APNEA THERAPY FOR EVERY DENTAL PRACTICE

Suzanne Haley DMD as previously presented on SleepScholar.com website January 20, 2016



Appliance on models


Bruxism is a condition in which a person grinds or clenches his teeth. People who have bruxism may unconsciously or consciously clench their teeth together during the day or clench and grind them at night. Signs and symptoms of bruxism may include: sounds of grinding or clenching; teeth that are flat, fractured, or chipped; teeth that have abfractions present; increased tooth sensitivity; jaw or facial pain; tight and sore facial muscles; sore jaws; headaches; periodontal tissue damage; and indentations on the tongue. The cause of bruxism is unknown but is linked to such factors as stress, anxiety, fatigue, snoring, and sleep apnea. People who clench or grind their teeth during sleep are more likely to have some degree of apnea present.

Obstructive sleep apnea (OSA) is the most common form of sleep apnea. Sleep apnea occurs when the muscles in the back of the throat fail to keep the airway open despite efforts to breathe. Sleep apnea is a medical condition in which breathing is briefly and repeatedly interrupted during sleep. An apnea occurs when the muscles fail to keep the airway open and there is a physical obstruction such as the tongue, pharyngeal muscles, epiglottis, and uvula that blocks the airway. This obstruction causes the patient to stop breathing during sleep. An apnea is an event where the patient stops breathing for a minimum of 10 seconds during sleep. A hypopnea is an event where the patient has significantly reduced airflow because of a partially blocked airway for at least 10 seconds while sleeping. Patients with obstructive sleep apnea will have multiple apneas/hypopneas every night while they sleep, with the potential to severely impact their health. There are three different types of obstructive sleep apnea. These classifications depend on the number of apneas and hypopneas, divided by the number of drops in oxygen saturation. OSA deprives the body of oxygen and untreated is a potentially deadly sleep disorder. OSA can increase an individual's risk for a heart attack, stroke, hypertension, and cardiac disease. Dentists have a unique position and can play a major role in their patient's health because many patients are seen several times in a year.



medical grade sleep bruxism monitor with bruxism episode index (BEI)


As dentists we have familiarity and access to the oral cavity, airway, and neck. As dentists we examine and focus on the head and neck of our patients. We can view the patient's airway, soft tissue, and dentition. We observe the tongue size, tongue shape, soft palate area, the patient's neck size, periodontium, and the wear on the patient's dentition. In the dental office, bruxism is seen in one out of every three patients. Two out of every five of these patients has undiagnosed or untreated obstructive sleep apnea. It is important to realize that patients who demonstrate bruxism often have obstructive sleep apnea. Sleep bruxism is considered a sleep related movement disorder. People who clench or grind their teeth during sleep are more likely to have other sleep disorders, such as snoring, pauses in breathing, and sleep apnea. Mild bruxism may not need to be treated. However, in some patients, bruxism can be frequent and severe enough to cause jaw disorders, damage to teeth, and headaches. Dentists can screen for teeth grinding and can tell if a patient is grinding their teeth at night. Bruxism can be treated with an appliance made to prevent grinding and /or clenching. Dentists can refer patients to their physicians for the diagnoses of sleep apnea and then dentists can treat sleep apnea patients with oral appliances as well.



medical Grade Sleep Bruxism Monitor Bruxism Episode Index (BEI)




medical grade sleep bruxism monitor Bruxism Episode Index (BEI)


However, because there is a link seen between grinding and sleep apnea, dentists need to play a larger role and have a relationship with a sleep physician and other medical doctors. Dentists can diagnose and provide the therapy needed for bruxism and provide the therapy for obstructive sleep apnea, once a physician diagnoses the apnea which is a medical condition requiring a medical diagnosis. Dental sleep medicine is a fast growing area of dentistry. There are approximately 40 million people in the United States with obstructive sleep apnea (OSA), with 90% of those undiagnosed. One in four patients with OSA suffer from nighttime teeth grinding. The ending of an apneic event may be accompanied by a number of mouth phenomena, such as snoring, gasps, grunts, and mainly teeth grinding. Teeth grinding occurs because of the significant attempts to open the mouth to breathe. Bruxism usually occurs after an apnea event. One of the ways the brain tries to reopen the airway, in an unconscious state, is by grinding and clenching the teeth. Teeth grinding is a major indicator that you are struggling to keep your airway open at night and might suffer from obstructive sleep apnea. When the airway collapses, breathing becomes compromised. This is where you get snoring, which is just the sound that's made when air is getting forced through a partially obstructed airway. Once the brain senses that breathing is dangerously compromised, it exits the deepest stage of sleep to regain control of the jaw muscles and reopen the airway – to keep a person breathing and alive. These sleep apnea cycles can occur from five to up to 70 times per hour during sleep. These events prevent one from entering the deepest stages of sleep where the brain and body tissues can repair themselves from the wear and tear of the day. A dentist's role in this process is to provide screening, therapy for bruxism, and therapy for obstructive sleep apnea when diagnosed. Dentists are not only qualified to provide the necessary dental treatment for this life threatening disorder but are uniquely in a position to screen and refer our own patients for sleep apnea diagnosis. Another screening application the dentist can provide is the Epworth Sleepiness Scale (ESS) to all patients. ESS is a scale, which measures a person's average level of daytime sleepiness.The scale consists of eight different routine life situations. Each question is rated from zero to three, with three having the highest chance of falling asleep. If a patient scores nine or above and demonstrates excessive daytime sleepiness this needs to be discussed and researched further for explanation on why the patient is excessively sleepy. When it is determined that a patient is a grinder/clencher, snores, and has an ESS score of 9 or above, the patient is a prime candidate for a sleep test. Patients may be referred to a sleep physician, pulmonologists, or their personal primary physician for a sleep study. The home bruxism/sleep test (STATDDS Bruxism/Sleep Monitor) is typically used to diagnose bruxism and sleep apnea (Figure 1). In the dental office, dentists can administer a home test to measure the patient for bruxism and at the same time receive the apnea/hypopnea index which measures obstructive sleep apnea. The AHI can be shared with the patient's physician. The dentist can work with the patient's physician as coprimary healthcare providers and come up with a treatment plan together that can address the bruxism and the obstructive sleep apnea. As dentists, we only diagnose the activities occurring during sleep that are related to the clenching and grinding. Heightened bruxism events occur more frequently at the end of an apneic episode. The results of the bruxism/sleep study are sent to a certified sleep physician who gathers the information and provides a diagnosis determined by the total number of pauses that occur per hour of sleep. If the patient has only grinding/clenching issues and no apneic events or drops in the oxygen saturation then a night guard is treatment planned for the patient. Dentists should not be fabricating and placing dental appliances without objective data from a bruxism/sleep test and a proper diagnosis, to avoid creating an obstruction in the patient's airway with the appliance for grinding/clenching (Figures 2 and 3). Moreover, if the study is returned with a diagnosis of mild or moderate obstructive sleep apnea, then a proper dental sleep appliance should be one of the recommendations for treatment. A mandibular advancement sleep appliance can be fabricated for that patient and can be titrated based on post testing with the home bruxism/sleep monitor. There are several types of sleep appliances for the treatment of obstructive sleep apnea (Figures 4 and 5). The devices move the



sleep bruxism




Sleep Bruxism


mandible and tongue forward allowing the airway to remain opened. There are appliances for a patient who is a bruxer and an OSA patient. There are oral appliances for an OSA only patient. Also, for severe sleep apnea sometimes a patient will wear a combination of an appliance with positive airway pressure therapy. Furthermore, for severe OSA who cannot tolerate a CPAP type device, an oral appliance is recommended as it is better for the patient to have some means of opening the airway and alleviating obstructive sleep apnea. Oral devices to treat obstructive sleep apnea must be prescribed by a physician and fabricated and fitted by a dentist. Dental oral appliances are convenient form of sleep apnea treatment. The compliance rate is higher than CPAP treatment with OSA patients. The devices offer the benefits of a significant reduction in apnea for mild to moderate OSA patients. Also, the elimination and or reduction in both grinding, clenching and snoring. Dental practices have the unique advantage of seeing their patients frequently and access to the oral cavity to identify potential sleep apnea patients.



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The genomic landscape of cutaneous melanoma

Summary

Somatic mutation analysis of melanoma has been done at the single gene level extensively over the past several decades. This has provided considerable insight into the critical pathways controlling melanoma initiation and progression. During the last five years next-generation sequencing (NGS) has enabled even more comprehensive mutational screening at the level of multi-gene panels, exomes and genomes. These studies have uncovered many new and unexpected players in melanoma development. The recent landmark study from The Cancer Genome Atlas (TCGA) consortium describing the genomic architecture of 333 cutaneous melanomas provides the largest and broadest analysis to date on the somatic aberrations underlying melanoma genesis. It thus seems timely to review the mutational landscape of melanoma and highlight the key genes and cellular pathways that appear to drive this cancer.

This article is protected by copyright. All rights reserved.



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Mutational characteristics of ANK1 and SPTB genes in hereditary spherocytosis

Abstract

The aim of the present study was to describe the mutational characteristics in Korean hereditary spherocytosis(HS) patients. Relevant literatures including genetically confirmed cases with well-documented clinical summaries and relevant information was also reviewed to investigate the mutational gene- or domain-specific laboratory and clinical association. Twenty-five HS patients carried one heterozygous mutation of ANK1(n=13) or SPTB(n=12) but not in SPTA1, SLC4A1, or EPB42. Deleterious mutations including frameshift, nonsense, and splice site mutations were identified in 91%(21/23) and non-hotspot mutations were dispersed across multiple exons. Genotype-phenotype correlation was clarified after combined analysis of the cases and the literature review; anemia was most severe in HS patients with mutations on the ANK1 spectrin binding domain (P<0.05), and SPTB mutations in HS patients spared the tetramerization domain in which mutations of hereditary elliptocytosis and pyropoikilocytosis are located. Splenectomy(17/75) was more frequent in ANK1 mutant HS(32%) than in HS with SPTB mutation(10%) (P = 0.028). Aplastic crisis occurred in 32.0% of the patients(8/25; 3 ANK1 and 5 SPTB) and parvovirus B19 was detected in 88%. The study clarifies ANK1 or SPTB mutational characteristics in HS Korean patients. The genetic association of laboratory and clinical aspects suggests comprehensive considerations for genetic-based management of HS.



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Home Sessualità Malattie veneree Sesso orale, virus HPV aumenta il rischio di tumori a testa e… – Ok Salute e Benessere

Home Sessualità Malattie veneree Sesso orale, virus HPV aumenta il rischio di tumori a testa e…
Ok Salute e Benessere
Il sesso orale può "darvi alla testa", e non è solo un modo di dire: tutta colpa dell'infezione da Papilloma virus (HPV), che può aumentare il rischio di sviluppare tumori di testa e collo fino a 22 volte. Il più pericoloso è il ceppo HPV-16, legato

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HPV e tumori di testa e collo: giovani sempre più colpiti – Ok Salute e Benessere

HPV e tumori di testa e collo: giovani sempre più colpiti
Ok Salute e Benessere
«I tumori di testa e collo sono malattie piuttosto rare che generalmente compaiono in età avanzata, ma negli ultimi anni stiamo osservando un inaspettato aumento dei casi tra i più giovani, anche sotto i 40 anni», afferma l'esperto di Ok Salute Antonio

and more »

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Incorporating Functional Genomic Information in Genetic Association Studies Using an Empirical Bayes Approach

ABSTRACT

There is a large amount of functional genetic data available, which can be used to inform fine-mapping association studies (in diseases with well-characterised disease pathways). Single nucleotide polymorphism (SNP) prioritization via Bayes factors is attractive because prior information can inform the effect size or the prior probability of causal association. This approach requires the specification of the effect size. If the information needed to estimate a priori the probability density for the effect sizes for causal SNPs in a genomic region isn't consistent or isn't available, then specifying a prior variance for the effect sizes is challenging. We propose both an empirical method to estimate this prior variance, and a coherent approach to using SNP-level functional data, to inform the prior probability of causal association. Through simulation we show that when ranking SNPs by our empirical Bayes factor in a fine-mapping study, the causal SNP rank is generally as high or higher than the rank using Bayes factors with other plausible values of the prior variance. Importantly, we also show that assigning SNP-specific prior probabilities of association based on expert prior functional knowledge of the disease mechanism can lead to improved causal SNPs ranks compared to ranking with identical prior probabilities of association. We demonstrate the use of our methods by applying the methods to the fine mapping of the CASP8 region of chromosome 2 using genotype data from the Collaborative Oncological Gene-Environment Study (COGS) Consortium. The data we analysed included approximately 46,000 breast cancer case and 43,000 healthy control samples.

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Advanced Management of Complex Cases: Children with Multiple Medical Conditions

Cochlear implantation was introduced in the United States as a viable treatment for hearing loss in the 1980s. Originally, the anticipated benefits were awareness of sound and enhancement of speech reading. Therefore, the early candidacy guidelines were very strict. There were concerns that the benefit from a cochlear implant would be limited or potentially be very difficult to measure, so the industry was conservative about who it considered for an implant. Original FDA GuidelinesAt the time of the original Food and Drug Administration (FDA) guidelines for the pediatric clinical trials, children 24 months of age and older were considered.

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The YY1/MMP2 axis promotes trophoblast invasion at the maternal-foetal interface

Abstract

YY1 is a sequence-specific DNA-binding transcription factor that has many important biological roles. However, its function in trophoblasts at the maternal-foetal interface remains to be elucidated. In this study, we used an mRNA microarray and reverse transcription qPCR and compared the YY1 mRNA expression level in trophoblasts between patients with recurrent miscarriage (RM) and healthy control subjects. Our results revealed that YY1 mRNA expression was significantly lower in the trophoblasts of the RM group compared with the healthy control group. Furthermore, immunofluorescence and immunohistochemical data showed that YY1 was highly expressed in human placental villi during early pregnancy, especially in cytotrophoblast cells and invasive extravillous trophoblasts, and it was expressed at a much lower level in the placental villi of term pregnancy. YY1 overexpression enhanced, and knockdown repressed, the invasion and proliferation of trophoblasts. Antibody array screening revealed that YY1 significantly promoted MMP2 expression in trophoblasts. Bioinformatics analysis identified three YY1-binding sites in the MMP2 promoter region, and chromatin immunoprecipitation analysis verified that YY1 binds directly to its promoter region. Importantly, inhibition of YY1 by siRNA clearly decreased trophoblast invasion in an ex vivo explant culture model. Overall, our findings revealed a new regulatory pathway of YY1/MMP2 in trophoblast cells invasion during early pregnancy, and indicated that YY1 may be involved in the pathogenesis of RM.



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Mutually exclusive BCOR internal tandem duplications and YWHAE-NUTM2 fusions in clear cell sarcoma of kidney (CCSK) : Not the full story…

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Abstract

Internal tandem duplication within the BCOR gene sequence that encodes the PUFD domain, important in the formation of the non-canonical or variant polycomb repressor complex 1 (v-PRC1), was very recently described in 100% of 20 clear cell sarcoma of kidney (CCSK). None of those 20 cases bore the YWHAE-NUTM2 transcript, previously described by us in CCSK, and which constitutes the only other recurrent genetic aberration observed in CCSK, prompting consideration that these mutations might be mutually exclusive in CCSK.

We analysed a cohort of 159 CCSKs and can now not only confirm that there is indeed mutual exclusivity of these BCOR and YWHAE mutations, but furthermore show that a substantial proportion (in this series 11.8 %) of CCSKs bear neither mutation when tested by these assays, raising the possibility of distinct aetiologies for subsets of CCSK. Clinical differences observed between the subsets support this notion. As CCSK may show poor chemo-responsiveness, and current treatment protocols mandate the use of doxorubicin with its associated side-effects, advances in understanding the disease biology with a view to more targeted and personalised treatment is a pressing need.



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Clonality analysis of multifocal papillary thyroid carcinoma by using genetic profiles

Abstract

Papillary thyroid carcinoma (PTC) is the most common adult thyroid malignancy and often presents with multiple anatomically distinct foci within the thyroid, known as multifocal papillary thyroid carcinoma (MPTC). The widespread application of the next-generation sequencing technologies in cancer genomics research provides novel insights into determining the clonal relationship between multiple tumours within the same thyroid gland. For eight MPTC patients, we performed whole-exome sequencing and targeted region sequencing to identify the non-synonymous point mutations and gene rearrangements of distinct and spatially separated tumour foci. Among these eight MPTCs, completely discordant mutational spectra were observed in the distinct cancerous nodules of patients MPTC1 and 5, suggesting that derivation of these nodules were from independent precursors. In another three cases (MPTC2, 6 and 8), the distinct MPTC foci of these patients had no other shared mutations except BRAF V600E, also indicating likely independent origins. Two patients (MPTC 3 and 4) shared almost identical mutational spectra amongst their separate tumour nodules, suggesting a common clonal origin. MPTC patient 7 had 7 cancer foci, of which 2 foci shared 66.7% of mutations, while the remaining cancer foci displayed no common non-synonymous mutations, indicating that MPTC7 has multiple independent origins accompanied by intraglandular disease dissemination.

In this study, we found that 75% of MPTC cases arose as independent tumours, which supports the field cancerization hypothesis describing multiple malignant lesions. MPTC may also arise from intra-thyroidal metastases from a single malignant clone, as well as multiple independent origins accompanied with intra-thyroidal metastasis.



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Mesothelial-to-mesenchymal transition in the pathogenesis of post-surgical peritoneal adhesions

cover.gif?v=1&s=a6fb6e56b7c271e97744ac7f

Abstract

Peritoneal adhesions (PAs) are fibrotic bands formed between bowel loops, solid organs and the parietal peritoneum, that may appear following surgery, infection or endometriosis. They represent an important health problem with no effective treatment. Mesothelial cells (MCs) line the peritoneal cavity and undergo a mesothelial-to-mesenchymal transition (MMT) under pathological conditions, transforming into myofibroblasts, which are abundant in peritoneal fibrotic tissue. The aim of this study was to investigate if peritoneal MCs undergo a MMT contributing to the formation of post-surgical adhesions. Biopsies from patients with PAs were analyzed by immunohistochemistry, immunofluorescence and quantitative RT-PCR. A mouse model of PAs based on ischemic buttons was used to modulate MMT by blocking the transforming growth factor-beta (TGF-β) pathway. The severity of adhesions and MMT-related marker expression were studied. We observed myofibroblasts derived from the conversion of MCs in submesothelial areas of patients with PAs. In addition, MMT-related markers were modulated in adhesion zones when compared to distant normal peritoneal tissue of the same patient. In animal experiments, blockage of TGF-β resulted in molecular reprogramming of markers related to the mesenchymal conversion of MCs and in a significant decrease in the severity of the adhesions. These data indicate for the first time that MMT is involved in PA pathogenesis. This finding opens new therapeutic strategies to interfere with adhesion formation by modulating MMT with a wide range of pharmacological agents.



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Tips and Tricks for Implementation of Sleep Dentistry into your Practice

I have been attending entry level Dental CE courses for snoring and sleep apnea for over 20 years. It has always been fascinating to me that a dentist can take hundreds of hours of course hours but never really manage to get Sleep Apnea Dentistry implemented into his or her practice. This is an all two common occurrence and I thought the article below by Dr Erin Elliott does a great job setting out some really clear, real world. tips for beating "Wednesday Morning Syndrome". The condition that some staff members find themselves in when the Dr gets back from a course with lots of new ideas is this generally results in the staff going home late until the Dr gets back on the program. Dr Elliott managed to avoid Wednesday morning syndrome and has built a tremendous footprint in Sleep Apnea Dentistry in her community and as President of the American Sleep and Breathing Academy. -ed

 

 

Golf and dental sleep medicine – This article previously appeared in Dental Economics January 2016

What I have learned from 6 years of bad shots

That's right your next six months don't have to be like my six years in dental sleep medicine. You have skills. Here are some tips to help you avoid some of the pitfalls that come with integrating anything new into your practice. Following these tips will let you spend more time on the fairway and less time looking for an errant drive. Fore!

I have an amazing team. Gosh, I think they know me better than my best friends do. They also know that I love continuing education and dentistry. Therefore, over the years they've developed "Wednesday morning syndrome". This means that when I come back from a course and I'm ready to implement a new program on Monday morning, all they have to do is avoid eye contact with me until Wednesday, and I'll give up.

Unfortunately for them (or so they thought at the time) this didn't happen with dental sleep medicine. I know it would be hard to navigate the medical world, and I knew trying to get paid from medical insurance would be an uphill climb. But I loved being able to screen otherwise undiagnosed patients and treat a life threatening disease. I was helping patients get their lives back.

So I kept it simple for a while. One main assistant and I did all of the dental sleep medicine. The other team members were happy to avoid all matters of sleep apnea because it was still very foreign, and I was afraid to "force" anything on them. Then came the turning point and the whole team had to jump in. We were busy- patients were calling and doctors were referring sleep medicine patients.

The best decision I made was taking an afternoon off to teach dental sleep medicine to my entire team. This enabled them to answer questions over the phone. Thereby saving the fate of hundreds of sticky notes. The hygienists learned how to screen for undiagnosed sleep apnea, and the office manager learned the tricks of billing medical insurance.

As in any dental office however, there was team turnover. Team members started showing up with baby bumps moving and of course, we had to terminate the rare team member who just wasn't a good performer.

How did I teach the new employees years of experience and get them treating sleep apnea patients in a short time? My answer I didn't. I had two chairside assistants for general dentistry and one main dental sleep medicine coordinator. My golf partner Julie was an ortho assistant with 25 years of ortho experience and zero years of general dentistry experience. When my chairside assistant left for maternity leave, I asked Julie to fill in. She became a permanent employee when my assistant decided to stay home with her bundle of joy.

General dentistry was foreign to Julie but she caught on quickly. Even though she was what we can call a "veteran" (i.e., older), she knew her way around computers, and she became a mama bear to the younger team members. As a bonus, she was able to help with my Six Month Smiles patients. She was always willing to help take impressions for our sleep apnea patients, but when it came time to do follow-up visits or deliveries, she bolted.

She said she didn't want to look like an idiot or like she was too old to learn anything new. She said there wasn't enough room in her brain to add sleep apnea. I gave her the bad news. We were moving to two and a half days of fulltime sleep apnea, so there was no avoiding it. She had to learn it. If a patient needed an appliance adjusted, she could easily perform it, as she was comfortable working with nightguards. But what if a patient came in with a (gasp) side effect? How could I teach Julie the ins and outs of the paperwork and familiarize her with medical billing? Can you see why it was the path of least resistance to have my already trained and willing dental sleep medicine coordinator take care of it all? I needed to give Julie a systematic approach to helping the team treat sleep apnea. It is an entirely different beast. I had her watch some of my past webinars to get the basics of dental sleep medicine, but more importantly, I sat down with her to go over how to do a consult, how to deliver, how to adjust and calibrate an appliance, and how to troubleshoot on follow-up visits.

This was a perfect analogy for the whole basis of our relationship— golf. She grew up on a golf course, and she was good at it and comfortable with it. I reluctantly learned golf as an adult, and I had been a beer cart girl for a local golf course in dental school. (I was a tutor and a beer cart girl. Isn't that an interesting combination?) I didn't want to learn golf because it didn't come naturally to me, and I wasn't instantly good at it. Besides, I grew up playing soccer. Now that was in my wheelhouse. Why learn something new now?

The biggest mistake I made was allowing many amateurs to coach me, and I practiced a horrible swing over and over again. I just jumped into it and got frustrated. But like any golfer, the one Ladies Professional Golf Association-type shot I managed to pull out once in a while is what brought me back for more, even though I had 100 other wayward shots. Plus, golf was a necessity with my family and friends. I couldn't give up.

After 10 years, I finally took lessons from a professional, and my favorite sound in the world is my golf ball dropping into the cup. I love golf! But what if I had started with lessons from a professional immediately rather than listening to amateurs? I would have loved the game that much more. I wouldn't have gotten frustrated, and I wouldn't have wanted to give up. What's my advice on becoming a good golfer? Take lessons from the start. Although I'm a far from perfect golfer, I can pull off a KP (closest to the pin) or longest drive award in my community golf tournaments. I can play a round with confidence. I can perform.

Just as the professional coach gave me confidence in my golf game, I have given Julie confidence in the dental sleep medicine world. I have even given her a few mulligans as she was learning. She speaks with authority and can answer any questions patients throw her way. She is capable of getting a "hole in one." The only reason I was able to coach her was because I gained confidence by taking the best courses in dental sleep medicine and continue to learn. It's persistence and practice, just like in golf. Become trained and get your team trained now. Don't give them a choice like I did. It's never too late to learn something new, and it's way better to learn how to do it correctly from the start. Change from an attitude of frustration (all of those missed shots!) to one of "I can do this!" LPGA, here I come!

Erin Elliott DDS

Erin Elliott DDS

ERIN E. ELLIOTT, DDS, is a practicing general dentist in Post Falls, Idaho, where she has successfully integrated dental sleep medicine into her practice. She has lectured extensively, educating dentists on the benefits of incorporating this growing field of dentistry into their practices. She is an active member of her local and state American Dental Association components and is a member of the American Academy of Sleep Medicine and American Academy of Dental Sleep Medicine. She is the president and diplomate of the American Sleep and Breathing Academy. She can be contacted at erinelliottdds@gmail.com.



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The β isoform of GSK3 mediates podocyte autonomous injury in proteinuric glomerulopathy

Abstract

Converging evidence points to glycogen synthase kinase (GSK) 3 as a key player in the pathogenesis of podocytopathy and proteinuria. However, it remains unclear if GSK3 is involved in podocyte autonomous injury in glomerular disease. In normal kidneys, the β isoform of GSK3 was found to be the major GSK3 expressed in glomeruli and intensely stained in podocytes. GSK3β expression in podocytes was markedly elevated in experimental or human proteinuric glomerulopathy. Podocyte specific somatic ablation of GSK3β in adult mice attenuated proteinuria and ameliorated podocyte injury and glomerular damage in experimental adriamycin (ADR) nephropathy. Mechanistically, actin cytoskeleton integrity in podocytes was largely preserved in GSK3β knockout mice following ADR insult, concomitant with a correction of podocyte hypermotility and lessened phosphorylation and activation of paxillin, a focal adhesion associated adaptor protein. In addition, GSK3β knockout diminished ADR induced NFκB RelA/p65 phosphorylation selectively at serine 467, suppressed de novo expression by podocytes of NFκB dependent podocytopathic mediators, including B7-1, cathepsin L and MCP-1, but barely affected the induction of NFκB target prosurvival factors, such as Bcl-xL. Moreover, the ADR-elicited podocytopenia and podocyte death was significantly attenuated in GSK3β knockout mice, associated with a protection against podocyte mitochondrial damage and reduced phosphorylation and activation of cyclophilin F, a structural component of mitochondria permeability transition pores. Overall, our findings suggest that the β isoform of GSK3 mediates autonomous podocyte injury in glomerulopathy by integrating multiple podocytopathic signalling pathways.



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TUSC3 promotes colorectal cancer progression and epithelial-mesenchymal transition (EMT) through WNT/β-catenin and MAPK signalling

Abstract

Colorectal cancer (CRC) is one of the most common malignancies and is the second leading cause of cancer death in humans. Tumour suppressor candidate 3 (TUSC3) plays an important role in embryogenesis and metabolism. Deletion of TUSC3 often causes non-syndromic mental retardation. Even though TUSC3 deregulation is frequently observed in epithelial cancers, the function of TUSC3 in CRC has remained unknown. In this study, we observed greater expression of TUSC3 at the mRNA and protein level in clinical colorectal tumour samples compared with paired normal tissues. Gain- and loss-of-function analyses were performed to evaluate the functional significance of TUSC3 in CRC initiation and progression. Immunoblotting, immunofluorescence, and co-immunoprecipitation analyses were used to identify potential pathways with which TUSC3 might be involved. Overexpression of TUSC3 in CRC cells induced epithelial-mesenchymal transition (EMT) in CRC cells, accompanied with down-regulation of the epithelial marker, E-Cadherin and up-regulation of the mesenchymal marker, vimentin. Increased proliferation, migration, and invasion as well as accelerated xenograft tumour growth were observed in TUSC3-overexpressing CRC cells, while opposite effects were achieved in TUSC3-silenced cells. In conclusion, our study demonstrated the oncogenic role of TUSC3 in CRC and showed that TUSC3 may be responsible for alternations in the proliferation ability, aggressiveness, and the invasive/metastatic potential of CRC through regulating the MAPK, PI3K/Akt, and Wnt/β-catenin signalling pathways.



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The genomic landscape of cutaneous melanoma

Summary

Somatic mutation analysis of melanoma has been done at the single gene level extensively over the past several decades. This has provided considerable insight into the critical pathways controlling melanoma initiation and progression. During the last five years next-generation sequencing (NGS) has enabled even more comprehensive mutational screening at the level of multi-gene panels, exomes and genomes. These studies have uncovered many new and unexpected players in melanoma development. The recent landmark study from The Cancer Genome Atlas (TCGA) consortium describing the genomic architecture of 333 cutaneous melanomas provides the largest and broadest analysis to date on the somatic aberrations underlying melanoma genesis. It thus seems timely to review the mutational landscape of melanoma and highlight the key genes and cellular pathways that appear to drive this cancer.

This article is protected by copyright. All rights reserved.



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Major involvement of trunk muscles in myotonic dystrophy type 1

Objectives

The motor impairments in Myotonic Dystrophy 1 (DM1) are assumed to progress from distal toward proximal parts of the extremities in the Juvenile and Adult forms of DM1. On occasion and late in progress spine deformity is observed. In this study we have examined whether and to what extent trunk muscles are impaired in DM1, and if this impairment is correlated with the duration of the disorder, walking capacity, mobility, balance, and CTG-repeats.

Materials & methods

Manual muscle testing (MMT) of skeletal muscle strength in trunk and extremities, reassessment of the mutation size, time since first symptom, the 6 min walk test (6MWT), Rivermead mobility index (RIM) and Timed up & go (TUG) were sampled in 38 adult DM1 outpatients.

Results

We found significant impairment in trunk muscles. Trunk muscle strength decreased significantly with increasing mutation size (r = −0.64, P < 0.001). Reduced walking capacity, mobility and balance were significantly related to decreased trunk muscle strength.

Conclusion

DM1 affects trunk muscle groups. The trunk impairments seem to occur relatively early in disease progression. Awareness of trunk impairments may be of importance for everyday functioning and for understanding the risk of injuries due to falls reported among DM1 patients. It may also help in identification of DM1 patients and considered outcome measure in future clinical trials.



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Anxiety in Multiple Sclerosis: psychometric properties of the State-Trait Anxiety Inventory

Objective

The aims of the present study were to examine psychometric properties of the Spielberger State-Trait Anxiety Inventory (STAI-Y-1 and STAI-Y-2, respectively) in a Multiple Sclerosis (MS) population and to identify a cut-off score to detect those MS patients with high level of state and/or trait anxiety who could be more vulnerable to development of depression and/or cognitive defects.

Material and methods

The STAI-Y-1 and STAI-Y-2 was completed by a group of patients (n = 175) affected by MS and a group of healthy subjects (n = 150) matched for age, educational level, and gender. In MS patients internal consistency, divergent and discriminant validities were evaluated. Construct validity was examined by exploratory factor analysis for each scale.

Results

There was no missing data, no floor or ceiling effects for both scales. The two scales showed high internal consistency, good divergent, and Known-groups validities. To identify high levels of state and trait anxiety in a patient with MS, we proposed three gender specific screening cut-off values (1, 1.5, 2 SD) for the STAI-Y-1 and the STAI-Y-2.

Conclusions

The findings showed that the STAI-Y-1 and the STAI-Y-2 are a valid tool for clinical use in MS patients and can be useful to measure the severity of anxiety and to identify those patients with high anxiety to introduce them in specific non-pharmacological intervention.



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Prevalence of Diabetic Retinopathy in a Population of Diabetics From the Middle East With Microvascular Ocular Motor Palsies.

Background: Vascular risk factors are increasing rapidly in the Middle East. Growing inactivity and obesity have contributed to an epidemic of Type 2 diabetes mellitus (DM) in the Arab population. Microvascular palsies of the third, fourth, and sixth cranial nerves, which occur in an isolated manner, are relatively common in patients with DM, hypertension, or other vascular risk factors. Methods: In this retrospective analysis, patients with diabetes with microvascular palsies were assessed for the prevalence of diabetic retinopathy (DR). We compared these data with the prevalence of DR in the general population of diabetics in Saudi Arabia and to a similar published study done in an American population. Results: In total, 126 patients with diabetes were included in the study. The sixth nerve was most frequently involved in 67 patients (53%). Seventy-seven patients (61%) had DR, compared with 49 (39%) without DR. The prevalence of DR in the general population of Saudi patients with diabetes ranged from 30% to 36.1%. Conclusions: Our study demonstrated a higher prevalence of DR in patients with microvascular palsies compared with the general population of patients with diabetes in the Arab population. This is in contrast to a previous study in an American population. Our results might be secondary to differences between the 2 populations, in particular, the continued increase in the prevalence of vascular risk factors (mainly diabetes) and poor control of these risk factors in the Middle East. (C) 2016 by North American Neuro-Ophthalmology Society

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Incorporating Functional Genomic Information in Genetic Association Studies Using an Empirical Bayes Approach

ABSTRACT

There is a large amount of functional genetic data available, which can be used to inform fine-mapping association studies (in diseases with well-characterised disease pathways). Single nucleotide polymorphism (SNP) prioritization via Bayes factors is attractive because prior information can inform the effect size or the prior probability of causal association. This approach requires the specification of the effect size. If the information needed to estimate a priori the probability density for the effect sizes for causal SNPs in a genomic region isn't consistent or isn't available, then specifying a prior variance for the effect sizes is challenging. We propose both an empirical method to estimate this prior variance, and a coherent approach to using SNP-level functional data, to inform the prior probability of causal association. Through simulation we show that when ranking SNPs by our empirical Bayes factor in a fine-mapping study, the causal SNP rank is generally as high or higher than the rank using Bayes factors with other plausible values of the prior variance. Importantly, we also show that assigning SNP-specific prior probabilities of association based on expert prior functional knowledge of the disease mechanism can lead to improved causal SNPs ranks compared to ranking with identical prior probabilities of association. We demonstrate the use of our methods by applying the methods to the fine mapping of the CASP8 region of chromosome 2 using genotype data from the Collaborative Oncological Gene-Environment Study (COGS) Consortium. The data we analysed included approximately 46,000 breast cancer case and 43,000 healthy control samples.

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Incorporating Functional Genomic Information in Genetic Association Studies Using an Empirical Bayes Approach

ABSTRACT

There is a large amount of functional genetic data available, which can be used to inform fine-mapping association studies (in diseases with well-characterised disease pathways). Single nucleotide polymorphism (SNP) prioritization via Bayes factors is attractive because prior information can inform the effect size or the prior probability of causal association. This approach requires the specification of the effect size. If the information needed to estimate a priori the probability density for the effect sizes for causal SNPs in a genomic region isn't consistent or isn't available, then specifying a prior variance for the effect sizes is challenging. We propose both an empirical method to estimate this prior variance, and a coherent approach to using SNP-level functional data, to inform the prior probability of causal association. Through simulation we show that when ranking SNPs by our empirical Bayes factor in a fine-mapping study, the causal SNP rank is generally as high or higher than the rank using Bayes factors with other plausible values of the prior variance. Importantly, we also show that assigning SNP-specific prior probabilities of association based on expert prior functional knowledge of the disease mechanism can lead to improved causal SNPs ranks compared to ranking with identical prior probabilities of association. We demonstrate the use of our methods by applying the methods to the fine mapping of the CASP8 region of chromosome 2 using genotype data from the Collaborative Oncological Gene-Environment Study (COGS) Consortium. The data we analysed included approximately 46,000 breast cancer case and 43,000 healthy control samples.

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The genomic landscape of cutaneous melanoma

Summary

Somatic mutation analysis of melanoma has been done at the single gene level extensively over the past several decades. This has provided considerable insight into the critical pathways controlling melanoma initiation and progression. During the last five years next-generation sequencing (NGS) has enabled even more comprehensive mutational screening at the level of multi-gene panels, exomes and genomes. These studies have uncovered many new and unexpected players in melanoma development. The recent landmark study from The Cancer Genome Atlas (TCGA) consortium describing the genomic architecture of 333 cutaneous melanomas provides the largest and broadest analysis to date on the somatic aberrations underlying melanoma genesis. It thus seems timely to review the mutational landscape of melanoma and highlight the key genes and cellular pathways that appear to drive this cancer.

This article is protected by copyright. All rights reserved.

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