The new issue is now available.Journal of The Japanese Stomatological Society

Vol.65 No.4

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A Multivariate Mixture Model to Estimate the Accuracy of Glycosaminoglycan Identifications Made by MS/MS and Database Search [Research]

We present a statistical model to estimate the accuracy of derivatized heparin and heparan sulfate (HS) glycosaminoglycan (GAG) assignments to tandem mass (MS/MS) spectra made by the first published database search application, GAG-ID. Employing a multivariate expectation-maximization algorithm, this statistical model distinguishes correct from ambiguous and incorrect database search results when computing the probability that heparin/HS GAG assignments to spectra are correct based upon database search scores. Using GAG-ID search results for spectra generated from a defined mixture of 21 synthesized tetrasaccharide sequences as well as 7 spectra of longer defined oligosaccharides, we demonstrate that the computed probabilities are accurate and have high power to discriminate between correctly, ambiguously, and incorrectly assigned heparin/HS GAGs. This analysis makes it possible to filter large MS/MS database search results with predictable false identification error rates.

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'Endure inconvenience due to demonetisation for a better future' - The Hindu

The Hindu

'Endure inconvenience due to demonetisation for a better future' The Hindu “Black money is like a cancer. The treatment for black money should also be as hard as chemotherapy is for cancer. Cancer patient survives and leads a better life after undergoing successful chemotherapy. The country and the people will also have a ... and more »

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For this cancer, “Stage 4” isn't as bad as it sounds - The Washington ... - Washington Post

Washington Post

For this cancer, “Stage 4” isn't as bad as it sounds - The Washington ... Washington Post Hearing the word “cancer” in a doctor's office is bad enough. Hearing “Stage 4” invokes even more dread. When I learned I had Stage 4 HPV-related oral cancer, ... and more »

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Blood-borne HPV antibodies indicate head, neck cancer prognosis

Source: medicalxpress.com Author: provided by Brown University People with head and neck cancers with evidence of human papillomavirus (HPV) infection generally […]

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Can cutting out chocolate really hold cancer at bay?

Source: scienceblog.cancerresearchuk.org Author: Emma Smith Chocolate, biscuits, crisps and ice cream; just some of our guilty pleasures, particularly at this time […]

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IBD Patients, Especially Those with Crohn's, at Thyroid Cancer Risk, Study Finds - IBD News Today

IBD News Today

IBD Patients, Especially Those with Crohn's, at Thyroid Cancer Risk, Study Finds IBD News Today Patients with Crohn's disease (CD) are at increased risk for developing thyroid cancer, although all inflammatory bowel disease patients show a “prevalence” for this cancer, a new study reports. The research, which com drew on evidence that people with ... and more »

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Calendar

Publication date: 28 December 2016
Source:Journal of Controlled Release, Volume 244, Part A





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Graphical Abstracts Contents Listing

Publication date: 28 December 2016
Source:Journal of Controlled Release, Volume 244, Part A





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Editorial Board

Publication date: 28 December 2016
Source:Journal of Controlled Release, Volume 244, Part A





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Ocular microparticle formulations for 6-month delivery of anti-VEGF

Publication date: 28 December 2016
Source:Journal of Controlled Release, Volume 244, Part A
Author(s): Kinam Park




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Peptides for bone tissue engineering

Publication date: 28 December 2016
Source:Journal of Controlled Release, Volume 244, Part A
Author(s): Rick Visser, Gustavo A. Rico-Llanos, Hertta Pulkkinen, Jose Becerra
Molecular signals in the form of growth factors are the main modulators of cell behavior. However, the use of growth factors in tissue engineering has several drawbacks, including their costs, difficult production, immunogenicity and short half-life. Furthermore, many of them are pleiotropic and, since a single growth factor can have different active domains, their effect is not always fully controllable. A very interesting alternative that has recently emerged is the use of biomimetic peptides. Sequences derived from the active domains of soluble or extracellular matrix proteins can be used to functionalize the biomaterials used as scaffolds for new tissue growth to either direct the attachment of cells or to be released as soluble ligands. Since these short peptides can be easily designed and cost-effectively synthesized in vitro, their use has opened up a world of new opportunities to obtain cheaper and more effective implants for regenerative medicine strategies. In this extensive review we will go through many of the most important peptides with potential interest for bone tissue engineering, not limiting to those that only mediate cell adhesion or induce the osteogenic differentiation of progenitor cells, but also focusing on those that direct angiogenesis because of its close relation with bone formation.

Graphical abstract

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Retinoic acid receptor signalling directly regulates osteoblast and adipocyte differentiation from mesenchymal progenitor cells

Publication date: Available online 10 December 2016
Source:Experimental Cell Research
Author(s): A.C. Green, P. Kocovski, T. Jovic, M.K. Walia, R.A.S. Chandraratna, T.J. Martin, E.K. Baker, L.E. Purton
Low and high serum retinol levels are associated with increased fracture risk and poor bone health. We recently showed retinoic acid receptors (RARs) are negative regulators of osteoclastogenesis. Here we show RARs are also negative regulators of osteoblast and adipocyte differentiation. The pan-RAR agonist, all-trans retinoic acid (ATRA), directly inhibited differentiation and mineralisation of early osteoprogenitors and impaired the differentiation of more mature osteoblast populations. In contrast, the pan-RAR antagonist, IRX4310, accelerated differentiation of early osteoprogenitors. These effects predominantly occurred via RARγ and were further enhanced by an RARα agonist or antagonist, respectively. RAR agonists similarly impaired adipogenesis in osteogenic cultures. RAR agonist treatment resulted in significant upregulation of the Wnt antagonist, Sfrp4. This accompanied reduced nuclear and cytosolic β-catenin protein and reduced expression of the Wnt target gene Axin2, suggesting impaired Wnt/β-catenin signalling. To determine the effect of RAR inhibition in post-natal mice, IRX4310 was administered to male mice for 10 days and bones were assessed by µCT. No change to trabecular bone volume was observed, however, radial bone growth was impaired. These studies show RARs directly influence osteoblast and adipocyte formation from mesenchymal cells, and inhibition of RAR signalling in vivo impairs radial bone growth in post-natal mice.

Graphical abstract

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Super-you: Your body is a nation of trillions

Think you’re only human? Legions of creatures inhabit the cracks, contours and crevices of your body — and they all contribute to who you are

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Super-you: Your body is a nation of trillions

Think you’re only human? Legions of creatures inhabit the cracks, contours and crevices of your body — and they all contribute to who you are

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Giant Solitary Schwannoma of Submandibular Salivary Gland—A Rare Entity

Abstract

Submandibular gland tumours, especially mesenchymal tumours, are extremely rare. Schwannoma of the salivary gland is a particularly rare form of an extracranial neurogenic tumor, of which ancient schwannoma is one of five variants. Since the first description, only a few ancient schwannomas have been reported in different locations in the head and neck region. In the submandibular gland it is very rare. This report presents a case of 26 year old male patient with an ancient schwannoma of the submandibular gland seems to be arising from parasympathetic fibers.

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NHERF1 in Microvilli of Vomeronasal Sensory Neurons

In most mammals, the vomeronasal system detects a variety of (semio)chemicals that mediate olfactory-driven social and sexual behaviors. Vomeronasal chemosensation depends on G protein-coupled receptors (V1R, V2R, and FPR-rs) that operate at remarkably low stimulus concentrations, thus, indicating a highly sensitive and efficient signaling pathway. We identified the PDZ domain-containing protein, Na⁺/H⁺ exchanger regulatory factor-1 (NHERF1), as putative molecular organizer of signal transduction in vomeronasal neurons. NHERF1 is a protein that contains 2 PDZ domains and a carboxy-terminal ezrin-binding domain. It localizes to microvilli of vomeronasal sensory neurons and interacts with V1Rs. Furthermore, NHERF1 and Gα_i2 are closely colocalized. These findings open up new aspects of the functional organization and regulation of vomeronasal signal transduction by PDZ scaffolding proteins.

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Characteristic Response to Chemosensory Signals in GABAergic Cells of Medial Amygdala Is Not Driven by Main Olfactory Input

Chemosensory stimuli from same species (conspecific) and different species (heterospecific) elicit categorically different immediate-early gene (IEG) response patterns in medial amygdala in male hamsters and mice. All heterospecific stimuli activate anterior medial amygdala (MeA) but only especially salient heterospecific stimuli, such as those from predators activate posterior medial amygdala (MeP). We previously reported that characteristic patterns of response in separate populations of cells in MeA and MeP distinguish between different conspecific stimuli. Both gamma aminobutyric acid (GABA)-immunoreactive (ir) cells and GABA-receptor-ir cells make this distinction. Here, using zinc sulfate lesions of the main olfactory epithelium, we show evidence that main olfactory input does not contribute to the characteristic patterns of response in GABA-ir cells of male hamster amygdala, either for conspecific or heterospecific stimuli. Some GABAergic cells are output neurons carrying information from medial amygdala to behavioral executive regions of basal forebrain. Thus, the differential response to different conspecific signals can lead to differential activation of downstream circuits based on nonolfactory input. Finally, we show that an intact vomeronasal organ is necessary and sufficient to produce the characteristic patterns of response to conspecific and heterospecific chemosensory stimuli in hamster medial amygdala. Although main olfactory input may be critical in species with less prominent vomeronasal input for equivalent medial amygdala responses, work presented here suggests that hamster medial amygdala uses primarily vomeronasal input to discriminate between important unlearned conspecific social signals, to distinguish them from the social signals of other species, and may convey that information to brain circuits eliciting appropriate social behavior.

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Erratum

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Editor-in-Chiefs Note - Thank you to Reviewers

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Adeno-Associated Virus-Mediated Gene Transfer into Taste Cells In Vivo

The sense of taste is achieved by cooperation of many signaling molecules expressed in taste cells, which code and transmit information on quality and intensity of taste to the nervous system. Viral vector-mediated gene transfer techniques have been proven to be useful to study and control function of a gene product in vivo. However, there is no transduction method for taste cells in live animals. Here, we have established a method for inducing foreign gene expression in mouse taste cells in vivo by recombinant adeno-associated virus (AAV) vector. First, using enhanced green fluorescent protein (EGFP) as a reporter, we screened 6 AAV serotypes along with a recombinant lentivirus vector for their ability to transduce taste cells. One week after viral injection into the submucosa of the tongue, EGFP expression in fungiform taste cells was observed only in animals injected with AAV-DJ, a synthetic serotype. Next, time course of AAV-DJ-mediated EGFP expression in fungiform taste cells was evaluated. Intragemmal EGFP signals appeared after a delay, rapidly increased until 7 days postinjection, and gradually decreased over the next few weeks probably because of the cell turnover. Finally, the taste cell types susceptible to AAV-DJ transduction were characterized. EGFP expression was observed in PLCβ2-immunoreactive type II and aromatic l-amino acid decarboxylase (AADC)-immunoreactive type III taste cells as well as in cells immunonegative for both PLCβ2 and AADC, demonstrating that AAV-DJ does not discriminate functional taste cell types. In conclusion, the method established in this study will be a promising tool to study the mechanism of taste.

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What are Probable Olfactory Markers of Alcohol Dependence?

As the olfactory system is closely connected with the brain areas responsible for the most crucial alterations in psychiatric populations, especially cognitive and emotional impairments, the study of olfactory processing may be a relevant approach to identify specific markers of alcohol dependence. The aim of this study was to propose the probable olfactory markers for alcohol dependence through a study of the olfactory parameters that involve the central olfactory pathway. We recruited the same 41 alcohol-dependent patients in an early (day 8) and late (day 67) stage of abstinence and 41 controls matched for gender, age, and smoking status. The participants underwent clinical assessments and several olfactory evaluations. The results revealed on one hand, the persistence of decreased intensity of positive emotion (happy), increased intensity of negative emotion (sad), and increased citation of surprise in patients, suggesting the presence of probable trait markers of alcohol dependence. On the other hand, we found decreased hedonic score for pleasant and neutral odorants, and decreased odor familiarity judgment only in the early stage of evaluation as probable state markers for alcohol dependence. These results may be underpinned by several neuropsychological alterations specific to this disease and their evolution after weaning. Further studies are needed to replicate these findings and to confirm the specificity and sensitivity of the olfactory tests in a larger sample of patients. The olfactory perception of all controls must be also retested in order to determine the specific state and/or trait markers of alcohol dependence.

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Lipid-Lowering Pharmaceutical Clofibrate Inhibits Human Sweet Taste

T1R2-T1R3 is a heteromeric receptor that binds sugars, high potency sweeteners, and sweet taste blockers. In rodents, T1R2-T1R3 is largely responsible for transducing sweet taste perception. T1R2-T1R3 is also expressed in non-taste tissues, and a growing body of evidence suggests that it helps regulate glucose and lipid metabolism. It was previously shown that clofibric acid, a blood lipid-lowering drug, binds T1R2-T1R3 and inhibits its activity in vitro. The purpose of this study was to determine whether clofibric acid inhibits sweetness perception in humans and is, therefore, a T1R2-T1R3 antagonist in vivo. Fourteen participants rated the sweetness intensity of 4 sweeteners (sucrose, sucralose, Na cyclamate, acesulfame K) across a broad range of concentrations. Each sweetener was prepared in solution neat and in mixture with either clofibric acid or lactisole. Clofibric acid inhibited sweetness of every sweetener. Consistent with competitive binding, inhibition by clofibric acid was diminished with increasing sweetener concentration. This study provides in vivo evidence that the lipid-lowering drug clofibric acid inhibits sweetness perception and is, therefore, a T1R carbohydrate receptor inhibitor. Our results are consistent with previous in vitro findings. Given that T1R2-T1R3 may in part regulate glucose and lipid metabolism, future studies should investigate the metabolic effects of T1R inhibition.

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Individual Differences in Verbal and Non-Verbal Affective Responses to Smells: Influence of Odor Label Across Cultures

Olfactory perception is highly variable from one person to another, as a function of individual and contextual factors. Here, we investigated the influence of 2 important factors of variation: culture and semantic information. More specifically, we tested whether cultural-specific knowledge and presence versus absence of odor names modulate odor perception, by measuring these effects in 2 populations differing in cultural background but not in language. Participants from France and Quebec, Canada, smelled 4 culture-specific and 2 non-specific odorants in 2 conditions: first without label, then with label. Their ratings of pleasantness, familiarity, edibility, and intensity were collected as well as their psychophysiological and olfactomotor responses. The results revealed significant effects of culture and semantic information, both at the verbal and non-verbal level. They also provided evidence that availability of semantic information reduced cultural differences. Semantic information had a unifying action on olfactory perception that overrode the influence of cultural background.

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Development and Validation of a Food-Associated Olfactory Test (FAOT)

Olfactory tests are an important tool in human nutritional research for studying food preferences, yet comprehensive tests dedicated solely to food odors are currently lacking. Therefore, within this study, an innovative food-associated olfactory test (FAOT) system was developed. The FAOT comprises 16 odorant pens that contain representative food odors relating to different macronutrient classes. The test underwent a sensory validation based on identification rate, intensity, hedonic value, and food association scores. The accuracy of the test was further compared to the accuracy of the established Sniffin’ Sticks identification test. The identification rates and intensities of this new FAOT were found to be comparable to the Sniffin’ Sticks olfactory identification test. The odorant pens were also assessed chemo-analytically and were found to be chemically stable for at least 24 weeks. Overall, this new identification test for use in assessing olfaction in a food-associated context is valid both in terms of its use in sensory perception studies and its chemical stability. The FOAT is particularly suited to examinations of the sense of smell regarding food odors.

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Sound-Triggered Production of Antiaggregation Pheromone Limits Overcrowding of Dendroctonus valens Attacking Pine Trees

For insects that aggregate on host plants, both attraction and antiaggregation among conspecifics can be important mechanisms for overcoming host resistance and avoiding overcrowding, respectively. These mechanisms can involve multiple sensory modalities, such as sound and pheromones. We explored how acoustic and chemical signals are integrated by the bark beetle Dendroctonus valens to limit aggregation in China. In its native North American range, this insect conducts nonlethal attacks on weakened trees at very low densities, but in its introduced zone in China, it uses mixtures of host tree compounds and the pheromone component frontalin to mass attack healthy trees. We found that exo-brevicomin was produced by both female and male D. valens, and that this pheromone functioned as an antiaggregating signal. Moreover, beetles feeding in pairs or in masses were more likely than were beetles feeding alone to produce exo-brevicomin, suggesting a potential role of sound by neighboring beetles in stimulating exo-brevicomin production. Sound playback showed that an agreement sound was produced by both sexes when exposed to the aggregation pheromone frontalin and attracts males, and an aggressive sound was produced only by males behaving territorially. These signals triggered the release of exo-brevicomin by both females and males, indicating an interplay of chemical and sonic communication. This study demonstrates that the bark beetle D. valens uses sounds to regulate the production of an antiaggregation pheromone, which may provide new approaches to pest management of this invasive species.

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Articles highlighted

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Table of Contents

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Subscriptions

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Editorial Board

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Cover

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A Case of Brachiocephalic Fistula Steal and the Emergency Physician's Approach to Hemodialysis Arteriovenous Fistula Complications

Publication date: Available online 10 December 2016
Source:The Journal of Emergency Medicine
Author(s): Erica Simon, Brit Long, Kyle Johnston, Shane Summers
BackgroundChronic kidney disease is common in the United States, with many patients maintained on hemodialysis (HD). The process of HD requires vascular access through an arteriovenous (AV) fistula, AV graft, or central venous catheter. Today, as a result of the National Kidney Foundation's “Fistula First” initiative, nearly 55% of HD patients utilize an AV fistula. As there is significant morbidity and mortality associated with fistula placement and recurrent fistula cannulation, emergency physicians must be equipped to recognize and treat fistula complications.ObjectiveTo detail a case study of vascular insufficiency (vascular steal) presenting to an emergency department (ED) and provide an evidence-based approach to the emergency assessment and management of HD AV fistula complications.DiscussionA 66-year-old man presented to the ED with left upper extremity pain, paresthesias, and loss of grip strength of 1-week duration 15 days after placement of left upper extremity brachiocephalic fistula. He was diagnosed with dialysis access-associated steal syndrome and taken to the operating room for revision. Patients with HD fistulas may experience several complications, including vascular insufficiency, hemorrhage, infection, stenosis, thrombosis, aneurysms, or pseudoaneurysms. Emergency physicians must be able to identify these complications and deliver timely treatment.ConclusionsA comprehensive understanding of the appropriate management of AV fistula complications is paramount for the emergency physician. Early recognition and treatment of vascular insufficiency resulting from fistula creation, fistula hemorrhage, fistula infection, stenosis, thrombosis, and aneurysms or pseudoaneurysms is vital to reducing the morbidity and mortality associated with HD.



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Spontaneous Esophageal Dissection

Publication date: Available online 10 December 2016
Source:The Journal of Emergency Medicine
Author(s): Kurt E. Schapira, Eric Tomich




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Treatment advances have not improved long-term health status of childhood cancer survivors - Science Daily

Treatment advances have not improved long-term health status of childhood cancer survivors Science Daily Advances in treatment and supportive care have led to improved survival for patients with childhood cancer. As adults, survivors may suffer from chronic medical conditions resulting from specific therapies and up to 25 percent report adverse health ... and more »

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Effect of Brain Computer Interface (BCI) in stress induced loss of cognition in hippocampus of wister albino rats

2016-12-11T03-54-58Z
Source: International Journal of Health and Rehabilitation Sciences (IJHRS)
Sivanandan Ramar, Mazen Alqahtani, Anandh Bose, Salameh Al Dajah.
Background: Brain-computer interface (BCI) is a collaboration between a brain and a device that enables signals from the brain to direct some external activity, which interface enables a direct communications pathway between the brain and the object to be controlled. By reading signals from an array of neurons and using computer chips and programs to translate the signals into action. The Magneto encephalography (MEG) is to record the firing of the neuron and absorb the brain activity as the magnetic field travels from region to region with in the brain. It has the potential to enhance the life style of the disabled person. The MEG Brain Computer Interface (BCI) impact on medicine and healthcare now may be subtle but is still revolutionary. Objectives: The purpose of this study was to develop novel methods and systems for rehabilitation and control of assistive devices using signals from the brain BCI on motor coding and on neural plasticity. Materials and methods: The experiment was carried out in 24 albino rats with Magneto encephalography (MEG). All the rats underwent BCI procedure except the first and second group which was exposed to fake intervention. The objective of this proof of concept closed loop BCI experiment was for the subject to control the positive movement of a rat in the radial arm maze to take the food even altered position which was recorded in the system. Results: An important finding in the present study was the enhancing effect of BCI against neurodegeneration. It shows that these rats achieve to learn the task. It suggests that the BCI activated the neurons in the hippocampus and makes it sufficient for normal acquisition. Conclusion: Stress induced hippocampal degeneration leads to significant impairment of cognitive functions especially in calculation, immediate recall and attention. In this present study, stress induced loss of cognition was studied by activating the neurons of the hippocampus by grid electrodes of BCI system. Keywords: Magneto encephalography (MEG), glucocorticoid, hippocampal formation & grid electrodes.


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Voice feminization in male-to-female transgendered clients after Wendler’s glottoplasty with vs. without voice therapy support

Abstract

The objective of this study was to evaluate the medium-term results of Wendler’s glottoplasty surgery (WG) and the effects of post-operative voice therapy in a group of male-to-female transsexuals. This is a retrospective study of 18 transsexuals who voluntarily underwent WG between 2010 and 2014 at a single hospital. Ten of the subjects underwent an additional voice therapy training. The group was assessed pre- vs. post-treatments with a limited battery of measures consisting of fundamental frequency (Fo), maximum phonation time, the TSEQ transgender self-assessment questionnaire, and perceptual assessment of the voice (Visual Analog Scale and a simplified version of the classical Hirano-GRBAS scale) by inter-rater agreement. The surgical procedure consisted of a de-epithelialization of the anterior third of both vocal folds; this area was sutured, and the surface of both vocal folds was vaporized with a laser diode. The results showed a significant increase in vocal tone and feminization of voice in all participants, including a significant increase in Fo 12 months after treatment. Significant improvements were also shown in other evaluated measures, such as self-reported satisfaction and the degree of feminization of the voice. However, no improvements in maximum phonation time were observed. The use of voice therapy appears decisive for optimal improvement of this class of patients. WG applied appropriately by well-trained hands is thus a very effective and less traumatic procedure than other techniques that aim for an acceptable feminization of the voice in MtoF transgendered clients.

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Assessment of endolymphatic hydrops and otolith function in patients with Ménière’s disease

Abstract

Ménière’s disease is associated with hydrops of the inner ear endolymphatic space, and histopathologically, the cochlea and vestibule are usually involved. We used gadolinium-enhanced magnetic resonance imaging and measured cervical and ocular vestibular evoked myogenic potentials and the gain in the utricular induced linear vestibulo-ocular reflex to test the hypothesis that vestibular hydrops in Ménière’s disease patients is associated with otolith organ dysfunction. We evaluated 21 patients diagnosed with unilateral definitive Ménière’s disease using gadolinium magnetic resonance imaging to detect endolymphatic hydrops in the cochlea and vestibule. Cervical and ocular vestibular evoked myogenic potentials and the gain in utricular induced linear vestibulo-ocular reflex during eccentric rotation were measured to assess otolith organ function. For eccentric rotation, patients were rotated while displaced from the axis of rotation, while linear acceleration stimulated the utricle and induced the vestibulo-ocular reflex. Magnetic resonance imaging revealed vestibular hydrops in 14 of 20 patients (70%). Among the 14 patients, ten (71%) had abnormal cervical and three (21%) had abnormal ocular vestibular evoked myogenic potentials. Four patients (4/21, 19%) had abnormal linear vestibulo-ocular reflexes, three of whom also had abnormal ocular vestibular evoked myogenic potentials. Overall, 16 of 17 patients had normal linear vestibulo-ocular reflexes and normal ocular vestibular evoked myogenic potentials. Vestibular endolymphatic hydrops in Ménière’s disease patients caused otolith organ dysfunction, mainly in the saccule. The number of Ménière’s disease patients with abnormal ocular vestibular evoked myogenic potentials was low (19%), and they also had abnormal utricular induced linear vestibulo-ocular reflexes.

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Two coffins and a funeral: early or late caspase activation determines two types of apoptosis induced by DNA damaging agents

Abstract

Cell cytoskeleton makes profound changes during apoptosis including the organization of an Apoptotic Microtubule Network (AMN). AMN forms a cortical structure which plays an important role in preserving plasma membrane integrity during apoptosis. Here, we examined the cytoskeleton rearrangements during apoptosis induced by camptothecin (CPT), a topoisomerase I inhibitor, in human H460 and porcine LLCPK-1α cells. Using fixed and living cell imaging, we showed that CPT induced two dose- and cell cycle-dependent types of apoptosis characterized by different cytoskeleton reorganizations, time-dependent caspase activation and final apoptotic cell morphology. In the one referred as “slow” (~h) or round-shaped, apoptosis was characterized by a slow contraction of the actinomyosin ring and late caspase activation. In “slow” apoptosis the γ-tubulin complexes were not disorganized and microtubules were not depolymerized at early stages. In contrast, “fast” (~min) or irregular-shaped apoptosis was characterized by early caspase activation followed by full contraction of the actinomyosin ring. In fast apoptosis γ-tubulin complexes were disorganized and microtubules were initially depolymerized. However, after actinomyosin contraction, microtubules were reformed adopting a cortical but irregular disposition near plasma membrane. In addition to distinctive cytoskeleton reorganization kinetics, round and irregular-shaped apoptosis showed different biological properties with respect to AMN maintenance, plasma membrane integrity and phagocytes response. Our results suggest that the knowledge and modulation of the type of apoptosis promoted by genotoxic agents may be important for deciding a better therapeutic option and predicting the immune response in cancer treatment.

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How challenging the meaning of ‘fuel’ lets the real world in

We know what the word "fuel" means – right? Not really, argues Karen Pinkus in her new book – outside the lab or policy office, nothing is simple

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IJMS, Vol. 17, Pages 2084: In Vitro Antitumor Active Gold(I) Triphenylphosphane Complexes Containing 7-Azaindoles

A series of gold(I) complexes of the general composition [Au(naza)(PPh3)] (1–8) was prepared and thoroughly characterized (e.g., electrospray ionization (ESI) mass spectrometry and multinuclear nuclear magnetic resonance (NMR) spectroscopy). The N1-deprotonated anions of 7-azaindole or its derivatives (naza) are coordinated to the metal centre through the N1 atom of their pyrrole ring, as proved by a single crystal X-ray analysis of the complexes [Au(3I5Braza)(PPh3)] (7) and [Au(2Me4Claza)(PPh3)]·½H2O (8′). The in vitrocytotoxicity of the complexes 1–8 was studied against both the cisplatin-sensitive and -resistant variants of the A2780 human ovarian carcinoma cell line, as well as against the MRC-5 human normal fibroblast cell line. The complexes 4, 5, and 8, containing deprotonated 3-iodo-7-azaindole, 5-bromo-7-azaindole, and 2-methyl-4-chloro-7-azaindole (2Me4Claza), respectively, showed significantly higher potency (IC50 = 2.8–3.5 µM) than cisplatin (IC50 = 20.3 µM) against the A2780 cells and markedly lower effect towards the MRC-5 non-cancerous cells (IC50 = 26.0–29.2 µM), as compared with the mentioned A2780 cancer cells. The results of the flow cytometric studies of the A2780 cell cycle perturbations revealed a G2-cell cycle phase arrest of the cells treated by the representative complexes 1 and 5, which is indicative of a different mechanism of action from cisplatin (induced S-cell cycle phase arrest). The stability of the representative complex 8 in the water-containing solution as well as its ability to interact with the reduced glutathione, cysteine and bovine serum albumin was also studied using 1H and 31P-NMR spectroscopy (studied in the 50% DMF-d7/50% D2O mixture) and ESI+ mass spectrometry (studied in the 50% DMF/50% H2O mixture); DMF = dimethylformamide. The obtained results are indicative for the release of the N-donor azaindole-based ligand in the presence of the used biomolecules.

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IJMS, Vol. 17, Pages 2083: Down-Regulation of Ca2+-Activated K+ Channel KCa1.1 in Human Breast Cancer MDA-MB-453 Cells Treated with Vitamin D Receptor Agonists

Vitamin D (VD) reduces the risk of breast cancer and improves disease prognoses. Potential VD analogs are being developed as therapeutic agents for breast cancer treatments. The large-conductance Ca2+-activated K+ channel KCa1.1 regulates intracellular Ca2+ signaling pathways and is associated with high grade tumors and poor prognoses. In the present study, we examined the effects of treatments with VD receptor (VDR) agonists on the expression and activity of KCa1.1 in human breast cancer MDA-MB-453 cells using real-time PCR, Western blotting, flow cytometry, and voltage-sensitive dye imaging. Treatments with VDR agonists for 72 h markedly decreased the expression levels of KCa1.1 transcripts and proteins in MDA-MB-453 cells, resulting in the significant inhibition of depolarization responses induced by paxilline, a specific KCa1.1 blocker. The specific proteasome inhibitor MG132 suppressed VDR agonist-induced decreases in KCa1.1 protein expression. These results suggest that KCa1.1 is a new downstream target of VDR signaling and the down-regulation of KCa1.1 through the transcriptional repression of KCa1.1 and enhancement of KCa1.1 protein degradation contribute, at least partly, to the antiproliferative effects of VDR agonists in breast cancer cells.

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IJMS, Vol. 17, Pages 2085: Inflammation in Chronic Wounds

Non-healing chronic wounds present a major biological, psychological, social, and financial burden on both individual patients and the broader health system. Pathologically extensive inflammation plays a major role in the disruption of the normal healing cascade. The causes of chronic wounds (venous, arterial, pressure, and diabetic ulcers) can be examined through a juxtaposition of normal healing and the rogue inflammatory response created by the common components within chronic wounds (ageing, hypoxia, ischaemia-reperfusion injury, and bacterial colonisation). Wound bed care through debridement, dressings, and antibiotics currently form the basic mode of treatment. Despite recent setbacks, pharmaceutical adjuncts form an interesting area of research.

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How challenging the meaning of ‘fuel’ lets the real world in

We know what the word "fuel" means – right? Not really, argues Karen Pinkus in her new book – outside the lab or policy office, nothing is simple

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A Case of Brachiocephalic Fistula Steal and the Emergency Physician's Approach to Hemodialysis Arteriovenous Fistula Complications

Publication date: Available online 10 December 2016
Source:The Journal of Emergency Medicine
Author(s): Erica Simon, Brit Long, Kyle Johnston, Shane Summers
BackgroundChronic kidney disease is common in the United States, with many patients maintained on hemodialysis (HD). The process of HD requires vascular access through an arteriovenous (AV) fistula, AV graft, or central venous catheter. Today, as a result of the National Kidney Foundation's “Fistula First” initiative, nearly 55% of HD patients utilize an AV fistula. As there is significant morbidity and mortality associated with fistula placement and recurrent fistula cannulation, emergency physicians must be equipped to recognize and treat fistula complications.ObjectiveTo detail a case study of vascular insufficiency (vascular steal) presenting to an emergency department (ED) and provide an evidence-based approach to the emergency assessment and management of HD AV fistula complications.DiscussionA 66-year-old man presented to the ED with left upper extremity pain, paresthesias, and loss of grip strength of 1-week duration 15 days after placement of left upper extremity brachiocephalic fistula. He was diagnosed with dialysis access-associated steal syndrome and taken to the operating room for revision. Patients with HD fistulas may experience several complications, including vascular insufficiency, hemorrhage, infection, stenosis, thrombosis, aneurysms, or pseudoaneurysms. Emergency physicians must be able to identify these complications and deliver timely treatment.ConclusionsA comprehensive understanding of the appropriate management of AV fistula complications is paramount for the emergency physician. Early recognition and treatment of vascular insufficiency resulting from fistula creation, fistula hemorrhage, fistula infection, stenosis, thrombosis, and aneurysms or pseudoaneurysms is vital to reducing the morbidity and mortality associated with HD.



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Spontaneous Esophageal Dissection

Publication date: Available online 10 December 2016
Source:The Journal of Emergency Medicine
Author(s): Kurt E. Schapira, Eric Tomich




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IJERPH, Vol. 13, Pages 1230: Disadvantaged Social Groups and the Cigarette Epidemic: Limits of the Diffusion of Innovations Vision

The original four-stage model of the cigarette epidemic has been extended with diffusion of innovations theory to reflect socio-economic differences in cigarette use. Recently, two revisions of the model have been proposed: (1) separate analysis of the epidemic stages for men and women, in order to improve generalization to developing countries, and; (2) addition of a fifth stage to the smoking epidemic, in order to account for the persistence of smoking in disadvantaged social groups. By developing a cohort perspective spanning a 35-year time period in France and the USA, we uncover distinctive features which challenge the currently held vision on the evolution of smoking inequalities within the framework of the cigarette epidemic. We argue that the reason for which the model may not be fit to the lower educated is that the imitation mechanism underlying the diffusion of innovations works well with regard to adoption of the habit, but is much less relevant with regard to its rejection. Based on those observations, we support the idea that the nature and timing of the epidemic differs enough to treat the stages separately for high and low education groups, and discuss policy implications.

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IJERPH, Vol. 13, Pages 1229: The Role of Soundscape in Nature-Based Rehabilitation: A Patient Perspective

Nature-based rehabilitation (NBR) has convincing support in research, yet the underlying mechanisms are not fully understood. The present study sought to increase understanding of the role of soundscapes in NBR, an aspect paid little attention thus far. Transcribed interviews with 59 patients suffering from stress-related mental disorders and undergoing a 12-week therapy programme in the rehabilitation garden in Alnarp, Sweden, were analysed using Interpretative Phenomenology Analysis (IPA). Described sounds were categorised as natural, technological or human. The results showed that patients frequently referred to natural sounds as being part of a pleasant and “quiet” experience that supported recovery and induced “soft fascination”. Technological sounds were experienced as disturbing, while perception of human sounds varied depending on loudness and the social context. The study further uncovered how sound influenced patients’ behaviour and experiences in the garden, through examination of three cross-theme dimensions that materialised in the study; sound in relation to overall perception, sound in relation to garden usage, and increased susceptibility to sound. The findings are discussed in relation to NBR; the need for a more nuanced understanding of susceptibility to sound among people suffering from mental fatigue was identified and design considerations for future rehabilitation gardens were formulated.

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IJERPH, Vol. 13, Pages 1228: Facilitators and Barriers of Smokers’ Compliance with Smoking Bans in Public Places: A Systematic Review of Quantitative and Qualitative Literature

Background: Environmental tobacco smoke (ETS) exposure is associated with an increased risk of many diseases. Many countries have ratified a national smoking ban in public places, but studies on factors related to smoking issues in public places post-ban are lacking. Aim: To identify facilitators and barriers that influenced smokers’ compliance with smoking bans in public places. Methods: Using PubMed, MEDLINE, and the Web of Science database, we conducted a systematic search of English articles published before June 2015 on factors of smokers’ compliance with the smoking bans in public places. Results: A total of 390 references were identified, among which seventeen articles (twelve quantitative studies, two qualitative studies, three mixed-method studies) were included in this review. These studies focused on four types of public places including recreational venues (n = 7), hospital (n = 5), school (n = 4), and workplace (n = 1). Factors at the  individual-, interpersonal-, and organizational-level were identified: at the individual level, nicotine dependence, insufficiency of tobacco-related knowledge, and the negative attitudes towards smoking bans were the most commonly identified barriers; at the interpersonal level, the smoking behaviors of people around, close relatives, and friends’ approval were the main barriers; and at the organizational level, the main barriers were inefficient implementation of the bans and the inconvenience of the designative smoking areas. Conclusions: This synthesis of the literature provided evidence of the identified barriers and facilitators of smokers’ compliance with the smoking bans. It will be beneficial for the policy-maker to consider interventions on multiple levels of factors to overcome the barriers and enhance smokers’ compliance with the smoking bans in public places.

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