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Albert Ardevol, Gerhard Hummer
Channelrhodopsin-2 (ChR2) is a light-sensitive ion channel widely used in optogenetics. Photoactivation triggers a trans -to- cis isomerization of a covalently bound retinal. Ensuing conformational changes open a cation-selective channel. We explore the structural dynamics in the early photocycle leading to channel opening by classical (MM) and quantum mechanical (QM) molecular simulations. With QM/MM simulations, we generated a protein-adapted force field for the retinal chromophore, which we validated against absorption spectra...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
E Verheij, L Elden, T B Crowley, F A Pameijer, E H Zackai, D M McDonald-McGinn, H G X M Thomeer
BACKGROUND AND PURPOSE: The 22q11.2 deletion syndrome is characterized by a heterogenic phenotype, including hearing loss. The underlying cause of hearing loss, especially sensorineural hearing loss, is not yet clear. Therefore, our objective was to describe anatomic malformations in the middle and inner ear in patients with 22q11.2 deletion syndrome. MATERIALS AND METHODS: A retrospective case series was conducted in 2 tertiary referral centers. All patients with 22q11...
March 15, 2018: AJNR. American Journal of Neuroradiology
Jian Payandeh, David H Hackos
The voltage-gated sodium (Nav) channel Nav1.7 has been the focus of intense investigation in recent years. Human genetics studies of individuals with gain-of-function and loss-of-function mutations in the Nav1.7 channel have implicated Nav1.7 as playing a critical role in pain. Therefore, selective inhibition of Nav1.7 represents a potentially new analgesic strategy that is expected to be devoid of the significant liabilities associated with available treatment options. Although the identification and development of selective Nav channel modulators have historically been challenging, a number of recent publications has demonstrated progression of increasingly subtype-selective small molecules and peptides toward potential use in preclinical or clinical studies...
March 13, 2018: Handbook of Experimental Pharmacology
M Gundogdu, L I Aladag
Objectives: The aim of the present study was to evaluate the effects of self-etch and self-adhesive resin cements on the shear bond strength of ceramic core materials bonded to dentin. Materials and Methods: Extracted, caries-free, human central maxillary incisor teeth were selected, and the vestibule surfaces were cut flat to obtain dentin surfaces. Ceramic core materials (IPS e.max Press and Prettau Zirconia) were luted to the dentin surfaces using three self-etch adhesive systems (Duo-Link, Panavia F 2...
March 2018: Nigerian Journal of Clinical Practice
Hiromasa Ninomiya, Nobutaka Ohgami, Reina Oshino, Masashi Kato, Kyoko Ohgami, Xiang Li, Dandan Shen, Machiko Iida, Ichiro Yajima, Charalampos E Angelidis, Hiroaki Adachi, Masahisa Katsuno, Gen Sobue, Masashi Kato
Previous studies showed that people in urban areas are possibly exposed to 60-110 dB of low frequency noise (LFN) defined as noise of ≤100 Hz in their daily life. Previous studies also showed increased health risks by exposure to high levels (130-140 dB) of LFN in animals. However, little is known about the health effects of exposure to an ordinary level of LFN. We biochemically and immunohistochemically assessed the effects of exposure to inaudible LFN for mice (12 h/day of 100 Hz LFN at 95 dB for 5 days), at a level to which people are possibly exposed in daily life, on a murine inner ear by targeting 9 stress-reactive molecules...
February 24, 2018: Hearing Research
Mei Xu, Xiaoling Xie, Xuhui Dong, Guoqing Liang, Lin Gan
LHX3, a LIM-homeodomain transcription factor, is broadly expressed in the developing pituitary, spinal cord, medulla, retina and inner ear, and plays essential roles during embryonic development. Mice with homozygous Lhx3 null mutation exhibit failure in the formation of pituitary gland and die perinatally. To facilitate the functional study of Lhx3 in mice, we engineered and characterized two novel Lhx3 mouse strains: Lhx3GFP reporter knock-in and Lhx3loxP conditional knockout mice. Co-immunolabeling of LHX3 and GFP shows that the expression pattern of the knock-in GFP reporter recapitulates that of endogenous LHX3 in cochlea, vestibule, retina, and spinal cord...
March 6, 2018: Genesis: the Journal of Genetics and Development
Brittani Jones, Allyson C Berent, Chick W Weisse, Robert Hart, Leilani Alvarez, Anthony Fischetti, B David Horn, Douglas Canning
CASE DESCRIPTION A 14-week-old 7.7-kg (16.9-lb) sexually intact female Golden Retriever was evaluated because of urine dripping from the caudoventral aspect of the abdomen. CLINICAL FINDINGS Ultrasonography, radiography, excretory CT urography, and vaginocystourethroscopy were performed. Results indicated eversion of the bladder through the ventral abdominal wall with exposure of the ureterovesicular junctions, pubic diastasis, and an open vulva and clitoral fossa. Clinical findings were suggestive of bladder exstrophy, a rare congenital anomaly...
March 15, 2018: Journal of the American Veterinary Medical Association
Pedro Christian Aravena, Camila Barrientos, Catalina Troncoso, Cesar Coronado, Pamela Sotelo-Hitschfeld
Background: The purpose of this study is to determine the effectiveness of warming anesthesia on the control of the pain produced during the administration of dental anesthesia injection and to analyze the role of Transient Receptor Potential Vanilloid-1 nociceptor channels in this effect. Patients and methods: A double-blind, split-mouth randomized clinical trial was designed. Seventy-two volunteer students (22.1±2.45 years old; 51 men) from the School of Dentistry at the Universidad Austral de Chile (Valdivia, Chile) participated...
2018: Local and Regional Anesthesia
Cheryl S Sultan, Andrea Saackel, Antonia Stank, Thomas Fleming, Maria Fedorova, Ralf Hoffmann, Rebecca C Wade, Markus Hecker, Andreas H Wagner
AIMS: High levels of glucose and reactive carbonyl intermediates of its degradation pathway such as methylglyoxal (MG) may contribute to diabetic complications partly via increased generation of reactive oxygen species (ROS). This study focused on glutathione peroxidase-1 (GPx1) expression and the impact of carbonylation as an oxidative protein modification on GPx1 abundance and activity in human umbilical vein endothelial cells (HUVEC) under conditions of mild to moderate oxidative stress...
February 27, 2018: Redox Biology
Shan Ding, Shibao Xie, Weiquan Chen, Lu Wen, Junyi Wang, Fan Yang, Gang Chen
Drug delivery to the inner ear by nanomedicine strategies has emerged as an effective therapeutic approach for the management of inner ear diseases including hearing and balance disorders. It is well accepted that substance enters the perilymph from the middle ear through the round window membrane (RWM), but the passage through the oval window (OW) has long been neglected. Up to now, researchers still know little about the pathway via which nanoparticles (NPs) enter the inner ear or how they reach the inner ear following local applications...
February 27, 2018: European Journal of Pharmaceutical Sciences
Anamika Sharma, Shatakshi Sharma, Harshita Garg, Vineeta Singhal, Pooja Mishra
This clinical report describes the successful use of lip repositioning technique for the reduction of excessive gingival display. The lip repositioning technique was performed with the main objective of reducing gummy smile by limiting the retraction of elevator muscles (e.g., zygomaticus minor, levator anguli, orbicularis oris, and levator labii superioris). This technique includes removing a strip of mucosa from the maxillary buccal vestibule, creating a partial-thickness flap between mucogingival junction and upper lip musculature, and suturing the lip mucosa with mucogingival junction, resulting in a narrow vestibule and restricted muscle pull, thereby reducing gingival display...
October 2017: Journal of Cutaneous and Aesthetic Surgery
Jingliang Dong, Yidan Shang, Lin Tian, Kiao Inthavong, Jiyuan Tu
Rats have been widely used as surrogates for evaluating the health effects of inhaled airborne particulate matter. To provide a thorough understanding of particle transport and deposition mechanisms in the rat nasal airway, this article presents a computational fluid dynamics (CFD) study of particle exposure in a realistic rat nasal passage under a resting flow condition. Particles covering a diameter range from 1 nm to 4 µm were passively released in front of the rat's breathing zone, and the Lagrangian particle tracking approach was used to calculate individual particle trajectories...
February 28, 2018: Inhalation Toxicology
Chengyu Li, Jianbo Jiang, Kanghyun Kim, Bradley A Otto, Alexander A Farag, Beverly J Cowart, Edmund A Pribitkin, Pamela Dalton, Kai Zhao
Nasal airflow that effectively transports ambient odors to the olfactory receptors is important for human olfaction. Yet, the impact of nasal anatomical variations on airflow pattern and olfactory function are not fully understood. In this study, 22 healthy volunteers were recruited and underwent CT scans for computational simulations of nasal airflow patterns. Unilateral odor detection thresholds (ODT) to l-Carvone, phenylethyl alcohol (PEA) and d-Limonene were also obtained for all participants. Significant normative variations in both nasal anatomy and aerodynamics were found...
February 21, 2018: Chemical Senses
H Jia, R Torres, Y Nguyen, D De Seta, E Ferrary, H Wu, O Sterkers, D Bernardeschi, I Mosnier
BACKGROUND AND PURPOSE: Intraoperative conebeam CT has been introduced into the operating room and provides quick radiologic feedback. This study aimed to investigate its utility in the assessment of the positioning of the electrode array after cochlear implantation. MATERIALS AND METHODS: This was a retrospective study of 51 patients (65 ears) with intraoperative imaging by conebeam CT (O-arm) after cochlear implantation between 2013 and 2017. Correct placement into the cochlea was immediately identified...
February 22, 2018: AJNR. American Journal of Neuroradiology
Tania Day, Geoff Otton, Ken Jaaback, Julie Weigner, James Scurry
OBJECTIVE: The aim of the study was to assess for the presence of vulvar lichen planus (LP) in association with human papillomavirus (HPV)-independent squamous cell carcinoma (SCC). MATERIALS AND METHODS: We performed a clinicohistopathologic review of consecutive vulvectomies and wide local excisions for HPV-independent vulvar or vaginal SCC from 2007 to 2017. Data collected included site of SCC, adjacent precursor lesions and dermatoses, dermatologic treatment, and outcome...
February 22, 2018: Journal of Lower Genital Tract Disease
Julia A Schultz, Irina Ruf, Thomas Martin
Middle ear ossicles (malleus, incus, stapes) are known for few multituberculate taxa, and three different stapedial morphotypes have been suggested: (i) slender, columelliform and microperforate, (ii) robust and rod-like, and (iii) bicrural. Reinvestigation of Upper Jurassic (Kimmeridgian) mammalian petrosals from the Guimarota coal mine in central Portugal (Western Europe) revealed an asymmetric bicrural stapes (ABS) in the paulchoffatiid Pseudobolodon oreas The middle ear ossicles displaced inside the osseous vestibule were detected by a µCT analysis...
February 28, 2018: Proceedings. Biological Sciences
D Vital, D Holzmann, G F Huber, H Moch, G B Morand, K Ikenberg
BACKGROUND: Aim was to analyse the role of PD-L1 in squamous cell carcinomas of the nasal vestibule. Advanced squamous cell carcinoma of the nasal vestibule is a highly aggressive tumour. The role of PD-L1 expression is unclear in this tumour type. METHODOLOGY: Forty-six patients diagnosed between 1995 and 2014 were analyzed. Baseline characteristics and outcome were correlated to immunohistochemical staining of PD-L1. PD-L1 positivity of tumour cells and tumour infiltrating immune cells (TIIC) was defined by any staining of more than 1% of the tumour cells...
February 21, 2018: Rhinology
Jasmine Abdulcadir, Sandra Marras, Lucrezia Catania, Omar Abdulcadir, Patrick Petignat
Female genital mutilation type III (infibulation) is achieved by narrowing the vaginal orifice by creating a covering seal, accomplished by cutting and appositioning the labia minora and/or labia majora, with or without clitoral excision. Infibulation is responsible for significant urogynecological, obstetrical, and psychosexual consequences that can be treated with defibulation (or de-infibulation), an operation that opens the infibulation scar, exposing the vulvar vestibule, vaginal orifice, external urethral meatus, and eventually the clitoris...
February 17, 2018: Journal of Sexual Medicine
Milad Kiaee, Herbert Wachtel, Michelle L Noga, Andrew R Martin, Warren H Finlay
The present work examines regional deposition within the nose for nasal sprays over a large and wide ranging parameter space by using numerical simulation. A set of seven realistic adult nasal airway geometries was defined based on Computed Tomography (CT) images. Deposition in six regions of each nasal airway geometry (the vestibule, valve, anterior turbinate, posterior turbinate, olfactory, and nasopharynx) was determined for varying particle diameter, spray cone angle, spray release direction, particle injection speed, and particle injection location...
February 17, 2018: International Journal for Numerical Methods in Biomedical Engineering
Norbert E Juettner, Stefan Schmelz, Jan P Bogen, Dominic Happel, Wolf-Dieter Fessner, Felicitas Pfeifer, Hans-Lothar Fuchsbauer, Andrea Scrima
Transglutaminase from Streptomyces mobaraensis (MTG) has become a powerful tool to covalently and highly specifically link functional amines to glutamine donor sites of therapeutic proteins. However, details regarding the mechanism of substrate recognition and interaction of the enzyme with proteinaceous substrates still remain mostly elusive. We have determined the crystal structure of the Streptomyces papain inhibitory protein (SPIp ), a substrate of MTG, to study the influence of various substrate amino acids on positioning glutamine to the active site of MTG...
February 12, 2018: Protein Science: a Publication of the Protein Society
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