bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Irradiation on laryngeal hydration and lubrication in rat larynx
Authors: Lee Songyi , Choi Jeong‐Seok , Kim Hun Jung , Kim Young‐Mo , Lim Jae‐Yol
Published: April 2015

Objectives

The larynx is susceptible to irradiation, which causes significant vocal fold (VF) edema and dehydration shortly after radiotherapy for head and neck cancers. However little is known about radiation‐induced damage to VF liquid homeostasis. To evaluate the effects of irradiation on VF hydration and lubrication, we investigated changes in water transporters (aquaporins [AQPs]) and mucin production in vivo and ex vivo, as well as morphometric changes in the laryngeal mucosa and glands of irradiated rat larynges.

Study Design

Animal study.

Materials and Methods

Local irradiation at 18 Gy was delivered to rat larynges. Histologic changes in laryngeal mucosa and glands were observed by light microscopy, and the distributions of AQPs and mucin were investigated by immunofluorescence staining 3 months after irradiation. Early effects on gene regulation of AQPs and mucin were evaluated by quantitative real‐time polymerase chain reaction of the extirpated VFs and subglottic laryngeal mucosa at 12, 24, and 72 hours after irradiation.

Results

Laryngeal glands exhibited severe atrophic changes and showed decreased density throughout the irradiated larynx. The expression of AQP1, 4, 5, and mucin in VFs, as well as AQP5 and mucin in submucosal laryngeal glands, decreased significantly 3 months after irradiation. An ex vivo study revealed that the gene expression of AQP5 in VF tissues was significantly downregulated at 12 hours postirradiation.

Conclusion

Laryngeal irradiation induces damage in laryngeal mucosal barriers and alters laryngeal liquid homeostasis, which may be one reason for vocal dysfunction following irradiation.

Level of Evidence

N/A. Laryngoscope, 125:1900–1907, 2015
Vestibular function in cochlear implantation: Correlating objectiveness and subjectiveness
Authors: Batuecas‐Caletrio Angel , Klumpp Micah , Santacruz‐Ruiz Santiago , Gonzalez Fernando Benito , Sánchez Enrique Gonzalez , Arriaga Moises
Published: April 2015

Objective

To evaluate vestibular function before and after cochlear implantation (CI)

Study Design

A prospective descriptive study.

Material and Methods: Thirty consecutive patients with profound sensorineural hearing loss undergoing CI. Objective assessment of vestibular function was performed with the caloric test and video head impulse test (vHIT) in patients before and after CI. Dizziness Handicap Inventory (DHI) was used for subjective assessment before and after CI.

Results

Thirty patients received CI with 21 by round window approach and nine by anteroinferior cochleostomy. Vestibular results were categorized into four groups: no changes (20 patients), changes in the caloric test and vHIT (3 patients, all with DHI changes; P = 0.0001), changes in vHIT gain but not in caloric test (3 patients, all with DHI changes; P = 0.005), no changes in the caloric test and vHIT gain but only saccades appear (4 patients, all with DHI changes; P = 0.011).

Conclusions

Although CI is a safe surgery with few major complications, it is a procedure that can produce dizziness. The vHIT reveals that 30% of patients demonstrate postoperative change in vestibular function. Therefore, when examining a CI patient with postoperative symptoms of dizziness, results of the vHIT test and gain as well as the presence of saccades, along with an increase DHI score, are parameters to consider in their evaluation.

Level of Evidence

4. Laryngoscope, 125:2371–2375, 2015
Impact of postoperative pneumonia following Pituitary surgery
Authors: Desai Stuti V. , Fang Christina H. , Raikundalia Milap D. , Baredes Soly , Liu James K. , Eloy Jean Anderson
Published: April 2015

Objectives/Hypothesis

Postoperative pneumonia (PNA) has been identified as a preventable never event by the Centers for Medicare and Medicaid Services (CMS). The CMS has discussed possibly discontinuing reimbursement for this postoperative complication. In this study, risk factors, patient outcomes, and hospital charges of care associated with postoperative PNA in patients undergoing pituitary surgery were evaluated.

Methods

Discharge data of patients who underwent pituitary surgery between 2002 and 2010 were obtained from the National Inpatient Sample database. Demographics, preexisting comorbidities, postoperative complications, morbidity, length of hospital stay, and hospital charges were analyzed.

Results

A total of 15,317 patients were included in this analysis. Ninety‐eight patients (0.6%) were diagnosed with PNA postoperatively. There was a significant association between postoperative PNA and older age (P < 0.001), male gender (P = 0.044), and transfrontal surgical approach (P < 0.001). Patients with anemia, congestive heart failure, chronic pulmonary disease, diabetes mellitus, fluid and electrolyte disorders, paralysis, and weight loss had a significantly higher rate of PNA. Patients with PNA had a significantly higher mortality (P < 0.001). They also incurred on average over four times the hospital charges and nearly five times longer hospitalizations compared to patients without PNA.

Conclusions

Variables associated with an increased risk of postoperative PNA in patients undergoing pituitary surgery include older age, male gender, and transfrontal surgical approach. Patients with postoperative PNA had a longer length of hospital stay, higher hospital charges, and increased mortality.

Level of Evidence

2C. Laryngoscope, 125:1792–1797, 2015
Provent therapy for obstructive sleep apnea: Impact of nasal obstruction
Authors: Friedman Michael , Hwang Michelle S , Yalamanchali Sreeya , Pott Thomas , Sidhu Mandeep , Joseph Ninos J.
Published: April 2015

Objectives/Hypothesis

Determine the impact of nasal obstruction on efficacy, success, and adherence of Provent therapy in patients with obstructive sleep apnea (OSA).

Study Design

Prospective, two‐arm, clinical pilot study at a single clinical site.

Methods

Patients with OSA who failed continuous positive airway pressure therapy were divided into two treatment arms: arm 1 were patients with no complaints of nasal obstruction and <50% nasal obstruction on exam, and arm 2 were patients with occasional complaints of nasal obstruction and 50% to 80% nasal obstruction on exam. Sleep testing at home was performed prior to the trial and on day 10 of the study with the use of Provent.

Results

Apnea‐hypopnea index (AHI) decreased significantly from 20.5 ± 14.8 to 11.5 ± 16.6 (P < .001) in our total patient population. Patients in arm 1 had statistically significant improvement in their AHI (18.1 ± 13.0 to 7.4 ± 10.1, P < .001), oxygen desaturation index (ODI) (16.3 ± 10.8 to 8.2 ± 9.0, P < .001), and minimum oxygen saturation (81.3% ± 6.7% to 86.9% ± 5.6%, P = 0.008) from baseline sleep study to sleep study 2. Patients in arm 2 had improvements in their AHI (23.4 ± 16.6 to 16.5 ± 21.4), ODI (21.5 ± 14.8 to 17.0 ± 16.0) and minimum 02%. However, none of these reached statistical significance.

Conclusions

In this study, Provent therapy had a high failure rate. Patients without nasal obstruction showed greater improvements using Provent than patients with obstruction. Correction of nasal obstruction may be a useful prerequisite for treatment with Provent.

Level of Evidence

2B. Laryngoscope, 126:254–259, 2016
Geographic variation of endoscopic sinus surgery in the united states
Authors: Rudmik Luke , Holy Chantal E. , Smith Timothy L.
Published: April 2015

Objectives/Hypothesis

The objective of this study was to examine the rates and geographic variation of endoscopic sinus surgery (ESS) in a representative sample of the US working population.

Study Design

Observational cohort study using the MarketScan Commercial Claim and Encounters database.

Methods

All patients who received ESS between 2009 and 2013 were included. The annual adjusted rates of ESS per 1,000 people were calculated for each US state. Geographic variations were evaluated using the extremal quotient (EQ), weighted coefficient of variation (CV), systematic component of variance (SCV), and empirical Bayes statistic. The χ2 statistic tests was used to quantify variation of the adjusted ESS rates across states within the US.

Results

The annual adjusted rate of ESS was 0.94 per 1,000 people in the US. South Dakota and Alabama were observed to have the highest rates of ESS, 1.80 and 1.69, respectively. Vermont and Arkansas were observed to have the lowest rates of ESS, 0.51 and 0.57, respectively. The mean EQ was 4.54, indicating a four‐ to fivefold difference between the highest (South Dakota) and lowest (Vermont) states. The mean CV was 31.4 and mean SCV was 10.1, which demonstrates very high variation.

Conclusions

This study observed very high geographic variation in the rates of ESS across the United States. Given that practice variation indicates the presence of potentially harmful and inefficient unwarranted care, outcomes from this study indicate a need to further evaluate the delivery of ESS to improve overall health system performance.

Level of Evidence

2b. Laryngoscope, 125:1772–1778, 2015
The value of 18F‐FDG‐PET/CT imaging in oral cavity cancer patients following surgical reconstruction
Authors: Müller Julian , Hüllner Martin , Strobel Klaus , Huber Gerhard F. , Burger Irene A. , Haerle Stephan K.
Published: April 2015

Objective

Follow‐up of patients with oral cavity squamous cell carcinoma (OCSCC) after tumor resection and reconstruction with tissue transfer is challenging. We compared contrast‐enhanced computed tomography (ceCT), 18F‐fluorodeoxyglucose‐positron emission tomography combined with noncontrast enhanced CT (18F‐FDG‐PET/CT), and 18F‐FDG‐PET combined with ceCT (18F‐FDG‐PET/ceCT) to determine the accuracy for detection of residual/recurrent disease after flap reconstruction for OCSCC.

Study Design and Methods

Two readers (R1, R2) retrospectively reviewed a total of 27 18F‐FDG‐PET/ceCT scans in patients after resection of stage II to IV OCSCC. They recorded the presence of local persistence/recurrence (LR), lymph node metastasis, or distant metastasis independently for ceCT, 18F‐FDG‐PET/CT, and 18F‐FDG‐PET/ceCT. Histological workup, imaging follow‐up, or clinical follow‐up served as the standard of reference. Maximum standardized uptake value (SUVmax) was evaluated to discriminate between physiological uptake and LR.

Results

The highest accuracy to detect LR was achieved with 18F‐FDG‐PET/ceCT, with a sensitivity/specificity of 88%/89% and 88%/79% for R1 and R2, respectively, as compared to ceCT with 75%/79% for R1 and 88%/68% for R2 and 18F‐FDG‐PET/CT with 88%/58% for both R1 and R2. Receiver‐operating‐characteristic analysis determined a cutoff value for SUVmax of 7.2, yielding a sensitivity and specificity of 75% and 94%, respectively, to distinguish LR from physiological 18F‐FDG uptake.

Conclusion

18F‐FDG‐PET/ceCT seems to be the most reliable tool for locoregional surveillance of OCSCC patients after resection and reconstruction.

Level of Evidence

4. Laryngoscope, 125:1861–1868, 2015
Characterization and optimization of the visualization performance of continuous flow overhauser DNP hyperpolarized water MRI: Inversion recovery approach
Authors: Terekhov Maxim , Krummenacker Jan , Denysenkov Vasyl , Gerz Kathrin , Prisner Thomas , Schreiber Laura Maria
Published: April 2015

Purpose

Overhauser dynamic nuclear polarization (DNP) allows the production of liquid hyperpolarized substrate inside the MRI magnet bore as well as its administration in continuous flow mode to acquire MR images with enhanced signal‐to‐noise ratio. We implemented inversion recovery preparation in order to improve contrast‐to‐noise ratio and to quantify the overall imaging performance of Overhauser DNP‐enhanced MRI.

Method

The negative enhancement created by DNP in combination with inversion recovery (IR) preparation allows canceling selectively the signal originated from Boltzmann magnetization and visualizing only hyperpolarized fluid. The theoretical model describing gain of MR image intensity produced by steady‐state continuous flow DNP hyperpolarized magnetization was established and proved experimentally.

Results

A precise quantification of signal originated purely from DNP hyperpolarization was achieved. A temperature effect on longitudinal relaxation had to be taken into account to fit experimental results with numerical prediction.

Conclusion

Using properly adjusted IR preparation, the complete zeroing of thermal background magnetization was achieved, providing an essential increase of contrast‐to‐noise ratio of DNP‐hyperpolarized water images. To quantify and optimize the steady‐state conditions for MRI with continuous flow DNP, an approach similar to that incorporating transient‐state thermal magnetization equilibrium in spoiled fast field echo imaging sequences can be used. Magn Reson Med 75:985–996, 2016. © 2015 Wiley Periodicals, Inc.
Tuning loading and release by modification of micelle core crystallinity and preparation
Authors: Glavas Lidija , Odelius Karin , Albertsson Ann‐Christine
Published: April 2015

Controlling and tuning the loading and release of incorporated drugs are vital parts of the advancement of drug delivery systems. Micelle systems that use core crystallinity to tune the loaded amount of hydrophobic molecules as well as their released amount were therefore developed. The conductive and electroactive aniline pentamer was incorporated into poly(ethylene glycol)–poly(ε‐caprolactone) (PEG–PCL) micelles with semi‐crystalline cores and poly(ethylene glycol)–poly(ε‐decalactone) (PEG–PεDL) micelles with amorphous cores. The difference in core crystallinity of the two micelle systems gave rise to highly different loading capacities and release rates. The loading capacity was strongly dependent on the core crystallinity, and the amorphous PEG–PεDL micelles had almost twice as high loading capacity as the semi‐crystalline PEG–PCL micelles. In addition, the loading capacity was highly influenced by the loading procedure. The dependence on core crystallinity was also evident for the release of the aniline pentamer. The release occurred faster for the PEG–PεDL micelles with amorphous cores compared with the PEG–PCL micelles with semi‐crystalline cores. The use of just these two systems gave us the ability to tune the released amount and rate, and a combination of these systems can enable access to a wide range of release profiles, thereby being available to a variety of drug delivery applications. © 2015 The Authors. Polymers for Advanced Technologies Published by John Wiley & Sons Ltd.
Pharmacokinetics of Continuous‐Infusion Meropenem for the Treatment of Serratia marcescens Ventriculitis in a Pediatric Patient
Authors: Cies Jeffrey J. , Moore Wayne S. , Calaman Sharon , Brown Melandee , Narayan Prithvi , Parker Jason , Chopra Arun
Published: April 2015

Neither guidelines nor best practices for the treatment of external ventricular drain (EVD) and ventriculoperitoneal shunt infections exist. An antimicrobial regimen with a broad spectrum of activity and adequate cerebrospinal fluid (CSF) penetration is vital in the management of both EVD and ventriculoperitoneal infections. In this case report, we describe the pharmacokinetics of continuous‐infusion meropenem for a 2‐year‐old girl with Serratia marcescens ventriculitis. A right frontal EVD was placed for the management of a posterior fossa mass with hydrocephalus and intraventricular hemorrhage. On hospital day 6, CSF specimens were cultured, which identified a pan‐sensitive Serratia marcescens with an initial cefotaxime minimum inhibitory concentration of 1 μg/ml or less. The patient was treated with cefotaxime monotherapy from hospital days 6 to 17, during which her CSF cultures and Gram's stain remained positive. On hospital day 26, Serratia marcescens was noted to be resistant to cefotaxime (minimum inhibitory concentration > 16 μg/ml), and the antimicrobial regimen was ultimately changed to meropenem and amikacin. Meropenem was dosed at 40 mg/kg/dose intravenously every 6 hours, infused over 30 minutes, during which, simultaneous serum and CSF meropenem levels were measured. Meropenem serum and CSF levels were measured at 2 and 4 hours from the end of the infusion with the intent to perform a pharmacokinetic/pharmacodynamic analysis. The resulting serum meropenem levels were 12 μg/ml at 2 hours and “undetectable” at 4 hours, with CSF levels of 1 and 0.5 μg/ml at 2 and 4 hours, respectively. On hospital day 27, the meropenem regimen was changed to a continuous infusion of 200 mg/kg/day, with repeat serum and CSF meropenem levels measured on hospital day 33. The serum and CSF levels were noted to be 13 and 0.5 μg/ml, respectively. The serum level of 13 μg/ml corresponds to an estimated meropenem clearance from the serum of 10.2 ml/kg/minute. Repeat meropenem levels from the serum and CSF on hospital day 37 were 15 and 0.5 μg/ml, respectively. After instituting the continuous‐infusion meropenem regimen, only three positive CSF Gram's stains were noted, with the CSF cultures remaining negative. The continuous‐infusion dosing regimen allowed for 100% probability of target attainment in the serum and CSF and a successful clinical outcome.
Experimental Study and DEM Simulation of Micro–Macro Behavior of TATB Granules During Compaction Using X‐ray Tomography
Authors: Dai Bin , Zhang Wei‐bin , Lan Lin‐gang , Tian Yong
Published: April 2015

In this study, a noninvasive experimental method and a discrete element method (DEM) model were used to investigate the micro–macro behavior of TATB granules including global deformations, contact forces, stress distributions, local coordination number, local pore ratio, particle kinematics, and granule displacement during compacting process. The TATB granule deformation and structural evolution during compaction process were studied by X‐ray tomography and the deformation characteristics of deformable material. The size and number of granules with different sizes were determined from the CT images. The digital microstructure can be directly used for the numerical simulation setup. The DEM method was used for the numerical simulation of TATB granules during compaction. The contact forces and displacement vectors in compaction process were obtained. The behaviors and stress distributions at different pressures were also derived from the simulation. This study evaluated the possibility to better describe the behaviors of TATB granules.
Detection of triacetone triperoxide using temperature cycled metal‐oxide semiconductor gas sensors
Authors: Warmer Johannes , Wagner Patrick , Schöning Michael J. , Kaul Peter
Published: April 2015

The temperature‐dependent sensing properties of metal‐oxide semiconductor gas sensors (MOX), based on SnO2 and WO3, to measure triacetone triperoxide (TATP), diacetone diperoxid (DADP), and di‐tert‐butyl‐peroxide (DTBP) and acetone are described. Conductivity measurements in the range from 100 to 400 °C operating temperature show two different reaction pathways on the surface for WO3 sensors. At temperatures below 150 °C organic peroxides react as an oxidizer which leads to an increase in the sensor resistance. Above 200 °C they react as a reducing agent that leads to a decrease of the sensor resistance. This effect is caused by two different, peroxide dependent reaction paths. The unique behavior of WO3‐based sensors can be used for selectivity enhancements in temperature cycle operation mode. With this method gas concentrations down to a few ppb are detectable.

Scheme of TATP reacting on tungsten oxide semiconductor gas sensor. TATP decomposes and this leads to an increase of the sensor resistance at low temperatures and a decrease of resistance at high temperatures.
Modeling micromechanical response to thermal history in bulk grown aluminum nitride
Authors: Karvani Payman , Maniatty Antoinette M.
Published: April 2015

A thermal‐elastic‐viscoplastic model suitable for modeling aluminum nitride (AlN) during crystal growth is presented. A crystal plasticity model that considers slip along crystallographic slip systems and the evolution of mobile and immobile dislocations on the prismatic and basal slip systems is developed. The model has been implemented into a finite element framework, and a sublimation growth process is modeled to demonstrate the model capability. The dislocation density, which characterizes the crystal quality, and the maximum tensile stress on the cleavage planes (m ‐planes), which leads to cracking, are computed. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Erratum: Influence of annealing on the properties of (Cd,Mn)Te crystals
Authors: Witkowska‐Baran M. , Kochanowska D. M. , Mycielski A. , Jakieła R. , Wittlin A. , Knoff W. , Suchocki A. , Nowa‐kowski P. , Korona K.
Published: April 2015

The authors have completed their institutions to properly reflect the contributions of the affiliated institutions.
Alantolactone from Saussurea lappa Exerts Antiinflammatory Effects by Inhibiting Chemokine Production and STAT1 Phosphorylation in TNF‐α and IFN‐γ‐induced in HaCaT cells
Authors: Lim Hye‐Sun , Jin Sung‐Eun , Kim Ohn‐Soon , Shin Hyeun‐Kyoo , Jeong Soo‐Jin
Published: April 2015

Skin inflammation is the most common condition seen in dermatology practice and can be caused by various allergic reactions and certain toxins or chemicals. In the present study, we investigated the antiinflammatory effects of Saussurea lappa, a medicinal herb, and its marker compounds alantolactone, caryophyllene, costic acid, costunolide, and dehydrocostuslactone in the HaCaT human keratinocyte cell line. HaCaT cells were stimulated with tumor necrosis factor‐alpha (TNF‐α) and interferon‐gamma (IFN‐γ), and treated with S. lappa or each of five marker compounds. Chemokine production and expression were analyzed by enzyme‐linked immunosorbent assay and reverse transcription–polymerase chain reaction, respectively. Phosphorylation of signal transducer and activator of transcription (STAT) 1 was determined by immunoblotting. Stimulation with TNF‐α and IFN‐γ significantly increased the production of the following chemokines: thymus‐regulated and activation‐regulated chemokine (TARC): regulated on activation, normal T‐cell expressed and secreted (RANTES): macrophage‐derived chemokine (MDC): and interleukin‐8 (IL‐8). By contrast, S. lappa and the five marker compounds significantly reduced the production of these chemokines by TNF‐α and IFN‐γ‐treated cells. S. lappa and alantolactone suppressed the TNF‐α and IFN‐γ‐stimulated increase in the phosphorylation of STAT1. Our results demonstrate that alantolactone from S. lappa suppresses TNF‐α and IFN‐γ‐induced production of RANTES and IL‐8 by blocking STAT1 phosphorylation in HaCaT cells. Copyright © 2015 John Wiley & Sons, Ltd.
Modelling of flow‐dependent ensemble‐based background‐error correlations using a wavelet formulation in 4D‐Var at Météo‐France
Authors: Berre Loïk , Varella Hubert , Desroziers Gérald
Published: April 2015

The use of a wavelet formulation and ensemble data assimilation is considered in this study, in order to specify flow‐dependent background‐error correlations for the Météo‐France global 4D‐Var system. This wavelet model is calibrated by using a temporal series of recent perturbed backgrounds, which is sampled in a sliding way. This approach is compared to a homogeneous and static spectral formulation of error correlations. Diagnostic studies are conducted in order to illustrate the representation of heterogeneous and flow‐dependent correlation features, corresponding for instance to smaller horizontal length‐scales in the vicinity of midlatitude lows and to larger vertical correlations in vertically unstable regions. The positive impact of the flow‐dependent wavelet formulation on the forecast quality is then shown during two contrasting three‐week periods. The impact of an increased ensemble size when using this approach is also illustrated, in terms of length‐scale dynamics and forecast quality.
Field testing of linear individual pitch control on the two‐bladed controls advanced research turbine
Authors: van Solingen E. , Fleming P. A. , Scholbrock A. , van Wingerden J. W.
Published: April 2015

This paper presents the results of field tests using linear individual pitch control (LIPC) on the two‐bladed Controls Advanced Research Turbine 2 (CART2) at the National Renewable Energy Laboratory (NREL). LIPC has recently been introduced as an alternative to the conventional individual pitch control (IPC) strategy for two‐bladed wind turbines. The main advantage of LIPC over conventional IPC is that it requires, at most, only two feedback loops to potentially reduce the periodic blade loads. In previous work, LIPC was designed to implement blade pitch angles at a fixed frequency [e.g., the once‐per‐revolution (1P) frequency], which made it only applicable in above‐rated wind turbine operating conditions. In this study, LIPC is extended to below‐rated operating conditions by gain scheduling the controller on the rotor speed. With this extension, LIPC and conventional IPC are successfully applied to the NREL CART2 wind turbine. The field‐test results obtained during the measurement campaign indicate that LIPC significantly reduces the wind turbine loads for both below‐rated and above‐rated operation. Copyright © 2015 John Wiley & Sons, Ltd.
Systems medicine: evolution of systems biology from bench to bedside
Authors: Wang Rui‐Sheng , Maron Bradley A. , Loscalzo Joseph
Published: April 2015

High‐throughput experimental techniques for generating genomes, transcriptomes, proteomes, metabolomes, and interactomes have provided unprecedented opportunities to interrogate biological systems and human diseases on a global level. Systems biology integrates the mass of heterogeneous high‐throughput data and predictive computational modeling to understand biological functions as system‐level properties. Most human diseases are biological states caused by multiple components of perturbed pathways and regulatory networks rather than individual failing components. Systems biology not only facilitates basic biological research but also provides new avenues through which to understand human diseases, identify diagnostic biomarkers, and develop disease treatments. At the same time, systems biology seeks to assist in drug discovery, drug optimization, drug combinations, and drug repositioning by investigating the molecular mechanisms of action of drugs at a system's level. Indeed, systems biology is evolving to systems medicine as a new discipline that aims to offer new approaches for addressing the diagnosis and treatment of major human diseases uniquely, effectively, and with personalized precision. WIREs Syst Biol Med 2015, 7:141–161. doi: 10.1002/wsbm.1297

This article is categorized under:

Analytical and Computational Methods > Computational Methods

Laboratory Methods and Technologies > Macromolecular Interactions, Methods

Translational, Genomic, and Systems Medicine > Translational Medicine
The Impact of Neurofibromatosis Type 1 on the Health and Wellbeing of Australian Adults
Authors: Crawford Hilda A. , Barton Belinda , Wilson Meredith J. , Berman Yemima , McKelvey‐Martin Valerie J. , Morrison Patrick J. , North Kathryn N.
Published: April 2015

The complications of neurofibromatosis type 1 (NF1) are widespread, unpredictable and variable and each person's experience of this disorder is unique. However, few studies have addressed the impact of NF1 from an individual's perspective. This qualitative study aims to identify the ways in which NF1 impacts upon affected Australian adults. Sixty adults with NF1, with a range of disease severity and visibility participated in a semi‐structured interview about the ways in which NF1 impacted upon their life and health. Data were analyzed using grounded theory methodology. Results indicated that NF1 impacts upon affected adults in five major ways: 1) cosmetic burden of disease 2) learning difficulties 3) concerns about the risk of passing NF1 to offspring 4) uncertain disease progression, and 5) pain. Participants identified the aspects of NF1 that bothered them the most, creating a hierarchy of NF1 concerns within the cohort. Importantly, mildly affected adults shared many of the same concerns as those more severely affected. This study enhances our current understanding of the impact of NF1 in adulthood, and augments existing recommendations for the care of these patients.
Trophic ecology of the European wild rabbitOryctolagus cuniculuson the Mediterranean island of Lemnos, Greece
Authors: Kontsiotis V. J. , Bakaloudis D. E. , Merou T. , Xofis P.
Published: April 2015

The European wild rabbit (Oryctolagus cuniculus) is a species with a wide distribution across the globe and a contradicting role in the ecological integrity of ecosystems and local economies. Despite the considerable amount of research that has been conducted on the trophic ecology of the species in continental environments, similar studies in insular environments are still fairly scarce. The article examines the trophic ecology of wild rabbit, using microhistological analysis to study its annual dietary composition in relation to the availability and quality of food sources, in two different habitats of a northeast Mediterranean island. A total of 112 species were found to participate, to a lower or greater degree, in the species diet across the year. The available food sources, as well as the identified food items, were classified in three feeding functional groups (FFGs), namely, grasses, forbs and parts of woody plants. Wild rabbit follows a diverse diet having adapted to the seasonal changes in the availability and quality of food sources. Forbs is the FFG which constitutes the main food source of the species, while grasses and parts of woody plants form occasionally an important component of its diet. The FFG of grasses is almost constantly preferred in both habitat types and plays a deterministic role in the trophic ecology of wild rabbit. During the critical dry season, where the availability of high quality food becomes limited, the species preferably consumes taxa that are generally less palatable and even toxic in its struggle for survival.
Rosiglitazone, but Not Epigallocatechin‐3‐Gallate, Attenuates the Decrease in PGC‐1α Protein Levels in Palmitate‐Induced Insulin‐Resistant C2C12 Cells
Authors: Karimfar Mohammad Hassan , Haghani Karimeh , Babakhani Azar , Bakhtiyari Salar
Published: April 2015

Alteration of lipid metabolism is an important mechanism for the treatment of insulin resistance. PGC‐1α, a key regulator of mitochondrial biogenesis and function, plays an important role in the improvement of insulin sensitivity by increasing fatty acids β‐oxidation. In the present study, the effects of epigallocatechin‐3‐gallate (EGCG), an anti‐obesity agent and enhancer of lipid catabolism, on PGC‐1α protein expression was examined and compared with anti‐diabetic drug rosiglitazone (RGZ). After differentiation of C2C12 myoblasts to myotubes, insulin resistance was induced by palmitate treatment. Then the expression of the PGC‐1a gene and glucose uptake were evaluated before and after treatment with RGZ and EGCG. Palmitate treatment significantly decreased PGC‐1α protein expression in C2C12 cells (P < 0.05). RGZ could restore the expression of PGC‐1α in palmitate treated cells (P > 0.05), while EGCG had no significant effect on the expression of this gene (P < 0.05). RGZ and EGCG significantly improved glucose uptake (by 2‐ and 1.54‐fold, respectively) in myotubes treated with palmitate. These data suggest that RGZ and EGCG both exert their anti‐diabetic activity by increasing insulin sensitivity, but with different molecular mechanisms. This effect of RGZ, unlike EGCG, is mediated, at least partly, by increasing PGC‐1α protein expression.
Determination of Oxidation of Methyl Ricinoleates
Authors: Wang Tong , Lee Show‐ling , da Silva José André C. , Hammond Earl , Yao Linxing
Published: April 2015

Ricinoleate esters have desirable properties as biolubricants, but their oxidative stability has been questioned. To systematically study the stability of ricinoleate ester and its derivative, methyl esters of castor oil were prepared and methyl ricinoleate was isolated by solvent partitioning. Methyl 12‐acetyl ricinoleate was synthesized from the methyl ricinoleate by interesterification with excess methyl acetate and was then purified by solvent partitioning. The rates of oxidation of methyl linoleate, methyl oleate and the two ricinoleate esters were measured by oxidation of lipid dispersed on glass beads under three temperatures (40–80 °C). The relative amounts of the unoxidized methyl esters were determined periodically by gas chromatography, and the peroxide value of the oils was also determined. The oxidation rates were determined as the peroxide value increase rate, as well as the ester disappearance rate, and the stability of the various esters was compared. Overall, methyl ricinoleate was much more oxidatively stable than methyl oleate at mildly elevated temperatures, and the acetylation of the hydroxyl group on the 12th carbon decreased the stability.
Selective Production of Diacylglycerols Through Glycerolysis by Ionic Liquid: 1‐Butyl‐3‐Methylimidazolium Imidazolide as Catalyst and Reaction Medium
Authors: Huang Yingsi , Gao Yongqing , Zhong Nanjing
Published: April 2015

In this study, 1‐butyl‐3‐methylimidazolium imidazolide ([Bmim]Im) was found effective to catalyze the glycerolysis of triacylglycerols (TAG) for selective production of diacylglycerols (DAG). About 60 % content of DAG and 80 % conversion of TAG were achieved with [Bmim]Im at 15 % (wt% based on TAG), without requirement of any other catalyst and reaction medium. In addition, the weight ratio of DAG to monoacylglycerols (MAG) was at 0.9 when the glycerol/TAG mole ratio was 5:1, indicating [Bmim]Im was selective for DAG generation.
Construire les mathématiques dans l'imagination
Authors: Patras Frédéric
Published: April 2015

L'extraordinaire progrès quantitatif de la science contemporaine masque souvent sa dimension qualitative. En mathématiques, la compréhension actuelle des phénomènes théoriques fondamentaux va bien au-delà de celle des périodes antérieures, fussent-elles récentes. Cette évolution s'accompagne par ailleurs d'une prise de distance à l'égard du structuralisme classique et du réductionnisme logique et, corrélativement, d'une attitude plus œverte, plus attentive à sa richesse et sa complexité, lorsqu'il s'agit de penser la nature du travail mathématique. Ces changements attendent pourtant toujours largement d'être théorisés philosophiquement. Ce sera le propos de cet article que de les envisager au filtre de thèmes bachelardiens.
Radiology in the Undergraduate Medical Curriculum: Too Little, Too Late?
Authors: Dmytriw Adam A. , Mok Philip S. , Gorelik Natalia , Kavanaugh Jordan , Brown Peter
Published: April 2015

There is an anecdotal need to increase radiology education in medical school. Surveys were distributed to three medical schools, with a respondency of 55 %. Over 91 % of students believed there should be more radiology teaching in medical school. Students prefer different methods of teaching, lectures, group learning, and web-based modules.
The effect of parental loss on cognitive and affective interference in adolescent boys from a post‐conflict region
Authors: Mueller S.C. , Baudoncq R. , De Schryver M.
Published: April 2015

Little is known about the impact of early‐life stressors such as parental loss on cognitive‐affective processing during adolescence, especially in regions chronically affected by war and armed conflict. Here, we tested 72 male adolescents living in Northern Uganda (ages 14–19), 52 of whom still had both of their parents and 20 participants who had experienced parental loss. Participants completed a classic color‐naming Stroop task as well as an affective interference task, the opposite emotions test (OET). Adolescents with parental loss showed a decrease in performance over time, especially on the Stroop task. Critically, this decrement in performance was positively associated with reported symptoms of trauma, but only in the parental loss group. The current data suggest a difficulty in maintaining cognitive control performance in youths with experience of parental loss. The findings are discussed in relation to traumatic stress and mental health in post‐conflict regions.
Annealed estimates on the Green functions and uncertainty quantification
Authors: Gloria Antoine , Marahrens Daniel
Published: April 2015

We prove Lipschitz bounds for linear elliptic equations in divergence form whose measurable coefficients are random stationary and satisfy a logarithmic Sobolev inequality, extending to the continuum setting results by Otto and the second author for discrete elliptic equations. This improves the celebrated De Giorgi–Nash–Moser theory in the large (that is, away from the singularity) for this class of coefficients. This regularity result is obtained as a corollary of optimal decay estimates on the derivative and mixed second derivative of the elliptic Green functions on

\mathbb{R}^{d}

. As another application of these decay estimates we derive optimal estimates on the fluctuations of solutions of linear elliptic PDEs with “noisy” diffusion coefficients.
Elimination of BMP7 from the developing limb mesenchyme leads to articular cartilage degeneration and synovial inflammation with increased age
Authors: Abula Kahaer , Muneta Takeshi , Miyatake Kazumasa , Yamada Jun , Matsukura Yu , Inoue Makiko , Sekiya Ichiro , Graf Daniel , Economides Aris N. , Rosen Vicki , Tsuji Kunikazu
Published: April 2015

While osteo‐ and chondro‐inductive activities of recombinant human bone morphogenetic protein 7 are well established, evaluation of the role of endogenous BMP7 in skeletal homeostasis has been hampered by perinatal lethality in BMP7 knockout mice. Here, we examined physiological roles of endogenous BMP7 in joint homeostasis and showed that proteoglycan contents in articular cartilage were significantly reduced in the absence of BMP7. Loss of BMP7 did not affect survival of articular cartilage cells, but resulted in reduced expression of aggrecan and enhanced expression of matrix metalloproteinase 13. We also found extensive synovial hyperplasia and enhanced expression of Activin A. These findings suggest that locally produced BMP7 is prerequisite for postnatal synovial joint homeostasis and may be involved in osteoarthritic changes in adults.
Novel insights into structure–function mechanism and tissue‐specific expression profiling of full‐lengthdxr gene fromCymbopogon winterianus
Authors: Devi Kamalakshi , Dehury Budheswar , Phukon Munmi , Modi Mahendra Kumar , Sen Priyabrata
Published: April 2015

The 1‐deoxy‐d‐xylulose‐5‐phosphate reductoisomerase (DXR; EC1.1.1.267), an NADPH‐dependent reductase, plays a pivotal role in the methylerythritol 4‐phosphate pathway (MEP), in the conversion of 1‐deoxy‐d‐xylulose‐5‐phosphate (DXP) into MEP. The sheath and leaf of citronella (Cymbopogon winterianus) accumulates large amount of terpenes and sesquiterpenes with proven medicinal value and economic uses. Thus, sequencing of full lengthdxr gene and its characterization seems to be a valuable resource in metabolic engineering to alter the flux of isoprenoid active ingredients in plants. In this study, full length DXR from citronella was characterized throughin silico and tissue‐specific expression studies to explain its structure–function mechanism, mode of cofactor recognition and differential expression. The modelled DXR has a three‐domain architecture and its active site comprised of a cofactor (NADPH) binding pocket and the substrate‐binding pocket. Molecular dynamics simulation studies indicated that DXR model retained most of its secondary structure during 10 ns simulation in aqueous solution. The modelled DXR superimposes well with its closest structural homolog but subtle variations in the charge distribution over the cofactor recognition site were noticed. Molecular docking study revealed critical residues aiding tight anchoring NADPH within the active pocket of DXR. Tissue‐specific differential expression analysis using semi‐quantitative RT‐PCR and qRT‐PCR in various tissues of citronella plant revealed distinct differential expression of DXR. To our knowledge, this is the first ever report on DXR from the important medicinal plant citronella and further characterization of this gene will open up better avenues for metabolic engineering of secondary metabolite pathway genes from medicinal plants in the near future.
Antipsychotics inhibit glucose transport: Determination of olanzapine binding site inStaphylococcus epidermidis glucose/H+ symporter
Authors: Babkin Petr , George Thompson Alayna M. , Iancu Cristina V. , Walters D. Eric , Choe Jun-yong
Published: April 2015

The antipsychotic drug olanzapine is widely prescribed to treat schizophrenia and other psychotic disorders. However, it often causes unwanted side effects, including diabetes, due to disruption of insulin‐dependant glucose metabolism through a mechanism yet to be elucidated. To determine if olanzapine can affect the first step in glucose metabolism – glucose transport inside cells – we investigated the effect of this drug on the transport activity of a model glucose transporter. The glucose transporter fromStaphylococcus epidermidis (GlcPSe) is specific for glucose, inhibited by various human glucose transporter (GLUT) inhibitors, has high sequence and structure homology to GLUTs, and is readily amenable to transport assay, mutagenesis, and computational modeling. We found that olanzapine inhibits glucose transport of GlcPSe with an IC50 0.9 ± 0.1 mM. Computational docking of olanzapine to the GlcPSe structure revealed potential binding sites that were further examined through mutagenesis and transport assay to identify residues important for olanzapine inhibition. These investigations suggest that olanzapine binds in a polar region of the cytosolic part of the transporter, and interacts with residues R129, strictly conserved in all GLUTs, and N136, conserved in only a few GLUTs, including the insulin‐responsive GLUT4. We propose that olanzapine inhibits GlcPSe by impeding the alternating opening and closing of the substrate cavity necessary for glucose transport. It accomplishes this by disrupting a key salt bridge formed by conserved residues R129 and E362, that stabilizes the outward‐facing conformation of the transporter.
Antenatal betamethasone produces protracted changes in anxiety‐like behaviors and in the expression of microtubule‐associated protein 2, brain‐derived neurotrophic factor and the tyrosine kinase B receptor in the rat cerebellar cortex
Authors: Pascual Rodrigo , Valencia Martina , Bustamante Carlos
Published: April 2015

Using classic Golgi staining methods, we previously showed that the administration of synthetic glucocorticoid betamethasone in equivalent doses to those given in cases of human premature birth generates long‐term alterations in Purkinje cell dendritic development in the cerebellar cortex. In the present study, we evaluated whether betamethasone alters the immunohistochemical expression of proteins that participate in cerebellar Purkinje cell dendritic development and maintenance, including microtubule‐associated protein 2 (MAP2), brain‐derived neurotrophic factor (BDNF) and the tyrosine kinase B receptor (TrkB), which are located predominantly in the cerebellar molecular layer where Purkinje cell dendritogenesis occurs. Consistent with our previous Golgi stain studies, we observed that animals prenatally exposed to a single course of betamethasone showed long‐term alterations in the expression of MAP2, BDNF and TrkB. Additionally, these protracted molecular changes were accompanied by anxiety‐like behaviors in the elevated plus maze and marble burying tests.
Financial benefits and risks of dependency in triadic supply chain relationships
Authors: Kim Yoon Hee , Henderson Darren
Published: April 2015

The economic consequences of interdependent relationships with suppliers and customers have long been of interest to supply chain managers and academics alike. Whereas previous studies have focused on the benefits or risks of embedded relationships that accrue to buying firms, this study simultaneously investigates the effects of a supplier's and a customer's embeddedness, arising from resource dependency, on a focal firm's financial performance in triadic supply chain relationships. Using 1,144 unique focal firm‐years for U.S. firms from Compustat, we find that a supplier's and a customer's dependency both increase the focal firm's performance in terms of return on assets (ROA) and return on sales (ROS) by increasing asset turnover (ATO). As levels of supplier and customer dependency on the focal firm increase, however, the economic benefits of customer dependency diminish beyond a certain point, while those of supplier dependency continue to increase above that threshold. Thus, our findings show the paradoxically differing risks of the supplier's versus the customer's dependency, while establishing the unequivocal economic benefits of supplier and customer relations for focal firms in the middle of concentrated triadic relationships.
Modulation of Cervical Facet Joint Nociception and Pain Attenuates Physical and Psychological Features of Chronic Whiplash: A Prospective Study
Authors: Smith Ashley Dean , Jull Gwendolen , Schneider Geoff M. , Frizzell Bevan , Hooper Robert A. , Sterling Michele
Published: April 2015

Objective

To investigate changes in clinical (physical and psychological) features of individuals with chronic whiplash−associated disorder who had previously undergone cervical radiofrequency neurotomy at the time point when the effects of radiofrequency neurotomy had dissipated and pain returned.

Design

Prospective cohort observational trial of consecutive patients.

Setting

Tertiary spinal intervention centre in Calgary, Alberta, Canada.

Patients

A total of 53 consecutive individuals with chronic whiplash−associated disorder.

Methods

Individuals underwent radiofrequency neurotomy and were assessed before radiofrequency neurotomy, at 1 and 3 months postprocedure, and then after the return of pain (approximately 10 months postprocedure).

Main Outcome Measurements

Quantitative sensory tests (pressure; thermal pain thresholds; brachial plexus provocation test), nociceptive flexion reflex, and motor function (cervical range of movement; craniocervical flexion test) were measured. Self‐reported disability, psychological distress, pain catastrophization, and posttraumatic stress disorder symptoms also were measured.

Results

Upon the return of pain after radiofrequency neurotomy, levels of disability increased (P < .0001), and were no different to those before radiofrequency neurotomy (P = .99). There also was a significant deterioration in quantitative sensory testing measures and reduced cervical range of motion after the return of pain (all P < .05); all approaching values were recorded before radiofrequency neurotomy (P > .22). There were no significant changes in pressure hyperalgesia (P > .054) or craniocervical flexion test performance (P > .07) after the return of pain. Psychological distress and pain catastrophizing increased significantly after the return of pain (P < .01), and again were no different than measures taken prior to radiofrequency neurotomy (P > .13). However, there was no difference in number or severity of posttraumatic stress symptoms after the return of pain (P > .30).

Conclusions

Physical and psychological features of chronic whiplash−associated disorder are modulated dynamically with cervical radiofrequency neurotomy. These findings indicate that peripheral nociception is involved in the manifestations of chronic whiplash−associated disorder in this cohort of individuals.