Publication date: Available online 7 October 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): D. Fietz
In various tissues, steroid hormones may be sulfated, glucuronidated or otherwise modified. For a long time, these hydrophilic molecules have been considered to be merely inactive metabolites for excretion via bile or urine. Nevertheless, different organs such as the placenta and breast tissue produce large amounts of sulfated steroids. After the discovery of the enzyme steroid sulfatase, which is able to re-activate sulfated steroids, these precursor molecules entered the focus of interest again as a local supply for steroid hormone synthesis with a prolonged half-life compared to their unconjugated counterparts. The first descriptions of this so-called sulfatase pathway in the placenta and breast tissue (with special regards to hormone-dependent breast cancer) were quickly followed by studies of steroid sulfate production and function in the testis. These hydrophilic molecules may not permeate the cell membrane by diffusion in the way that unbound steroids can, but need to be transported through the plasma membrane by transport systems. In the testis, a functional sulfatase pathway requires the expression of specific uptake carrier and efflux transporters in testicular cells, i.e. Sertoli, Leydig and germ cells. Main focus has to be placed on Sertoli cells, as these cells build up the blood-testis barrier.In this review, an overview of carrier expression pattern in the human as well as rodent testis is provided with special interest towards implications on fertility.
http://ift.tt/2xs2osM
Κυριακή 8 Οκτωβρίου 2017
Transporter for sulfated steroid hormones in the testis − expression pattern, biological significance and implications for fertility in men and rodents
A new practical classification for spatial distribution and morphology of human hair: Ahmad's LGMA classification
Summary
Background
The human hair is a complex structure with a diversity within itself. There is a wide variation in distribution and spatial arrangement of hairs.
Methods
The current classification was developed on the basis of high-resolution photographs of adult human scalp.
Results
On the observation, the new classification consisted of 4 categories.
Conclusions
It will help the hair restoration surgeons and dermatologists to identify the various pattern and also to help in deciding the appropriate size of the punch in FUE.
http://ift.tt/2kywpRH
A new practical classification for spatial distribution and morphology of human hair: Ahmad's LGMA classification
Summary
Background
The human hair is a complex structure with a diversity within itself. There is a wide variation in distribution and spatial arrangement of hairs.
Methods
The current classification was developed on the basis of high-resolution photographs of adult human scalp.
Results
On the observation, the new classification consisted of 4 categories.
Conclusions
It will help the hair restoration surgeons and dermatologists to identify the various pattern and also to help in deciding the appropriate size of the punch in FUE.
http://ift.tt/2kywpRH
Investigating the role of chemical and physical processes on organic aerosol modelling with CAMx in the Po Valley during a winter episode
Source:Atmospheric Environment
Author(s): A. Meroni, G. Pirovano, S. Gilardoni, G. Lonati, C. Colombi, V. Gianelle, M. Paglione, V. Poluzzi, G.M. Riva, A. Toppetti
Traditional aerosol mechanisms underestimate the observed organic aerosol concentration, especially due to the lack of information on secondary organic aerosol (SOA) formation and processing. In this study we evaluate the chemical and transport model CAMx during a one-month in winter (February 2013) over a 5 km resolution domain, covering the whole Po valley (Northern Italy). This works aims at investigating the effects of chemical and physical atmospheric processing on modeling results and, in particular, to evaluate the CAMx sensitivity to organic aerosol (OA) modeling schemes: we will compare the recent 1.5D-VBS algorithm (CAMx-VBS) with the traditional Odum 2-product model (CAMx-SOAP). Additionally, the thorough diagnostic analysis of the reproduction of meteorology, precursors and aerosol components was intended to point put strength and weaknesses of the modeling system and address its improvement.Firstly, we evaluate model performance for criteria PM concentration. PM10 concentration was underestimated both by CAMx-SOAP and even more by CAMx-VBS, with the latter showing a bias ranging between -4.7 and -7.1 μg m−3. PM2.5 model performance was to some extent better than PM10, showing a mean bias ranging between -0.5 μg m−3 at rural sites and -5.5 μg m−3 at urban and suburban sites. CAMx performance for OA was clearly worse than for the other PM compounds (negative bias ranging between -40% and -75%). The comparisons of model results with OA sources (identified by PMF analysis) shows that the VBS scheme underestimates freshly emitted organic aerosol while SOAP overestimates. The VBS scheme correctly reproduces biomass burning (BBOA) contributions to primary OA concentrations (POA). In contrast VBS slightly underestimates the contribution from fossil-fuel combustion (HOA), indicating that POA emissions related to road transport are either underestimated or associated to higher volatility classes. The VBS scheme under-predictes the SOA too, but to a lesser extent than CAMx-SOAP. SOA underestimation can be related to corresponding underestimation of either aging processes or precursor emissions. This indicates that improvements in the emission inventories for semi- and intermediate-volatility organic compounds are needed for further progress in this area. Finally, the comparison between modeled and observed SOA sources points out the urgency to include processing of OA in particle water phase into SOA formation mechanisms, to reconcile model results and observations.
http://ift.tt/2wHOPkO
Quantitative assessment of source contributions to PM2.5 on the west coast of Peninsular Malaysia to determine the burden of Indonesian peatland fire
Source:Atmospheric Environment
Author(s): Yusuke Fujii, Susumu Tohno, Norhaniza Amil, Mohd Talib Latif
Almost every dry season, peatland fires occur in Sumatra and Kalimantan Inlands. Dense smoke haze from Indonesian peatland fires (IPFs) causes impacts on health, visibility, transport and regional climate in Southeast Asian countries such as Indonesia, Malaysia, and Singapore. Quantitative knowledge of IPF source contribution to ambient aerosols in Southeast Asia (SEA) is so useful to make appropriate suggestions to policy makers to mitigate IPF-induced haze pollution. However, its quantitative contribution to ambient aerosols in SEA remains unclarified. In this study, the source contributions to PM2.5 were determined by the Positive Matrix Factorization (PMF) model with annual comprehensive observation data at Petaling Jaya on the west coast of Peninsular Malaysia, which is downwind of the IPF areas in Sumatra Island, during the dry (southwest monsoon: June–September) season. The average PM2.5 mass concentration during the whole sampling periods (Aug 2011–Jul 2012) based on the PMF and chemical mass closure models was determined as 20–21 μg m−3. Throughout the sampling periods, IPF contributed (on average) 6.1–7.0 μg m−3 to the PM2.5, or ∼30% of the retrieved PM2.5 concentration. In particular, the PM2.5 was dominantly sourced from IPF during the southwest monsoon season (51–55% of the total PM2.5 concentration on average). Thus, reducing the IPF burden in the PM2.5 levels would drastically improve the air quality (especially during the southwest monsoon season) around the west coast of Peninsular Malaysia.
http://ift.tt/2y4vVpM
20Q: Current Perspectives on Hyperacusis
A Q & A discussion that reviews current knowledge of hyperacusis. Topics include definition, symptoms, prevalence, and suspected pathophysiology, as well as clinical assessment, treatment, and resources, based on the latest research in this area.
http://ift.tt/2yAtWg4
Toward multi-day-ahead forecasting of suspended sediment concentration using ensemble models
Abstract
This study explores two ideas to made an improvement on the artificial neural network (ANN)-based models for suspended sediment forecasting in several time steps ahead. In this regard, both observed and forecasted time series are incorporated as input variables of the models when applied for more than one lead time. Secondly, least-square ensemble models employing multiple wavelet-ANN models are developed to increase the performance of the single model. For this purpose, different wavelet families are linked with the ANN model and performance of each model is evaluated using error measures. The Skagit River near Mount Vernon in Washington county is selected as the case study. The daily flow discharge and suspended sediment concentration (SSC) in the current day are considered as input variables to predict suspended sediment concentration in the next day. For more lead times, the input structure is updated by adding the forecast of SSC in the previous time step. Results of this study demonstrate that incorporating both observed and predicted variables in the input structure improves performance of conventional models in which those only employ observed time series as input variables. Moreover, ensemble model developed for each lead time outperforms the best single wavelet-ANN model which indicates superiority of the ensemble model over the other one. Findings of this study reveal that acceptable forecasts of daily suspended sediment concentration up to 3 days in advance can be achieved using the proposed methodology.
http://ift.tt/2y9ro7E
Vitamin D and the Skin: An Update for Dermatologists
Abstract
Vitamin D plays a key role in skeletal and cardiovascular disorders, cancers, central nervous system diseases, reproductive diseases, infections, and autoimmune and dermatological disorders. The two main sources of vitamin D are sun exposure and oral intake, including vitamin D supplementation and dietary intake. Multiple factors are linked to vitamin D status, such as Fitzpatrick skin type, sex, body mass index, physical activity, alcohol intake, and vitamin D receptor polymorphisms. Patients with photosensitive disorders tend to avoid sun exposure, and this practice, along with photoprotection, can put this category of patients at risk for vitamin D deficiency. Maintaining a vitamin D serum concentration within normal levels is warranted in atopic dermatitis, psoriasis, vitiligo, polymorphous light eruption, mycosis fungoides, alopecia areata, systemic lupus erythematosus, and melanoma patients. The potential determinants of vitamin D status, as well as the benefits and risks of vitamin D (with a special focus on the skin), will be discussed in this article.
http://ift.tt/2gmQfL9
Biofilm formation by Candida albicans is inhibited by photodynamic antimicrobial chemotherapy (PACT), using chlorin e6: increase in both ROS production and membrane permeability
Abstract
Candida albicans is an opportunistic fungal producing both superficial and systemic infections in immunocompromised patients. Furthermore, it has been described an increase in the frequency of infections which have become refractory to standard antifungal therapy. Photodynamic antimicrobial chemotherapy (PACT) is a potential antimicrobial therapy that combines visible light and a nontoxic dye, known as a photosensitizer, producing reactive oxygen species (ROS) that can kill the treated cells. The objective of this study was to investigate the effects of PACT, using chlorin e6, as a photosensitizer on C. albicans. In this work, we studied the effect of PACT on both cell growth and biofilm formation by C. albicans. In addition, both ROS production and cell permeability were determined after PACT. PACT inhibited both growth and biofilm formation by C. albicans. We have also observed that PACT increased both ROS production (six times) and cell membrane permeability (five times) in C. albicans. PACT decreased both cell growth and biofilm development. The effect of PACT using chlorin e6 on C. albicans could be associated with an increase in ROS production, which could increase cell permeability, producing permanent damage to the cell membranes, leading to the cell death.
http://ift.tt/2fWgWG3
An inexact multistage fuzzy-stochastic programming for regional electric power system management constrained by environmental quality
Abstract
Electric power system involves different fields and disciplines which addressed the economic system, energy system, and environment system. Inner uncertainty of this compound system would be an inevitable problem. Therefore, an inexact multistage fuzzy-stochastic programming (IMFSP) was developed for regional electric power system management constrained by environmental quality. A model which concluded interval-parameter programming, multistage stochastic programming, and fuzzy probability distribution was built to reflect the uncertain information and dynamic variation in the case study, and the scenarios under different credibility degrees were considered. For all scenarios under consideration, corrective actions were allowed to be taken dynamically in accordance with the pre-regulated policies and the uncertainties in reality. The results suggest that the methodology is applicable to handle the uncertainty of regional electric power management systems and help the decision makers to establish an effective development plan.
http://ift.tt/2y61yzm
cBiT: A transcriptomics database for innovative biomaterial engineering
Publication date: December 2017
Source:Biomaterials, Volume 149
Author(s): Dennie G.A.J. Hebels, Aurélie Carlier, Maarten L.J. Coonen, Daniël H. Theunissen, Jan de Boer
Creating biomaterials that are suited for clinical application is still hampered by a lack of understanding of the interaction between a cell and the biomaterial surface it grows on. This surface communication can strongly impact cellular behavior, which in turn affects the chances of a successful interaction between a material and the host tissue. Transcriptomics data have previously been linked to measurements of biomaterial properties in order to explain the biological mechanisms underlying these cell-biomaterial interactions. However, such multi-assay data are highly complex and therefore require careful and unambiguous characterization and storage. Failure to do so may result in loss of valuable data or erroneous data analysis. In order to start a new initiative that tackles these issues and offers a platform for innovative biomaterial development, we have created a publically accessible repository called The Compendium for Biomaterial Transcriptomics (cBiT, http://ift.tt/2y6bAjN). cBiT is a data warehouse that gives users the opportunity to search through biomaterial-based transcriptomics data sets using a web interface. Data of interest can be selected and downloaded, together with associated measurements of material properties. Researchers are also invited to add their data to cBiT in order to further enhance its scientific value. We aim to make cBiT the hub for biomaterial-associated data, thereby enabling major contributions to a more efficient development of new materials with improved body integration. Here, we describe the structure of cBiT and provide a use case with clinically applied materials to demonstrate how cBiT can be used to correlate data across transcriptomics studies.
Graphical abstract
http://ift.tt/2y5UhiO
Neuro-Psychiatric Comorbidity among Psoriatic Adolescents
Abstract
Background
Psoriasis is a known risk factor for neuro-psychiatric diseases among adults. Less is known regarding adolescents.
Objective
Investigating the association between psoriasis and neuro-psychiatric comorbidity and social skills among adolescents.
Methods
A population based cross-sectional study between January 1st, 1999 and January 1st, 2014 was conducted. The study included 1746 and 1366 adolescents (aged 16 to 18) with mild and moderate to severe psoriasis, respectively. All psoriasis patients were diagnosed by a dermatologist. Neuro-psychiatric diseases were diagnosed by a neurologist and a psychiatrist, accordingly. Social skills were evaluated by a psychosocial assessment. Psoriasis patients were compared to 884653 healthy control patients by a multivariate analysis adjusted for age, sex, country of origin, socio-economic status, cognitive skills and body mass index. A subgroup evaluation was done for comorbidity which could only be evaluated for part of the recruitment years, by a univariate analysis.
Results
Overall chronic headaches (8.1% vs. 3.4%), intermediate frequency migraine (4.8% vs. 1.6%), low frequency migraine and non-migraine headaches (3.4% vs. 1.8%) were associated only with moderate to severe psoriasis compared to healthy controls [Adjusted odds ratios (adj. ORs) 1.9, 2.3, 1.5; 95% confidence intervals (CIs) 1.6-2.4, 1.8-3.0 and 1.1-2.1, respectively]. Anxiety disorders (2.1% vs. 0.7%) and impaired social adjustment skills (7.5% vs. 4.2%) were also associated only with moderate to severe psoriasis compared to healthy controls (ORs 2.9, 1.9; 95% CIs 1.6-5.5 and 1.3-2.6; Of 466 vs. 265023, respectively).
Conclusion
Psoriasis among adolescents is associated with neuro-psychiatric co-morbidities and impaired adjustment skills, depending on disease severity.
This article is protected by copyright. All rights reserved.
http://ift.tt/2wGhQNB
Neuro-Psychiatric Comorbidity among Psoriatic Adolescents
Abstract
Background
Psoriasis is a known risk factor for neuro-psychiatric diseases among adults. Less is known regarding adolescents.
Objective
Investigating the association between psoriasis and neuro-psychiatric comorbidity and social skills among adolescents.
Methods
A population based cross-sectional study between January 1st, 1999 and January 1st, 2014 was conducted. The study included 1746 and 1366 adolescents (aged 16 to 18) with mild and moderate to severe psoriasis, respectively. All psoriasis patients were diagnosed by a dermatologist. Neuro-psychiatric diseases were diagnosed by a neurologist and a psychiatrist, accordingly. Social skills were evaluated by a psychosocial assessment. Psoriasis patients were compared to 884653 healthy control patients by a multivariate analysis adjusted for age, sex, country of origin, socio-economic status, cognitive skills and body mass index. A subgroup evaluation was done for comorbidity which could only be evaluated for part of the recruitment years, by a univariate analysis.
Results
Overall chronic headaches (8.1% vs. 3.4%), intermediate frequency migraine (4.8% vs. 1.6%), low frequency migraine and non-migraine headaches (3.4% vs. 1.8%) were associated only with moderate to severe psoriasis compared to healthy controls [Adjusted odds ratios (adj. ORs) 1.9, 2.3, 1.5; 95% confidence intervals (CIs) 1.6-2.4, 1.8-3.0 and 1.1-2.1, respectively]. Anxiety disorders (2.1% vs. 0.7%) and impaired social adjustment skills (7.5% vs. 4.2%) were also associated only with moderate to severe psoriasis compared to healthy controls (ORs 2.9, 1.9; 95% CIs 1.6-5.5 and 1.3-2.6; Of 466 vs. 265023, respectively).
Conclusion
Psoriasis among adolescents is associated with neuro-psychiatric co-morbidities and impaired adjustment skills, depending on disease severity.
This article is protected by copyright. All rights reserved.
http://ift.tt/2wGhQNB
Epigenetic regulation of DNA repair genes and implications for tumor therapy
Publication date: Available online 7 October 2017
Source:Mutation Research/Reviews in Mutation Research
Author(s): Markus Christmann, Bernd Kaina
DNA repair represents the first barrier against genotoxic stress causing metabolic changes, inflammation and cancer. Besides its role in preventing cancer, DNA repair needs also to be considered during cancer treatment with radiation and DNA damaging drugs as it impacts therapy outcome. The DNA repair capacity is mainly governed by the expression level of repair genes. Alterations in the expression of repair genes can occur due to mutations in their coding or promoter region, changes in the expression of transcription factors activating or repressing these genes, and/or epigenetic factors changing histone modifications and CpG promoter methylation or demethylation levels. In this review we provide an overview on the epigenetic regulation of DNA repair genes. We summarize the mechanisms underlying CpG methylation and demethylation, with de novo methyltransferases and DNA repair involved in gain and loss of CpG methylation, respectively. We discuss the role of components of the DNA damage response, p53, PARP-1 and GADD45a on the regulation of the DNA (cytosine-5)-methyltransferase DNMT1, the key enzyme responsible for gene silencing. We stress the relevance of epigenetic silencing of DNA repair genes for tumor formation and tumor therapy. A paradigmatic example is provided by the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT), which is silenced in up to 40% of various cancers through CpG promoter methylation. The CpG methylation status of the MGMT promoter strongly correlates with clinical outcome and, therefore, is used as prognostic marker during glioblastoma therapy. Mismatch repair genes are also subject of epigenetic silencing, which was shown to correlate with colorectal cancer formation. For many other repair genes shown to be epigenetically regulated the clinical outcome is not yet clear. We also address the question of whether genotoxic stress itself can lead to epigenetic alterations of genes encoding proteins involved in the defense against genotoxic stress.
http://ift.tt/2y2bsnL
Fast in situ gamma spectroscopy using hand-held spectrometer with NaI probe
Source:Journal of Environmental Radioactivity
Author(s): Szymon Guguła, Krzysztof Kozak, Jadwiga Mazur, Dominik Grządziel, Mariusz Mroczek
In this work a hand-held spectrometer InSpector 1000 with NaI (Tl) 2″ x 2″ detector has been adapted to fast in situ gamma-ray spectroscopy. Two specially designed mounting stands with shielding have been built, allowing conducting measurements in different geometries. Three particular geometries (NW, IS50, IS00) have been chosen for efficiency calibration and further study. The first one (NW) is intended for small environmental samples (volume ca 140 cm3) collected on site. IS50 geometry is a typical in situ geometry meant for radioactivity measurements in soil with detector pointed towards the ground. In this geometry the probe is shielded and mounted 50 cm above the soil surface. The new proposed geometry IS00 is designed in the way that the detector is inserted directly into the soil in order to increase the counting efficiency. The methods of efficiency calibration involved using calibration standards (in NW geometry) and the results obtained in previous in situ measurements with InSpector 2000 portable spectrometer with HPGe detector and ISOCS™ Shield Systems, which is routinely used in environmental measurements.NW geometry turned out to be useful for natural radioisotopes concentrations (K-40, U-238 and Th-232), which significantly exceed typical values of those concentrations observed in Poland. Both IS50 and IS00 geometries are applicative for quick (2 h long measurement) evaluation of typical concentrations of K, U and Th in soils. The newly proposed geometry IS00 is superior as it showed lower detection limits and uncertainties as well as its handling was far easier than of IS50. Authors have proven that hand-held spectrometer InSpector 1000, together with mounting stands and shielding, can be successfully used for fast in situ gamma-spectroscopy. Its relatively small weight and good mobility are additional assets. Moreover, detailed procedures for measurements in each geometry have been developed to conduct such analyses properly.
http://ift.tt/2xs2agy
Ponatinib in chronic myeloid leukemia (CML): Consensus on patient treatment and management from a European expert panel
Source:Critical Reviews in Oncology/Hematology
Author(s): Martin C. Müller, Francisco Cervantes, Henrik Hjorth-Hansen, Jeroen J.W.M. Janssen, Dragana Milojkovic, Delphine Rea, Gianantonio Rosti
Five tyrosine kinase inhibitors (TKIs) are currently approved in the European Union for treatment of chronic myeloid leukemia (CML) and all have considerable overlap in their indications. While disease-specific factors such as CML phase, mutational status, and line of treatment are key to TKI selection, other important features must be considered, such as patient-specific comorbidities and TKI safety profiles. Ponatinib, the TKI most recently approved, has demonstrated efficacy in patients with refractory CML, but is associated with an increased risk of arterial hypertension, sometimes severe, and serious arterial occlusive and venous thromboembolic events. A panel of European experts convened to discuss their clinical experience in managing patients with CML. Based on the panel discussions, scenarios in which a CML patient may be an appropriate candidate for ponatinib therapy are described, including presence of the T315I mutation, resistance to other TKIs without the T315I mutation, and intolerance to other TKIs.
http://ift.tt/2z6Cqsh
MicroRNAs in glioblastoma pathogenesis and therapy: A comprehensive review
Source:Critical Reviews in Oncology/Hematology
Author(s): Bhavesh K. Ahir, Howard Ozer, Herbert H. Engelhard, Sajani S. Lakka
Glioblastoma (GBM), also known as grade IV astrocytoma, is the most aggressive primary intracranial tumor of the adult brain. MicroRNAs (miRNAs), a class of small non-coding RNA species, have critical functions across various biological processes. A great deal of progress has been made recently in dissecting miRNA pathways associated with the pathogenesis of GBM. miRNA expression signatures called gene signatures also characterize and contribute to the phenotypic diversity of GBM subclasses through their ability to regulate developmental growth and differentiation. miRNA molecules have been identified as diagnostic and prognostic biomarkers for patient stratification and may also serve as therapeutic targets and agents. This review summarizes: (i) the current understanding of the roles of miRNAs in the pathogenesis of GBM, (ii) the potential use of miRNAs in GBM diagnosis and glioma grading, (iii) further prospects of developing miRNAs as novel biomarkers and therapeutic targets for GBM, and (iv) important practical considerations when considering miRNA therapy for GBM patients.
http://ift.tt/2y9J5DG
Comparison of gamma- and DVH-based in vivo dosimetric plan evaluation for pelvic VMAT treatments
Source:Radiotherapy and Oncology
Author(s): Erik van der Bijl, René F.M. van Oers, Igor Olaciregui-Ruiz, Anton Mans
Background and purposeTo compare DVH-based quality assurance to a multi-parametric γ-based methodology for in vivo EPID dosimetry for VMAT to the pelvis.Materials and methodsFor 47 rectum, 37 prostate, and 44 bladder VMAT treatments we reconstructed the 3D dose distributions of 387 fractions from in vivo EPID dosimetry. The difference between planned and measured dose was evaluated using γ analysis (3%/3mm) in the 50% isodose volume (IDV) and DVH differences (ΔD2, ΔD50 and ΔD98) of targets and organs at risk. The γ-indicators mean γ, γ pass rate and γ1% were compared to DVH-differences and their correlations were studied. DVH-based alerts on PTV and IDV were compared to γ-based alerts.ResultsAverage PTV D50 and D98 dose differences were 0.0±2.2% (1SD) and −1.4±2.9% (1SD). Alert criteria of |ΔD50|<3.5–4.5% corresponded to an alert rate of about 10%. Strong correlations between mean γ and γ pass rate and difference in PTV ΔD50 were observed for all sites. DVH- and γ-based alerts agreed on >80% of the fractions for the majority of compared alert thresholds and methods. This agreement is >90% for the larger deviations.ConclusionsStrong correlations between some γ- and DVH indicators were found. Our comparison of multi-parametric alert strategies showed clinical equivalence for γ- and DVH-based methods.
http://ift.tt/2y7OTOg
Thyroid hormone levels in late preterm, early term and term infants: a study with healthy neonates revealing reference values and factors affecting thyroid hormones
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
http://ift.tt/2y5ReY6
Severe complications after initial management of hyperglycemic hyperosmolar syndrome and diabetic ketoacidosis with a standard diabetic ketoacidosis protocol
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
http://ift.tt/2yz2nUc
The relationship between non-alcoholic fatty liver disease and small intestinal bacterial overgrowth among overweight and obese children and adolescents
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
http://ift.tt/2y4GR6N
Persistent de Quervain tenosynovitis induced by somatotropin treatment
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
http://ift.tt/2wFLPp5
Oral health status of children with type 1 diabetes: a comparative study
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
http://ift.tt/2kxDCkZ
Makorin ring finger 3 gene analysis in Koreans with familial precocious puberty
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
http://ift.tt/2wGwYuD
Emerging targets in cancer immunotherapy
Source:Seminars in Cancer Biology
Author(s): Samantha Burugu, Amanda R. Dancsok, Torsten O. Nielsen
The first generation of immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1/PD-L1) targeted natural immune homeostasis pathways, co-opted by cancers, to drive anti-tumor immune responses. These agents led to unprecedented results in patients with previously incurable metastatic disease and may become first-line therapies for some advanced cancers. However, these agents are efficacious in only a minority of patients. Newer strategies are becoming available that target additional immunomodulatory mechanisms to activate patients' own anti-tumor immune responses. Herein, we present a succinct summary of emerging immune targets with reported pre-clinical efficacy that have progressed to active investigation in clinical trials. These emerging targets include co-inhibitory and co-stimulatory markers of the innate and adaptive immune system. In this review, we discuss: 1) T lymphocyte markers: Lymphocyte Activation Gene 3 [LAG-3], T-cell Immunoglobulin- and Mucin-domain-containing molecule 3 [TIM-3], V-domain containing Ig Suppressor of T cell Activation [VISTA], T cell ImmunoGlobulin and ITIM domain [TIGIT], B7-H3, Inducible T-cell Co-stimulator [ICOS/ICOS-L], CD27/CD70, and Glucocorticoid-Induced TNF Receptor [GITR]; 2) macrophage markers: CD47/Signal-Regulatory Protein alpha [SIRPα] and Indoleamine-2,3-Dioxygenase [IDO]; and 3) natural killer cell markers: CD94/NKG2A and the Killer Immunoglobulin-like receptor [KIR] family. Finally, we briefly highlight combination strategies and potential biomarkers of response and resistance to these cancer immunotherapies.
http://ift.tt/2wFHrq3
A new technique for adult hypospadias repair: A combination of TIPU and Mathieu techniques
Publication date: Available online 7 October 2017
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Murat Zor, Hasret Topac, Onder Ors
http://ift.tt/2fUbV0D
Hybrid polymer films based ZnS nanocomposites and its optical and morphological properties: Monitoring the role of the binding-site interaction
Publication date: February 2018
Source:Materials Research Bulletin, Volume 98
Author(s): Guadalupe del C. Pizarro, Oscar G. Marambio, Manuel Jeria-Orell, Diego P. Oyarzún, Julio Sánchez
A series of hybrid polymer films were prepared using self-assembly block copolymers as nanoreactor of ZnS nanoparticles (NPs). The self-assembled poly(acrylic acid)-block-poly(N-phenylmaleimide) was prepared by Atom-Transfer Radical Polymerization (ATRP) in different block composition. Subsequently the fluorescent NPs were synthesized into the polymer matrices in order to modify its optical and thermal properties and to analyze its effect on the morphology properties (roughness and porosity).As results, significant effects on the properties of the hybrid materials were obtained under different percentages of the NPs. These materials exhibited blue- or red-shift emission bands depending on the length of hydrophilic domain. Additionally, a quenched emission band is seen, which may also be attributed primarily to the composition of the hydrophilic domain and to the greater percentage of ZnS NPs. The hybrid polymer films showed effects on the porosity and roughness of the surfaces, which was analyzed by AFM and SEM microscopic techniques.
Graphical abstract
http://ift.tt/2xrWZ07
Eyes have ears: Indexing the orienting response to sound using pupillometry
Source:International Journal of Psychophysiology
Author(s): Alexandre Marois, Katherine Labonté, Mark Parent, François Vachon
The rare occurrence of a sound deviating from the auditory background tends to trigger attentional orienting. While some sympathetic physiological responses can be used to index this orienting response, findings surrounding the pupillary dilation response (PDR) as a proxy for the orienting response are conflicting. The current study was tailor-designed to examine whether the PDR satisfies specific criteria of an orienting response index, namely the classic habituation pattern and a sensitivity to the size of the deviation. The PDR decrement to a repeated standard sound, recovery to a deviant sound, and dishabituation to the re-presentation of the standard were assessed for small and large deviations embedded in irrelevant auditory sequences. The PDR not only showed habituation and dishabituation, but also recovered in correspondence with the magnitude of the acoustic deviation. This consistency between variations of the PDR and orienting response's properties indicates that the PDR is a valid index of the auditory orienting response.
http://ift.tt/2g2zubw
Using theta and alpha band power to assess cognitive workload in multitasking environments
Source:International Journal of Psychophysiology
Author(s): Sébastien Puma, Nadine Matton, Pierre-V. Paubel, Éric Raufaste, Radouane El-Yagoubi
Cognitive workload is of central importance in the fields of human factors and ergonomics. A reliable measurement of cognitive workload could allow for improvements in human machine interface designs and increase safety in several domains. At present, numerous studies have used electroencephalography (EEG) to assess cognitive workload, reporting the rise in cognitive workload to be associated with increases in theta band power and decreases in alpha band power. However, results have been inconsistent with some failing to reach the required level of significance. We hypothesized that the lack of consistency could be related to individual differences in task performance and/or to the small sample sizes in most EEG studies. In the present study we used EEG to assess the increase in cognitive workload occurring in a multitasking environment while taking into account differences in performance. Twenty participants completed a task commonly used in airline pilot recruitment, which included an increasing number of concurrent sub-tasks to be processed from one to four. Subjective ratings, performances scores, pupil size and EEG signals were recorded. Results showed that increases in EEG alpha and theta band power reflected increases in the involvement of cognitive resources for the completion of one to three subtasks in a multitasking environment. These values reached a ceiling when performances dropped. Consistent differences in levels of alpha and theta band power were associated to levels of task performance: highest performance was related to lowest band power.
http://ift.tt/2wFw3KH
The Utility of MRI in the Diagnosis of Takayasu Arteritis
Takayasu Arteritis (TA) is an inflammatory disorder involving the thoracoabdominal aorta and its branches and the pulmonary arteries, with eventual vascular stenosis, occlusion, or aneurysm formation. Conventional angiography has been the reference imaging standard for diagnosis of TA. The purpose of this case report is to demonstrate the utility of MR imaging and MR angiography in the diagnosis of Takayasu Arteritis in a pediatric patient. The patient is a 15-year-old female patient presenting with anemia, hypertension, and acute kidney injury. Initial chest CT demonstrated ectasia of the ascending and focal stenosis of the descending thoracic aorta, prompting further evaluation with MRI and MRA. MRI/MRA demonstrated mural thickening with luminal stenosis of the aorta and aortic branch vessels. These imaging findings were suggestive of a large vessel arteritis and along with the clinical presentation and laboratory abnormalities the diagnosis of Takayasu Arteritis was suggested. Several case series in adults have described the cross-sectional findings of TA. However, this case report demonstrates the utility of MRI/MRA in the evaluation of TA in children and in the course of follow-up, as it provides a noninvasive method for evaluating a child without ionizing radiation or iodinated contrast.
http://ift.tt/2xrsyY5
Cytomegalovirus Associated Duodenal Ulcer and Duodenitis in a Malnourished Pediatric Patient
Cytomegalovirus (CMV) duodenitis is a rare occurrence, especially in pediatric patients. A thirteen-month-old female presented to the Emergency Department for a febrile seizure. She was incidentally admitted for severe malnutrition with an initial workup remarkable for only a slight elevation in her ALT at 48. The patient was found to have an oral aversion requiring nasogastric tube feeds for adequate caloric intake. She continued to fail to gain weight and underwent an EGD that demonstrated a duodenal ulcer. She was consequently started on sucralfate and omeprazole. Post-EGD lab work demonstrated a pronounced increase in AST and ALT. Pathology from the EGD biopsies later demonstrated viral inclusion bodies consistent with CMV duodenitis. Apart from malnutrition, other causes of immune deficiency were eliminated from the differential diagnosis due to negative HIV PCR and normal immunoglobulins. While on antiviral treatment, her viral load of 1080 IU/mL trended to resolution and her liver enzymes normalized. The patient was ultimately discharged home demonstrating adequate weight gain via gastrostomy tube feeds. This case advocates for pediatricians to include immunodeficiency and infectious etiologies in their differential for malnourished patients in order to lead to earlier diagnosis and management of this treatable condition.
http://ift.tt/2xpbBCx
Development of a microarray-based assay for efficient testing of new HSP70/DnaK inhibitors
Publication date: Available online 7 October 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Sona Mohammadi-Ostad-Kalayeh, Vjaceslavs Hrupins, Sabine Helmsen, Frank Stahl, Thomas Scheper, Matthias Preller, Frank Surup, Marc Stadler, Andreas Kirschning, Carsten Zeilinger
A facile method for testing ATP binding in a highly miniaturized microarray environment using human HSP70 and DnaK from Mycobacterium tuberculosis as biological targets is reported. Supported by molecular modelling studies we demonstrate that the position of the fluorescence label on ATP has a strong influence on the binding to human HSP70. Importantly, the label has to be positioned on the adenine ring and not to the terminal phosphate group. Unlabelled ATP displaced bound Cy5-ATP from HSP70 in the micromolar range. The affinity of a well-known HSP70 inhibitor VER155008 for the ATP binding site in HSP70 was determined, with a EC50 in the micromolar range, whereas reblastin, a HSP90-inhibitor, did not compete for ATP in the presence of HSP70. The applicability of the method was demonstrated by screening a small compound library of natural products. This unraveled that terphenyls rickenyl A and D, recently isolated from cultures of the fungus Hypoxylon rickii, are inhibitors of HSP70. They compete with ATP for the chaperone in the range of 29 µM (Rickenyl D) and 49 µM (Rickenyl A). Furthermore, the microarray-based test system enabled protein-protein interaction analysis using full-length HSP70 and HSP90 proteins. The labelled full-length human HSP90 binds with a half-maximal affinity of 5.5 µg/ml (∼40 µM) to HSP70. The data also demonstrate that the microarray test has potency for many applications from inhibitor screening to target-oriented interaction studies.
Graphical abstract
http://ift.tt/2wGtxnE
The burden of atopic dermatitis in US adults: Health care resource utilization data from the 2013 National Health and Wellness Survey
Publication date: Available online 7 October 2017
Source:Journal of the American Academy of Dermatology
Author(s): Laurent Eckert, Shaloo Gupta, Caroline Amand, Abhijit Gadkari, Puneet Mahajan, Joel M. Gelfand
BackgroundThere is a lack of data on the burden of atopic dermatitis (AD) in adults relative to the general population.ObjectiveTo characterize the AD burden in adult patients relative to both matched non-AD controls and matched patients with psoriasis in terms of comorbidities, health care resource utilization (HCRU), and costs.MethodsAdults (≥18 years) who self-reported a diagnosis of AD or psoriasis and adult non-AD controls were identified from the 2013 US National Health and Wellness Survey. Patients with AD were propensity score–matched with non-AD controls and patients with psoriasis on demographic variables. Patient-reported outcomes were analyzed between matched cohorts.ResultsPatients with AD had a significantly greater risk for atopic comorbidities, as well as significantly greater HCRU and total cost compared with non-AD controls. The burden of AD was generally comparable to that of psoriasis, although patients with AD reported increased use of emergency room visits compared with patients with psoriasis.LimitationsPatient-reported data are susceptible to recall bias and erroneous classification.ConclusionsAdult patients with AD reported a substantial disease burden, suggesting an unmet need for more effective AD treatment options.
http://ift.tt/2xqI3iK
The Frisbee Maneuver: A Novel Method to Abort Acute Attacks of Raynaud’s Phenomenon
Publication date: Available online 7 October 2017
Source:Journal of the American Academy of Dermatology
Author(s): Paul Curtiss, Gabriela Cobos, Kristen Lo Sicco, Andrew Franks
http://ift.tt/2yzaUq4
Focal Atrichia: A Diagnostic Clue in Female Pattern Hair Loss
Publication date: Available online 7 October 2017
Source:Journal of the American Academy of Dermatology
Author(s): Elise A. Olsen, David A. Whiting
BackgroundFocal atrichia is a common clinical finding in female pattern hair loss whose specificity and histologic findings need further clarification.ObjectiveTo determine the frequency of focal atrichia in various types of hair loss and its histologic characteristics in female pattern hair loss.MethodsPart 1: Review of 250 consecutive female patients seen with hair loss for the presence of focal atrichia and Part 2: paired biopsies of haired areas vs focal atrichia in 18 subjects with female pattern hair lossResultsFocal atrichia was seen in 46/104 (44%) of women with female pattern hair loss, including 67% of late onset vs 15% of early onset, compared to 3/146 (2%) of those with other hair disorders Biopsy findings of focal atrichia in female pattern hair loss showed primarily a more progressive miniaturization process than that of haired areas of the scalp.LimitationsSome women with female pattern hair loss may have had concomitant chronic telogen effluviumConclusionsWhen present, focal atrichia is a clinical clue to the diagnosis of female pattern hair loss, particularly late onset subtype.
http://ift.tt/2xr5t7M
Alternating histopathological pattern in blaschkoid dermatoses with epidermal changes: A retrospective series of 61 cases
Publication date: Available online 7 October 2017
Source:Journal of the American Academy of Dermatology
Author(s): Vishal Gupta, Sujay Khandpur, Sudheer Arava, M. Ramam
http://ift.tt/2yzaW1a
QTc prolongation during phenol-croton oil peels
Publication date: Available online 7 October 2017
Source:Journal of the American Academy of Dermatology
Author(s): Carlos Gustavo Wambier, Sarah Perillo de Farias Wambier, Liliana Elias Pena Pilatti, Jessica Adriana Grabicoski, Luis Fernando Wambier, André Schmidt
http://ift.tt/2yzaTT2
Response to the letter to the editor regarding “The outcomes of overlay myringoplasty: Endoscopic versus microscopic approach”
Source:American Journal of Otolaryngology
Author(s): Yuvatiya Plodpai, Nanatphong Paje
http://ift.tt/2z7MDof
Small percentage of anaphylactic reactions treated with epinephrine during food challenges in Dutch children
Source:Annals of Allergy, Asthma & Immunology
Author(s): Johanna P.M. van der Valk, Irene Berends, Roy Gerth van Wijk, Nicolette. J.T. Arends, Maurits S. van Maaren, Hans de Groot, Harry J. Wichers, Joyce A.M. Emons, Anthony E.J. Dubois, Nicolette W. de Jong
BackgroundSevere allergic reactions, including anaphylaxis, occur during oral food challenges (OFCs) and the first-line treatment of anaphylaxis is epinephrine.ObjectiveTo evaluate the percentage of anaphylactic reactions treated with epinephrine during OFCs and to identify associated factors for the administration of epinephrine.MethodsChildren who underwent an OFC with peanut, hazelnut, cow's milk, hen's egg, or cashew nut from 2005 through 2015 in the Netherlands were evaluated. Children with reactions meeting the criteria for anaphylaxis according to the European Academy of Allergy and Clinical Immunology guidelines for food allergy and anaphylaxis were included. Children with an anaphylactic reaction treated with vs without epinephrine were compared. Possible factors associated with the administration of epinephrine, such as age, sex, symptoms consistent with asthma, history of an allergic reaction to the tested allergen, and symptom types during the anaphylactic reaction, were evaluated using logistic regression analysis.ResultsEighty-three children in clinical and research settings (43% boys; median age, 7 years; range, 1–17) who met the criteria for anaphylaxis were included in this study. Thirty-two of 83 children (39%) with anaphylaxis were treated with epinephrine. Respiratory symptoms during the OFC were treated significantly more often with epinephrine than gastrointestinal symptoms (P = .01).ConclusionOnly 39% of children with anaphylaxis, according to the guideline criteria, were treated with epinephrine during the OFC and most of these children had respiratory symptoms. There is need for an easy-to-use international guideline for the treatment of allergic symptoms during OFCs.
http://ift.tt/2fTytPb
Immediate reactions to iodinated contrast media
Source:Annals of Allergy, Asthma & Immunology
Author(s): Cristina Morales-Cabeza, Dasha Roa-Medellín, Inés Torrado, Manuel De Barrio, Carmen Fernández-Álvarez, Juan Francisco Montes-Aceñero, Inmaculada De La Riva, Alicia Prieto-García
BackgroundImmediate hypersensitivity reactions (IHRs) to iodinated contrast media (ICMs) remain a common clinical concern. Positive skin test and basophil activation test results suggest a specific IgE-mediated mechanism in some cases. Skin test and controlled challenge test (CCT) are useful to manage these patients.ObjectiveTo study clinical and allergologic features of IHRs to ICMs in a Spanish tertiary hospital during a 7-year period.MethodsDemographic and clinical data concerning the reaction were recorded. Patients treated at the Allergy Department of Hospital General Universitario Gregorio Marañón, Madrid, Spain, underwent skin tests. In those with positive results, CCTs with an alternative skin-test-negative ICM was performed. Global reaction rate was calculated and compared for each ICM.ResultsA total of 342 reactions occurred in 329 patients. Cutaneous symptoms were the most common (87.7%). A total of 196 patients underwent an allergy workup, 15 (7.6%) of whom had positive skin test results. Reactions were more severe in patients with positive vs negative skin test results (grade 1, 46.7% vs 73.6%; grade 2, 33.3% vs 20.9%; grade 3, 20% vs 5.46%; P < .05). Three patients had cross-reactivity to 3 ICMs, all including ioversol and iomeprol. Six patients allergic to iopamidol tolerated ioversol and 1 tolerated iomeprol. Four patients allergic to ioversol and 1 allergic to iomeprol tolerated iopamidol. The global reaction rate was 0.2%, differing for each ICM (iopamidol, 0.14%; ioversol, 0.2%; and iomeprol, 0.4%; P < .001). Positive skin test results were found in a low percentage of patients in whom skin test–based CCT identified an alternative non–cross-reactive ICM. Low-grade cross-reactivity was found, especially between iopamidol and ioversol. Reactions were more severe in patients with positive skin test results. The reaction rate was greater for iomeprol compared with iopamidol (reaction rate, 2.8%) and ioversol (reaction rate, 2%).ConclusionsThis study identified a possible underlying specific IgE-mediated mechanism by positive skin test result in a low percentage of patients with IHRs to ICMs. In these patients, the CCT based on skin test results was useful for identifying an alternative non–cross-reactive ICM. More studies are needed to investigate the underlying mechanism in patients with IHRs and negative skin test results.
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Successful perinatal management of hereditary angioedema with normal C1 esterase inhibitor and factor XII mutation using C1 esterase inhibitor therapy
Source:Annals of Allergy, Asthma & Immunology
Author(s): Kathleen R. Gibbons, Tina Abraham, Monica Sandhu, Brian P. Peppers, Julia F. Girzhel, Robert W. Hostoffer
http://ift.tt/2fTyrH3
Supraglottoplasty for laryngomalacia: The experience from Concepcion, Chile
Publication date: Available online 7 October 2017
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Sahba Sedaghat, Felipe Fredes, Mario Tapia
ObjectiveTo review the clinical manifestations and outcomes of supraglottoplasty in patients with moderate to severe laryngomalacia at Guillermo Grant Benavente Hospital between January 2015 and January 2017.MethodsRetrospective study of patients with laryngomalacia who underwent CO2 laser supraglottoplasty at a tertiary referral center. A review of medical records of these patients was performed. Epidemiological data along with symptoms, comorbidities, morphological type of laryngomalacia, synchronous airway lesions, surgery outcomes and satisfaction of parents after the procedure were recorded. Surgical success was defined as the resolution of the criteria of severity of laryngomalacia.ResultsTwenty-four patients were operated, 1 was excluded due to prior tracheostomy. Twenty-three patients were included, the median age at the time of surgery was 5.5 months. All the patients had stridor, 87% presented feeding difficulties, 34.8 % had cyanosis and 21.7% had failure to thrive. Six cases had congenital anomalies and four cases had nongenetic comorbidities. Fifteen patients (65.2%) had synchronous airway lesions. 17.4% had type I laryngomalacia and 82.6% were type 2. The postoperative average hospital stay was 1.3 days. The average follow-up was 14 months and no complications were reported. The overall success rate of surgery was 95%.ConclusionsPatients with laryngomalacia and any symptom of severity should undergo a full airway evaluation, to rule out synchronous airway lesions, and supraglottoplasty if needed, as it has been shown to be a safe and effective technique for the management of these patients.
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Pain control following tonsillectomy in children: A survey of patients
Publication date: Available online 7 October 2017
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Philip Persino, Lena Saleh, David Walner
ObjectiveThis prospective study aimed to survey pediatric patients and their parents after tonsillectomy to assess their pain management utilization and satisfaction.IntroductionTonsillectomy is the second most common surgical procedure performed in pediatric patients. Postoperative recovery is often associated with high levels of pain and severe functional limitations. There is currently no consensus on pain control regimens. Additionally, a recent FDA Black Box Warning on narcotic use has caused more uncertainty in appropriate pain control regimens.Methods111 pediatric patients (≤18 years) included in this study underwent tonsillectomy with or without adenoidectomy between October 2013 and August 2015. Postoperatively, each patient/parent was counseled to alternate on an over-the-counter regimen of acetaminophen and ibuprofen and given an additional as-needed acetaminophen with hydrocodone prescription. A survey was administered during the patient's 2-week follow-up that included questions regarding pain levels, worst post-op pain day, pain medications taken during recovery, and patient/parental perceived satisfaction of having the acetaminophen with hydrocodone prescription.Results84 patients/parents (75.7%) felt that OTC medications were not adequate for pain control and used hydrocodone at least once. Between those who took hydrocodone versus those who did not, there was no significant difference in mean age (6.7 ± 2.9 vs. 6.0 ± 2.4 years), percentage of patients with severe pain (36.9% vs. 22.2%) and worst post-op pain day (4.3 ± 1.5 vs. 3.9 ± 1.9 days) (p > 0.05). However, regardless of pain control regimen followed, the majority of patients/parents found it valuable to have the hydrocodone prescription (p = 0.004).ConclusionPost-tonsillectomy patients and their parents find being provided with an acetaminophen-hydrocodone prescription is therapeutically valuable, and many find it necessary in their postoperative pain management. However, further studies are needed to determine patient factors that influence narcotic utilization.
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Direct tracheobronchopexy via left lateral thoracotomy for severe tracheobronchomalacia
Publication date: Available online 7 October 2017
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Evan J. Propst, Faisal Zawawi, Roxanne E. Kirsch, Osami Honjo
An infant with pulmonary atresia/ventricular septal defect/major aortopulmonary collateral arteries underwent unifocalization, ventriculoseptal defect closure and placement of a right ventricle to pulmonary artery conduit via median sternotomy. Aortopexy and pulmonary arteriopexy via redo sternotomy were insufficient to allow weaning of continuous positive airway pressure and he required direct tracheobronchopexy via left lateral thoracotomy to alleviate posterior trachealis intrusion along the length of the trachea and left main bronchus. He also underwent laryngotracheoplasty with placement of a posterior costal cartilage graft for bilateral vocal cord paralysis. The patient was weaned from positive pressure and discharged in stable condition.
http://ift.tt/2fVOvrK
Structural requirements of flavonoids to induce heme oxygenase-1 expression
Publication date: December 2017
Source:Free Radical Biology and Medicine, Volume 113
Author(s): K.D. Croft, D. Zhang, R. Jiang, A. Ayer, S. Shengule, R.J. Payne, N.C. Ward, R. Stocker
Population studies suggest cardiovascular health benefits of consuming fruits and vegetables rich in polyphenolic compounds such as flavonoids. We reported previously that the flavonoid quercetin protects arteries from oxidant-induced endothelial dysfunction and attenuates atherosclerosis in apolipoprotein E gene knockout mice, with induction of heme oxygenase-1 (Hmox1) playing a critical role. The present study investigated the structural requirements of flavonoids to induce Hmox1 in human aortic endothelial cells (HAEC). We identified ortho-dihydroxyl groups and an α,β-unsaturated system attached to a catechol as the key structural requirements for Hmox1 induction. Active but not inactive flavonoids had a low oxidation potential and prevented ascorbate autoxidation, suggesting that Hmox1 inducers readily undergo oxidation and that oxidized, rather than reduced, flavonoids may be the biological inducer of Hmox1. To test this hypothesis, we synthesized stable derivatives of caffeic acid (3-(3,4-dihyroxyphenyl)-2-propenoic acid) containing either ortho-dihydroxy or ortho-dioxo groups. Compared with the dihydroxy compound, the quinone analog induced Hmox1 more potently in HAEC and also provided enhanced protection to arteries of wild type animals against oxidant-induced endothelial dysfunction. In contrast, the quinone analog failed to provide protection against oxidant-induced endothelial dysfunction in arteries of Hmox1–/– mice, establishing a key role for Hmox1 in vascular protection. These results suggest that oxidized forms of dietary polyphenols are the likely inducers of Hmox1 and may explain in part the protective cardiovascular effects of diets rich in these compounds.
Graphical abstract
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UCP2 inhibition induces ROS/Akt/mTOR axis: Role of GAPDH nuclear translocation in genipin/everolimus anticancer synergism
Publication date: December 2017
Source:Free Radical Biology and Medicine, Volume 113
Author(s): Ilaria Dando, Raffaella Pacchiana, Elisa Dalla Pozza, Ivana Cataldo, Stefano Bruno, Paola Conti, Marco Cordani, Anna Grimaldi, Giovanna Butera, Michele Caraglia, Aldo Scarpa, Marta Palmieri, Massimo Donadelli
Several studies indicate that mitochondrial uncoupling protein 2 (UCP2) plays a pivotal role in cancer development by decreasing reactive oxygen species (ROS) produced by mitochondrial metabolism and by sustaining chemoresistance to a plethora of anticancer drugs. Here, we demonstrate that inhibition of UCP2 triggers Akt/mTOR pathway in a ROS-dependent mechanism in pancreatic adenocarcinoma cells. This event reduces the antiproliferative outcome of UCP2 inhibition by genipin, creating the conditions for the synergistic counteraction of cancer cell growth with the mTOR inhibitor everolimus. Inhibition of pancreatic adenocarcinoma cell growth and induction of apoptosis by genipin and everolimus treatment are functionally related to nuclear translocation of the cytosolic glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH). The synthetic compound (S)-benzyl-2-amino-2-(S)-3-bromo-4,5-dihydroisoxazol-5-yl-acetate (AXP3009), which binds GAPDH at its redox-sensitive Cys152, restores cell viability affected by the combined treatment with genipin and everolimus, suggesting a role for ROS production in the nuclear translocation of GAPDH. Caspase-mediated apoptosis by genipin and everolimus is further potentiated by the autophagy inhibitor 3-methyladenine revealing a protective role for Beclin1-mediated autophagy induced by the treatment. Mice xenograft of pancreatic adenocarcinoma further confirmed the antiproliferative outcome of drug combination without toxic effects for animals. Tumor masses from mice injected with UCP2 and mTOR inhibitors revealed a strong reduction in tumor volume and number of mitosis associated with a marked GAPDH nuclear positivity. Altogether, these results reveal novel mechanisms through which UCP2 promotes cancer cell proliferation and support the combined inhibition of UCP2 and of Akt/mTOR pathway as a novel therapeutic strategy in the treatment of pancreatic adenocarcinoma.
http://ift.tt/2fVVD7J
Redox imbalance due to the loss of mitochondrial NAD(P)-transhydrogenase markedly aggravates high fat diet-induced fatty liver disease in mice
Publication date: December 2017
Source:Free Radical Biology and Medicine, Volume 113
Author(s): Claudia D.C. Navarro, Tiago R. Figueira, Annelise Francisco, Genoefa A. Dal'Bó, Juliana A. Ronchi, Juliana C. Rovani, Cecilia A.F. Escanhoela, Helena C.F. Oliveira, Roger F. Castilho, Anibal E. Vercesi
The mechanisms by which a high fat diet (HFD) promotes non-alcoholic fatty liver disease (NAFLD) appear to involve liver mitochondrial dysfunctions and redox imbalance. We hypothesized that a HFD would increase mitochondrial reliance on NAD(P)-transhydrogenase (NNT) as the source of NADPH for antioxidant systems that counteract NAFLD development. Therefore, we studied HFD-induced liver mitochondrial dysfunctions and NAFLD in C57Unib.B6 congenic mice with (Nnt+/+) or without (Nnt-/-) NNT activity; the spontaneously mutated allele (Nnt-/-) was inherited from the C57BL/6J mouse substrain. After 20 weeks on a HFD, Nnt-/- mice exhibited a higher prevalence of steatohepatitis and content of liver triglycerides compared to Nnt+/+ mice on an identical diet. Under a HFD, the aggravated NAFLD phenotype in the Nnt-/- mice was accompanied by an increased H2O2 release rate from mitochondria, decreased aconitase activity (a redox-sensitive mitochondrial enzyme) and higher susceptibility to Ca2+-induced mitochondrial permeability transition. In addition, HFD led to the phosphorylation (inhibition) of pyruvate dehydrogenase (PDH) and markedly reduced the ability of liver mitochondria to remove peroxide in Nnt-/- mice. Bypass or pharmacological reactivation of PDH by dichloroacetate restored the peroxide removal capability of mitochondria from Nnt-/- mice on a HFD. Noteworthy, compared to mice that were chow-fed, the HFD did not impair peroxide removal nor elicit redox imbalance in mitochondria from Nnt+/+ mice. Therefore, HFD interacted with Nnt mutation to generate PDH inhibition and further suppression of peroxide removal. We conclude that NNT plays a critical role in counteracting mitochondrial redox imbalance, PDH inhibition and advancement of NAFLD in mice fed a HFD. The present study provide seminal experimental evidence that redox imbalance in liver mitochondria potentiates the progression from simple steatosis to steatohepatitis following a HFD.
Graphical abstract
http://ift.tt/2y8Ekuu
Modulating microfibrillar alignment and growth factor stimulation to regulate mesenchymal stem cell differentiation
Publication date: Available online 7 October 2017
Source:Acta Biomaterialia
Author(s): Dinorath Olvera, Binulal N. Sathy, Simon F. Carroll, Daniel J. Kelly
The ideal tissue engineering (TE) strategy for ligament regeneration should recapitulate the bone – calcified cartilage – fibrocartilage – soft tissue interface. Aligned electrospun-fibers have been shown to guide the deposition of a highly organized extracellular matrix (ECM) necessary for ligament TE. However, recapitulating the different tissues observed in the bone-ligament interface using such constructs remains a challenge. This study aimed to explore how fiber alignment and growth factor stimulation interact to regulate the chondrogenic and ligamentous differentiation of mesenchymal stem cells (MSCs). To this end aligned and randomly-aligned electrospun microfibrillar scaffolds were seeded with bone marrow derived MSCs and stimulated with transforming growth factor β3 (TGFβ3) or connective tissue growth factor (CTGF), either individually or sequentially. Without growth factor stimulation, MSCs on aligned-microfibers showed higher levels of tenomodulin (TNMD) and aggrecan gene expression compared to MSCs on randomly-oriented fibers. MSCs on aligned-microfibers stimulated with TGFβ3 formed cellular aggregates and underwent robust chondrogenesis, evidenced by increased type II collagen expression and sulphated glycosaminoglycans (sGAG) synthesis compared to MSCs on randomly-oriented scaffolds. Bone morphogenetic protein 2 (BMP2) and type I collagen gene expression were higher on randomly-oriented scaffolds stimulated with TGFβ3, suggesting this substrate was more supportive of an endochondral phenotype. In the presence of CTGF, MSCs underwent ligamentous differentiation, with increased TNMD expression on aligned compared to randomly aligned scaffolds. Upon sequential growth factor stimulation, MSCs expressed types I and II collagen and deposited higher overall levels of collagen compared to scaffolds stimulated with either growth factor in isolation. These findings demonstrate that modulating the alignment of microfibrillar scaffolds can be used to promote either an endochondral, chondrogenic, fibro-chondrogenic or ligamentous MSC phenotype upon presentation of appropriate biochemical cues.Statement of significancePolymeric electrospun fibers can be tuned to match the fibrillar size and anisotropy of collagen fibers in ligaments, and can be mechanically competent. Therefore, their use is attractive when attempting to tissue engineer the bone-ligament interface. A central challenge in this field is recapitulating the cellular phenotypes observed across the bone-ligament interface. Here we demonstrated that it is possible to direct MSCs seeded onto aligned electrospun fibres towards either a ligamentogenic, chondrogenic or fibrochondrogenic phenotype upon presentation of appropriate biochemical cues. This opens the possibility of using aligned microfibrillar scaffolds that are spatially functionalized with specific growth factors to direct MSC differentiation for engineering the bone-ligament interface.
Graphical abstract
http://ift.tt/2y8CYj2
A comprehensive review of non-enterica subspecies of Salmonella enterica
Publication date: Available online 7 October 2017
Source:Microbiological Research
Author(s): Alexandre Lamas, José Manuel Miranda, Patricia Regal, Beatriz Vázquez, Carlos Manuel Franco, Alberto Cepeda
Salmonella is a major foodborne pathogen with a complex nomenclature. This genus is composed of two species, S. enterica and S. bongori. S. enterica is divided into six subspecies. S. enterica subspecies enterica is composed of more than 1,500 serotypes with some of great importance, such as S. Typhimurium and S. Enteritidis. S. enterica subsp. enterica is responsible of more than 99% of human salmonellosis and therefore it is widely studied. However, the non-enterica subspecies of S. enterica have been little studied. These subspecies are considered to be related to cold-blooded animals and their pathogenicity is very limited. Phenotype and genotype information generated from different studies of non-enterica subspecies reveal poor ability to invade host cells and the absence or modification of important virulence factors. Also, the great majority of human infections due to non-enterica subspecies are related to a previous depressed immune system. Therefore, we propose to treat these subspecies only as opportunistic pathogens. For establish this premise, the present review evaluated, among other things, the genomic characteristics, prevalence, antimicrobial resistance and reported human cases of the non-enterica subspecies.
http://ift.tt/2xpqQLw
Automated segmentation of abdominal subcutaneous adipose tissue and visceral adipose tissue in obese adolescent in MRI
Source:Magnetic Resonance Imaging
Author(s): Steve C.N. Hui, Teng Zhang, Lin Shi, Defeng Wang, Chei-Bing Ip, Winnie C.W. Chu
PurposeTo develop a reliable and reproducible automatic technique to segment and measure SAT and VAT based on MRI.Materials and methodsChemical-shift water-fat MRI were taken on twelve obese adolescents (mean age: 16.1±0.6, BMI: 31.3±2.3) recruited under the health monitoring program. The segmentation applied a spoke template created using Midpoint Circle algorithm followed by Bresenham's Line algorithm to detect narrow connecting regions between subcutaneous and visceral adipose tissues. Upon satisfaction of given constrains, a cut was performed to separate SAT and VAT. Bone marrow was consisted in pelvis and femur. By using the intensity difference in T2*, a mask was created to extract bone marrow adipose tissue (MAT) from VAT. Validation was performed using a semi-automatic method. Pearson coefficient, Bland-Altman plot and intra-class coefficient (ICC) were applied to measure accuracy and reproducibility.ResultsPearson coefficient indicated that results from the proposed method achieved high correlation with the semi-automatic method. Bland-Altman plot and ICC showed good agreement between the two methods. Lowest ICC was obtained in VAT segmentation at lower regions of the abdomen while the rests were all above 0.80. ICC (0.98–0.99) also indicated the proposed method performed good reproducibility.ConclusionNo user interaction was required during execution of the algorithm and the segmented images and volume results were given as output. This technique utilized the feature in the regions connecting subcutaneous and visceral fat and T2* intensity difference in bone marrow to achieve volumetric measurement of various types of adipose tissue in abdominal site.
http://ift.tt/2z6uAyN
An Augmented Reality Magic Mirror as Additive Teaching Device for Gross Anatomy
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Daniela Kugelmann, Leonard Stratmann, Nils Nühlen, Felix Bork, Saskia Hoffmann, Golbarg Samarbarksh, Anna Pferschy, Anna Maria von der Heide, Andreas Eimannsberger, Pascal Fallavollita, Nassir Navab, Jens Waschke
When preparing young medical students for clinical activity, it is indispensable to acquaint them with anatomical section images which enable them to use the clinical application of imaging methods A new Augmented Reality Magic Mirror (AR MM) system, which provides the advantage of a novel, interactive learning tool in addition to a regular dissection course, was therefore tested and evaluated by 880 first-year medical students as part of the macroscopic anatomy course in 2015/16 at Ludwig-Maximilians-Universität (LMU) in Munich. The system consists of an RGB-D sensor as a real-time tracking device, which enables the system to link a deposited section image to the projection of the user's body, as well as a large display mimicking a real-world physical mirror. Using gesture input, the users have the ability to interactively explore radiological images in different anatomical intersection planes. We designed a tutorial during which students worked with the system in groups of about 12 and evaluated the results. Subsequently, each participant was asked to assess the system's value by filling out a Likert-scale questionnaire. The respondents approved all statements which stressed the potential of the system to serve as an additional learning resource for anatomical education. In this case, emphasis was put on active learning, 3-dimensional understanding, and a better comprehension of the course of structures. We are convinced that such an AR MM system can be beneficially installed into anatomical education in order to prepare medical students more effectively for the clinical standards and for more interactive, student-centered learning.
http://ift.tt/2y2hjcE
A preliminary study to design a floating treatment wetland for remediating acid mine drainage-impacted water using vetiver grass ( Chrysopogon zizanioides )
Abstract
Acid mine drainage (AMD) is extremely acidic, sulfate-rich effluent from abandoned or active mine sites that also contain elevated levels of heavy metals. Untreated AMD can contaminate surface and groundwater and pose severe ecological risk. Both active and passive methods have been developed for AMD treatment consisting of abiotic and biological techniques. Abiotic techniques are expensive and can create large amounts of secondary wastes. Passive biological treatment mainly consists of aerobic or anaerobic constructed wetlands. While aerobic wetlands are economical, they are not effective if the pH of the AMD is < 5. Anaerobic wetlands use organic-rich substrates to provide carbon source to iron- and sulfate-reducing bacteria. The efficiency of these systems declines overtime and requires continuous maintenance. Our objective is to develop an alternative, low-cost, and sustainable floating wetland treatment (FWT) system for AMD for the abandoned Tab-Simco coal mining site in Illinois using vetiver grass (Chrysopogon zizanioides). Tab-Simco AMD is highly acidic, with mean pH value of 2.64, and contains high levels of sulfate and metals. A greenhouse study was performed for a 30-day period in order to screen and optimize the necessary parameters to design a FWT system. Water quality and plant growth parameters were continuously monitored. Results show significant SO42− removal, resulting in increased pH, particularly at higher planting densities. Vetiver also helped in metal removal; high amounts of Fe, Zn, and Cu were removed, with relatively lower amounts of Pb, Al, and Ni. Iron plaque formation on the root was observed, which increased metal stabilization in root and lowered root to shoot metal translocation. Vetiver was tolerant of AMD, showing minimal change in biomass and plant growth. Results obtained are encouraging, and a large scale mesocosm study is now in progress, as the next step to develop the vetiver-based system for AMD treatment.
http://ift.tt/2xqypg1
Organic horizon and mineral soil mercury along three clear-cut forest chronosequences across the northeastern USA
Abstract
Mercury (Hg) is a globally distributed pollutant trace metal that has been increasing in terrestrial environments due to rising anthropogenic emissions. Vegetation plays an important role in Hg sequestration in forested environments, but increasing tree removal for biofuels and wood products may affect this process. The long-term effect of clear-cutting on forest soil Hg remains uncertain, since most studies are limited to measuring changes for < 10 years following a single harvest event. The chronosequence approach, which substitutes space for time using forest stands of different ages since clear-cutting, allows for investigation of processes occurring over decades to centuries. Here, we utilized three clear-cut forest soil chronosequences across the northeastern USA to understand Hg accumulation and retention over several decades. Total Hg concentrations and pools were quantified for five soil depth increments along three chronosequences. Our results showed Hg concentrations and pools decreased in the initial 20 years following clear-cutting. Mineral soil Hg pools decreased 21–53% (7–14 mg m−2) between 1–5-year-old stands and 15–25-year-old stands but mineral soil Hg pools recovered in 55–140-year-old stands to similar values as measured in 1–5-year-old stands. Our study is one of the first to demonstrate a decrease and recovery in Hg pool size. These changes in Hg did not correspond with changes in bulk density, soil C, or pH. We utilized a simple two-box model to determine how different Hg fluxes affected organic and mineral soil horizon Hg pools. Our simple model suggests that changes in litterfall and volatilization rates could have caused the observed changes in organic horizon Hg pools. However, only increases in leaching could reproduce observed decreases to mineral soil Hg pools. Further studies are needed to determine the mechanism of Hg loss from forest soils following clear-cutting.
http://ift.tt/2wFhGpZ
Turning an environmental problem into an opportunity: potential use of biochar derived from a harmful marine biomass named Cladophora glomerata as anode electrode for Li-ion batteries
Abstract
The electrochemical performance of lithium ion battery was enhanced by using biochar derived from Cladophora glomerata (C. glomerata) as widespread green macroalgae in most areas of the Iran's Caspian sea coast. By the utilization of the structure of the biochar, micro-/macro-ordered porous carbon with olive-shaped structure was successfully achieved through pyrolysis at 500 °C, which is the optimal temperature for biofuel production, and was activated with HCl. The biochar and HCl treatment biochar (HTB) were applied as anode electrode in lithium ion batteries. Then, electrochemical measurements were conducted on the electrodes via galvanostatic charge–discharge, cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) analyses. The electrochemical results indicated a higher specific discharge capacity (700 mAh g−1) and good cycling stability for HTB at the current density of 0.1 A g−1 as compared to the biochar. The reason that HTB electrode works better than the biochar could be due to the higher surface area, formation functional groups, removal impurities, and formation some micropores after HCl treatment. The biochar derived from marine biomass and treatment process developed here could provide a promising path for the low-cost, renewable, and environmentally friendly electrode materials.
Graphical abstract
http://ift.tt/2xqOJNX
Pitfalls and errors in measuring jitter
Publication date: November 2017
Source:Clinical Neurophysiology, Volume 128, Issue 11
Author(s): Erik Stålberg, Donald B. Sanders, João Aris Kouyoumdjian
The safety factor of neuromuscular transmission can be assessed by measuring the neuromuscular jitter, which reflects the time variability of processes in the motor end-plate. Jitter is increased in any condition with disturbed end-plate function, such as myasthenic conditions and ongoing reinnervation. Jitter is increasingly being measured with concentric needle (CN) electrodes, which are more prone to artefacts than single fiber EMG recordings.The objective of this review is to identify and demonstrate pitfalls that can be seen with CN jitter measurements, made with both voluntary activation and electrical stimulation.With voluntary activation, errors are caused by poor signal quality; inappropriate time reference points on the signal; an irregular firing rate; and signals with dual latencies, i.e., "flip-flop." With electrical stimulation, additional errors result from insufficient stimulation intensity; from abrupt change in firing rate; and from axon reflexes.Many pitfalls cannot be avoided during recording and can only be detected during post-processing.It is critical to be aware of these artefacts when measuring jitter with CN electrodes.
http://ift.tt/2xqOEtL
Eye movements in genetic parkinsonisms affecting the α-synuclein, PARK9, and manganese network
Source:Clinical Neurophysiology
Author(s): Elena Pretegiani, Francesca Rosini, Antonio Federico, Lance M. Optican, Alessandra Rufa
http://ift.tt/2wEMyGZ
Efficacy of long pulse Nd:YAG laser versus fractional Er:YAG laser in the treatment of hand wrinkles
Abstract
There are different modalities for hand rejuvenation. Fractional Er:YAG laser and long pulse Nd:YAG laser were introduced for treating hand wrinkles. We plan to compare fractional Er:YAG laser and long pulse Nd:YAG laser in a randomized controlled double-blind design with multiple sessions and larger sample size in comparison with previous studies. Thirty-three participants with hand wrinkles entered this study. They were randomly allocated to undergo three monthly laser treatments on each hand, one with a fractional Er:YAG laser and the other with a long pulse Nd:YAG laser. The evaluations included assessment of clinical improvement determined by two independent dermatologists not enrolled in the treatment along with measuring skin biomechanical property of hands using a sensitive biometrologic device with the assessment of cutaneous resonance running time (CRRT). Moreover, potential side effects and patients' satisfaction have been documented at baseline, 1 month after each treatment, and 3 months after the final treatment session. Clinical evaluation revealed both modalities significantly reduce hand wrinkles (p value < 0.05), with no significant difference between two lasers. Mean CRRT values also decreased significantly after the laser treatment compared to those of the baseline in both laser groups. There was no serious persistent side effect after both laser treatments. Both fractional Er:YAG and long pulse Nd:YAG lasers show substantial clinical improvement of hand skin wrinkles with no serious side effects. However, combination treatment by these lasers along with the other modalities such as fat transfer could lead to better outcomes in hand rejuvenation. Trial registration: IRCT2016032020468N4
http://ift.tt/2wEvnVZ
Effects of supramaximal balloon dilatation pressures on adult cricoid and tracheal cartilage: A cadaveric study
Objectives/Hypothesis
Cricoid fracture is a serious concern for balloon dilatation in airway stenosis. Furthermore, there are no studies examining tracheal rupture in balloon dilatation of stenotic segments. The aim of this study was to evaluate the effect of supramaximal pressures of balloons on the cricoid and tracheal rings.
Study Design
Prospective cadaveric study.
Methods
Seven cadaveric laryngotracheal complexes of normal adults with intact cricothyroid membranes were acquired. Noncompliant vascular angioplasty balloons (BARD-VIDA) were used for dilatation. The subglottis and trachea were subjected to supramaximal dilatation pressures graduated to nominal burst pressure (NBP) and, if necessary, rated burst pressure (RBP). Larger-diameter balloons, starting from 18 mm size to 24 mm, were used. Dilatations were maintained for 3 minutes.
Results
The cricoid ring was disrupted by larger-diameter balloons (22 mm and 24 mm) even at lower pressures (less than NBP) in six cases. Tracheal cartilages were very distensible, and external examination after supramaximal dilatation (24 mm close to RBP) revealed no obvious cartilage fractures or trachealis tears. Histopathological examination revealed sloughing of mucosa in the areas corresponding to balloon placement, but no microfractures or disruption of the perichondrium of tracheal ring cartilages.
Conclusions
These results indicate that the cricoid is vulnerable to injury from larger balloons even at lower dilatation pressures. The tracheal cartilages and the membranous wall of the trachea remained resilient to supramaximal dilatation and larger balloons.
Level of Evidence
NA Laryngoscope, 2017
http://ift.tt/2kwDvGv
Upper esophageal sphincter augmentation reduces pharyngeal reflux in nasogastric tube–fed patients
Objectives/Hypothesis
Aspiration of gastric refluxate is one of the most commonly observed complications among long-term nasogastric tube (NGT) fed patients. The upper esophageal sphincter (UES) pressure barrier is the main defense mechanism against pharyngeal reflux of gastric contents. Our objective was to investigate the efficacy and safety of the UES assist device (UES-AD) in preventing gastric reflux through the UES in long-term NGT-fed patients.
Study Design
Self-Controlled Case series.
Methods
We studied 10 patients (mean age = 90.6 ± 3.4 years, four females) with dysphagia caused by stroke or dementia who were fed for 0.5 to 5 years (median = 3 years) by NGT. External pressures of 20 to 30 mm Hg were applied by using a handmade UES-AD, which was started 2 hours after the beginning of NGT infusion and was alternated between periods of 2 hours on and 2 hours off, for a total of 12 hours. Placement of the impedance sensors within the UES was guided by high-resolution manometry. Trans-UES and intraesophageal reflux events were recorded by using 24-hour combined pH-impedance measurements.
Results
No aspiration pneumonia events were noted in the period 1 month before or during the study in any of the cohort. Baseline UES pressure averaged 17.5 ± 9.4 mm Hg and was increased to 38.9 ± 11.9mm Hg after application of the UES-AD. Overall frequency of trans-UES reflux decreased significantly with the UES-AD compared to without (0.8 ± 0.9 vs. 3.3 ± 2.8, P < .05 for the 12-hour study period). There was no effect of the UES-AD on esophageal reflux events (7.4 ± 4.4 vs. 6.4 ± 3.0, P > .05).
Conclusions
UES-AD significantly decreases the number of trans-UES reflux events and can potentially reduce the aspiration risk associated with NGT feeding.
Level of Evidence
4. Laryngoscope, 2017
http://ift.tt/2wEtCIv
A prospective crossover trial of botulinum toxin chemodenervation versus injection augmentation for essential voice tremor
Objectives/Hypothesis
Botulinum toxin chemodenervation (BTX) is used to treat essential voice tremor (EVT), but results are not uniformly satisfactory. This study sought to assess the comparative utility of injection augmentation (IA) for EVT.
Study Design
Prospective crossover treatment study.
Methods
Patients with EVT underwent BTX. After washout patients underwent IA. Multidimensional assessment carried out prior to and 30 days after each treatment included 1) videostroboscopy graded by the Vocal Tremor Scoring System (VTSS), 2) acoustic and aerodynamic assessment (cepstral peak prominence, cepstral spectral index of dysphonia, cepstral peak prominence fundamental frequency, airflow, peak air pressure and intensity, maximum phonation time, and amplitude/frequency of tremor), 3) audio-perceptual assessment via Consensus Audio-Perceptual Evaluation of Voice (CAPE-V), and 4) patient self-assessment via Voice Handicap Index-10 (VHI-10) and Percent of Normal Function (PNF) scale. Findings were analyzed via paired t tests and Wilcoxon rank sum tests.
Results
Seven patients (five female and two male; mean age 67 years old; range, 46–82 years old) participated. VTSS grading showed divergent outcomes for certain individual sites of tremor, but without significant differences. Airflow increased following BTX and decreased following IA, and VHI-10 scores indicated slight improvement post-BTX (26.29–23.57), and decline post-IA (25.86–29.86), although differences were not significant. Only changes in audio-perceptual ratings of loudness achieved significance, which decreased with BTX and increased with IA. Five patients chose to resume BTX; two elected long-term IA. No findings supported patient preferences.
Conclusions
IA demonstrated no advantage over BTX in the treatment of EVT.
Level of Evidence
2b Laryngoscope, 2017
http://ift.tt/2kwWvog
Survival of renal cell carcinoma metastatic to nonthyroid head and neck region: A systematic review
Objective
Metastasis of renal cell carcinoma to nonthyroid head and neck region is rare. Survival benefit for complete metastasectomy of more common renal cell foci has been reported in the literature. It is uncertain whether metastasectomy in nonthyroid head and neck region would provide a similar benefit.
Data Sources
We conducted a retrospective review of all renal cell metastases to the head and neck region treated in the past 15 years at an academic hospital, and a systematic review of all relevant reports with survival data in the literature between 1960 and 2016.
Review Methods
An analysis of pooled data was performed to estimate overall survival.
Results
Six cases from our institution and 260 independent cases reported in the literature were included in the survival analyses (n = 266). The median follow-up time was 12 months (range 0–180 months). The overall median survival was 36 months (95% confidence interval [CI] 23.7–48.3). The median survival for those who underwent complete metastasectomy in the head and neck was significantly higher at 60 months (95% CI 41.1–78.9) than those who had incomplete or no metastasectomy (12 months, 95% CI 9.5–14.5). Multivariable Cox proportional hazards model estimated that, after controlling for potential confounders, complete metastasectomy remained associated with reduced risk of death (hazard ratio 0.44, 95% CI 0.29–0.69).
Conclusion
Complete metastasectomy was associated with 4-year longer median overall survival than incomplete metastasectomy or no metastasectomy. Laryngoscope, 2017
http://ift.tt/2wFv51i
Treatment, survival, and costs of oropharyngeal cancer care in the elderly
Objectives/Hypothesis
To examine associations between treatment, survival, and costs in elderly patients with oropharyngeal squamous cell cancer (OPSCC).
Study Design
Retrospective cross-sectional analysis of Surveillance, Epidemiology, and End Results–Medicare data.
Methods
We evaluated 666 patients diagnosed with OPSCC from 2004 to 2007 using cross-tabulations, multivariate logistic and generalized linear regression modeling, and survival analysis.
Results
The majority of patients were nonsmokers (79%), had advanced-stage disease (59%), and received chemoradiation (38%) or radiation (28%). Surgery with postoperative radiation (hazard ratio [HR]: 0.33 [95% CI: 0.20-0.53]) and chemoradiation (HR: 0.45 [95% CI: 0.29-0.71]) were associated with improved survival, whereas stage IV disease was associated with poorer survival (HR: 1.95 [95% CI: 1.13-3.38]). Additional cancer-directed treatment after primary treatment was more likely following chemoradiation (odds ratio [OR]: 3.44 [95% CI: 1.78-6.63]). Salvage surgery was performed in 25% of patients undergoing subsequent additional cancer-directed treatment, and was associated with high-volume hospitals (OR: 2.81 [95% CI: 1.07-7.74]). Additional radiation (HR: 0.47 [95% CI: 0.31-0.72]) and salvage surgery (HR: 0.61 [95% CI: 0.38-0.99]) were associated with improved overall survival when performed >6 months following initial treatment, whereas salvage neck dissection alone was not significantly associated with survival after controlling for time to salvage (HR: 0.38 [95% CI: 0.05-2.78]). Treatment and 5-year overall costs were highest for chemoradiation, surgery with postoperative radiation, and additional cancer-directed treatment.
Conclusions
Multimodality treatment in elderly OPSCC patients was associated with improved survival and increased costs. Chemoradiation was associated with an increased likelihood of additional cancer-directed treatment. Salvage surgery was centralized at high-volume hospitals, and was associated with improved survival when performed >6 months after last initial treatment date, but was performed in <20% of patients undergoing additional treatment.
Level of Evidence
2c Laryngoscope, 2017
http://ift.tt/2kzrNeq
Malignant fibrous histiocytoma: Database review suggests a favorable prognosis in the head and neck
Objective
The malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma of the head and neck. Currently, most of the data on this tumor relies on small retrospective studies. The objective of this study is to use the Surveillance, Epidemiology, and End Results (SEER) database to compare characteristics of this tumor based on location to better understand its prognosis in the head and neck region. This article represents the largest study analyzing prognosis of this tumor in the head and neck to date.
Study Design
Retrospective analysis of SEER database.
Methods
Using the SEER database, 395 patients with MFH of the head and neck were compared with 3,968 patients with MFH of the trunk and extremities. Disease-specific survival was carried out comparing these two cohorts, as well as univariate and multivariate analysis to determine hazard ratios.
Results
Head and neck MFH had a significantly higher disease-specific survival compared with trunk and extremity disease. However, head and neck tumors were more frequently a smaller size (P < .0001) and lower grade (P < .0001). Larger tumors and grade III and IV tumors conferred a worse prognosis (P < .0001).
Conclusion
Head and neck malignant fibrous histiocytoma presents at a smaller size and lower grade, likely due to earlier presentation in this region. Because of this, head and neck malignant fibrous histiocytoma represents a more favorable survival prognosis compared with trunk and extremity disease.
Level of Evidence
4. Laryngoscope, 2017
http://ift.tt/2wFuY5S
Positive fresh frozen section margins as an adverse independent prognostic factor for local recurrence in oral cancer patients
Objectives
To access 1) the value of further surgical resection (completion surgery) in cases with a positive intraoperative margin analysis, and 2) whether cancers that undergo completion surgery following positive intraoperative margin analysis with subsequent negative margins should be considered true margin-negative (R0) resections in terms of adjuvant treatment planning.
Study Design
Retrospective analysis of patients with primary oral cancer.
Methods
One hundred and fifty-one patients underwent primary surgical resection of oral squamous cell carcinoma with intraoperative margin examination. In all cases for which frozen section margin analysis was positive, an extended resection was performed. Only patients with clear final margins were included in the study.
Results
The intraoperative analysis of surgical margins revealed that cancer-free margins were achieved in 123 cases (81.5%). In 28 specimens (18.5%), the surgical margins were positive. Local recurrence was observed in 28 (18.5%) patients, whereas regional recurrence developed in 30 (19.9%) patients. Factors significantly (P < 0.05) increased the risk of local recurrence: advanced stage of the disease (III/IV), node N-positive status, lymphovascular invasion and positive fresh frozen surgical margins. On multivariate analysis, only positive fresh frozen surgical margins remained significant independent adverse factors.
Conclusion
Our study demonstrates that positive fresh frozen margins, regardless of re-resection to R0 status, could be a powerful adverse factor that determines an aggressive nature of the tumor. This feature should be taken into consideration in adjuvant treatment planning. The greatest impact this could have is in borderline clinical situations for which the indication for adjuvant treatment may be questionable.
Level of Evidence
4. Laryngoscope, 2017
http://ift.tt/2wFuQmU
Evidence against the mucosal traction theory in cholesteatoma
Objectives
To investigate the distribution of ciliated epithelium in the human middle ear and its potential role in the formation of cholesteatoma.
Study Design
Comparative human temporal bone study.
Methods
We selected temporal bones from 14 donors with a diagnosis of cholesteatoma, 15 with chronic otitis media without retraction pockets, 14 with chronic otitis media with retraction pockets, 14 with cystic fibrosis (CF), and 16 controls. We mapped the distribution of the ciliated cells in the mucosal lining of the middle ear and tympanic membrane using three-dimensional reconstruction analysis, and counted the number of ciliated cells in the middle ear mucosa.
Results
Ciliated cells are extremely sparse in the epithelial lining of the lateral surface of the ossicles in the epitympanum and the medial surface of the tympanic membrane. Furthermore, there is a significant decrease in the number of ciliated cells in these areas in temporal bones with cholesteatoma, chronic otitis media, chronic otitis media with retraction pockets, and CF compared to controls. Ciliated cells most commonly are located at the hypotympanum and the Eustachian tube opening but not the tympanic membrane or epitympanum.
Conclusion
The paucity of ciliated epithelial cells on the medial side of the tympanic membrane and the lateral surface of the ossicles in the epitympanum in cases with cholesteatoma and/or chronic otitis media do not support the mucosal migration theory of cholesteatoma formation.
Level of Evidence
NA. Laryngoscope, 2017
http://ift.tt/2kA3Fs7
Clinical utility of 18F-fluorodeoxyglucose/positron emission tomography in diagnosis of immunoglobulin G4–related sclerosing sialadenitis
Objectives/Hypothesis
The aim of this study was to evaluate the utility of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for accurately diagnosing immunoglobulin G4-related sclerosing sialadenitis (IgG4-SS).
Study Design
Retrospective cohort study.
Methods
We reviewed the records of 64 patients with IgG4-SS (35 male and 29 female patients) and 10 patients with clinically suspected IgG4-SS. Pathological diagnoses of patients clinically suspected with IgG4-SS included four cases of malignant lymphoma, one case of multicentric Castleman disease, one case of Sjögren's syndrome, and four cases of sialadenitis. All patients underwent submandibular gland (SMG) biopsies and baseline FDG-PET/CT evaluation. Clinical, serological, pathological, and PET/CT findings were analyzed. We also investigated maximum standardized uptake values (SUVmax) in the salivary glands of 15 patients with malignant disease of the salivary glands during the same period.
Results
Increased FDG uptake in the SMG and parotid gland was found in 63 (98%) and 23 (35%) patients with IgG4-SS, respectively. FDG uptake of the bilateral SMG and unilateral SMG was recorded in 57 patients (89%) and six patients (9%), respectively. Mean SUVmax in patients with malignant disease of the salivary glands was significantly higher than that in patients with IgG4-SS (P = .035). We defined a positive test for IgG4-SS diagnosis as high SMG FDG uptake and serum IgG4 level ≥135 mg/dL, resulting in a sensitivity, specificity, and accuracy of 96.9%, 90.0%, and 86.4%, respectively.
Conclusions
FDG-PET/CT findings in combination with serological and clinical findings may have the capacity to diagnose IgG4-SS and lead to less-invasive biopsy procedures.
Level of Evidence
4. Laryngoscope, 2017
http://ift.tt/2wEyZao