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Σάββατο, 30 Δεκεμβρίου 2017

Comparison of detection methods for HPV status as a prognostic marker for loco-regional control after radiochemotherapy in patients with HNSCC

To compare six HPV detection methods in pre-treatment FFPE tumour samples from patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who received postoperative (N = 175) or primary (N = 90) radiochemotherapy.

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Evaluation of Virtual Monoenergetic Imaging Algorithms for Dual-Energy Carotid and Intracerebral CT Angiography: Effects on Image Quality, Artefacts and Diagnostic Performance for the Detection of Stenosis

Publication date: Available online 30 December 2017
Source:European Journal of Radiology
Author(s): Doris Leithner, Scherwin Mahmoudi, Julian L. Wichmann, Simon S. Martin, Lukas Lenga, Moritz H. Albrecht, Christian Booz, Christophe T. Arendt, Martin Beeres, Tommaso D'Angelo, Boris Bodelle, Thomas J. Vogl, Jan-Erik Scholtz
PurposeTo investigate the impact of traditional (VMI) and noise-optimized virtual monoenergetic imaging (VMI+) algorithms on quantitative and qualitative image quality, and the assessment of stenosis in carotid and intracranial dual-energy CTA (DE-CTA).Materials and methodsDE-CTA studies of 40 patients performed on a third-generation 192-slice dual-source CT scanner were included in this retrospective study. 120-kVp image-equivalent linearly-blended, VMI and VMI+ series were reconstructed. Quantitative analysis included evaluation of contrast-to-noise ratios (CNR) of the aorta, common carotid artery, internal carotid artery, middle cerebral artery, and basilar artery. VMI and VMI+ with highest CNR, and linearly-blended series were rated qualitatively. Three radiologists assessed artefacts and suitability for evaluation at shoulder height, carotid bifurcation, siphon, and intracranial using 5-point Likert scales. Detection and grading of stenosis were performed at carotid bifurcation and siphon.ResultsHighest CNR values were observed for 40-keV VMI+ compared to 65-keV VMI and linearly-blended images (P < 0.001). Artefacts were low in all qualitatively assessed series with excellent suitability for supraaortic artery evaluation at shoulder and bifurcation height. Suitability was significantly higher in VMI+ and VMI compared to linearly-blended images for intracranial and ICA assessment (P<0.002). VMI and VMI+ showed excellent accordance for detection and grading of stenosis at carotid bifurcation and siphon with no differences in diagnostic performance.Conclusion40-keV VMI+ showed improved quantitative image quality compared to 65-keV VMI and linearly-blended series in supraaortic DE-CTA. VMI and VMI+ provided increased suitability for carotid and intracranial artery evaluation with excellent assessment of stenosis, but did not translate into increased diagnostic performance.



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Specialized Plant Metabolism Characteristics and Impact on Target Molecule Biotechnological Production

Abstract

Plant secondary metabolism evolved in the context of highly organized and differentiated cells and tissues, featuring massive chemical complexity operating under tight environmental, developmental and genetic control. Biotechnological demand for natural products has been continuously increasing because of their significant value and new applications, mainly as pharmaceuticals. Aseptic production systems of plant secondary metabolites have improved considerably, constituting an attractive tool for increased, stable and large-scale supply of valuable molecules. Surprisingly, to date, only a few examples including taxol, shikonin, berberine and artemisinin have emerged as success cases of commercial production using this strategy. The present review focuses on the main characteristics of plant specialized metabolism and their implications for current strategies used to produce secondary compounds in axenic cultivation systems. The search for consonance between plant secondary metabolism unique features and various in vitro culture systems, including cell, tissue, organ, and engineered cultures, as well as heterologous expression in microbial platforms, is discussed. Data to date strongly suggest that attaining full potential of these biotechnology production strategies requires being able to take advantage of plant specialized metabolism singularities for improved target molecule yields and for bypassing inherent difficulties in its rational manipulation.



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A review of mathematical modeling and simulation of controlled-release fertilizers

Publication date: 10 February 2018
Source:Journal of Controlled Release, Volume 271
Author(s): Sayed Ameenuddin Irfan, Radzuan Razali, KuZilati KuShaari, Nurlidia Mansor, Babar Azeem, Ashlee N. Ford Versypt
Nutrients released into soils from uncoated fertilizer granules are lost continuously due to volatilization, leaching, denitrification, and surface run-off. These issues have caused economic loss due to low nutrient absorption efficiency and environmental pollution due to hazardous emissions and water eutrophication. Controlled-release fertilizers (CRFs) can change the release kinetics of the fertilizer nutrients through an abatement strategy to offset these issues by providing the fertilizer content in synchrony with the metabolic needs of the plants. Parametric analysis of release characteristics of CRFs is of paramount importance for the design and development of new CRFs. However, the experimental approaches are not only time consuming, but they are also cumbersome and expensive. Scientists have introduced mathematical modeling techniques to predict the release of nutrients from the CRFs to elucidate fundamental understanding of the dynamics of the release processes and to design new CRFs in a shorter time and with relatively lower cost. This paper reviews and critically analyzes the latest developments in the mathematical modeling and simulation techniques that have been reported for the characteristics and mechanisms of nutrient release from CRFs. The scope of this review includes the modeling and simulations techniques used for coated, controlled-release fertilizers.

Graphical abstract

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Enhanced antitumor and anti-metastasis efficacy against aggressive breast cancer with a fibronectin-targeting liposomal doxorubicin

Publication date: 10 February 2018
Source:Journal of Controlled Release, Volume 271
Author(s): Kejun Jiang, Xu Song, Liuqing Yang, Lin Li, Zhuoya Wan, Xun Sun, Tao Gong, Qing Lin, Zhirong Zhang
The chemotherapy of aggressive breast tumor is usually accompanied by a poor prognosis because of the metastasis of tumor cells. Thus, it is important to simultaneously enhance antitumor and anti-metastasis efficacy. Fibronectin and its complexes are expressed on the walls of tumor vessels and in tumor stroma. Moreover, the expression of fibronectin in metastatic sites is even higher than that in primary tumors. Herein, we designed a fibronectin-targeting CREKA-modified liposomal doxorubicin (CREKA-Lipo-Dox) for the therapy of metastatic breast tumor. CREKA-Lipo was uniformly formed with high entrapment efficiency. It exhibited longer blood circulation time compared with free Dox, and there was no significant change compared with PEG-Lipo-Dox. Immunofluorescence results revealed that the CREKA-Lipo-Dox could specifically bind to fibronectin in the tumor vessels and tumor stroma. The antitumor and anti-metastasis efficacy of CREKA-loaded liposome was more obvious than that of free Dox or unmodified Dox-Lipo. Taken together, binding fibronectin by CREKA could be an attractive therapeutic strategy for metastatic breast cancer in the future.

Graphical abstract

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Bacillus spore-based oral carriers loading curcumin for the therapy of colon cancer

Publication date: 10 February 2018
Source:Journal of Controlled Release, Volume 271
Author(s): Liang Yin, Zhan Meng, Yuxiao Zhang, Kaikai Hu, Wuya Chen, Kaibin Han, Bao-Yan Wu, Rong You, Chu-Hua Li, Ying Jin, Yan-Qing Guan
Oral drug delivery has attracted substantial attention due to its advantages over other administration routes. Bacillus spores, as oral probiotic agents, are applied widely. In this paper, a novel Bacillus spore-based oral colon targeted carrier loading curcumin was developed for colon cancer treatment. Curcumin was linked covalently with the outer coat of Bacillus spore and folate, respectively (SPORE-CUR-FA). Bacillus spores are capable of delivering drugs to the colon area through gastric barrier, taking the advantage of its tolerance to the harsh conditions and disintegration of the outer coat of spores after germination in the colon. The drug release in vitro and in vivo of SPORE-CUR-FA was investigated. Results showed that SPORE-CUR-FA had the characteristics of colon-targeted drug release. Pharmacokinetic studies confirmed that Bacillus spore-based carriers could efficiently improve the oral bioavailability of curcumin. In vitro and in vivo anti-tumor studies showed that SPORE-CUR-FA had substantial ability for inhibiting colon cancer cells. These findings suggest that this Bacillus spore-based oral drug delivery system has a great potential for the treatment of colon cancer.

Graphical abstract

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Combined electrical stimulation and exercise for swallow rehabilitation post-stroke: a pilot randomized control trial

Abstract

Background

Dysphagia is common after stroke, affecting up to 50% of patients initially. It can lead to post-stroke pneumonia, which causes 30% of stroke-related deaths, a longer hospital stay and poorer health outcomes. Dysphagia care post-stroke generally focuses on the management of symptoms, via modified oral intake textures and adapted posture, rather than direct physical rehabilitation of the swallowing function. Transcutaneous neuromuscular electrical stimulation (NMES) is a promising rehabilitation technology that can be used to stimulate swallowing; however, findings regarding efficacy have been conflicting.

Aims

This pilot randomized controlled study involving three UK sites compared the efficacy of the Ampcare Effective Swallowing Protocol (ESP), combining NMES with swallow-strengthening exercises, with usual care in order to clarify evidence on NMES in the treatment of dysphagia post-stroke. A further objective was to pilot recruitment procedures and outcome measures in order to inform the design of a full-scale trial.

Methods & Procedures

Thirty patients were recruited and randomized into either (1) usual speech and language therapy dysphagia care; or (2) Ampcare ESP, receiving treatment 5 days/week for 4 weeks. Outcome measures included: the Functional Oral Intake Scale (FOIS), the Rosenbek Penetration-Aspiration Scale (PAS) and patient-reported outcomes (Swallow Related Quality of Life—SWAL-QOL).

Outcomes & Results

Thirty patients were recruited; 15 were randomized to the Ampcare ESP intervention arm and 15 to usual care. A greater proportion (75%, or 9/12) of patients receiving Ampcare ESP improved compared with 57% (or 8/14) of the usual-care group. Patients receiving Ampcare ESP also made clinically meaningful change (a comparative benefit of 1.5 on the FOIS, and on the PAS: 1.35 for diet and 0.3 for fluids) compared with usual care. The intervention group also reported much better outcome satisfaction.

Conclusions & Implications

The pilot demonstrated successful recruitment, treatment safety and tolerability and clinically meaningful outcome improvements, justifying progression to a fully powered study. It also showed clinically meaningful treatment trends for the Ampcare ESP intervention.



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health technology; +150 new citations

150 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

health technology

These pubmed results were generated on 2017/12/30

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.



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The large mouth of largemouth bass is of interest to scientists trying to understand how joints work

Inside the bass’s mouth is a system of linked muscle and bone that resembles the mechanism of an oil rig. NYTimes:



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Posted at Clinical Cases and Images. Stay updated and subscribe, follow us on Twitter and connect on Facebook.


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Exploring the universe – and how we found our place in it

jf90c7-800x533.jpg

Enjoy the spectacular cosmos with this illustrated guide to astronomy, ranging from an iconic diagram by Copernicus to one of NASA's 2017 Jupiter photos

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Pilot study of parathyroid glands in adult and pediatric subjects exposed to ionizing radiation after the ChNPP accident, methodology of parathyroid diagnostic ultrasound.

Related Articles

Pilot study of parathyroid glands in adult and pediatric subjects exposed to ionizing radiation after the ChNPP accident, methodology of parathyroid diagnostic ultrasound.

Probl Radiac Med Radiobiol. 2017 Dec;22:382-394

Authors: Kaminskyi OV, Kopylova OV, Afanasyev DY, Mazurenko OV, Berezovskyi SY

Abstract
OBJECTIVE: Estimation of the parathyroid hyperplasia prevalence after the ChNPP accident in adults exposed to ion izing radiation and their descendants using the diagnostic ultrasound and its methodology elaboration.
MATERIALS AND METHODS: The pilot prospective study of the prevalence of parathyroid hyperplasia among the Chornobyl Nuclear Power Plant (ChNPP) accident adult survivors (n=686) and their descendants (54 children) was performed using diagnostic ultrasound examination of thyroid and parathyroids. Among the study subjects there were 339 ChNPP accident clean up workers (ACUW), 32 persons were evacuated from the 30 km exclusion zone and 224 ones were included to the control group. Diagnostic ultrasound of thyroid and parathyroids was performed according to the standard method. Additionally, in children with parathyroid hyperplasia an additional assay of 25 hydroxyvitamin D levels in serum was performed. In calculating the statistical significance, its level p < 0.05 was considered statistically significant.
RESULTS: Parathyroids are a few small but critically important endocrine glands that synthesize parathyroid hormone, regulating mainly phosphoric calcium metabolism. Insufficient (hypoparathyroidism) or excessive (hyperparathy roidism) function of parathyroids is harmful to the patients affecting the state of nervous and cardiovascular sys tem. Parathyroidss can accumulate isotopes of cesium, strontium and radioactive iodine. The available data testify to an increased incidence of clinically significant hyperplasia of parthyroids (more than 9 mm in adults and more than 5 mm in children) among persons exposed toionizng radiation as a result of the accident at the ChNPP (28.64%) and their descendants (23.8-70.6%). First of all are concerned those adults who live in contaminated areas in comparison with the control group (24.15% in not irradiated). Evacuees from the 30 km exclusion zone being the category of people who were exposed to the absorbed iodine isotopes in the first days of the Chernobyl accident are the another risk group. These data demonstrate sensitivity of parathyroidss to the impact of incorpo rated isotopes (iodine, cesium and strontium), which in the long term exposure create conditions for structural and functional changes in regulation of phosphorous calcium metabolism being the basis for a significant prevalence of osteopenia and osteoporosis in irradiated individuals and their descendants. A number of further studies are required to clarify the findings and to disclose the hormonal mechanisms of radiation effects on parathyroids.
CONCLUSIONS: Parathyroid glands are radiosensitive and susceptible to effects of strontium, cesium and iodine iso topes, which cause parathyroid irradiation and subsequent structural and functional changes, being a prerequisite for development of osteopenia and osteoporosis in the ChNPP accident survivors and their descendants. High inci dence of parathyroid hypertrophy is found in the inhabitants of the radiation contaminated territories (long term irradiation by cesium isotopes), as well as in evacuated from the 30 km exclusion zone (irradiation by iodine iso topes in the early days of the accident).

PMID: 29286522 [PubMed - in process]



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Cerebral impact of prenatal irradiation by 131I: an experimental model of clinical neuroradioembryological effects.

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Cerebral impact of prenatal irradiation by 131I: an experimental model of clinical neuroradioembryological effects.

Probl Radiac Med Radiobiol. 2017 Dec;22:238-269

Authors: Talko VV, Loganovsky KM, Drozd IP, Tukalenko YV, Loganovska TK, Nechayev SY, Masiuk SV, Prokhorova YM

Abstract
Human brain in prenatal period is a most vulnerable to ionizing radiation body structure. Unlike atomic bombings or radiological interventions in healthcare leading at most to external irradiation the intensive internal exposure may occur upon nuclear reactor accidents followed by substantial release and fallout of radioactive 131I. The latter can lead to specific neuroradioembryological effects.
OBJECTIVE: To create an experimental model of prenatal cerebral radiation effects of 131I in human and to determine the experimental and clinical neuroradioembryological effects.Study object. The neuroradioembryological effects in Vistar rats exposed to 131I in prenatal period. Nervous system status and mental status in 104 persons exposed to ionizing radiation in utero due to the ChNPP accident and the same in 78 not exposed subjects.
METHODS: Experimental i.e. behavioral techniques, including the spontaneous locomotive, exploratory activity and learning ability assessment, clinical i.e. neuropsychiatric, neuro and psychometric, neuropsychological, neurophys iological methods, both with dosimetric and statistical methods were applied.
RESULTS: Intrauterine irradiation of Wistar rats by 131I was simulated on a model of one time oral 27.5 kBq radionu clide administration in the mid gestation period (0.72±0.14 Gy fetal thyroid dose), which provides extrapolation of neuroradioembryological effects in rats to that in humans exposed to intrauterine radiation as a result of the Chornobyl catastrophe. Abnormalities in behavioral reactions and decreased output of conditioned reflex reactions identified in the 10 month old rats suggest a deterioration of cerebral cognition in exposed animals. Specific cog nitive deficit featuring a disharmonic intellectual development through the relatively decreased verbal intelligence versus relative increase of nonverbal one is remained in prenatally exposed persons. This can indicate to dysfunc tion of cortical limbic system with especial involvement of a dominant hemisphere hippocampus. Decreased theta band spectral power (4-7 Hz range) of cerebral bioelectrical activity in the left frontotemporal area is suggestive of hippocampal dysfunction mainly in dominant hemisphere of prenatally irradiated persons. Disorders of hippocam pal neurogenesis due to prenatal exposure by radioactive iodine can be a biologic basis here. Innovative approach es in social adaptation, psychoprophylaxis and psychorehabilitation involve the maximum effective application and development of just the most developed psychological and cognitive abilities in survivors.

PMID: 29286511 [PubMed - in process]



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Exploring the universe – and how we found our place in it

Enjoy the spectacular cosmos with this illustrated guide to astronomy, ranging from an iconic diagram by Copernicus to one of NASA's 2017 Jupiter photos

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Properties of global- and local-ancestry adjustments in genetic association tests in admixed populations

Abstract

Population substructure can lead to confounding in tests for genetic association, and failure to adjust properly can result in spurious findings. Here we address this issue of confounding by considering the impact of global ancestry (average ancestry across the genome) and local ancestry (ancestry at a specific chromosomal location) on regression parameters and relative power in ancestry-adjusted and -unadjusted models. We examine theoretical expectations under different scenarios for population substructure; applying different regression models, verifying and generalizing using simulations, and exploring the findings in real-world admixed populations. We show that admixture does not lead to confounding when the trait locus is tested directly in a single admixed population. However, if there is more complex population structure or a marker locus in linkage disequilibrium (LD) with the trait locus is tested, both global and local ancestry can be confounders. Additionally, we show the genotype parameters of adjusted and unadjusted models all provide tests for LD between the marker and trait locus, but in different contexts. The local ancestry adjusted model tests for LD in the ancestral populations, while tests using the unadjusted and the global ancestry adjusted models depend on LD in the admixed population(s), which may be enriched due to different ancestral allele frequencies. Practically, this implies that global-ancestry adjustment should be used for screening, but local-ancestry adjustment may better inform fine mapping and provide better effect estimates at trait loci.



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John R. Fowler Jr., Nandkumar M. Rawool: Ultrasound of the hand and upper extremity. A step-by-step guide : Thieme, New York Stuttgart Delhi Rio de Janeiro, 2018, 188 p., format 18 × 25.5 cm, ISBN 978-1-6262 -3688-2, eISBN 978-1-6262 -3887-9.

Related Articles

John R. Fowler Jr., Nandkumar M. Rawool: Ultrasound of the hand and upper extremity. A step-by-step guide : Thieme, New York Stuttgart Delhi Rio de Janeiro, 2018, 188 p., format 18 × 25.5 cm, ISBN 978-1-6262 -3688-2, eISBN 978-1-6262 -3887-9.

Surg Radiol Anat. 2017 Dec 28;:

Authors: Grignon B

PMID: 29285658 [PubMed - as supplied by publisher]



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Inter-individual variations and hemispheric asymmetries in structural connectivity patterns of the inferior fronto-occipital fascicle: a diffusion tensor imaging tractography study.

Related Articles

Inter-individual variations and hemispheric asymmetries in structural connectivity patterns of the inferior fronto-occipital fascicle: a diffusion tensor imaging tractography study.

Surg Radiol Anat. 2017 Dec 28;:

Authors: Vassal F, Pommier B, Sontheimer A, Lemaire JJ

Abstract
PURPOSE: Precise knowledge of the structural connectivity of white matter fascicles could yield new insights into function and is important for neurosurgical planning. Therefore, we aimed to provide a detailed map of the cortical terminations of the inferior fronto-occipital fascicle (IFOF), with special emphasis on putative inter-individual variations and hemispheric asymmetries.
METHODS: Deterministic diffusion tensor imaging-based tractography was used to perform virtual dissection of the IFOF in 20 healthy subjects. The IFOF was probed from a single seed region of interest placed within the external/extreme capsule, i.e. the white matter region of "obligatory passage" along the known path of the IFOF. This enabled to reconstruct all the fibers belonging to the IFOF and to provide the complete map of their cortical terminations.
RESULTS: We observed widespread projections over a total of 11 cortical territories within the occipital, parietal, temporal and frontal lobes. Importantly, compared to previous studies we consistently found some inter-individual variability with several distinct patterns connecting subsets of the 11 cortical territories, and tangible differences between the two hemispheres. IFOF terminations within the superior parietal lobule were rightward lateralized, whereas terminations within the inferior frontal gyrus were leftward lateralized.
CONCLUSIONS: Our results provide a clinically relevant map of IFOF's cortical terminations, including intra- and inter-individual variations. Right-left differences in connectivity patterns might be related to known functional asymmetries in the human brain, and reinforce the general evidence that the IFOF likely supports distinct clinical features and functional roles according to the (affected) hemisphere, such as language and spatial attention.

PMID: 29285657 [PubMed - as supplied by publisher]



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Optimising care in an age of austerity: patient-reported outcome measures in paediatric ENT, journal bias, tonsillectomy and endoscopic ear surgery.

Optimising care in an age of austerity: patient-reported outcome measures in paediatric ENT, journal bias, tonsillectomy and endoscopic ear surgery.

J Laryngol Otol. 2018 Jan;132(1):1

Authors: Fisher E, Youngs R, Hussain M, Fishman J

PMID: 29286000 [PubMed - in process]



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health technology; +150 new citations

150 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

health technology

These pubmed results were generated on 2017/12/30

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.



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Fractionation enhances acute oligodendrocyte progenitor cell radiation sensitivity and leads to long term depletion

Abstract

Ionizing radiation (IR) is commonly used to treat central nervous system (CNS) cancers and metastases. While IR promotes remission, frequent side effects including impaired cognition and white matter loss occur following treatment. Fractionation is used to minimize these CNS late side effects, as it reduces IR effects in differentiated normal tissue, but not rapidly proliferating normal or tumor tissue. However, side effects occur even with the use of fractionated paradigms. Oligodendrocyte progenitor cells (OPCs) are a proliferative population within the CNS affected by radiation. We hypothesized that fractionated radiation would lead to OPC loss, which could contribute to the delayed white matter loss seen after radiation exposure. We found that fractionated IR induced a greater early loss of OPCs than an equivalent single dose exposure. Furthermore, OPC recovery was impaired following fractionated IR. Finally, reduced OPC differentiation and mature oligodendrocyte numbers occurred in single dose and fractionated IR paradigms. This work demonstrates that fractionation does not spare normal brain tissue and, importantly, highlights the sensitivity of OPCs to fractionated IR, suggesting that fractionated schedules may promote white matter dysfunction, a point that should be considered in radiotherapy.

Thumbnail image of graphical abstract

Main Points

Fractionated radiation depletes oligodendrocyte progenitor cells (OPC) through direct killing of dividing cells and stimulating OPC proliferation. Together with effects on the microenvironment, this leads to long-term defects in white matter.



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ProMoIJ: A new tool for automatic three-dimensional analysis of microglial process motility

Abstract

Microglia, the immune cells of the central nervous system, continuously survey the brain to detect alterations and maintain tissue homeostasis. The motility of microglial processes is indicative of their surveying capacity in normal and pathological conditions. The gold standard technique to study motility involves the use of two-photon microscopy to obtain time-lapse images from brain slices or the cortex of living animals. This technique generates four dimensionally-coded images which are analyzed manually using time-consuming, non-standardized protocols. Microglial process motility analysis is frequently performed using Z-stack projections with the consequent loss of three-dimensional (3D) information. To overcome these limitations, we developed ProMoIJ, a pack of ImageJ macros that perform automatic motility analysis of cellular processes in 3D. The main core of ProMoIJ is formed by two macros that assist the selection of processes, automatically reconstruct their 3D skeleton, and analyze their motility (process and tip velocity). Our results show that ProMoIJ presents several key advantages compared with conventional manual analysis: (1) reduces the time required for analysis, (2) is less sensitive to experimenter bias, and (3) is more robust to varying numbers of processes analyzed. In addition, we used ProMoIJ to demonstrate that commonly performed 2D analysis underestimates microglial process motility, to reveal that only cells adjacent to a laser injured area extend their processes toward the lesion site, and to demonstrate that systemic inflammation reduces microglial process motility. ProMoIJ is a novel, open-source, freely-available tool which standardizes and accelerates the time-consuming labor of 3D analysis of microglial process motility.

Thumbnail image of graphical abstract

Main Points

ProMoIJ allows 3D analysis of cell process motility and presents several advantages compared with manual protocols:

  • Reduced analysis time.
  • Reduced sensitiveness to experimenter bias.
  • Increased robustness to the number of processes analyzed.


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Correlations Between the Degree of Endolymphatic Hydrops and Symptoms and Audiological Test Results in Patients With Menière's Disease: A Reevaluation.

Correlations Between the Degree of Endolymphatic Hydrops and Symptoms and Audiological Test Results in Patients With Menière's Disease: A Reevaluation.

Otol Neurotol. 2017 Dec 28;:

Authors: Yang S, Zhu H, Zhu B, Wang H, Chen Z, Wu Y, Chen B, Shi H, Li Y, Zou J, Yin S

Abstract
OBJECTIVE: This study was performed to reevaluate the diagnostic significance of clinically well-accepted audiological tests in indicating endolymphatic hydrops (EH) in Menière's disease (MD).
STUDY DESIGN: Retrospective case review.
SETTINGS: Hospital.
PATIENTS: Fifty patients (52 affected ears) diagnosed with MD were enrolled.
INTERVENTION: Diagnostic.
MAIN OUTCOME MEASURE: To analyze the correlations between endolymphatic hydrops and results of audiological test including the pure-tone audiometry threshold, suprathreshold function tests, electrocochleogram, and glycerol test.
RESULTS: Three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging demonstrated EH in either the vestibule or cochlea to various degrees in all of the MD patients, 24 hours after intratympanic gadolinium chelate injection. Both vestibular and cochlear EH were significantly correlated with PTA threshold. However, EH was not associated with alternate binaural loudness balance or the tone decay test, although a correlation was observed with the short-increment sensitivity index. There was also a correlation between vestibular EH, but not cochlear EH, and the negative summating potential/action potential (-SP/AP) ratio. Neither vestibular EH nor cochlear EH was correlated with the glycerol test results. In addition, the frequency of vertigo attacks, the existence of tinnitus, and aural fullness did not correlate with EH.
CONCLUSIONS: Disrupted ionic homeostasis in the inner ear, but not the EH, may contribute to changes in the -SP/AP ratio. The relevance of glycerol test in identifying EH through detection of hearing changes needs further investigation in the future.

PMID: 29287037 [PubMed - as supplied by publisher]



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An Applied Anatomical Study of the Ethmoidal Arteries: Computed Tomographic and Direct Measurements in Human Cadavers.

An Applied Anatomical Study of the Ethmoidal Arteries: Computed Tomographic and Direct Measurements in Human Cadavers.

J Craniofac Surg. 2018 Jan;29(1):212-216

Authors: Felding UA, Karnov K, Clemmensen A, Thomsen C, Darvann TA, Buchwald CV, Tranum-Jensen J

Abstract
Computed tomography (CT) images have been used in very few studies on distances to the ethmoidal arteries in the orbit. Most other studies have included direct measurements on cadavers and frequently quote the 24-12-6 mm rule to describe distances from the anterior lacrimal crest to the anterior and posterior ethmoidal foramina (AEF and PEF), optic canal (OC), respectively. However, the large interindividual variation of distances renders absolute values less applicable in a clinical setting. Preoperative measurements on CT images may provide more precise distances than absolute rules and thus lead to safer orbital surgery. The authors hypothesize that the distances to the ethmoidal arteries and the length of the medial wall are positively correlated and that measurements of the distances from the posterior lacrimal crest (PLC) on CT images are feasible with a low intra- and interobserver variability.Fifty intact orbits from 25 Caucasian cadavers were exenterated and examined. In additional, high-resolution CT scans of 48 orbits from 24 other Caucasian nonexenterated cadavers were examined. Distances were measured from 4 different anterior landmarks to the AEF and PEF and the OC.Distances from the most anterior landmarks to the arteries were positively correlated with the length of the medial wall. Measurements of the distances from the PLC to the ethmoidal arteries on CT images were feasible with a low intra- and interobserver variability. In conclusion, iatrogenic damage to the ethmoidal arteries in the orbit may be best avoided by using CT measurements in presurgical planning.

PMID: 29287000 [PubMed - in process]



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Platelet indices in laryngeal cancer.

Platelet indices in laryngeal cancer.

Cancer Biomark. 2017 Dec 22;:

Authors: Fu S, Liu L, Zhang X, Liu ZP, Wang RT

Abstract
BACKGROUND: Laryngeal cancer is one of the most common malignancies in the head and neck. Activated platelets play a critical role in cancer development and progression. Altered mean platelet volume (MPV) and platelet distribution width (PDW) have been found in various types of cancer. The purpose of the current study was to investigate the association of platelet indices with laryngeal cancer.
STUDY DESIGN: The study included 216 patients with laryngeal cancer, 189 subjects with benign laryngeal disease, and 213 control subjects between January 2015 and December 2015. All participants' clinical and laboratory characteristics at initial diagnosis were collected.
RESULT: MPV was significantly lower and PDW was markedly higher in laryngeal cancer patients compared with control subjects and patients with benign laryngeal disease. A significant correlation between MPV and lymph node metastasis was found. The prevalence of laryngeal cancer increased as MPV quartiles decreased and PDW quartiles increased. Furthermore, MPV and PDW were independent risk factors for distinguishing laryngeal cancer from benign laryngeal disease.
CONCLUSIONS: The patients with laryngeal cancer have reduced MPV and increased PDW compared to the subjects without laryngeal cancer. In addition, MPV and PDW play different roles in laryngeal cancer from benign laryngeal disease.

PMID: 29286923 [PubMed - as supplied by publisher]



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Systematic review of low-level laser therapy for adult androgenic alopecia.

Systematic review of low-level laser therapy for adult androgenic alopecia.

J Cosmet Laser Ther. 2017 Dec 29;:1-8

Authors: Delaney SW, Zhang P

Abstract
Alopecia is a common disorder affecting over half of the world's population. Within this condition, androgenic alopecia (AA) is the most common type, affecting 50% of males over 40 and 75% of females over 65. Anecdotal paradoxical hypertrichosis noted during laser epilation has generated interest in the possibility of using laser to stimulate hair growth. In this study, we aimed to critically appraise the application of low-level laser therapy for the treatment of AA in adults. A systematic review was performed on studies identified on Medline, EMBASE, Cochrane database, and clinicaltrials.org. Double-blinded randomized controlled trials were selected and analyzed quantitatively (meta-analysis) and qualitatively (quality of evidence, risk of bias). Low-level laser therapy appears to be a promising noninvasive treatment for AA in adults that is safe for self-administration in the home setting. Although shown to effectively stimulate hair growth when compared to sham devices, these results must be interpreted with caution. Further studies with larger samples, longer follow-up, and independent funding sources are necessary to determine the clinical effectiveness of this novel therapy.

PMID: 29286826 [PubMed - as supplied by publisher]



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Dosimetric Validation of Volumetric Modulated Arc Therapy with Three 6MV Beam-Matched Linear Accelerators

Dosimetric Validation of Volumetric Modulated Arc Therapy with Three 6MV Beam-Matched Linear Accelerators

Asian Pac J Cancer Prev. 2017 Dec 29;18(12):3439-3444

Authors: Ashokkumar S, Ganesh KM, Ramalingam K, Karthikeyan K, Jagadheeskumar N

Abstract
Background: To avoid inconvenience to patients due to linear accelerator down time in busy radio-therapy departments, treatment plans can be switched between linear accelerators provided that all exhibit the same same dosimetric characteristics. In other words linear accelerators should be beam-matched. Aim: The aim of this study was to evaluate the clinical significance of beam-matching using VMAT plans. Materials and Methods: Dosimetric data with a 6MV beam from am Clinac 2100CD were taken as baseline values and other two units, a 2300CD and a Unique Performance, were factory tuned in accordance. An analysis of PDD data was performed for different field sizes to evaluate energy matching. Beam profiles for field sizes of 10×10 cm2 and 40 × 40 cm2 at depths of 1.5 cm and 10 cm were analyzed. The relative output factor and MLC dosimetric properties were compared with each machine to determine variability among the different models. Thirty patients from our database were selected, ten each for head and neck, thorax and pelvis sites. VMAT plans were created in the Eclipse treatment planning system for a Clinac 2100 CD for reference. and verification plans were created for each to compare point dose measurements. Results: The TPR 20/10 for 10 × 10 cm2 was well matched, showing no energy differences. Deviation of all point dose measurements fell within ±3%. Planar dose maps all showed greater than 95% of points with a passed area γ-value less than 1. Conclusion: Our study evaluation of beam matching with treatment planning modeling showed good agreement fior 6 MV beams across all three linear accelerators used in our clinical environment.

PMID: 29286616 [PubMed - as supplied by publisher]



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Impact of alcohol dehydrogenase-aldehyde dehydrogenase polymorphism on clinical outcome in patients with hypopharyngeal cancer.

Impact of alcohol dehydrogenase-aldehyde dehydrogenase polymorphism on clinical outcome in patients with hypopharyngeal cancer.

Head Neck. 2017 Dec 29;:

Authors: Avinçsal MO, Shinomiya H, Teshima M, Kubo M, Otsuki N, Kyota N, Sasaki R, Zen Y, Nibu KI

Abstract
BACKGROUND: The purpose of this research was to investigate the association between alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2) polymorphisms and hypopharyngeal squamous cell carcinoma (SCC) survival.
METHODS: We genotyped ADH1B (rs1229984) and ALDH2 (rs671) single nucleotide polymorphisms (SNPs) in 85 Japanese male patients with hypopharyngeal SCC. The independent prognostic values of ADH1B-ALDH2 genotypes were analyzed by univariate and multivariate proportional hazard Cox regression, taking well-known clinical risk factors into account.
RESULTS: Heavy drinkers with ALDH2*2 allele resulted in significantly worse overall survival (OS; P = .028) and disease-free survival (DFS; P = .029) compared with other patients. Heavy drinkers with ALDH2*2 allele remained statistically significant in multivariate analysis for OS and DFS, indicating independent poor prognostic factor (hazard ratio [HR] 2.251; 95% confidence interval [CI] 1.018-4.975 and HR 2.261; 95% CI 1.021-5.006, respectively).
CONCLUSION: We conclude that heavy drinkers with the ALDH2*2 allele are associated with poor outcome in hypopharyngeal SCC.

PMID: 29286190 [PubMed - as supplied by publisher]



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In vitro biofilm growth on modern voice prostheses.

In vitro biofilm growth on modern voice prostheses.

Head Neck. 2017 Dec 29;:

Authors: Leonhard M, Zatorska B, Tan Y, Moser D, Schneider-Stickler B

Abstract
BACKGROUND: Biofilm formation on voice prostheses in laryngectomized patients usually limits the lifetime of the device. The purpose of this study was to compare the biofilm resistance of different valve flaps of modern voice prostheses in an in vitro simulation of an oropharyngeal biofilm.
METHODS: Growth of biofilm deposits on valve flaps (n = 12) removed from Provox 2, Provox Vega, Provox ActiValve, Blom Singer Advantage, and Phonax voice prostheses was evaluated and compared to medical-grade silicone (n = 12) in an in vitro biofilm model (22 days) after incubation with a multispecies bacterial-fungal biofilm composition.
RESULTS: The Provox ActiValve and the Blom Singer Advantage prostheses showed significantly less surface biofilm formation than the other prostheses and then silicone.
CONCLUSION: The use of silver oxide and Teflon as valve flap materials proves to reduce long-term biofilm formation in vitro. The applied model allows rapid screening for novel biofilm-inhibitive materials and durable coatings designated for more biofilm resistant medical devices.

PMID: 29286184 [PubMed - as supplied by publisher]



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Leiomyosarcoma of the head and neck: A 17-year single institution experience and review of the National Cancer Data Base.

Leiomyosarcoma of the head and neck: A 17-year single institution experience and review of the National Cancer Data Base.

Head Neck. 2017 Dec 29;:

Authors: Workman AD, Farquhar DR, Brody RM, Parasher AK, Carey RM, Purkey MT, Nagda DA, Brooks JS, Hartner LP, Brant JA, Newman JG

Abstract
BACKGROUND: Leiomyosarcoma is a rare neoplasm of the head and neck. The purpose of this study was to present our single-institution case series of head and neck leiomyosarcoma and a review of cases in the National Cancer Data Base (NCDB).
METHODS: Patients with head and neck leiomyosarcoma at the University of Pennsylvania and in the NCDB were identified. Demographic characteristics, tumor factors, treatment paradigms, and outcomes were evaluated for prognostic significance.
RESULTS: Nine patients with head and neck leiomyosarcoma from the institution were identified; a majority had high-grade disease and cutaneous leiomyosarcoma, with a 5-year survival rate of 50%. Two hundred fifty-nine patients with leiomyosarcoma were found in the NCDB; macroscopic positive margins and high-grade disease were associated with poor prognosis (P < .01), and positive surgical margins were related to adjuvant radiation (P < .001).
CONCLUSION: Head and neck leiomyosarcoma presents at a high grade and is preferentially treated with surgery. Several demographic and tumor-specific factors are associated with outcomes and prognosis.

PMID: 29286183 [PubMed - as supplied by publisher]



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Computer-aided system for diagnosing thyroid nodules on ultrasound: A comparison with radiologist-based clinical assessments.

Computer-aided system for diagnosing thyroid nodules on ultrasound: A comparison with radiologist-based clinical assessments.

Head Neck. 2017 Dec 29;:

Authors: Gao L, Liu R, Jiang Y, Song W, Wang Y, Liu J, Wang J, Wu D, Li S, Hao A, Zhang B

Abstract
BACKGROUND: The purpose of this study was to compare the diagnostic efficiency of a thyroid ultrasound computer-aided diagnosis (CAD) system with that of 1 radiologist.
METHODS: This study retrospectively reviewed 342 surgically resected thyroid nodules from July 2013 to December 2013 at our center. The nodules were assessed on typical ultrasound images using the CAD system and reviewed by 1 experienced radiologist. The radiologist stratified the risk of malignancy using the Thyroid Imaging Reporting and Data Systems (TIRADS) and the American Thyroid Association (ATA) guidelines.
RESULTS: The radiologist, using TI-RADS and ATA guidelines, performed better than the CAD system (P < .01). The sensitivity of the CAD system was similar to that of an experienced radiologist (P > .05; P < .01; and P > .05). However, we found that the CAD system had lower specificity (P < .01).
CONCLUSION: The sensitivity of a thyroid ultrasound CAD system in differentiating nodules was similar to that of an experienced radiologist. However, the CAD system had lower specificity.

PMID: 29286180 [PubMed - as supplied by publisher]



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GC7 enhances cisplatin sensitivity via STAT3 signaling pathway inhibition and eIF5A2 inactivation in mesenchymal phenotype oral cancer cells.

GC7 enhances cisplatin sensitivity via STAT3 signaling pathway inhibition and eIF5A2 inactivation in mesenchymal phenotype oral cancer cells.

Oncol Rep. 2017 Dec 15;:

Authors: Fang L, Gao L, Xie L, Xiao G

Abstract
Eukaryotic initiation factor 5A2 (eIF5A2), a newly identified oncogene, promotes cell survival, proliferation and motility in tumorigenesis. Drug resistance and dose-related adverse side-effects greatly reduce the efficiency and safety of cisplatin-based chemotherapy in advanced or recurrent oral squamous cell carcinoma (OSCC) patients. The present study investigated the effect of eIF5A2 combined with N1-guanyl-1,7-diaminoheptane (GC7, a novel eIF5A2 inhibitor) or siRNA. We found that low concentrations of GC7 (≤5 µM) had little effect on OSCC cell viability, but significantly enhanced cisplatin cytotoxicity. Compared with cisplatin, GC7/cisplatin had little effect on cisplatin-promoted mesenchymal-epithelial transition in mesenchymal phenotype Tca8113 and HN30 cells, or on cisplatin-induced epithelial-mesenchymal transition (EMT) in epithelial phenotype Cal27 and HN4 cells. Further research revealed that the upregulation of p-STAT3 and c-Myc which was induced by the single treatment with either cisplatin or GC7 was significantly reversed by the GC7/cisplatin combination in mesenchymal phenotype Tca8113 and HN30 cells. In in vivo treatment, we revealed that the GC7/cisplatin combination presented significant tumor volume reduction without distinct body weight loss. In conclusion, our data indicated that eIF5A2 is a potent therapeutic target in OSCC treatment. Our results revealed a novel mechanism by which GC7/cisplatin combination therapy may offer an efficient and safe therapeutic alternative to advanced or recurrent OSCC patients.

PMID: 29286162 [PubMed - as supplied by publisher]



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Epithelial mesenchymal transition induced by the CXCL9/CXCR3 axis through AKT activation promotes invasion and metastasis in tongue squamous cell carcinoma.

Epithelial mesenchymal transition induced by the CXCL9/CXCR3 axis through AKT activation promotes invasion and metastasis in tongue squamous cell carcinoma.

Oncol Rep. 2017 Dec 20;:

Authors: Li Z, Liu J, Li L, Shao S, Wu J, Bian L, He Y

Abstract
The present study aimed to assess the induction of epithelial-mesenchymal transition (EMT), invasion, and metastasis by the chemokine CXCL9/receptor CXCR3 axis in tongue squamous cell carcinoma (TSCC), unveiling the underlying mechanisms and providing new insights into the prevention and treatment of oral cancer metastasis. The expression levels of CXCL9 and CXCR3 in TSCC tissue specimens were determined by immunohistochemistry, assessing differences between samples with cervical lymph node metastasis and those without. Moreover, protein expression or activity in the TSCC Cal-27 cell line was controlled by neutralizing antibodies, gene transfection, or knock-out. Then, alterations of cell proliferation, migration, invasion, and the cytoskeleton were analyzed by CCK-8, cell scratch, Transwell, and cyto-skeleton staining assays, respectively. Alterations of EMT markers (E-cadherin and vimentin) in Cal-27 cells were detected by immunofluorescence and western blotting. In addition, western blotting was utilized to detect protein expression levels of Akt2, p-Akt2, eIF4E and p-eIF4E, and to explore the regulatory roles and mechanisms of the CXCL9/CXCR3 axis in invasion and metastasis. Significantly increased expression levels of CXCL9 and CXCR3 were detected in tissue specimens with lymph node metastasis compared with those without (P<0.01). Overexpression of CXCL9/CXCR3 in Cal-27 cells resulted in cytoskeleton alterations, decreased E-cadherin expression, increased vimentin levels, enhanced migration and invasion (P<0.05), and increased phosphorylated Akt2 and eIF4E levels (P<0.05). These results revealed that in TSCC, the CXCL9/CXCR3 axis could activate the Akt signaling pathway, with EMT and cytoskeleton rearrangement, promoting invasion and metastasis.

PMID: 29286143 [PubMed - as supplied by publisher]



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Effects of epidermal growth factor receptor fusion protein on the cytotoxic activity of SOCS1-silenced dendritic cells in vitro.

Effects of epidermal growth factor receptor fusion protein on the cytotoxic activity of SOCS1-silenced dendritic cells in vitro.

Oncol Rep. 2017 Dec 15;:

Authors: Jiang Q, Wang X, Qian M, Chen D, Xu Y

Abstract
The aim of the present study was to observe the effects of cytokine signaling suppressor 1 (SOCS1)-silenced dendritic cells (DCs) pulsed with epidermal growth factor receptor (EGFR) fusion protein on the activation of T lymphocyte and cytotoxic T-lymphocyte (CTL) activity against Hep-2 cells. DCs were derived from the medullary cells of mice and authenticated by flow cytometry (FCM). Recombinant glutathione-S-transferase (GST)-EGFR fusion protein was produced and purified. After being pulsed with it, DCs were modified by recombinant SOCS1-siRNA adenoviral to silence SOCS1 gene expression. The maturation of DCs was evaluated by FCM. The effects of modified DCs on T-cell proliferation were assessed by MTT assay. The killing effects against Hep-2 cells of CTL were assessed by lactate dehydrogenase (LDH) release assay. High-purity DCs from the medullary cells of mice were obtained. Compared with the control, EGFR-pulsed DCs displayed higher expression of cell surface molecules, including CD83, CD860 and HLA-DR. The MTT assay revealed that all of the EGFR-pulsed, SOCS1‑silenced and EGFR-pulsed plus SOCS1-silenced DCs had an enhanced capacity to stimulate T-lymphocyte proliferation. As expected, EGFR-pulsed plus SOCS1-silenced DCs had the strongest effects on T-cell proliferation. The splenic T cells isolated from both EGFR-pulsed DC-immunized mice and EGFR-pulsed plus SOCS1-silenced DC-immunized mice enhanced the cytotoxicity against Hep-2 cells, while T cells from EGFR‑pulsed plus SOCS1-silenced DC-immunized mice exhibited significantly higher cytotoxicity than those from EGFR-DC-immunized mice. The EGFR-pulsed SOCS1‑siRNA-silenced DCs had the strongest effects on activation of T-cell proliferation and the CTL activity against Hep-2 cells.

PMID: 29286121 [PubMed - as supplied by publisher]



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Influence of static magnetic fields on human myoblast/mesenchymal stem cell co‑cultures.

Influence of static magnetic fields on human myoblast/mesenchymal stem cell co‑cultures.

Mol Med Rep. 2017 Dec 20;:

Authors: Mueller CE, Birk R, Kramer B, Wenzel A, Sommer JU, Hörmann K, Stern-Straeter J, Weilbach C

Abstract
The results of surgical repair of extensive muscle tissue defects are still of primary concern, leaving patients with residual cosmetic and functional impairments. Therefore, skeletal muscle tissue engineering attempts to grow functional neo‑tissue from human stem cells to promote tissue regeneration and support defect closure. Despite intensive research efforts, the goal of stable induction of myogenic differentiation in expanded human stem cells by using clinically feasible stimuli, has not yet been reached to a sufficient extent. Therefore, the present study investigated the differentiation potential of static magnetic fields (SMFs), using co‑cultures of human satellite cells and human mesenchymal stem cells (MSCs). It has previously been demonstrated that SMFs may act as a promising myogenic stimulus. Tests were performed on co‑cultures with and without SMF exposure, using growth medium [high growth factor concentrations (GM)] and differentiation medium [low growth factors concentrations (DM)]. AlamarBlue® assay‑based cell proliferation analysis revealed no significant difference between co‑cultures with, vs. without SMF stimulation, regardless of growth factor concentrations in the cell culture medium. To determine the degree of differentiation in co‑cultures under stimulation with SMFs, semi‑quantitative gene expression measurements of the following marker genes were performed: Desmin, myogenic factor 5, myogenic differentiation antigen 1, myogenin, adult myosin heavy chain 1 and skeletal muscle α1 actin. In neither GM nor DM was a steady, significant increase in marker gene expression detected. Verifying the gene expression findings, immunohistochemical antibody staining against differentiation markers revealed that SMF exposure did not enhance myogenic maturation. Therefore, SMF treatment of human satellite cell/MSC co‑cultures did not result in the desired increase in myogenic differentiation. Further studies are required to identify a suitable stimulus for skeletal muscle tissue engineering.

PMID: 29286120 [PubMed - as supplied by publisher]



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Tetrandrine enhances radiosensitivity through the CDC25C/CDK1/cyclin B1 pathway in nasopharyngeal carcinoma cells.

Tetrandrine enhances radiosensitivity through the CDC25C/CDK1/cyclin B1 pathway in nasopharyngeal carcinoma cells.

Cell Cycle. 2017 Dec 29;:1-33

Authors: Wang J, Chang L, Lai X, Li X, Wang Z, Huang Z, Huang J, Zhang G

Abstract
The increasing resistance of nasopharyngeal carcinoma to irradiation makes the exploration of effective radiosensitizers necessary. Tetrandrine is known to be an antitumor drug, but little is known regarding its radiosensitization effect on nasopharyngeal carcinoma. We investigated the effect of combined treatment of irradiation and maximum non-cytotoxic doses of tetrandrine on the nasopharyngeal carcinoma cell lines CNE1 and CNE2. The maximum non-cytotoxic doses of tetrandrine in CNE1 and CNE2 cells were assessed using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The radiosensitization of cells receiving the maximum non-cytotoxic doses of tetrandrine was assessed by evaluating cell proliferation and DNA damage repair using MTT, clonogenic, comet assays and detection of caspase-3 and phosphorylated histone H2AX (γ-H2AX). The cell cycle was assessed by flow cytometry, and protein expression was detected by western blot analysis. The maximum non-cytotoxic doses of tetrandrine in CNE1 and CNE2 cells were 1.5 μmol/L and 1.8 μmol/L, respectively. When cells were exposed to irradiation and the maximum non-cytotoxic doses of tetrandrine, the survival fraction was decreased. DNA damage and γ-H2AX levels markedly increased. Moreover, tetrandrine abrogated the G2/M phase arrest caused by irradiation. Combined treatment with the maximum non-cytotoxic dose of tetrandrine and irradiation caused suppression of the phosphorylation of CDK1 and CDC25C and increase in the expression of cyclin B1. The study in vivo also showed that the maximum non-cytotoxic dose of tetrandrine could reduce tumor growth in xenograft tumor model. Our results suggest that the maximum non-cytotoxic dose of tetrandrine can enhance the radiosensitivity of CNE1 and CNE2 cells and that the underlying mechanism could be associated with abrogation of radiation-induced G2/M arrest via activation of the CDC25C/CDK1/Cyclin B1 pathway.

PMID: 29285984 [PubMed - as supplied by publisher]



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EZH2 overexpression in head and neck cancer is related to lymph node metastasis.

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EZH2 overexpression in head and neck cancer is related to lymph node metastasis.

J Oral Pathol Med. 2017 Dec 29;:

Authors: Nienstedt JC, Schroeder C, Clauditz T, Simon R, Sauter G, Muenscher A, Blessmann M, Hanken H, Pflug C

Abstract
BACKGROUND: Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the polycomb repressive complex 2, plays an important role in tumor development and progression by interacting with histone and non-histone proteins. EZH2 represents a putative therapeutic target and has been suggested as a prognostic marker in several cancer types.
MATERIAL AND METHODS: The present study investigates the prognostic relevance of immunohistochemical EZH2 expression in head and neck squamous cell carcinoma. Tissue microarray sections with 667 cancers of oral cavity, oro- and hypopharynx and larynx were analyzed for EZH2 expression.
RESULTS: Nuclear EZH2 staining was recorded in 322 (81.8%) of 394 cases. Staining was weak in 33 (10.2%), moderate in 128 (39.6%) and strong in 103 (32.0%) cancers. The prevalence of EZH2 expression in tumors of the oral cavity and the orohypopharynx was higher as compared to cancers of the larynx (p=0.0023). EZH2 expression was correlated to presence of lymph node metastasis (p=0.0089) but was unrelated to histological grade, tumor stage, surgical margin or distant metastasis. EZH2 expression had no impact on patient survival.
CONCLUSION: The high prevalence of EZH2 expression in head and neck squamous cell carcinoma stresses its capability as a therapeutic target. This article is protected by copyright. All rights reserved.

PMID: 29285811 [PubMed - as supplied by publisher]



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Balloon dilatation of the Eustachian tube in adult patients with chronic dilatory tube dysfunction: a retrospective cohort study.

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Balloon dilatation of the Eustachian tube in adult patients with chronic dilatory tube dysfunction: a retrospective cohort study.

Eur Arch Otorhinolaryngol. 2017 Dec 29;:

Authors: Satmis MC, van der Torn M

Abstract
OBJECTIVES: The aim of this study is to assess the subjective and objective short-term results and safety of transnasal balloon dilatation of the Eustachian tube (BET) in adult patients with chronic dilatory Eustachian tube dysfunction (ETD).
DESIGN: Retrospective cohort study. Data collection was performed preoperatively, 1 and 3 months after BET.
SETTING: Tertiary referral hospital.
PARTICIPANTS: A cohort of 42 consecutive patients (66 ears).
MAIN OUTCOME MEASURES: ETDQ-7 score, bone conduction threshold, air-bone gap, the ability to perform Valsalva's and/or Toynbee's manoeuvre, tympanic membrane and middle ear conditions were collected pre- and postoperatively. Subjective satisfaction and complications were collected postoperatively.
RESULTS: The ETDQ-7 score improved significantly from 4.28 to 3.09 1 month postoperatively and from 4.10 to 2.96 3 months postoperatively. Bone conduction thresholds did not differ significantly postoperatively. A significant improvement of air-bone gap was found postoperatively. The tympanic membrane and middle ear condition showed improvement in 62%. Subjective satisfaction 1 and 3 months postoperatively was around 43 and 48%. A small number of minor (self-limiting) complications did occur.
CONCLUSIONS: BET has shown to be a safe intervention, which may have a positive effect on objective and subjective indicators for chronic dilatory ETD in adult patients. We observed subjective positive effects in less than half of the patients. For certain indications, there was a measurable positive effect on the findings of the eardrum and ETDQ-7, whereas in other patients it seemed not to have any effect at all. Careful patient selection may improve this success rate. Randomized controlled trials with a prolonged follow-up are required to assess the value of BET in comparison to grommets.

PMID: 29285624 [PubMed - as supplied by publisher]



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Primary Cancer vs Competing Causes of Death in Survivors of Head and Neck Cancer.

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Primary Cancer vs Competing Causes of Death in Survivors of Head and Neck Cancer.

JAMA Oncol. 2017 Dec 28;:

Authors: Simpson MC, Massa ST, Boakye EA, Antisdel JL, Stamatakis KA, Varvares MA, Osazuwa-Peters N

PMID: 29285537 [PubMed - as supplied by publisher]



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Scaffold-Assisted Artificial Hair Implantation in a Rat Model.

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Scaffold-Assisted Artificial Hair Implantation in a Rat Model.

JAMA Facial Plast Surg. 2017 Dec 28;:

Authors: Au JK, Palma Diaz MF, Aghaloo T, St John MA

Abstract
Importance: Current treatments for alopecia with autograft hair transplantation face limitations that may preclude complete hair restoration and leave patients with donor site scars. Scaffold assisted artificial hair implantation as demonstrated in a rat model may provide an adjunct for hair restoration without donor site morbidity.
Objective: To design and create porous high-density polyethylene (PHDPE) and expanded polytetrafluoroethylene (ePTFE) hair-bearing scaffolds and evaluate their biocompatibility in a rat model.
Design, Setting, and Participants: For this single-institution randomized prospective animal study, 34 Sprague Dawley rats were randomly selected into 2 groups: 24 rats for direct implantation and 10 rats for delayed implantation. The direct-implantation group was randomly divided into 3 subgroups of 8 rats, which were observed for 2, 12, and 24 week.
Interventions: Each rat dorsum was implanted with 4 scaffolds-PHDPE and ePTFE with and without hair-in a randomized 4-quadrant manner. The rats in the direct-implantation group were observed to their selected time points of 2, 12, and 24 weeks. The rats in the delayed-implantation group were observed for 4 weeks at which, all well-healed scaffolds without hair were then percutaneously implanted with 2 follicular units of hair. These rats were then observed for another 4 weeks.
Main Outcomes and Measures: During the clinical observation period, scaffolds were observed for signs of infection, extrusion, and persistence of follicular units. Following sacrifice, sagittal sections of scaffold and surrounding skin were fixed in formalin, stained with hematoxylin-eosin, and evaluated for degree of fibrovascular invasion and acute and chronic inflammation.
Results: Overall 94.5% (86 of 91) of the scaffolds were well healed at time of evaluation (2 week, 100% [32 of 32]; 12 week, 96.3% [26 of 27]; 24 week, 87.5% [28 of 32]); while 85.6% of artificial hair follicular units were intact at time of evaluation (2 week, 93.8% [30 of 32]; 12 week, 86.7% [26 of 30]; 24 week, 75.0% [21 of 28]). Within the delayed implant group 100% (19 of 19) of the hair-implanted scaffolds were well healed at 8 weeks, with 94.7% (36 of 38) of the follicular units intact; 100% of the delayed-hair implant scaffolds were well healed with 86.1% (36 of 38) of the follicular units intact. Kaplan-Meier log-rank analysis showed no significant difference in survival between ePTFE and PHDPE scaffolds, as well as scaffolds with hair and scaffolds without hair. Upon histological analysis, overall scaffolds with hair were noted to have greater chronic inflammation (95% CI, -0.81 to -1.10; P = .01), and PHDPE was noted to have significantly great fibrovascular integration (95% CI, -11.42 to -1.96; P = .01) compared with ePTFE.
Conclusions and Relevance: Overall, PHDPE and ePTFE hair bearing scaffolds were well tolerated in a rat model. Progressive loss of artificial hair may be percutaneously implanted without significant increases in infection or extrusion.
Level of Evidence: NA.

PMID: 29285533 [PubMed - as supplied by publisher]



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Expression of Topoisomerase II-α protein in salivary gland tumors.

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Expression of Topoisomerase II-α protein in salivary gland tumors.

Mol Clin Oncol. 2017 Dec;7(6):1064-1068

Authors: Shvero A, Hilly O, Bubis G, Hamzany Y, Koren R, Rath-Wolfson L

Abstract
Salivary glands give rise to approximately 30 histological distinct tumor types, which results in a diagnostic challenge for the pathologist. The present retrospective, immunohistochemical study aimed to evaluate the expression of Topoisomerase II-α, a nuclear enzyme, as a diagnostic and prognostic marker in benign and malignant salivary gland tumors, including leomorphic adenoma, mucoepidermoid carcinoma, acinic cell carcinoma and carcinoma ex-pleomorphic adenoma. A total of 59 cases of benign and malignant salivary gland tumors were included in the present study. Representative paraffin-embedded sections were immunostained for Topoisomerase II-α (Topo II-α). The expression level was semi-quantified for each case and then correlated with the histological diagnosis using hematoxylin and eosin-stained slides, grade of tumor and total survival. Significant differences were revealed between the expression level of Topo II-α in pleomorphic adenoma and mucoepidermoid carcinoma (P<0.001), carcinoma ex-pleomorphic adenoma (P<0.001), acinic cell carcinoma (P=0.005) and a group composed of all the malignant tumors (P<0.001). Cancer-specific survival rates were insignificantly increased in tumors expressing low levels of Topo II-α (P=0.464). Thus, the present study demonstrated different expression levels of Topo II-α in benign and malignant salivary gland tumors. These differing expression levels may act as valuable biomarkers for the correct histological diagnosis. Further studies conducted on a larger scale may lead to even more conclusive results.

PMID: 29285375 [PubMed]



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Utility of chemoradioselection for the optimization of treatment intensity in advanced hypopharyngeal and laryngeal carcinoma.

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Utility of chemoradioselection for the optimization of treatment intensity in advanced hypopharyngeal and laryngeal carcinoma.

Mol Clin Oncol. 2017 Dec;7(6):965-970

Authors: Masuda M, Wakasaki T, Toh S, Uchida Y, Rikimaru H, Kunitake N, Higaki Y

Abstract
Definitive concomitant chemoradiotherapy (CRT) with high-dose cis-platinum (CDDP) is a current standard protocol for advanced laryngeal and hypopharyngeal cancer sparing surgery for salvage. However, this modality is associated with limited feasibility and frequent sever toxicities. In the present study, a 'chemoradioselection' protocol with minimal toxicity was developed using initial response to CRT as a biomarker for patient selection. Between 2000, March and 2012, September 123 patients with stage III (44), IV (79) laryngeal (64) and hypopharyngeal carcinoma (59) excluding T4 cases were enrolled to this protocol. Two cycles of split (15 mg/m2 ×5 days, 2000-2008) or bolus (80 mg/m2, 2009-present) CDDP was concurrently administered. Tumor responses were evaluated after 40 Gy of CRT and 64 responders (chemoradioselected, CRS) received further CRT up to 70 Gy, while radical surgery was recommended for the 59 non-responders (N-CRS), and 34 underwent surgery (N-CRS-ope). The remaining 25 patients who refused surgery (N-CRS-refu) were treated with continuous CRT. The 5-year overall survival (OS) and disease-specific survival (DSS) were 67, and 77%, respectively. The CRS demonstrated favorable 5-year OS (73%) and laryngo-esophageal dysfunction-free survival (LEDFS, 69%) rates. In contrast, the N-CRS-refu showed significantly lower 5-year OS (47%) compared with CRS (73%) and N-CRS-ope (70%) (P=0.0193), and significantly lower 5-year LEDFS (20%) compared with the CRS (69%) (P<0.0001). On multivariate analyses, including T, N, primary site and planned treatment (CRS + N-CRS-ope) or not (N-CRS-refu), unplanned treatment alone showed a significant correlation with poor OS [hazard ratio (HR), 2.584; 95% confidence interval (CI), 1.313-4.354; P=0.007). Chemoradioselection reflects the biological aggressiveness of each tumor, and is able to segregate patients for functional laryngeal preservation with moderate intensity CRT (150-160 mg/m2 of CDDP) from those who would be better treated with surgery. This strategy may be useful for the optimization of the therapeutic intensity.

PMID: 29285357 [PubMed]



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A standardised method for interpreting the association between mutations and phenotypic drug resistance in Mycobacterium tuberculosis.

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A standardised method for interpreting the association between mutations and phenotypic drug resistance in Mycobacterium tuberculosis.

Eur Respir J. 2017 Dec;50(6):

Authors: Miotto P, Tessema B, Tagliani E, Chindelevitch L, Starks AM, Emerson C, Hanna D, Kim PS, Liwski R, Zignol M, Gilpin C, Niemann S, Denkinger CM, Fleming J, Warren RM, Crook D, Posey J, Gagneux S, Hoffner S, Rodrigues C, Comas I, Engelthaler DM, Murray M, Alland D, Rigouts L, Lange C, Dheda K, Hasan R, Ranganathan UDK, McNerney R, Ezewudo M, Cirillo DM, Schito M, Köser CU, Rodwell TC

Abstract
A clear understanding of the genetic basis of antibiotic resistance in Mycobacterium tuberculosis is required to accelerate the development of rapid drug susceptibility testing methods based on genetic sequence.Raw genotype-phenotype correlation data were extracted as part of a comprehensive systematic review to develop a standardised analytical approach for interpreting resistance associated mutations for rifampicin, isoniazid, ofloxacin/levofloxacin, moxifloxacin, amikacin, kanamycin, capreomycin, streptomycin, ethionamide/prothionamide and pyrazinamide. Mutation frequencies in resistant and susceptible isolates were calculated, together with novel statistical measures to classify mutations as high, moderate, minimal or indeterminate confidence for predicting resistance.We identified 286 confidence-graded mutations associated with resistance. Compared to phenotypic methods, sensitivity (95% CI) for rifampicin was 90.3% (89.6-90.9%), while for isoniazid it was 78.2% (77.4-79.0%) and their specificities were 96.3% (95.7-96.8%) and 94.4% (93.1-95.5%), respectively. For second-line drugs, sensitivity varied from 67.4% (64.1-70.6%) for capreomycin to 88.2% (85.1-90.9%) for moxifloxacin, with specificity ranging from 90.0% (87.1-92.5%) for moxifloxacin to 99.5% (99.0-99.8%) for amikacin.This study provides a standardised and comprehensive approach for the interpretation of mutations as predictors of M. tuberculosis drug-resistant phenotypes. These data have implications for the clinical interpretation of molecular diagnostics and next-generation sequencing as well as efficient individualised therapy for patients with drug-resistant tuberculosis.

PMID: 29284687 [PubMed - in process]



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Is the concept of clinical equipoise still relevant to research?

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Is the concept of clinical equipoise still relevant to research?

BMJ. 2017 Dec 28;359:j5787

Authors: Hey SP, London AJ, Weijer C, Rid A, Miller F

PMID: 29284666 [PubMed - in process]



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Existential decision-making in a fatal progressive disease: how much do legal and medical frameworks matter?

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Existential decision-making in a fatal progressive disease: how much do legal and medical frameworks matter?

BMC Palliat Care. 2017 Dec 28;16(1):80

Authors: Weber C, Fijalkowska B, Ciecwierska K, Lindblad A, Badura-Lotter G, Andersen PM, Kuźma-Kozakiewicz M, Ludolph AC, Lulé D, Pasierski T, Lynöe N

Abstract
BACKGROUND: Healthcare legislation in European countries is similar in many respects. Most importantly, the framework of informed consent determines that physicians have the duty to provide detailed information about available therapeutic options and that patients have the right to refuse measures that contradict their personal values. However, when it comes to end-of-life decision-making a number of differences exist in the more specific regulations of individual countries. These differences and how they might nevertheless impact patient's choices will be addressed in the current debate.
MAIN TEXT: In this article we show how the legal and medical frameworks of Germany, Poland and Sweden differ with regard to end-of-life decisions for patients with a fatal progressive disease. Taking Amyotrophic Lateral Sclerosis (ALS) as an example, we systematically compare clinical guidelines and healthcare law, pointing out the country-specific differences most relevant for existential decision-making. A fictional case report discusses the implications of these differences for a patient with ALS living in either of the three countries. Patients with ALS in Germany, Poland and Sweden are confronted with a similar spectrum of treatment options. However, the analysis of the normative frameworks shows that the conditions for making existential decisions differ considerably in Germany, Poland and Sweden. Specifically, these differences concern (1) the legal status of advance directives, (2) the conditions under which life-sustaining therapies are started or withheld, and (3) the legal regulations on assisted dying.
CONCLUSION: According to the presented data, regulations of terminating life-sustaining treatments and the framework of "informed consent" are quite differently understood and implemented in the legal setting of the three countries. It is possible, and even likely, that these differences in the legal and medical frameworks have a considerable influence on existential decisions of patients with ALS.

PMID: 29284475 [PubMed - in process]



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Alopecia areata: An appraisal of new treatment approaches and overview of current therapies.

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Alopecia areata: An appraisal of new treatment approaches and overview of current therapies.

J Am Acad Dermatol. 2018 Jan;78(1):15-24

Authors: Strazzulla LC, Wang EHC, Avila L, Lo Sicco K, Brinster N, Christiano AM, Shapiro J

Abstract
Many therapies are available for the treatment of alopecia areata, including topical, systemic, and injectable modalities. However, these treatment methods produce variable clinical outcomes and there are no currently available treatments that induce and sustain remission. When making management decisions, clinicians must first stratify patients into pediatric versus adult populations. Disease severity should then be determined (limited vs extensive) before deciding the final course of therapy. The second article in this continuing medical education series describes the evidence supporting new treatment methods, among them Janus kinase inhibitors. We evaluate the evidence concerning the efficacy, side effects, and durability of these medications. An overview of conventional therapy is also provided with new insights gleaned from recent studies. Finally, future promising therapeutic options that have not yet been fully evaluated will also be presented.

PMID: 29241773 [PubMed - indexed for MEDLINE]



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Alopecia areata: Disease characteristics, clinical evaluation, and new perspectives on pathogenesis.

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Alopecia areata: Disease characteristics, clinical evaluation, and new perspectives on pathogenesis.

J Am Acad Dermatol. 2018 Jan;78(1):1-12

Authors: Strazzulla LC, Wang EHC, Avila L, Lo Sicco K, Brinster N, Christiano AM, Shapiro J

Abstract
Alopecia areata (AA) is a common, inflammatory, nonscarring type of hair loss. Significant variations in the clinical presentation of AA have been observed, ranging from small, well-circumscribed patches of hair loss to a complete absence of body and scalp hair. Patients affected by AA encompass all age groups, sexes, and ethnicities, and may experience frustration with the unpredictable nature of their disease for which there is currently no definitive treatment. The cause of AA remains incompletely understood, though it is believed to result-at least in part-from a loss of immune privilege in the hair follicle, autoimmune-mediated hair follicle destruction, and the upregulation of inflammatory pathways. Patients with AA frequently experience marked impairment in psychological well-being, self-esteem, and may be more likely to suffer from psychiatric comorbidities. Part one of this two-part continuing medical education series describes the epidemiology, clinical evaluation, prognosis, and recent advancements in the understanding of the pathogenesis of AA.

PMID: 29241771 [PubMed - indexed for MEDLINE]



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Burden of skin pain in atopic dermatitis.

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Burden of skin pain in atopic dermatitis.

Ann Allergy Asthma Immunol. 2017 Dec;119(6):548-552.e3

Authors: Vakharia PP, Chopra R, Sacotte R, Patel KR, Singam V, Patel N, Immaneni S, White T, Kantor R, Hsu DY, Silverberg JI

Abstract
BACKGROUND: Atopic dermatitis (AD) is associated with itch, skin inflammation and barrier disruption, and scratching, all of which may be associated with skin pain.
OBJECTIVE: To characterize the patient burden of skin pain in AD.
METHODS: We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist.
RESULTS: Overall, 305 patients (age range, 13-97 years) were included in the study, with 564 encounters. The cohort included 195 females (63.9%) and 193 whites (63.7%). The mean (SD) age at enrollment was 42.3 (18.1) years, and the mean (SD) age of patient-reported AD onset was 29.6 (31.9) years. At baseline, 144 patients (42.7%) reported skin pain in the past week, with 42 (13.8%) reporting severe or very severe pain. Twenty-four (16.8%) thought the skin pain was part of their itch, 16 (11.2%) from scratching, and 77 (72.0%) from both. Patients with skin pain were more likely to describe their itch using terms that resembled neuropathic pain. Prevalence of skin pain was increased in patients with vs without excoriations (72.6% vs 57.6%; χ2 test P = .02) but not other morphologic characteristics. Skin pain severity was most strongly correlated with the Patient-Oriented Eczema Measure (Spearman ρ = 0.54), followed by ItchyQOL (ρ = 0.52), 5-dimensions of itch scale (ρ = 0.47), Dermatology Life Quality Index (ρ = 0.45), numeric rating scale for itch (ρ = 0.43) and sleep (ρ = 0.36), Patient Health Questionnaire 9 (ρ = 0.36), patient-reported global AD severity (ρ = 0.34), Eczema Area and Severity Index (ρ = 0.23), and objective Scoring AD index (ρ = 0.20) (P < .001 for all). Patients with both severe itch and pain vs those with only one or neither symptom being severe had significant increases in all these measures.
CONCLUSION: Skin pain is a common and burdensome symptom in AD. Skin pain severity should be assessed with itch severity in AD patients and may be an important end point for monitoring treatment response.

PMID: 29223299 [PubMed - indexed for MEDLINE]



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Comparison of construct validity of two short forms of Stroke-Specific Quality of Life scale.

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Comparison of construct validity of two short forms of Stroke-Specific Quality of Life scale.

PLoS One. 2017;12(12):e0188478

Authors: Chou CY, Huang CY, Huang YJ, Lin GH, Huang SL, Lee SC, Hsieh CL

Abstract
BACKGROUND: No studies have compared the 2-factor structures of Wong's and Post's versions of the short-form Stroke-Specific Quality of Life (i.e., 12-item SSQOL) scale. This study compared the construct validity of 2 short-forms of the 12-item-SSQOL (not the 12-domain-SSQOL).
METHODS: Data were obtained from a previous validation study of the original 49-item SSQOL in 263 patients. Construct validity was tested by confirmatory factor analysis (CFA) to examine whether the two-factor structure, including psychosocial and physical domains, was supported in both versions. The CFA tested the data-model fit by indices: chi-square χ2/df ratio, root mean square error of approximation (RMSEA), comparative fit index (CFI), nonnormative fit index (NNFI), standard root mean square residual (SRMR), and parsimony normed fit index (PNFI). Item factor loadings (cutoffs: .50) were examined. Model fit was compared using Akaike information criterion (AIC) and consistent AIC (i.e., CAIC) values.
RESULTS: All model fit indices for Post's version fell within expected ranges: χ2/df ratio = 2.02, RMSEA = 0.05, CFI = 0.97, NNFI = 0.97, SRMR = 0.06, and PNFI = 0.76. In the psychosocial domain, the item factor loadings ranged from 0.46 to 0.63. In the physical domain, all items (except the language and vision items) had acceptable factor loadings (0.68 to 0.88). However, in Wong's version, none of the model indices met the criteria for good fit. In model fit comparisons, Post's version had smaller AIC and CAIC values than did Wong's version.
CONCLUSIONS: All fit indices supported Post's version, but not Wong's version. The construct validity of Post's version with a 2-factor structure was confirmed, and this version of the 12-item SSQOL is recommended.

PMID: 29211759 [PubMed - indexed for MEDLINE]



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The experience of stuttering among Ultra-Orthodox and Secular/Traditional Jews.

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The experience of stuttering among Ultra-Orthodox and Secular/Traditional Jews.

J Fluency Disord. 2017 Dec;54:24-34

Authors: Freud D, Ezrati-Vinacour R, Katz-Bernstein N, Fostick L

Abstract
PURPOSE: This groundbreaking research compares the experience of stuttering among adult male People Who Stutter (PWS) from the ultra-Orthodox (UO) Jewish community in Israel to those from Secular/Traditional (ST) backgrounds.
METHODS: Participants were 32 UO and 31 ST PWS, aged 18-67 years. Self-report questionnaires utilized: Perceived Stuttering Severity (PSS); Overall Assessment of the Speaker's Experience of Stuttering (OASES-A); Students' Life Satisfaction Scale (SLSS); Situation Avoidance Behavior Checklist (SABC). Demographic, religious, and stuttering information was collected. Groups were compared on scales, and correlations between scales and the PSS.
RESULTS: Subjective stuttering severity ratings were significantly higher among the UO. A significant group effect was found for the OASES-A quality of life subscale, but not other subscales. Significant positive correlations were found between: 1) PSS and OASES-A Total Impact; 2) PSS and 3 OASES subscales; and 3) PSS and SABC (indicating increased avoidance with increased stuttering severity rating). A significant negative correlation was found between the PSS and SLSS, indicating lower life satisfaction with higher rates of stuttering severity among the ST. Interestingly, when tested by group, significant correlations between the PSS and all other study measures were observed only among the ST.
CONCLUSION: UO participants showed higher subjective stuttering severity ratings, yet less impact on quality of life, and no correlation between subjective stuttering and other measures of stuttering experience. These novel findings may result from the combined protective effect of religiosity and socio-cultural characteristics on UO PWS' well-being, despite heightened concern about social consequences of stuttering within UO society.

PMID: 29195625 [PubMed - indexed for MEDLINE]



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Guiding principles for use of newer biologics and bronchial thermoplasty for patients with severe asthma.

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Guiding principles for use of newer biologics and bronchial thermoplasty for patients with severe asthma.

Ann Allergy Asthma Immunol. 2017 Dec;119(6):533-540

Authors: Blaiss MS, Castro M, Chipps BE, Zitt M, Panettieri RA, Foggs MB

Abstract
BACKGROUND: Severe asthma poses significant disease-related and economic burdens in the United States. Challenges in practice include how to define "severe asthma" for a given patient, knowing which are the right tests to perform and when, and having a better understanding of a patient's asthma phenotype. Furthermore, current guidelines do not address a clear, practical approach to treatment that is based on a patient's asthma phenotype.
OBJECTIVE: To develop a consensus on the definition of severe asthma, the role of biomarkers and phenotyping severe asthma, and the use of newer biologic therapies and bronchial thermoplasty to help guide practicing clinicians.
METHODS: A roundtable meeting was convened with a panel of severe asthma experts to discuss areas in practice that are not adequately addressed by current guidelines, specifically phenotype-guided treatment.
RESULTS: We describe a consensus on the definition of severe asthma, asthma phenotyping with the use of available biomarkers, and guiding principles for newer biologic therapies and bronchial thermoplasty.
CONCLUSION: To optimize therapy and improve outcomes such as daily symptoms, quality of life, exacerbations, and hospitalizations, a clear picture of a patient's asthma phenotype is needed to guide therapy. Determining asthma phenotypes is the foundation of precision medicine for this persistent, often difficult-to-treat disease.

PMID: 29103801 [PubMed - indexed for MEDLINE]



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Baseline asthma burden, comorbidities, and biomarkers in omalizumab-treated patients in PROSPERO.

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Baseline asthma burden, comorbidities, and biomarkers in omalizumab-treated patients in PROSPERO.

Ann Allergy Asthma Immunol. 2017 Dec;119(6):524-532.e2

Authors: Chipps BE, Zeiger RS, Luskin AT, Busse WW, Trzaskoma BL, Antonova EN, Pazwash H, Limb SL, Solari PG, Griffin NM, Casale TB

Abstract
BACKGROUND: Patients included in clinical trials do not necessarily reflect the real-world population.
OBJECTIVE: To understand the characteristics, including disease and comorbidity burden, of patients with asthma receiving omalizumab in a real-world setting.
METHODS: The Prospective Observational Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab (PROSPERO) was a US-based, multicenter, single-arm, and prospective study. Patients (≥12 years of age) with allergic asthma initiating omalizumab treatment based on physician-assessed need were included and followed for 12 months. Exacerbations, health care use, adverse events, and Asthma Control Test (ACT) scores were assessed monthly. Biomarkers (blood eosinophils, fractional exhaled nitric oxide, and periostin) were evaluated and patient-reported outcomes (Asthma Quality of Life Questionnaire for 12 Years and Older [AQLQ+12] and Work Productivity and Activity Impairment: Asthma questionnaire [WPAI:Asthma]) were completed at baseline and months 6 and 12. The Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) was completed at baseline and 12 months.
RESULTS: Most of the 806 enrollees (91.4%) were adults (mean age 47.3 years, SD 17.4), white (70.3%), and female (63.5%). Allergic comorbidity was frequently reported (84.2%), as were hypertension (35.5%) and depression (22.1%). In the 12 months before study entry, 22.1% of patients reported at least 1 asthma-related hospitalization, 60.7% reported at least 2 exacerbations, and 83.3% reported ACT scores no higher than 19 (uncontrolled asthma). Most patients had low biomarker levels based on prespecified cut-points. Baseline mean patient-reported outcome scores were 4.0 (SD 1.4) for AQLQ+12, 2.7 (SD 1.4) for MiniRQLQ, and 47.7 (SD 28.9) for WPAI:Asthma percentage of activity impairment and 33.5 (SD 28.7) for percentage of overall work impairment.
CONCLUSION: The population initiating omalizumab in PROSPERO reported poorly controlled asthma and a substantial disease burden.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01922037.

PMID: 29054589 [PubMed - indexed for MEDLINE]



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Contraceptive Coverage and the Balance Between Conscience and Access.

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Contraceptive Coverage and the Balance Between Conscience and Access.

JAMA. 2017 Dec 12;318(22):2179-2180

Authors: Stahl RY, Lynch HF

PMID: 29049513 [PubMed - indexed for MEDLINE]



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Predicting health-related quality of life in people living with HIV in Nepal: mental health disorders and substance use determinants.

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Predicting health-related quality of life in people living with HIV in Nepal: mental health disorders and substance use determinants.

AIDS Care. 2017 Sep;29(9):1137-1143

Authors: Pokhrel KN, Sharma VD, Shibanuma A, Pokhrel KG, Mlunde LB, Jimba M

Abstract
HIV-positive people often experience mental health disorders and engage in substance use. Such conditions tend to impair their health-related quality of life (QOL). Evidence, however, is limited about the influence of mental health disorders and substance use on QOL by gender. Also, little is known about the influences of anxiety and high levels of stress on QOL. We recruited 682 HIV-positive people in Nepal and measured their depression, anxiety, stress levels, substance use, and QOL. Multiple linear regressions assessed the association of mental health disorders and substance use with QOL. Presence of depressive symptoms was negatively associated with all domains of QOL including the physical (men: β = -0.68, p = 0.037; women: β = -1.37, p < 0.001) and the psychological (men: β = -1.08, p <  0.001; women: β = -1.13, p <  0.001). Those who experienced anxiety had lower scores in the physical (β = -0.89, p = 0.027) and psychological (β = -1.75, p = 0.018) QOL domains among men and in the spiritual QOL domain (β = -0.061, p = 0.043) among women. High stress levels were associated with lower scores across all QOL domains including the physical (men: β = -0.16, p < 0.001; women: β = -0.14, p <  0.001) and the psychological (men: β = -0.09, p < 0.001; women: β = -0.10, p < 0.001). Substance-using men were more likely to have lower scores in physical (β = -0.70, p = 0.039) and psychological (β = -0.073, p = 0.002) domains. Among women, meanwhile, substance use was negatively associated with the psychological domain only (β = -0.77, p = 0.005). In conclusion, mental health disorders and substance use had negative associations with QOL. Attention should be given to addressing the mental health care needs of HIV-positive people to improve their QOL.

PMID: 28547996 [PubMed - indexed for MEDLINE]



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