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Tuesday, April 10, 2018

Brain Metastases in Oncogene-Addicted Non-Small Cell Lung Cancer Patients: Incidence and Treatment

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J. Remon, Benjamin Besse

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Classical NF-κB Metabolically Reprograms Sarcoma Cells Through Regulation of Hexokinase 2

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Priya Londhe, Peter Y. Yu, Yuichi Ijiri, Katherine J. Ladner, Joelle M. Fenger, Cheryl London, Peter J. Houghton, Denis C. Guttridge

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Acuedan definiciones biológicas para investigar | Nuevo marco de investigación biológica para el Alzheimer

La Asociación de Alzheimer convoca un esfuerzo para actualizar la definición de la enfermedad

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Editorial Board

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Publication date: May 2018
Source:Peptides, Volume 103





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Toxins, Vol. 10, Pages 152: Bovine Peripheral Blood Mononuclear Cells Are More Sensitive to Deoxynivalenol Than Those Derived from Poultry and Swine

Toxins, Vol. 10, Pages 152: Bovine Peripheral Blood Mononuclear Cells Are More Sensitive to Deoxynivalenol Than Those Derived from Poultry and Swine

Toxins doi: 10.3390/toxins10040152

Authors: Barbara Novak Eleni Vatzia Alexandra Springler Alix Pierron Wilhelm Gerner Nicole Reisinger Sabine Hessenberger Gerd Schatzmayr Elisabeth Mayer

Deoxynivalenol (DON) is one of the most prevalent mycotoxins, contaminating cereals and cereal-derived products. Its derivative deepoxy-deoxynivalenol (DOM-1) is produced by certain bacteria, which either occur naturally or are supplemented in feed additive. DON-induced impairments in protein synthesis are particularly problematic for highly proliferating immune cells. This study provides the first comparison of the effects of DON and DOM-1 on the concanavalin A-induced proliferation of porcine, chicken, and bovine peripheral blood mononuclear cells (PBMCs). Therefore, isolated PBMCs were treated with DON (0.01–3.37 µM) and DOM-1 (1.39–357 µM) separately, and proliferation was measured using a bromodeoxyuridine (BrdU) assay. Although pigs are considered highly sensitive to DON, the present study revealed a substantially higher sensitivity of bovine (IC50 = 0.314 µM) PBMCs compared to chicken (IC50 = 0.691 µM) and porcine (IC50 = 0.693 µM) PBMCs. Analyses on the proliferation of bovine T-cell subsets showed that all major subsets, namely, CD4+, CD8β+, and γδ T cells, were affected to a similar extent. In contrast, DOM-1 did not affect bovine PBMCs, but reduced the proliferation of chicken and porcine PBMCs at the highest tested concentration (357 µM). Results confirm the necessity of feed additives containing DON-to-DOM-1-transforming bacteria and highlights species-specific differences in the DON sensitivity of immune cells.



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Different Levels of Expression of the Clock Protein PER and the Glial Marker REPO in Ensheathing and Astrocyte-Like Glia of the Distal Medulla of Drosophila Optic Lobe

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Wojciech Krzeptowski, Lucyna Walkowicz, Alicja Płonczyńska, Jolanta Górska-Andrzejak

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The Contribution of Different Components in QiShenYiQi Pills® to Its Potential to Modulate Energy Metabolism in Protection of Ischemic Myocardial Injury

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Yuan-Chen Cui, Li Yan, Chun-Shui Pan, Bai-He Hu, Xin Chang, Jing-Yu Fan, Jing-Yan Han

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Evaluation of Reference Genes for Real-Time Quantitative PCR Analysis in Larvae of Spodoptera litura Exposed to Azadirachtin Stress Conditions

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Benshui Shu, Jingjing Zhang, Gaofeng Cui, Ranran Sun, Veeran Sethuraman, Xin Yi, Guohua Zhong

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Brain Sciences, Vol. 8, Pages 64: Exploring Behavioral Correlates of Afferent Inhibition

Brain Sciences, Vol. 8, Pages 64: Exploring Behavioral Correlates of Afferent Inhibition

Brain Sciences doi: 10.3390/brainsci8040064

Authors: Claudia Turco Mitchell Locke Jenin El-Sayes Mark Tommerdahl Aimee Nelson

(1) Background: Afferent inhibition is the attenuation of the muscle response evoked from transcranial magnetic stimulation (TMS) by a prior conditioning electrical stimulus to a peripheral nerve. It is unclear whether the magnitude of afferent inhibition relates to sensation and movement; (2) Methods: 24 healthy, young adults were tested. Short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI) were obtained following median and digital nerve stimulation. Temporal tactile acuity was assessed with a temporal order judgement (TOJ) task, spatial tactile acuity was assessed using a grating orientation task (GOT), and fine manual dexterity was assessed with the Pegboard task; (3) Results: Correlation analyses revealed no association between the magnitude of SAI or LAI with performance on the TOJ, GOT, or Pegboard tasks; (4) Conclusion: The magnitude of SAI and LAI does not relate to performance on the sensory and motor tasks tested. Future studies are needed to better understand whether the afferent inhibition phenomenon relates to human behavior.



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Social Impact of Recharging Activity in Long-Term HRI and Verbal Strategies to Manage User Expectations During Recharge

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Amol Deshmukh, Katrin Solveig Lohan, Gnanathusharan Rajendran, Ruth Aylett

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A Protein-Truncating HSD17B13 Variant and Protection from Chronic Liver Disease

TBA

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Editors

EDITOR

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Editorial Board



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Clampless facilitated anastomosis with HEARSTRING to reduce cerebral damage during off-pump coronary bypass grafting. Don't forget it: Easy to use!

In their prospective randomized study, Halkos and colleagues1 highlight a strategy to reduce the risk of cerebral embolism during on-pump and off-pump aortic coronary bypass grafting (CABG) surgery. The authors compared 4 groups of patients according to the surgical technique used. Because of the low number of patients in each group, the main purpose of the study was to detect the high-intensity transient signals (HITS) by transcranial Doppler ultrasonography instead of the incidence of major neurologic events such as cerebral stroke.

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Table of Contents



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AATS Surgical Patient Safety Course 2018

June 29-30, 2018

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Discussion

Dr Shaf Keshavjee (Toronto, Ontario, Canada). Congratulations, Konrad, on an outstanding presentation, and I would like to also congratulate the Vienna group on their outstanding leadership in this area of extracorporeal membrane oxygenation (ECMO) support and ECMO in lung transplantation. I have no specific conflicts of interest to declare. Konrad, the first question I have for you is the primary graft dysfunction rate was not significantly different between the ECMO and the no ECMO group, but the long-term survival, as you have shown, was impressively better.

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We are on the slope together

"If in doubt, give the patient the benefit of the doubt."—Dr Robert Ginsberg1

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Data support continued role for straight deep hypothermic circulatory arrest

We thank Drs Formica, D'Allesandro, and Messina for their kind comments.

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Is parameter T staging influenced by tumor behavior?

We read with interest the article by Hattori and colleagues1 about the prognostic value of the ground glass opacity (GGO) component on prognosis and its effect on parameter T in non–small cell lung cancer staging. This is an extremely current and meaningful topic. In an extension of their previous article in 2016,2 the authors did a good job, and the article is well designed and written. Its central message is that if a nodule presents with a partial GGO feature, survival will be different from the same T stage pure solid tumor in early non–small cell lung cancer (N0, M0).

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Use of clampless facilitating devices in patients with low-grade aortic disease: is the cost justified by the theoretic risk reduction?

I appreciate the commentary of Formica and colleagues regarding the use of clampless facilitating devices (CFDs) in patients undergoing coronary artery bypass grafting (CABG). The quest to reduce stroke after CABG has led to numerous observational and prospective trials with a variety of approaches, including off-pump CABG, anaortic approaches, hybrid revascularization, and CFDs. With regard to my group's recent prospective, randomized trial,1 we agree with Formica and colleagues that there were limitations with our study, specifically that the primary end point was a surrogate for stroke, transcranial Doppler high-intensity transient signals (HITS) rather than a hard clinical end point.

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Straight deep hypothermic circulatory arrest: Should we definitively give up or should we keep on?

In their retrospective monocentric study, Damberg and colleagues1 highlight their experience with the use of deep hypothermic circulatory arrest (DHCA) as a cerebral protection strategy during aortic arch operations. The authors analyzed data on 613 consecutive patients between 2003 and 2015. The majority of patients (n = 529; 86.3%) underwent elective surgery, and 474 (77.3%) underwent hemiarch replacement. Total aortic arch replacement was performed in 125 patients (20.4%). The authors reported a stroke incidence of 2% (n = 12), whereas minor cerebral damage, such as seizure and temporary neurologic deficit, were observed in 1% (n = 6) and 5.1% (n = 31), respectively.

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Information for Readers



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Recent Papers in the Seminars and Op Techs

Readers who found these articles interesting may also like to read these papers that can be found in recent issues of our sister publications, Seminars in Thoracic and Cardiovascular Surgery and Operative Techniques in Thoracic and Cardiovascular Surgery.

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New era defining a novel clinical T staging in non–small cell lung cancer

We are grateful for the letter of Baisi et al1 regarding our recent study in the Journal.2

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ABTS Requirements for the 10-Year Milestone for Maintenance of Certification

Diplomates of the American Board of Thoracic Surgery (ABTS) who plan to participate in the 10-Year Milestone for the Maintenance of Certification (MOC) process as Certified-Active must hold a currently valid, full, and unrestricted license to practice medicine. Diplomates must have privileges at a hospital(s) accredited by the JCAHO or other institutions judged acceptable by the Board. Diplomates must also submit letter(s) of reference documenting their level of clinical activity and stature within the surgical community from the VP of Medical Affairs and one other responsible member on staff at their principal hospital.

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GSE31791 An Esrrb and Nanog Cell Fate Regulatory Module Controlled by Feedback Interactions [gene expression]

Contributors : Ana Sevilla ; Dimitri Papatsenko ; Amin Mazloom ; Huilei Xu ; Ana Vasileva ; Richard Unwin ; Gary LeRoy ; Edward Chen ; Francine Garrett ; Dung-Fang Lee ; Benjamin Trinite ; Ryan L Webb ; Zichen Wang ; Jie Su ; Julian Gingold ; Ari Melnick ; Benjamin Garcia ; Anthony Whetton ; B D MacArthur ; Avi Ma'ayan ; Ihor R Lemischka
Series Type : Expression profiling by array
Organism : Mus musculus

Cell fate decisions during development are governed by multi-factorial regulatory mechanisms including chromatin remodelling, DNA methylation, binding of transcription factors to specific loci, RNA transcription and protein synthesis. However, the mechanisms by which such regulatory 'dimensions' coordinate cell fate decisions are currently poorly understood. Here we quantified the multi-dimensional molecular changes that occur in mouse embryonic stem cells (mESCs) upon depletion of Estrogen related receptor beta (Esrrb), a key pluripotency regulator. Analyses of coordinated expression changes identified strikingly different epigenetic regulatory patterns of pluripotency and differentiation states. Comparative analyses of expression changes subsequent to depletion of Esrrb or Nanog, indicated that a system of interlocked feed-forward loops involving both factors plays a central part in regulating the timing of mESC fate decisions. Taken together, our meta-analyses support a hierarchical model in which pluripotency is maintained by an Oct4-Sox2 regulatory module, while the timing of differentiation is regulated by a Nanog-Esrrb



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GSE33191 An Esrrb and Nanog Cell Fate Regulatory Module Controlled by Feedback Interactions [methylation]

Contributors : Ana Sevilla ; Dimitri Papatsenko ; Amin Mazloom ; Huilei Xu ; Ana Vasileva ; Richard Unwin ; Gary LeRoy ; Edward Chen ; Francine Garrett ; Dung-Fang Lee ; Benjamin Trinite ; Ryan L Webb ; Zichen Wang ; Jie Su ; Julian Gingold ; Ari Melnick ; Benjamin Garcia ; Anthony Whetton ; B D MacArthur ; Avi Ma'ayan ; Ihor R Lemischka
Series Type : Methylation profiling by genome tiling array
Organism : Mus musculus

Cell fate decisions during development are governed by multi-factorial regulatory mechanisms including chromatin remodelling, DNA methylation, binding of transcription factors to specific loci, RNA transcription and protein synthesis. However, the mechanisms by which such regulatory 'dimensions' coordinate cell fate decisions are currently poorly understood. Here we quantified the multi-dimensional molecular changes that occur in mouse embryonic stem cells (mESCs) upon depletion of Estrogen related receptor beta (Esrrb), a key pluripotency regulator. Analyses of coordinated expression changes identified strikingly different epigenetic regulatory patterns of pluripotency and differentiation states. Comparative analyses of expression changes subsequent to depletion of Esrrb or Nanog, indicated that a system of interlocked feed-forward loops involving both factors plays a central part in regulating the timing of mESC fate decisions. Taken together, our meta-analyses support a hierarchical model in which pluripotency is maintained by an Oct4-Sox2 regulatory module, while the timing of differentiation is regulated by a Nanog-Esrrb



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GSE112900 Expression data from knockdown of UGT8 in MDA-MB231 cells

Contributors : Qianhua Cao ; Chenfang Dong
Series Type : Expression profiling by array
Organism : Homo sapiens

UGT8 is the first key enzyme that catalyzes the transfer of galactose to ceramide for the synthesis of galactosylceramide. We used microarray analysis to identify the genes that are regulated by UGT8 in MDA-MB231 cells.



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GSE112911 Genome-wide analysis of Differential Responses of Pseudomonas aeruginosa PAO1 and PA14 cells to Interfacial Stress

Contributor : Tagbo Niepa
Series Type : Expression profiling by high throughput sequencing
Organism : Pseudomonas aeruginosa PA14 ; Pseudomonas aeruginosa PAO1

Analysis of gene expression level of P. aeruginosa confined to Hexadecane-water interfaces. The hypothesis tested in the present study was to determine if interfacial confinements at hexadecane-water affect microbial metabolism through regulation of stress response.



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GSE104075 Chromatin accessibility based characterization of gene regulatory network of P. falciparum blood stage development

Contributors : Richárd Bártfai ; Christa G Toenhake ; Sabine K Fraschka
Series Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencing
Organism : Plasmodium falciparum

We present ATAC-seq combined with direction RNA seq data for eight time points across the intraerythorcytic development cycle of Plasmodium falciparum 3D7. ATAC peaks were called by MACS2 using ATAC-seq libraries generated with genomic DNA as a control. The majority of identified ATAC peaks were located in intergenic regions and captured most (95%) of previously identified binding sites of the transcription factor required for the expression of most invasion-related genes PfAP2-I (Santos et al., 2017). The robustness of the ATAC-seq dataset was confirmed with a second biological replicate both in terms of peak location and relative peak accessibility pattern. Peaks were assigned to the closest gene and the majority of peaks showed a clear positive correlation between chromatin accessibility pattern and relative mRNA abundance (Pearson correlation > 0.6). In addition, they were sufficient to drive the stage-specific expression of a reporter gene, demonstrating their functionality. Motif searches restricted to accessible regions showed enrichment of several predicted Plasmodium motifs while also predicting several novel regulatory elements.



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GSE31842 An Esrrb and Nanog Cell Fate Regulatory Module Controlled by Feedback Interactions

Series Type : Genome binding/occupancy profiling by high throughput sequencing ; Expression profiling by array ; Methylation profiling by genome tiling array ; Non-coding RNA profiling by array
Organism : Homo sapiens ; Human alphaherpesvirus 1 ; Human alphaherpesvirus 2 ; Human betaherpesvirus 5 ; Human gammaherpesvirus 4 ; Human gammaherpesvirus 8 ; Human immunodeficiency virus 1 ; Human polyomavirus 1 ; JC polyomavirus ; Macaca mulatta polyomavirus 1 ; Merkel cell polyomavirus ; Murid betaherpesvirus 1 ; Murid gammaherpesvirus 4 ; Mus musculus ; Rattus norvegicus

This SuperSeries is composed of the SubSeries listed below.



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GSE57371 An Esrrb and Nanog Cell Fate Regulatory Module Controlled by Feedback Interactions [miRNA profiling]

Contributors : Ana Sevilla ; Dimitri Papatsenko ; Amin Mazloom ; Huilei Xu ; Ana Vasileva ; Richard Unwin ; Gary LeRoy ; Edward Chen ; Francine Garrett ; Dung-Fang Lee ; Benjamin Trinite ; Ryan L Webb ; Zichen Wang ; Jie Su ; Julian Gingold ; Ari Melnick ; Benjamin Garcia ; Anthony Whetton ; B D MacArthur ; Avi Ma'ayan ; Ihor R Lemischka
Series Type : Non-coding RNA profiling by array
Organism : Homo sapiens ; Human alphaherpesvirus 1 ; Human alphaherpesvirus 2 ; Human betaherpesvirus 5 ; Human gammaherpesvirus 4 ; Human gammaherpesvirus 8 ; Human immunodeficiency virus 1 ; Human polyomavirus 1 ; JC polyomavirus ; Macaca mulatta polyomavirus 1 ; Merkel cell polyomavirus ; Murid betaherpesvirus 1 ; Murid gammaherpesvirus 4 ; Mus musculus ; Rattus norvegicus

Cell fate decisions during development are governed by multi-factorial regulatory mechanisms including chromatin remodelling, DNA methylation, binding of transcription factors to specific loci, RNA transcription and protein synthesis. However, the mechanisms by which such regulatory 'dimensions' coordinate cell fate decisions are currently poorly understood. Here we quantified the multi-dimensional molecular changes that occur in mouse embryonic stem cells (mESCs) upon depletion of Estrogen related receptor beta (Esrrb), a key pluripotency regulator. Analyses of coordinated expression changes identified strikingly different epigenetic regulatory patterns of pluripotency and differentiation states. Comparative analyses of expression changes subsequent to depletion of Esrrb or Nanog, indicated that a system of interlocked feed-forward loops involving both factors plays a central part in regulating the timing of mESC fate decisions. Taken together, our meta-analyses support a hierarchical model in which pluripotency is maintained by an Oct4-Sox2 regulatory module, while the timing of differentiation is regulated by a Nanog-Esrrb



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GSE31640 An Esrrb and Nanog Cell Fate Regulatory Module Controlled by Feedback Interactions [ChIP-seq]

Contributors : Ana Sevilla ; Dimitri Papatsenko ; Amin Mazloom ; Huilei Xu ; Ana Vasileva ; Richard Unwin ; Gary LeRoy ; Edward Chen ; Francine Garrett ; Dung-Fang Lee ; Benjamin Trinite ; Ryan L Webb ; Zichen Wang ; Jie Su ; Julian Gingold ; Ari Melnick ; Benjamin Garcia ; Anthony Whetton ; B D MacArthur ; Avi Ma'ayan ; Ihor R Lemischka
Series Type : Genome binding/occupancy profiling by high throughput sequencing
Organism : Mus musculus

Cell fate decisions during development are governed by multi-factorial regulatory mechanisms including chromatin remodelling, DNA methylation, binding of transcription factors to specific loci, RNA transcription and protein synthesis. However, the mechanisms by which such regulatory 'dimensions' coordinate cell fate decisions are currently poorly understood. Here we quantified the multi-dimensional molecular changes that occur in mouse embryonic stem cells (mESCs) upon depletion of Estrogen related receptor beta (Esrrb), a key pluripotency regulator. Analyses of coordinated expression changes identified strikingly different epigenetic regulatory patterns of pluripotency and differentiation states. Comparative analyses of expression changes subsequent to depletion of Esrrb or Nanog, indicated that a system of interlocked feed-forward loops involving both factors plays a central part in regulating the timing of mESC fate decisions. Taken together, our meta-analyses support a hierarchical model in which pluripotency is maintained by an Oct4-Sox2 regulatory module, while the timing of differentiation is regulated by a Nanog-Esrrb



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IJMS, Vol. 19, Pages 1150: Localization Microscopy of Actin Cytoskeleton in Human Platelets

IJMS, Vol. 19, Pages 1150: Localization Microscopy of Actin Cytoskeleton in Human Platelets

International Journal of Molecular Sciences doi: 10.3390/ijms19041150

Authors: Sandra Mayr Fabian Hauser Anja Peterbauer Andreas Tauscher Christoph Naderer Markus Axmann Birgit Plochberger Jaroslaw Jacak

Here, we measure the actin cytoskeleton arrangement of different morphological states of human platelets using a new protocol for photo-switching of rhodamine class fluorophores. A new medium composition was established for imaging the cytoskeleton using Alexa Fluor 488 conjugated to phalloidin. Morphological states of platelets bound to a glass substrate are visualized and quantified by two-dimensional localization microscopy at nanoscopic resolution. Marker-less drift correction yields localization of individual Alexa 488 conjugated to phalloidin with a positional accuracy of 12 nm.



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Down-Regulated miR-125a-5p Promotes the Reprogramming of Glucose Metabolism and Cell Malignancy by Increasing Levels of CD147 in Thyroid Cancer

Thyroid, Ahead of Print.


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Reply to Rucinski et. al. Letter



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Eight years of clinical Legionella PCR testing illustrate seasonal pattern

LegionellaPCRsummerlegionellosis

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Factors Associated With Prolonged Viral Shedding in Patients With Avian Influenza A(H7N9) Virus Infection

Abstract
Background
Data are limited on the impact of neuraminidase inhibitor (NAI) treatment on avian influenza A(H7N9) virus RNA shedding.
Methods
In this multicenter, retrospective study, data were collected from adults hospitalized with A(H7N9) infection during 2013–2017 in China. We compared clinical features and A(H7N9) shedding among patients with different NAI doses and combination therapies and evaluated factors associated with A(H7N9) shedding, using Cox proportional hazards regression.
Results
Among 478 patients, the median age was 56 years, 71% were male, and 37% died. The median time from illness onset to NAI treatment initiation was 8 days (interquartile range [IQR], 6–10 days), and the median duration of A(H7N9) RNA detection from onset was 15.5 days (IQR, 12–20 days). A(H7N9) RNA shedding was shorter in survivors than in patients who died (P < .001). Corticosteroid administration (hazard ratio [HR], 0.62 [95% confidence interval {CI}, .50–.77]) and delayed NAI treatment (HR, 0.90 [95% CI, .91–.96]) were independent risk factors for prolonged A(H7N9) shedding. There was no significant difference in A(H7N9) shedding duration between NAI combination treatment and monotherapy (P = .65) or between standard-dose and double-dose oseltamivir treatment (P = .70).
Conclusions
Corticosteroid therapy and delayed NAI treatment were associated with prolonged A(H7N9) RNA shedding. NAI combination therapy and double-dose oseltamivir treatment were not associated with a reduced A(H7N9) shedding duration as compared to standard-dose oseltamivir.

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Mild Blast Injury Produces Acute Changes in Basal Intracellular Calcium Levels and Activity Patterns in Mouse Hippocampal Neurons

Journal of Neurotrauma, Ahead of Print.


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Letter in response to Google DeepMind and healthcare in an age of algorithms



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The Heart of the Matter: An artful show helps heal broken hearts

A new show that lets you hold a heart in your hands may help people suffering from complex conditions get a much better feel for them

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Life on nearest exoplanet may have been wiped out by superflare

Bad news for life near Proxima Centauri – the star has been seen emitting explosive blasts of radiation that would destroy the ozone on its Earth-like planet

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EphA3 maintains radioresistance in head and neck cancers through epithelial mesenchymal transition

Publication date: Available online 10 April 2018
Source:Cellular Signalling
Author(s): Song Hee Kim, Won Hyeok Lee, Seong Who Kim, Je Hyoung Uk, Jong Cheol Lee, Hyo Won Chang, Young Min Kim, Kyungbin Kim, Sang Yoon Kim, Myung Woul Han
Radiotherapy is a well-established therapeutic modality used in the treatment of many cancers. However, radioresistance remains a serious obstacle to successful treatment. Radioresistance can cause local recurrence and distant metastases in some patients after radiation treatment. Thus, many studies have attempted to identify effective radiosensitizers. Eph receptor functions contribute to tumor development, modulating cell-cell adhesion, invasion, neo-angiogenesis, tumor growth and metastasis. However, the role of EphA3 in radioresistance remains unclear. In the current study, we established a stable radioresistant head and neck cancer cell line (AMC HN3R cell line) and found that EphA3 was expressed predominantly in the radioresistant head and neck cancer cell line through DNA microarray, real time PCR and Western blotting. Additionally, we found that EphA3 was overexpressed in recurrent laryngeal cancer specimens after radiation therapy. EphA3 mediated the tumor invasiveness and migration in radioresistant head and neck cancer cell lines and epithelial mesenchymal transition- related protein expression. Inhibition of EphA3 enhanced radiosensitivity in the AMC HN 3R cell line in vitro and in vivo study. In conclusion, our results suggest that EphA3 is overexpressed in radioresistant head and neck cancer and plays a crucial role in the development of radioresistance in head and neck cancers by regulating the epithelial mesenchymal transition pathway.



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Characterization of AJH-836, a DAG-lactone with selectivity for novel PKC isozymes [Signal Transduction]

Diacylglycerol (DAG) is a key lipid second messenger downstream of cellular receptors that binds to the C1 domain in many regulatory proteins. Protein kinase C (PKC) isoforms constitute the most prominent family of signaling proteins with DAG-responsive C1 domains, but six other families of proteins, including the chimaerins, Ras-guanyl nucleotide releasing proteins (RasGRPs), and Munc13 isoforms, also play important roles. Their significant involvement in cancer, immunology, and neurobiology has driven intense interest in the C1 domain as a therapeutic target. As with other classes of targets, however, a key issue is the establishment of selectivity. Here, using [3H]phorbol 12,13-dibutyrate ([3H]PDBu) competition binding assays, we found that a synthetic DAG-lactone, AJH-836, preferentially binds to the novel PKC isoforms PKCδ and PKC relative to classic PKCα and PKCβII. Assessment of intracellular translocation, a hallmark for PKC activation, revealed that AJH-836 treatment stimulated a striking preferential redistribution of PKC to the plasma membrane relative to PKCα. Moreover, unlike with the prototypical phorbol ester phorbol myristate acetate (PMA), prolonged exposure of cells with AJH-836 selectively down-regulated PKCδ and PKC without affecting PKCα expression levels. Biologically, AJH-836 induced major changes in cytoskeletal reorganization in lung cancer cells, as determined by the formation of membrane ruffles, via activation of novel PKCs. We conclude that AJH-836 represents a C1 domain ligand with PKC-activating properties distinct from those of natural DAGs and phorbol esters. Our study supports the feasibility of generating selective C1 domain ligands that promote novel biological response patterns.

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Structural model of a porin-cytochrome electron conduit from the outer membrane of a metal reducing bacterium suggests electron transfer via periplasmic redox partners. [Protein Structure and Folding]

Many subsurface microorganisms couple their metabolism to the reduction or oxidation of extracellular substrates. For example, anaerobic mineral-respiring bacteria can use external metal oxides as terminal electron acceptors during respiration. Porin–cytochrome complexes facilitate the movement of electrons generated through intracellular catabolic processes across the bacterial outer membrane to these terminal electron acceptors. In the mineral-reducing model bacterium Shewanella oneidensis MR-1, this complex is composed of two decaheme cytochromes (MtrA and MtrC) and an outer-membrane β-barrel (MtrB). However, the structures and mechanisms by which porin–cytochrome complexes transfers electrons are unknown. Here, we used small-angle neutron scattering (SANS) to study the molecular structure of the transmembrane complexes MtrAB and MtrCAB. Ab initio modeling of the scattering data yielded a molecular envelope with dimensions of ~105 × 60 × 35 Ã… for MtrAB and ~170 × 60 × 45 Ã… for MtrCAB. The shapes of these molecular envelopes suggested that MtrC interacts with the surface of MtrAB, extending ~70 Ã… from the membrane surface and allowing the terminal hemes to interact with both MtrAB and an extracellular acceptor. The data also reveal that MtrA fully extends through the length of MtrB, with ~30 Ã… being exposed into the periplasm. Proteoliposome models containing membrane associated MtrCAB and internalized small tetraheme cytochrome (STC) indicate that MtrCAB could reduce Fe(III) citrate with STC as an electron donor, disclosing a direct interaction between MtrCAB and STC. Taken together, both structural and proteoliposome experiments support porin-cytochrome–mediated electron transfer via periplasmic cytochromes such as STC.

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TLR4, TRIF, and MyD88 are essential for myelopoiesis and CD11c+ adipose tissue macrophage production in obese mice [Metabolism]

Obesity induced chronic inflammation is associated with metabolic disease. Results from mouse models utilizing a high-fat diet (HFD) have indicated that an increase in activated macrophages, including CD11c+ adipose tissue macrophages (ATMs), contributes to insulin resistance. Obesity primes myeloid cell production from hematopoietic stem cells (HSCs), and toll-like receptor 4 (TLR4) and the downstream TIR domain–containing adapter protein–inducing interferon-β (TRIF)- and MyD88-mediated pathways regulate production of similar myeloid cells after lipopolysaccharide stimulation. However, the role of these pathways in HFD-induced myelopoiesis are unknown. We hypothesized that saturated fatty acids and HFD alter myelopoiesis by activating TLR4 pathways in HSCs, differentially producing pro-inflammatory CD11c+myeloid cells that contribute to obesity-induced metabolic disease. Results from reciprocal bone marrow transplants (BMTs) with Tlr4-/- and wildtype (WT) mice indicated that TLR4 is required for HFD-induced myelopoiesis and production of CD11c+ ATMs. Experiments with homozygous knockouts of Irakm (encodinga suppressor of MyD88 inactivation) and Trif in competitive BMTs revealed that MyD88 is required for HFD expansion of granulocyte monocyte progenitors and that Trif is required for pregranulocyte macrophage progenitor expansion. A comparison of WT, Tlr4-/-, Myd88-/-, and Trif-/-mice on HFD demonstrated that TLR4 plays a role in the production of CD11c+ ATMs, and both Myd88-/- and Trif-/- mice produced fewer ATMs than WT mice. Moreover, HFD-induced TLR4 activation inhibited macrophage proliferation, leading to greater accumulation of recruited CD11c+ ATMs. Our results indicate that HFD potentiates TLR4 and both its MyD88 and TRIF mediated downstream pathways within progenitors and adipose tissue and leads to macrophage polarization.

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IJMS, Vol. 19, Pages 1148: Deoxyribonucleic Acid Damage and Repair: Capitalizing on Our Understanding of the Mechanisms of Maintaining Genomic Integrity for Therapeutic Purposes

IJMS, Vol. 19, Pages 1148: Deoxyribonucleic Acid Damage and Repair: Capitalizing on Our Understanding of the Mechanisms of Maintaining Genomic Integrity for Therapeutic Purposes

International Journal of Molecular Sciences doi: 10.3390/ijms19041148

Authors: Jolene Helena Anna Joubert Simone Grobbelaar Elsie Nolte Marcel Nel Michael Pepper Magdalena Coetzee Anne Mercier

Deoxyribonucleic acid (DNA) is the self-replicating hereditary material that provides a blueprint which, in collaboration with environmental influences, produces a structural and functional phenotype. As DNA coordinates and directs differentiation, growth, survival, and reproduction, it is responsible for life and the continuation of our species. Genome integrity requires the maintenance of DNA stability for the correct preservation of genetic information. This is facilitated by accurate DNA replication and precise DNA repair. DNA damage may arise from a wide range of both endogenous and exogenous sources but may be repaired through highly specific mechanisms. The most common mechanisms include mismatch, base excision, nucleotide excision, and double-strand DNA (dsDNA) break repair. Concurrent with regulation of the cell cycle, these mechanisms are precisely executed to ensure full restoration of damaged DNA. Failure or inaccuracy in DNA repair contributes to genome instability and loss of genetic information which may lead to mutations resulting in disease or loss of life. A detailed understanding of the mechanisms of DNA damage and its repair provides insight into disease pathogeneses and may facilitate diagnosis and the development of targeted therapies.



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IJMS, Vol. 19, Pages 1149: The Role, Involvement and Function(s) of Interleukin-35 and Interleukin-37 in Disease Pathogenesis

IJMS, Vol. 19, Pages 1149: The Role, Involvement and Function(s) of Interleukin-35 and Interleukin-37 in Disease Pathogenesis

International Journal of Molecular Sciences doi: 10.3390/ijms19041149

Authors: Ramatu Omenesa Bello Voon Chin Mohammad Abd Rachman Isnadi Roslaini Abd Majid Maizaton Atmadini Abdullah Tze Lee Zainul Amiruddin Zakaria Mohd Hussain Rusliza Basir

The recently identified cytokines—interleukin (IL)-35 and interleukin (IL)-37—have been described for their anti-inflammatory and immune-modulating actions in numerous inflammatory diseases, auto-immune disorders, malignancies, infectious diseases and sepsis. Either cytokine has been reported to be reduced and in some cases elevated and consequently contributed towards disease pathogenesis. In view of the recent advances in utilizing cytokine profiles for the development of biological macromolecules, beneficial in the management of certain intractable immune-mediated disorders, these recently characterized cytokines (IL-35 and IL-37) offer potential as reasonable targets for the discovery of novel immune-modulating anti-inflammatory therapies. A detailed comprehension of their sophisticated regulatory mechanisms and patterns of expression may provide unique opportunities for clinical application as highly selective and target specific therapeutic agents. This review seeks to summarize the recent advancements in discerning the dynamics, mechanisms, immunoregulatory and anti-inflammatory actions of IL-35 and IL-37 as they relate to disease pathogenesis.



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Suggestions Offered to Reduce Physician Frustration With EHRs

TUESDAY, April 10, 2018 -- Changes can be implemented to help reduce physician frustration with electronic health records (EHRs), according to an article published in Medical Economics. In order to help physicians become more efficient and reduce...

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New Staging System Predicts CKD Progression in Children

TUESDAY, April 10, 2018 -- A new staging system can help better predict the length of time until a child with chronic kidney disease (CKD) will progress to end-stage renal disease (ESRD), according to a study published online April 10 in the...

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Polycystic Ovary Syndrome Tied to Risk of Mental Health Issues

TUESDAY, April 10, 2018 -- Polycystic ovary syndrome (PCOS) is associated with higher risk of psychiatric conditions, according to a study published online April 10 in the Journal of Clinical Endocrinology & Metabolism. Thomas R. Berni, from...

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Considerable Differences in Burden of Disease at State Level

TUESDAY, April 10, 2018 -- There are considerable differences in the burden of disease at the state level, according to a study published in the April 10 issue of the Journal of the American Medical Association. Ali H. Mokdad, Ph.D., from the...

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Metabolic Syndrome Common in Patients With Lupus

TUESDAY, April 10, 2018 -- As with the general population, metabolic syndrome (MetS) is common among patients with systemic lupus erythematosus (SLE), according to a study published online April 3 in the International Journal of Rheumatic...

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The epidemiology of Helicobacter pylori infection in Europe and the impact of lifestyle on its natural evolution toward stomach cancer after infection: A systematic review

Helicobacter, EarlyView.


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Bufalin suppresses endometriosis progression by inducing pyroptosis and apoptosis

The steroid receptor coactivator (SRC)-1 isoform/estrogen receptor (ER)-β axis has an essential role in endometriosis progression. In this context, therefore, bufalin was employed as a 'tool compound' to evaluate inhibitors of SRC in alternative endometriosis treatment. Bufalin effectively suppressed the growth of primary human endometrial stroma cells isolated from endometriosis patients compared to women without endometriosis and immortalized human endometrial epithelial and stromal cells expressing the SRC-1 isoform compared to their parental cells in vitro. In vivo, compared to the vehicle, bufalin treatment significantly suppressed the growth of endometriotic lesions in mice with surgically induced endometriosis because bufalin disrupted the functional axis of SRC-1 isoform/ERβ by increasing SRC-1 isoform protein stability, hyperactivating the transcriptional activity of the SRC-1 isoform, and degrading the ERβ protein by proteasome 26S subunit, non-ATPase 2 in endometriotic lesions. Bufalin treatment elevated the apoptosis signaling in epithelial cells of endometriotic lesions. In stromal cells of endometriotic lesions, bufalin treatment increased the levels of pyroptosis markers (caspase 1 and the active form of interleukin 1β) and reduced proliferation. In addition, bufalin treatment increased the expression levels of endoplasmic reticulum (ER)-stress markers (PKR-like ER kinase, protein disulfide isomerase and binding immunoglobulin) in endometriotic lesions. Collectively, the bufalin-induced disruption of the SRC-1 isoform/ERβ axis might dysregulate apoptosis, pyroptosis and ER-stress signaling in endometriotic lesions, causing the suppression of endometriosis. Therefore, future generations of SRC-modulators could be employed as an alternative medical approach for endometriosis treatment.



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Estrogen receptor subtypes dictate the proliferative nature of the mammary gland

Estrogen induces proliferation of breast epithelial cells and is responsible for breast development at puberty. This tightly regulated control is lost in estrogen receptor positive (ER+) breast cancers, which comprise over 70% of all breast cancers. Currently breast cancer diagnosis and treatment considers only the α isoform of ER, however there is a second ER, ERβ. Whilst ERα mediates estrogen-driven proliferation of the normal breast in puberty and breast cancers, ERβ has been shown to exert an anti-proliferative effect on the normal breast. It is not known how the expression of each ER (alone or in combination) correlates with the ability of estrogen to induce proliferation in the breast. We assessed the levels of each ER in normal mouse mammary glands subdivided into proliferative and non-proliferative regions. ERα was most abundant in the proliferative regions of younger mice with ERβ expressed most abundantly in old mice. We correlated this expression profile with function by showing the ability of estrogen to induce proliferation was reduced in older mice. To show that the ER profile associated with breast cancer risk we assessed ER expression in parous mice which are known to have a reduced risk of developing ERα breast cancer. ERα expression was significantly decreased yet co-localisation analysis revealed ERβ expression increased with parity. Parous mice had less unopposed nuclear ERα expression and increased levels of ERβ. These changes suggest the nuclear expression of ERs dictates the proliferative nature of the breast and may explain the decreased breast cancer risk with parity.



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Ice‐marginal forced regressive deltas in glacial lake basins: geomorphology, facies variability and large‐scale depositional architecture

Boreas, EarlyView.


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Editorial Board

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Publication date: 1 April 2018
Source:Journal of Neuroscience Methods, Volume 299





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The Architecture of Interaction Between Visual Working Memory and Visual Attention.

Author: Bahle, Brett; Beck, Valerie M.; Hollingworth, Andrew
DOI: 10.1037/xhp0000509
Publication Date: POST AUTHOR CORRECTIONS, 9 April 2018


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Emotional Prosody of Task-Irrelevant Speech Interferes With the Retention of Serial Order.

Author: Kattner, Florian; Ellermeier, Wolfgang
DOI: 10.1037/xhp0000537
Publication Date: POST AUTHOR CORRECTIONS, 9 April 2018


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Combining CO2 reduction with propane oxidative dehydrogenation over bimetallic catalysts

41467_2018_3793_Fig2_HTML.jpg

Combining CO2 reduction with propane oxidative dehydrogenation over bimetallic catalysts

Combining CO<sub>2</sub> reduction with propane oxidative dehydrogenation over bimetallic catalysts, Published online: 11 April 2018; doi:10.1038/s41467-018-03793-w

The oxidative dehydrogenation of propane by CO2 (CO2-ODHP) can potentially fill the gap of propylene production while consuming a greenhouse gas. Here, the authors identify non-precious FeNi and precious NiPt catalysts supported on CeO2 as promising catalysts for CO2-ODHP and dry reforming, respectively, in flow reactor studies.

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Combining chloroquine with RAD001 inhibits tumor growth in a NEN mouse model

NEN patients often require systemic treatment, which is frequently limited by the emergence of drug resistance. mTOR inhibitors (mTORi) such as RAD001 (everolimus) has been shown to inhibit tumor progression. mTORi stimulates autophagy, a degradation pathway that might promote the survival of tumor cells that are exposed to anti-cancer therapy. Chloroquine (CQ), a well-known anti-malarial and anti-rheumatic drug, suppress autophagy. Based on our previous results, we hypothesized that CQ may enhance the anti-tumorigenic effects of mTORi by inhibiting autophagy. In the current study we aim to examine the anti-tumorigenic effect of CQ, alone or in combination with RAD001. We established a NEN subcutaneous xenograft mouse model, and evaluated the effect of the drugs on tumor growth, mTOR pathway, autophagy and apoptosis. We present here that CQ alone and in combination with RAD001 significantly decreased tumor volume. Histopathological analysis revealed that the combination of CQ and RAD001 markedly inhibited mTOR activity and tumor cell growth, along with accumulation of autophagosomes and increased apoptosis. Therefore we concluded that CQ enhances the anti-tumorigenic effect of RAD001 in vivo by inhibiting autophagy. Clinical trials addressing the effects of CQ therapy on tumor progression in patients with NENs, mainly in those treated with mTORi, are warranted.



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Frequency of Patent Foramen Ovale and Migraine in Patients With Cryptogenic Stroke [Original Contributions]

Background and Purpose—Individuals with migraine are at higher risk for stroke, but the mechanism has not been established. On the basis of the association between migraine and intracardiac right-to-left shunt, it has been proposed that stroke in migraineurs could be caused by a paradoxical embolus passing through a patent foramen ovale (PFO) or pulmonary arteriovenous malformation. The aim of this study was to determine the prevalence of PFO with right-to-left shunt in patients who presented with cryptogenic stroke and had a history of migraine.Methods—Patients between 18 and 60 years old who presented with an ischemic stroke were characterized based on ASCOD phenotyping (atherosclerosis; small-vessel disease; cardiac pathology; other causes; dissection). A migraine diagnosis was identified by reviewing physician notes, and frequent aura was defined if present in at least 50% of attacks. A PFO with right-to-left shunt diagnosis was identified by the presence of a positive bubble contrast study with either transcranial Doppler, transthoracic, or transesophageal echocardiography.Results—Of the 712 patients who presented with ischemic stroke, 127 (18%) were diagnosed as cryptogenic; 68 patients had adequate testing for PFO and a documented migraine history. The prevalence of PFO in patients with cryptogenic stroke without migraine was elevated (59%) compared with the general population (18%). Patients with both cryptogenic stroke and migraine had a higher prevalence of PFO (79%). In patients with cryptogenic stroke who had migraine with frequent aura, the prevalence of PFO was 93%. Only 5 patients (4%) had a history compatible with migrainous infarction.Conclusions—In patients with cryptogenic stroke who have migraine, there is a high prevalence (79%) of PFO with right-to-left shunt. The timing of the stroke in migraineurs is usually not related to a migraine attack. These observations are consistent with the hypothesis that the mechanism of stroke in migraineurs is most likely because of a paradoxical embolus. Future cryptogenic stroke classification schemes should consider including PFO as a separate etiologic category.

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Impact of Smoking on Clinical Outcome and Recanalization After Intravenous Thrombolysis for Stroke [Original Contributions]

Background and Purpose—The impact of smoking on prognosis after stroke is controversial. We aimed to assess the relationship between smoking status and stroke outcome after intravenous thrombolysis in a large cohort study by adjusting for potential confounders and incorporating recanalization rates.Methods—In a prospective observational multicenter study, we analyzed baseline and outcome data of consecutive patients with acute ischemic stroke treated with intravenous thrombolysis. Using uni- and multivariable modeling, we assessed whether smoking was associated with favorable outcome (modified Rankin Scale score of 0–1) and mortality. In addition, we also measured the occurrence of symptomatic intracranial hemorrhage and recanalization of middle cerebral artery. Patients reporting active cigarette use were classified as smokers.Results—Of 1865 patients, 19.8% were smokers (n=369). They were younger (mean 63.5 versus 71.3 years), less often women (56% versus 72.1%), and suffered less often from hypertension (61.3% versus 70.1%) and atrial fibrillation (22.7% versus 35.6%) when compared with nonsmokers. Favorable outcome and 3-month mortality were in favor of smokers in unadjusted analyses (45.8% versus 39.5% and 9.3% versus 15.8%, respectively), whereas symptomatic intracranial hemorrhage was comparable in both cohorts. Smoking was not associated with clinical outcome and mortality after adjusting for confounders (odds ratio, 1.20; 95% confidence interval, 0.91–1.61; P=0.197 and odds ratio, 1.08; 95% confidence interval, 0.68–1.71; P=0.755, respectively). However, smoking still independently predicted recanalization of middle cerebral artery in multivariable analyses (odds ratio, 2.68; 95% confidence interval, 1.11–6.43; P=0.028).Conclusions—Our study suggests that good outcome in smokers is mainly related to differences in baseline characteristics and not to biological effects of smoking. The higher recanalization rates in smokers, however, call for further studies.

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Beneficial Role of Neutrophils Through Function of Lactoferrin After Intracerebral Hemorrhage [Original Contributions]

Background and Purpose—Intracerebral hemorrhage (ICH) is a devastating disease with a 30-day mortality of ~50%. There are no effective therapies for ICH. ICH results in brain damage in 2 major ways: through the mechanical forces of extravasated blood and then through toxicity of the intraparenchymal blood components including hemoglobin/iron. LTF (lactoferrin) is an iron-binding protein, uniquely abundant in polymorphonuclear neutrophils (PMNs). After ICH, circulating blood PMNs enter the ICH-afflicted brain where they release LTF. By virtue of sequestrating iron, LTF may contribute to hematoma detoxification.Methods—ICH in mice was produced using intrastriatal autologous blood injection. PMNs were depleted with intraperitoneal administration of anti-Ly-6G antibody. Treatment of mouse brain cell cultures with lysed RBC or iron was used as in vitro model of ICH.Results—LTF mRNA was undetectable in the mouse brain, even after ICH. Unlike mRNA, LTF protein increased in ICH-affected hemispheres by 6 hours, peaked at 24 to 72 hours, and remained elevated for at least a week after ICH. At the single cell level, LTF was detected in PMNs in the hematoma-affected brain at all time points after ICH. We also found elevated LTF in the plasma after ICH, with a temporal profile similar to LTF changes in the brain. Importantly, mrLTF (recombinant mouse LTF) reduced the cytotoxicity of lysed RBC and FeCl3 to brain cells in culture. Ultimately, in an ICH model, systemic administration of mrLTF (at 3, 24, and 48 hours after ICH) reduced brain edema and ameliorated neurological deficits caused by ICH. mrLTF retained the benefit in reducing behavioral deficit even with 24-hour treatment delay. Interestingly, systemic depletion of PMNs at 24 hours after ICH worsened neurological deficits, suggesting that PMN infiltration into the brain at later stages after ICH could be a beneficial response.Conclusions—LTF delivered to the ICH-affected brain by infiltrating PMNs may assist in hematoma detoxification and represent a powerful potential target for the treatment of ICH.

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IJMS, Vol. 19, Pages 1147: Multifaceted Role of Pneumolysin in the Pathogenesis of Myocardial Injury in Community-Acquired Pneumonia

IJMS, Vol. 19, Pages 1147: Multifaceted Role of Pneumolysin in the Pathogenesis of Myocardial Injury in Community-Acquired Pneumonia

International Journal of Molecular Sciences doi: 10.3390/ijms19041147

Authors: Ronald Anderson Jan Nel Charles Feldman

Pneumolysin (PLY), a member of the family of Gram-positive bacterial, cholesterol-dependent, β-barrel pore-forming cytolysins, is the major protein virulence factor of the dangerous respiratory pathogen, Streptococcus pneumoniae (pneumococcus). PLY plays a major role in the pathogenesis of community-acquired pneumonia (CAP), promoting colonization and invasion of the upper and lower respiratory tracts respectively, as well as extra-pulmonary dissemination of the pneumococcus. Notwithstanding its role in causing acute lung injury in severe CAP, PLY has also been implicated in the development of potentially fatal acute and delayed-onset cardiovascular events, which are now recognized as being fairly common complications of this condition. This review is focused firstly on updating mechanisms involved in the immunopathogenesis of PLY-mediated myocardial damage, specifically the direct cardiotoxic and immunosuppressive activities, as well as the indirect pro-inflammatory/pro-thrombotic activities of the toxin. Secondly, on PLY-targeted therapeutic strategies including, among others, macrolide antibiotics, natural product antagonists, cholesterol-containing liposomes, and fully humanized monoclonal antibodies, as well as on vaccine-based preventive strategies. These sections are preceded by overviews of CAP in general, the role of the pneumococcus as the causative pathogen, the occurrence and types of CAP-associated cardiac complication, and the structure and biological activities of PLY.



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Natural killer cells target and differentiate cancer stem-like cells/undifferentiated tumors: strategies to optimize their growth and expansion for effective cancer immunotherapy

Publication date: April 2018
Source:Current Opinion in Immunology, Volume 51
Author(s): Kawaljit Kaur, Milica Perišić Nanut, Meng-Wei Ko, Tahmineh Safaie, Janko Kos, Anahid Jewett
Natural killer (NK) cells are known to select and differentiate cancer stem-like cells/undifferentiated tumors via lysis, and secreted/membrane bound IFN-γ and TNF-α respectively, resulting in the control of tumor growth. Several in vivo mouse models including humanized-BLT mice have been used to study the biology and significance of NK cells in selection/differentiation of stem-like tumors within the context of a reconstituted human immune system. In addition, we discuss the evidence and significance of NK cell loss at the pre-neoplastic stage. Therefore, because of their indispensable role in targeting CSCs/undifferentiated tumors, NK-cells should be placed high in the armamentarium of tumor therapy.



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A Break up Letter to the Z-Pack

A Break up Letter to the Z-Pack

Dear Z-pack,

We've had a good run together. But, my dearest azithromycin, it is time for us to end our love affair. It's not you. It's me.

When I met you, I thought you were the most wonderful thing in the world—and you were. Your perspective—your spectrum, if you will—is so broad. You are so well tolerated that everyone loved you, even my grandmother.

You even have a great nickname! Z-pack! Z-pack! How great it was to tell everyone about my beloved Z-pack!

We went on great adventures together. But then, I took you on some serious misadventures. I diagnosed "sinusitis" in every patient with the sniffles. I gave you to everybody with "bronchitis," even though I knew it was viral. I told everybody with a cough that they could have "atypical pneumonia," when I knew it was probably just a cough. I even took you to places you should never have been, using you to treat ear infections and strep throat when Penny Cillin and her friends were MUCH better for the job.

And, I always knew you were a cutie, but unfortunately your QT prolongation just proved too much for me, and for the people around me.

I messed things up for us and, so now, it's time for us to break up. We're just not right for each other anymore. I took things too far. I can't use you for Streptococcus pneumoniae anymore! Sinusitis, either. I need to be able to do these things so it's time for me to move on.

This doesn't mean we shouldn't stay friends. We'll always have bona fide atypical pneumonia. We'll always have chlamydia. And don't forget that you always brighten the lives of people with asthma and COPD with your beautiful anti-inflammatory smile.

But, we can't go on the way we have up until now. It's not right for either of us.

I will always remember the great days we had together and I will always love you.

Yours truly,

PCP



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Clinical significance of IgM and IgA class anti-NMDAR antibodies in herpes simplex encephalitis

Publication date: Available online 10 April 2018
Source:Journal of Clinical Virology
Author(s): Gabriel Westman, Azita Sohrabian, Elisabeth Aurelius, Clas Ahlm, Silvia Schliamser, Fredrik Sund, Marie Studahl, Johan Rönnelid
BackgroundHerpes simplex encephalitis (HSE) is a devastating disease, often leaving patients with severe disabilities. It has been shown that IgG anti-N-methyl-D-aspartate receptor (NMDAR) antibodies appear in approximately 25% of HSE patients and could be associated with impaired recovery of cognitive performance.ObjectivesTo characterize the prevalence of IgM and IgA anti-NMDAR antibodies in HSE patients, in relation to subsequent development of IgG anti-NMDAR and correlation to cognitive performance.Study designA total of 48 subjects were included from a previously described cohort of patients with HSE verified by HSV-1 PCR. Cerebrospinal fluid (CSF) and serum samples drawn close to onset of disease, after 14–21 days of iv aciclovir treatment and after 90 days of follow-up, were analyzed for the presence of IgM and IgA anti-NMDAR, and related to IgG anti-NMDAR. Antibody levels were correlated to the recovery of cognitive performance, as estimated by the Mattis Dementia Rating Scale (MDRS), for a total of 24 months.ResultsIn total, 27 of 48 (56%) study subjects were anti-NMDAR positive, defined as the presence of IgG (12/48, 25%), IgM (14/48, 29%) or IgA (13/48, 27%) antibodies in CSF and/or serum. IgM or IgA anti-NMDAR did not predict subsequent IgG autoimmunization and did not correlate to cognitive outcome. IgG anti-NMDAR serostatus, but not antibody titers, correlated to impaired recovery of cognitive performance.ConclusionsA majority of HSE patients develop IgG, IgM or IgA anti-NMDAR antibodies. However, the predictive value and clinical relevance of non-IgG isotypes remains to be shown in this setting.



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Evaluation of RIDA®GENE Norovirus GI/GII Real Time RT-PCR Using Stool Specimens Collected from Children and Adults with Acute Gastroenteritis

Publication date: Available online 10 April 2018
Source:Journal of Clinical Virology
Author(s): N. Kanwar, F. Hassan, L. Barclay, C. Langley, J. Vinjé, P.W. Bryant, K. St. George, L. Mosher, J.M. Matthews-Greer, M.A. Rocha, D.O. Beenhouwer, C.J. Harrison, M. Moffatt, N. Shastri, R. Selvarangan
BackgroundNorovirus is the leading cause of epidemic and sporadic acute gastroenteritis (AGE) in the United States. Widespread prevalence necessitates implementation of accurate norovirus detection assays in clinical diagnostic laboratories.ObjectiveTo evaluate RIDA®GENE norovirus GI/GII real-time RT-PCR assay (RGN RT-PCR) using stool samples from patients with sporadic AGE.Study designPatients between 14 days to 101 years of age with symptoms of AGE were enrolled prospectively at four sites across the United States during 2014-2015. Stool specimens were screened for the presence of norovirus RNA by the RGN RT-PCR assay. Results were compared with a reference method that included conventional RT-PCR and sequencing of a partial region of the 5'end of the norovirus ORF2 gene.ResultsA total of 259 (36.0%) of 719 specimens tested positive for norovirus by the reference method. The RGN RT-PCR assay detected norovirus in 244 (94%) of these 259 norovirus positive specimens. The sensitivity and specificity (95% confidence interval) of the RGN RT-PCR assay for detecting norovirus genogroup (G) I was 82.8% (63.5-93.5) and 99.1% (98.0-99.6) and for GII was 94.8% (90.8-97.2) and 98.6% (96.9-99.4), respectively. Seven specimens tested positive by the RGN-RT PCR that were negative by the reference method. The fifteen false negative samples were typed as GII.4 Sydney, GII.13, GI.3, GI.5, GI.2, GII.1, and GII.3 in the reference method.ConclusionsThe RGN RT-PCR assay had a high sensitivity and specificity for the detection of norovirus in stool specimens from patients with sporadic AGE.



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Evaluation of the National Laboratory-based Surveillance System for Respiratory Syncytial Virus in Sweden, 2015-2016

Publication date: Available online 10 April 2018
Source:Journal of Clinical Virology
Author(s): Heli Harvala, AnnaSara Carnahan, Sarah Axelsson, Maria Brytting
BackgroundMost laboratories use RSV PCR but near-patient tests (NPT) performed at paediatric clinics are believed to be increasingly used. Anonymised data on RSV infections has been collected since 1990 in Sweden. No evaluation of Swedish RSV surveillance or use of laboratory testing had previously been performed.ObjectivesSwedish RSV data and methods used for RSV laboratory testing and reporting were evaluated in order to improve RSV surveillance in a forthcoming vaccine era.Study DesignRSV data obtained in Sweden 2015-2016 were reviewed. Data on methods used for the RSV laboratory detection and reporting were collected via on-line questionnaires submitted to laboratories (n = 26) and clinics (n = 4) known to perform virological testing. Swedish Quality Control Program reports from 2013-2015 on the performance of RSV testing were also evaluated.ResultsOver 60% of RSV infections were diagnosed in children under 5 years (1917/2925), but infections were also common in those 65 years and older (n = 607). Two laboratories limited RSV testing to children only. RSV NPT was utilised in eight clinics; four participated in RSV surveillance. RSV NPTs evaluated could only detect 50% of RSV positive samples. Reporting was complete and timely, but took too much time (18 minutes/week/laboratory).ConclusionsAlthough most common in children, RSV infections are also common in the elderly, and testing should not be limited to children only. The poor performance of RSV NPT and importance of confirming results should be communicated to all relevant laboratories and clinics. All clinics should be encouraged to participate in surveillance. Automated case-based reporting should be considered.



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Commentary on: Thoughts on the American Board of Radiology Examinations and the Resident Experience in Radiation Oncology

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Publication date: Available online 10 April 2018
Source:Practical Radiation Oncology
Author(s): Paul E. Wallner, Lisa A. Kachnic, Anthony M. Gerdeman




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The long-term sequelae of palliative radiotherapy to Lumbo-sacral spine using conventional PA-single portal technique

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Publication date: Available online 10 April 2018
Source:Practical Radiation Oncology
Author(s): Kuan-Yin Hsiao, Hui-Chuan Wang, Steve H Fung, Waqar Haque, E Brian Butler, Bin S Teh




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The Application of Improved Spherical Harmonics Expansion-Based Multilevel Fast Multipole Algorithm in the Solution of Volume-Surface Integral Equation

During the solution of volume-surface integral equation (VSIE), to reduce the core memory requirement of the radiation patterns (RPs) of the basis functions, an improved spherical harmonics expansion-based multilevel fast multipole algorithm (SE-MLFMA) using the mixed-potential representation and the triangle-/tetrahedron-based grouping scheme is applied. Numerical results show that accompanying with a faster speed, the memory requirement of the RPs in the improved SE-MLFMA is several times less than that in the conventional MLFMA without compromising accuracy. A result employing the OpenMP parallelization and vector arithmetic logic unit (VALU) hardware acceleration technique is also shown to illustrate the robustness and scalability of the improved SE-MLFMA method.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2Hsqaac

A New Type of Graphical Passwords Based on Odd-Elegant Labelled Graphs

Graphical password (GPW) is one of various passwords used in information communication. The QR code, which is widely used in the current world, is one of GPWs. Topsnut-GPWs are new-type GPWs made by topological structures (also, called graphs) and number theory, but the existing GPWs use pictures/images almost. We design new Topsnut-GPWs by means of a graph labelling, called odd-elegant labelling. The new Topsnut-GPWs will be constructed by Topsnut-GPWs having smaller vertex numbers; in other words, they are compound Topsnut-GPWs such that they are more robust to deciphering attacks. Furthermore, the new Topsnut-GPWs can induce some mathematical problems and conjectures.

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Synaptic Paths to Neurodegeneration: The Emerging Role of TDP-43 and FUS in Synaptic Functions

TAR DNA-binding protein-43 KDa (TDP-43) and fused in sarcoma (FUS) as the defining pathological hallmarks for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), coupled with ALS-FTD-causing mutations in both genes, indicate that their dysfunctions damage the motor system and cognition. On the molecular level, TDP-43 and FUS participate in the biogenesis and metabolism of coding and noncoding RNAs as well as in the transport and translation of mRNAs as part of cytoplasmic mRNA-ribonucleoprotein (mRNP) granules. Intriguingly, many of the RNA targets of TDP-43 and FUS are involved in synaptic transmission and plasticity, indicating that synaptic dysfunction could be an early event contributing to motor and cognitive deficits in ALS and FTD. Furthermore, the ability of the low-complexity prion-like domains of TDP-43 and FUS to form liquid droplets suggests a potential mechanism for mRNP assembly and conversion. This review will discuss the role of TDP-43 and FUS in RNA metabolism, with an emphasis on the involvement of this process in synaptic function and neuroprotection. This will be followed by a discussion of the potential phase separation mechanism for forming RNP granules and pathological inclusions.

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Current trends in the medical management of osteoradionecrosis using triple therapy

Publication date: Available online 9 April 2018
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): J. Dhanda, L. Rennie, R. Shaw
Recent guidelines from the National Institute for Health and Care Excellence (NICE) have suggested that the medical management of osteoradionecrosis (ORN) of the jaws should be used in clinical trials only, and some drugs and therapeutics committees have withdrawn funds for such prescriptions. With increased scrutiny on the use of these agents, the aims of this study were to ascertain current trends in the presentation and management of ORN, with particular focus on which agents are being used.



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The impact of weather, road surface, time‐of‐day, and light conditions on severity of bicycle‐motor vehicle crash injuries

American Journal of Industrial Medicine, EarlyView.


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Hypoxia‐Activated Adipose Mesenchymal Stem Cells Prevents Irradiation‐Induced Salivary Hypofunction by Enhanced Paracrine Effect Through Fibroblast Growth Factor 10

STEM CELLS, EarlyView.


from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2vbd9iP

Follistatin‐Like 3 Enhances the Function of Endothelial Cells Derived from Pluripotent Stem Cells by Facilitating β‐Catenin Nuclear Translocation Through Inhibition of Glycogen Synthase Kinase‐3β Activity

STEM CELLS, EarlyView.


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Is refreshing in working memory impaired in older age? Evidence from the retro‐cue paradigm

Annals of the New York Academy of Sciences, EarlyView.


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Are there multiple ways to direct attention in working memory?

Annals of the New York Academy of Sciences, EarlyView.


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Neural correlates of enhanced executive functions: is less more?

Annals of the New York Academy of Sciences, EarlyView.


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Working memory consolidation: insights from studies on attention and working memory

Annals of the New York Academy of Sciences, EarlyView.


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The relationship between masking and short‐term consolidation during recall from visual working memory

Annals of the New York Academy of Sciences, EarlyView.


from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2v3B0km

Re: re: Retroseptal transconjunctival approach for fractures of the zygomaticomaxillary complex: a retrospective study

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Publication date: Available online 9 April 2018
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): R. Sharma




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Tetanus after a penetrating injury to the right globe: a case report

Publication date: Available online 9 April 2018
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): B. Rushworth, L. Carter
A 24-year-old man attended the emergency department with a penetrating injury to the right globe after a road traffic accident. He later contracted tetanus for which he was given human tetanus immunoglobulin. Although it is rare, tetanus is life-threatening and a thorough immunisation history should be obtained before treatment of tetanus-prone injuries.



from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2v57OJx

Use of patient-reported outcome measures in oral and maxillofacial trauma surgery: a review

Publication date: Available online 9 April 2018
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): R. Ologunde, N.M.H. McLeod
In the UK, about one person/100/year sustains a facial injury, so trauma surgery accounts for a considerable part of the caseload in oral and maxillofacial surgery (OMFS). Patient-reported outcome measures (PROM) allow for patient-centred assessment of postoperative outcomes, but to our knowledge, most research in OMFS trauma does not currently include them. To investigate their use, we searched Medline to find relevant studies that reported outcomes from inception in January 1879 to August 2016. Those not in the English language and those that did not report operations were excluded. We retrieved 416 articles, of which 21 met the inclusion criteria (five randomised controlled trials and 16 cohort studies) yielding 16 outcome measures. Most of these had been devised by authors (eight studies), four studies reported use of the Geriatric Oral Health Assessment Index, and three the Nasal Obstruction Symptom Evaluation. Most were used in studies on mandibular surgery (n=13), followed by those on nasal and facial surgery (n=3 each). There is a great heterogeneity in the use of these assessments in OMF trauma. In view of their increasing importance compared with simpler objective measures that may not be relevant to the patients' own perception, more research is needed to establish which of them can be used to measure the QoL of patients treated for OMF trauma.



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Dentin dysplasia type I—A dental disease with genetic heterogeneity

Oral Diseases, EarlyView.


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Revisiting the need for virtue in medical practice: a reflection upon the teaching of Edmund Pellegrino

Edmund Pellegrino considered medicine as a skill, art, and perhaps most importantly, a moral enterprise. In this essay, I attempt to exemplify how the legacy and contributions of Edmund Pellegrino, as a teache...

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Morphosyntactic abilities of toddlers with hearing impairment and normal hearing: evidence from a sentence‐repetition task

International Journal of Language &Communication Disorders, EarlyView.


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Pulsed dye laser treatment of rosacea using a novel 15 mm diameter treatment beam

Lasers in Surgery and Medicine, EarlyView.


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EMBO Course: Microbial Metagenomics: A 360º Approach

23–30 April 2018, Heidelberg, Germany

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2JBy6qi

ESGAR Liver Imaging Workshop, Warsaw 2018

26–27 April 2018, Warsaw, Portugal

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Pharmaceutical Development of ATMPs

26–27 April 2018, London, United Kingdom

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THE 5TH INTERNATIONAL CONFERENCE ON INDUSTRIAL ENGINEERING AND APPLICATIONS

26–28 April 2018, Singapore, Singapore

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Luminal GI imaging

27 April 2018, London, United Kingdom

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14th International Congress of Immunology and Allergy

26–28 April 2018, Tehran, Iran, Islamic Republic Of

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2JzWDMd

Occupational contact dermatitis caused by polyurethane foam: 6 cases

Contact Dermatitis, EarlyView.


from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2v8qQ1Y

Allergic reaction to 3 tattoo inks containing Pigment Yellow 65

Contact Dermatitis, EarlyView.


from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2Hrxy5w

Activation of T cells by dendritic cells exposed to a reference sensitizer: Towards a promising model to assess the allergenic potential of chemicals

Contact Dermatitis, EarlyView.


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Occupational contact dermatitis caused by hydroxychloroquine sulfate

Contact Dermatitis, EarlyView.


from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2HrxxP0

Neonatal Compartment Syndrome - Everything You Need To Know - Dr. Nabil Ebraheim

Dr. Ebraheim's educational animated video describing the condition of neonatal compartment syndrome of the forearm.



Follow me on twitter:
https://twitter.com/#!/DrEbraheim_UTMC



from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://www.youtube.com/watch?v=6zXF_Vl7q0o

Differential Proteomic Analysis of Actinic Keratosis, Bowen’s Disease and Cutaneous Squamous Cell Carcinoma by Label-Free LC-MS/MS

Cutaneous SCC (cSCC) and its precursor lesions Actinic Keratosis (AK) and Bowen's Disease (BD) are common types of non-melanoma skin cancer (NMSC) originating from an uncontrolled growth of abnormal squamous keratinocytes in the epidermis layer of the skin.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2v6rGMB

RIPK1 downregulation in keratinocyte enhances TRAIL signaling in psoriasis

Psoriasis, a common inflammatory skin disorder characterized by scaly erythemas and plaques, affects around 2% of the population [1]. Dysregulated interactions of innate and adaptive immunities are deeply involved in the pathomechanism. Complexes of epidermis-derived antimicrobial peptide, LL-37, and host DNA are thought to act as an initiating factor via stimulating IFN-α-production from dermal plasmacytoid dendritic cells [2]. Consequently, activated myeloid dendritic cell (DC) populations release TNF-α and IL-23, and stimulate Th1 cells and T helper cell 17 (Th17) to produce IFN-γ, IL-17 and IL-22 [3,4].

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2Hrz2wz

[Corrections] Correction to Lancet Glob Health 2018; 6 (suppl 2): S15

Bruce J, Chantler T, Kumakech E, et al. Evaluation of a data-informed community engagement strategy to increase immunisation coverage in northern Uganda: a cluster-randomised controlled trial with an embedded process evaluation. Lancet Glob Health 2018; 6 (suppl 2): S15—In this Abstract, corrections have been made to the spelling of Ashiraf Mawanda's name, the authorship order, the corresponding author, and L Kiapi's affiliation details. These corrections have been made as of April 10, 2018.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2IHNpfz

[Comment] Clinical innovation in stroke: getting the simple things right

In many high-income countries, most biomedical research funding has been spent on laboratory-based research aimed at understanding the molecular and cellular processes that underpin health or disease, with only a fraction targeted at clinical innovation.1 Yet, the benefits of clinical innovation are evident in almost all areas of medicine and particularly in surgery, as illustrated by innovations such as joint replacement, cataract removal, endoscopic treatment of gastrointestinal or urological disease, endovascular interventions (eg, arterial angioplasty or stenting or coiling of cerebral aneurysms), minimally invasive surgery, and stereotactic neurosurgery, to name but a few.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2GOxNGD

Impact of acute administration of sodium oxybate on heart rate variability in children with type 1 narcolepsy

Cardiovascular measurements in children affected with type 1 narcolepsy (NT1) have never been investigated, neither have their modulation by the administration of sodium oxybate (SO).

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Pulmonary rehabilitation and oropharyngeal exercises as an adjunct therapy in obstructive sleep apnea: a randomized controlled trial

It is well recognized that the most effective treatment for obstructive sleep apnea (OSA) is continuous positive airway pressure (CPAP). Different treatment possibilities comprise surgery, mandibular advancement, pulmonary rehabilitation, and oropharyngeal and facial exercises (PR program). However, these treatments showed inconsistent results.The purpose of the study was to compare the short-term effects of CPAP and the combination of PR program with CPAP on OSA severity, ventilatory functions, and changes in body characteristics in a newly diagnosed patient.

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NREM parasomnias: a treatment approach based upon a retrospective case series of 512 patients

Non-REM parasomnias are not uncommon conditions in the general population. Current treatment options are based on small case series and reports. In this study, we aimed to present the clinical experience from a large cohort of patients.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2HrqCp8

CPAP therapy improves erectile function in patients with severe obstructive sleep apnea

Erectile dysfunction (ED) is highly prevalent in obstructive sleep apnea (OSA), however, the effect of continuous positive airway pressure (CPAP) therapy on erectile function has not yet been thoroughly investigated in these patients.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2v98b64

An actigraphic study of the sleep patterns of younger and older school-age children

Sleep is viewed as being relatively consistent across the school-age period (6–13 years of age), but this has not been empirically supported. The objective of this study was to document the duration, schedule, variability, and week versus weekend discrepancies of sleep in three distinct age groups within the school-age period.

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System 83 Plus Automated Endoscope Reprocessors (AERs) by Custom Ultrasonics: FDA Safety Communication - Completed Validation Testing

Audience: Risk Manager, Gastroenterology, Infectious Disease, Pulmonology Including the System 83 Plus, System 83 Plus 2, and the System 83 Plus 9 [Posted 04/10/2018] ISSUE: The FDA is notifying health care facilities that Custom Ultrasonics has...

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[Department of Error] Department of Error

Das P, Horton R. Pollution, health, and the planet: time for decisive action. Lancet 2018; 391: 407–08—In the acknowledgments section of this Comment (published online first on Oct 19, 2017), the Governments of Germany, Norway, and Sweden should have been thanked for their "funding of the report, input, or both". This correction has been made to the online version as of April 10, 2018.

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FDA OKs First Contact Lenses That Adapt to Light

The FDA has cleared for marketing the first contact lenses that darken when exposed to bright light — similar to eyeglasses that darken in the sun...

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2v3fkVl

Does volumetric measurement of cervical lymph nodes serve as an imaging biomarker for locoregional recurrence of oral squamous cell carcinoma?

Publication date: Available online 10 April 2018
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Ali-Farid Safi, Martin Kauke, Hendrik Jung, Marco Timmer, Jan Borggrefe, Thorsten Persigehl, Hans-Joachim Nickenig, Max Zinser, David Maintz, Matthias Kreppel, Joachim Zöller




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Thermo-setting glass ionomer cements promote variable biological responses of human dental pulp stem cells

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Publication date: Available online 9 April 2018
Source:Dental Materials
Author(s): Mar Collado-González, Miguel R. Pecci-Lloret, Christopher J. Tomás-Catalá, David García-Bernal, Ricardo E. Oñate-Sánchez, Carmen Llena, Leopoldo Forner, Vinicius Rosa, Francisco J. Rodríguez-Lozano
ObjectiveTo evaluate the in vitro cytotoxicity of Equia Forte (GC, Tokyo, Japan) and Ionostar Molar (Voco, Cuxhaven, Germany) on human dental pulp stem cells (hDPSCs).MethodshDPSCs isolated from third molars were exposed to several dilutions of Equia Forte and Ionostar Molar eluates (1/1, 1/2 and 1/4). These eluates were obtained by storing material samples in respective cell culture medium for 24h (n=40). hDPSCs in basal growth culture medium were the control. Cell viability and cell migration assays were performed using the MTT and wound-healing assays, respectively. Also, induction of apoptosis and changes in cell phenotype were evaluated by flow cytometry. Changes in cell morphology were analysed by immunocytofluorescence staining. To evaluate cell attachment to the different materials, hDPSCs were directly seeded onto the material surfaces and analyzed by scanning electron microscopy (SEM). The chemical composition of the materials was determined by energy dispersive X-ray (EDX) and eluates were analyzed by inductively coupled plasma-mass spectrometry (ICP-MS). Statistical analysis was performed with analysis of variance (ANOVA) and Student's t-test (α<0.05).ResultsUndiluted Equia Forte extracts led to a similar cell proliferation rates than the control group from 72h onwards. There were no significance differences between Equia Forte and Ionostar Molar in terms of cell apoptosis and phenotype. However, in presence of Equia extracts the migration capacity of hDPSCs was higher than in presence of Ionostar Molar (p<0.05). Also, SEM studies showed a higher degree of cell attachment when Equia Forte extracts were used. Finally, EDX analysis pointed to different weight percentages of C, O and Ca ions in glass ionomer cements, while other elements such as La, Al, Si, W, Mo and F were also detected.SignificanceIn summary, Equia Forte promoted better biological responses in hDPSCs than Ionostar Molar.



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Numerical fatigue analysis of premolars restored by CAD/CAM ceramic crowns

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Publication date: Available online 10 April 2018
Source:Dental Materials
Author(s): Ehsan Homaei, Xiao-Zhuang Jin, Edmond Ho Nang Pow, Jukka Pekka Matinlinna, James Kit-Hon Tsoi, Khalil Farhangdoost
ObjectivesThe purpose of this study was to estimate the fatigue life of premolars restored with two dental ceramics, lithium disilicate (LD) and polymer infiltrated ceramic (PIC) using the numerical method and compare it with the published in vitro data.MethodsA premolar restored with full-coverage crown was digitized. The volumetric shape of tooth tissues and crowns were created in Mimics®. They were transferred to IA-FEMesh for mesh generation and the model was analyzed with Abaqus. By combining the stress distribution results with fatigue stress–life (S–N) approach, the lifetime of restored premolars was predicted.ResultsThe predicted lifetime was 1,231,318 cycles for LD with fatigue load of 1400N, while the one for PIC was 475,063 cycles with the load of 870N. The peak value of maximum principal stress occurred at the contact area (LD: 172MPa and PIC: 96MPa) and central fossa (LD: 100MPa and PIC: 64MPa) for both ceramics which were the most seen failure areas in the experiment. In the adhesive layer, the maximum shear stress was observed at the shoulder area (LD: 53.6MPa and PIC: 29MPa).SignificanceThe fatigue life and failure modes of all-ceramic crown determined by the numerical method seem to correlate well with the previous experimental study.



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Does volumetric measurement of cervical lymph nodes serve as an imaging biomarker for locoregional recurrence of oral squamous cell carcinoma?

Publication date: Available online 10 April 2018
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Ali-Farid Safi, Martin Kauke, Hendrik Jung, Marco Timmer, Jan Borggrefe, Thorsten Persigehl, Hans-Joachim Nickenig, Max Zinser, David Maintz, Matthias Kreppel, Joachim Zöller




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Opioid utilization following cervical spine surgery: trends and factors associated with long-term use

Limited or no data exist evaluating risk-factors associated with prolonged opioid use following cervical arthrodesis.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2IHhKLo

Preoperative Serum ST2 Level Predicts Acute Kidney Injury After Adult Cardiac Surgery

The purpose of this study was to evaluate the relationship between preoperative levels of serum ST2 and acute kidney injury following cardiac surgery. Previous research has shown that biomarkers facilitate the prediction of acute kidney injury and other complications after cardiac surgery.

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Lymphangiography and Thoracic Duct Embolization following Unsuccessful Thoracic Duct Ligation: Imaging Findings and Outcomes

To summarize the imaging findings and outcomes of thoracic duct embolization (TDE) performed on patients with chylous leaks persisting after thoracic duct (TD) ligation

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Implementation of the aortic no-touch technique to reduce stroke after off-pump coronary surgery

Despite substantial scientific effort, the relationship between stroke after CABG and the use of the aortic no-touch off-pump technique (anOPCAB) remains incompletely understood. The present study aims to define the impact of anOPCAB on the occurrence and time point of stroke.

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Lower versus upper leg saphenous vein composite grafts based on the left internal thoracic artery: A randomized study

The "lower versus upper leg saphenous vein (SV) composite graft based on the left internal thoracic artery (ITA) for coronary artery bypass grafting" trial was designed to compare the histologic, immunohistochemical and angiographic findings of lower versus upper leg SV composite grafts.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2JBxkt1

Modified technique for Melody valve implantation in the mitral position



from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2JCdD4i

Acute adrenal cortex injury during cardiopulmonary bypass in a canine model

Cardiopulmonary bypass (CPB) may induce systemic inflammatory responses that cause acute injuries to multiple organs. However, no direct evidence exists to determine whether CPB leads to adrenal cortex injury or to describe its underlying mechanism.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2EzjPXi

Combining CO2 reduction with propane oxidative dehydrogenation over bimetallic catalysts

41467_2018_3793_Fig2_HTML.jpg



from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2HpIzUZ

Cycle length identifies obstructive sleep apnea and central sleep apnea in heart failure with reduced ejection fraction

Abstract

Aim

To clarify whether unmasking of central sleep apnea during continuous positive airway pressure (CPAP) initiation can be identified from initial diagnostic polysomnography (PSG) in patients with heart failure with reduced ejection fraction (HFREF) and obstructive sleep apnea (OSA)

Materials and methods

Forty-three consecutive patients with obstructive sleep apnea and central sleep apnea (OSA/CSA) in HFREF were matched with 43 HFREF patients with OSA and successful CPAP initiation. Obstructive apneas during diagnostic PSG were then analyzed for cycle length (CL), ventilation length (VL), apnea length (AL), time to peak ventilation (TTPV), and circulatory delay (CD). We calculated duty ratio (DR) as the ratio of VL/CL and mathematic loop gain (LG).

Results

While AL was similar, CL, VL, TTPV, CD, and DR was significantly longer in patients with OSA/CSA compared to those with OSA, and LG was significantly higher. Receiver operator curves identified optimal cutoff values of 50.2 s for CL (area under the curve (AUC) 0.85, 29.2 s for VL (AUC 0.92), 11.5 s for TTPV (AUC 0.82), 26.4 s for CD (AUC 0.79), and 3.96 (AUC 0.78)) respectively for LG to identify OSA/CSA.

Conclusion

OSA/CSA in HFREF can be identified by longer CL, VL, TTPV, and CD from obstructive events in initial diagnostic PSG. The underlying mechanisms seem to be the presence of an increased LG.



from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2JCsWdC

Covered versus uncovered self-conformable metal stent for palliation of primary malignant extrahepatic biliary strictures: a randomized multicenter study

Self-expandable metal stents (SEMSs) are used to relieve malignant biliary obstruction. We aimed to compare stent patency, adverse events rate and overall survival of covered (Niti-S Biliary ComVi) versus uncovered (Niti-s D type) self-conformable metal stents in patients with primary malignant extrahepatic biliary stricture, not eligible for surgery.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2qmBwo0

Risk factors for postoperative delirium in patients undergoing free flap reconstruction for oral cancer

The aim of this study was to investigate risk factors for postoperative delirium in patients undergoing free flap reconstruction for defects after oral cancer resection. This was a non-randomized, retrospective cohort study involving 102 patients who underwent oral cancer resection and free flap reconstruction. Data were collected from the medical records. Postoperative delirium occurred in 34 patients (33.3%), of whom 27 were male and seven were female. High preoperative total protein and albumin, diabetes mellitus, history of smoking, use of hypnotics or antipsychotics, time until getting out of bed after surgery, and postoperative insomnia were significantly related to delirium in the univariate analysis (P<0.05).

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2GRsUR9

Clinicopathological investigation of odontogenic fibroma in tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is an autosomal dominant inherited disease characterized by systemic hamartoma and diverse systemic features. TSC1 and TSC2 are the causative genes, and mental retardation, epileptic seizures, and facial angiofibroma develop in many patients with the disease. The case of a patient with TSC who developed a central odontogenic fibroma of the mandible is reported here. The patient was a 21-year-old woman who was referred with a swelling of the labial gingiva in the region of the right lower lateral incisor and canine.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2GOawbN

Palatal orthodontic miniscrew insertion using a CAD-CAM surgical guide: description of a technique

The aim of this report was to describe a new computer-guided technique for a controlled site preparation and palatal orthodontic miniscrew insertion using a dedicated software. A surgical guide was designed after planning the appropriate insertion sites on three-dimensional images created by the fusion of cone-beam computed tomography (CBCT) and digital dental model images. Pre- and postoperative CBCT images were compared and the angular, coronal, and apical deviations between the planned and the placed miniscrews were calculated.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2qnQ070

A prospective study examining the effects of treatment timing in the management of mandible fractures

The ideal timing for treatment of mandible fractures has not been well established. The objective of this study was to analyse the effects of treatment timing in the surgical management of mandible fractures. A prospective evaluation of 215 continuous patients with a total of 359 mandible fractures was undertaken. Nine outcome variables were analysed in relation to treatment delay by logistic regression modelling: wound dehiscence, hardware exposure, local postoperative infection, malocclusion, trismus, nerve damage, fracture non-union, return to theatre, and radiographic outcome.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2qmZxev

Preschool and School-Age Irritability Predict Reward-Related Brain Function

Although chronic irritability in childhood is prevalent, impairing, and predictive of later maladjustment, its pathophysiology is largely unknown. Deficits in reward processing are hypothesized to play a role in irritability. The current study aimed to identify how the developmental timing of irritability during preschool and school-age relates to reward-related brain function during school-age.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2v9ixTc

A prospective study examining the effects of treatment timing in the management of mandible fractures

Publication date: Available online 10 April 2018
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): M.J.L. Hurrell, M.C. David, M.D. Batstone
The ideal timing for treatment of mandible fractures has not been well established. The objective of this study was to analyse the effects of treatment timing in the surgical management of mandible fractures. A prospective evaluation of 215 continuous patients with a total of 359 mandible fractures was undertaken. Nine outcome variables were analysed in relation to treatment delay by logistic regression modelling: wound dehiscence, hardware exposure, local postoperative infection, malocclusion, trismus, nerve damage, fracture non-union, return to theatre, and radiographic outcome. Nineteen additional variables were included in the analysis to adjust for potential confounding. Delay was measured in days and ranged from 0 to 41days, with a mean delay of 4.6days. The incidence of wound dehiscence, hardware exposure, local postoperative infection, trismus, nerve damage, fracture non-union and return to theatre was 6%, 4%, 11%, 8.5%, 47%, 2% and 8%, respectively. Objective malocclusion and poor radiographic outcomes were evident in 13% and 4.5% of cases, respectively.No statistically significant association was found between treatment delay and treatment outcomes.The findings of this study suggest it may be safe to delay the definitive treatment of mandible fractures. Treatment delay may allow for improved resource distribution and prioritization of more time-dependent interventions.



from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2JBz8Td

Identification of ‘Point A’ as the prevalent source of error in cephalometric analysis of lateral radiographs

Publication date: Available online 10 April 2018
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): P. Grogger, C. Sacher, S. Weber, G. Millesi, R. Seemann
Deviations in measuring dentofacial components in a lateral X-ray represent a major hurdle in the subsequent treatment of dysgnathic patients. In a retrospective study, we investigated the most prevalent source of error in the following commonly used cephalometric measurements: the angles Sella-Nasion-Point A (SNA), Sella-Nasion-Point B (SNB) and Point A-Nasion-Point B (ANB); the Wits appraisal; the anteroposterior dysplasia indicator (APDI); and the overbite depth indicator (ODI). Preoperative lateral radiographic images of patients with dentofacial deformities were collected and the landmarks digitally traced by three independent raters. Cephalometric analysis was automatically performed based on 1116 tracings. Error analysis identified the x-coordinate of Point A as the prevalent source of error in all investigated measurements, except SNB, in which it is not incorporated. In SNB, the y-coordinate of Nasion predominated error variance. SNB showed lowest inter-rater variation. In addition, our observations confirmed previous studies showing that landmark identification variance follows characteristic error envelopes in the highest number of tracings analysed up to now. Variance orthogonal to defining planes was of relevance, while variance parallel to planes was not. Taking these findings into account, orthognathic surgeons as well as orthodontists would be able to perform cephalometry more accurately and accomplish better therapeutic results.



from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2EBo9Fl

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