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Τρίτη, 6 Φεβρουαρίου 2018

Comparison of dosimetric parameters derived from whole organ and wall contours for bladder and rectum in cervical cancer patients treated with intracavitary and interstitial brachytherapy

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Publication date: Available online 6 February 2018
Source:Radiotherapy and Oncology
Author(s): Rachel Gerber, Alexandra Rink, Jennifer Croke, Jette Borg, Akbar Beiki-Ardakani, Anthony Fyles, Michael Milosevic, Jason Xie, Harald Keller, Kathy Han
For volumes up to 2 cm3 of the bladder and possibly up to 5 cm3 of the rectum, doses computed from the whole organ were good estimates of the doses in the wall in cervix brachytherapy, and there were no significant differences between patients treated with or without interstitial needles.



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Clinical implementation of contrast-enhanced four-dimensional dual-energy computed tomography for target delineation of pancreatic cancer

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Publication date: Available online 6 February 2018
Source:Radiotherapy and Oncology
Author(s): Shingo Ohira, Kentaro Wada, Takero Hirata, Naoyuki Kanayama, Toshiki Ikawa, Tsukasa Karino, Yuya Nitta, Masaru Isono, Yoshihiro Ueda, Masayoshi Miyazaki, Masahiko Koizumi, Teruki Teshima
Background and purposeThe accurate delineation of pancreatic tumor with respiratory motion is challenging. This study demonstrates the application of contrast-enhanced four-dimensional dual-energy computed tomography (CE-4D-DECT) for tumor delineation and assesses the objective and subjective image quality.Material and methodsTwelve patients underwent CE-4D-DECT, and quantitative spectral analysis was performed on the resulting virtual monochromatic images (VMI) to determine the optimal VMI (O-VMI) with the highest contrast-to-noise ratio (CNR). The objective value of the CNR between pancreatic parenchyma and tumor, and the subjective measurement with five-point scale were compared between O-VMI, standard VMI (S-VMI, 77 keV) and single energy CT (SECT, 120 kVp).ResultsThe CNR was the highest in the VMI at 60 keV, and the corresponding CNR in the O-VMI (3.4) was significantly higher (p < 0.05) than that in the S-VMI (2.4) and the SECT (2.7). The overall mean subjective measurements among 4 radiation oncologists were higher for the O-VMI over the S-VMI and SECT with respect to overall image quality (4.0, 3.3 and 3.7, respectively), tumor enhancement (3.4, 2.6 and 3.2, respectively), and vessel delineation (4.2, 3.6 and 4.2, respectively).ConclusionsThe O-VMI derived from the CE-4D-DECT demonstrated its superiority over the S-VMI and SECT in depicting pancreatic tumor.



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Intraosseous venous structures adjacent to the jugular tubercle associated with an anterior condylar dural arteriovenous fistula

Abstract

Purpose

Although involvement of the osseous component with an anterior condylar dural arteriovenous fistula (AC-DAVF) has been frequently described, osseous venous structures in which AC-DAVFs develop have not been fully elucidated. We investigated osseous venous structures adjacent to the hypoglossal canal in normal controls and patients with AC-DAVFs.

Methods

The study included 50 individuals with unruptured aneurysms as normal controls and seven patients with AC-DAVFs. Osseous venous structures adjacent to the hypoglossal canal in normal controls were analyzed using computed tomography (CT) digital subtraction venography. In patients with AC-DAVFs, the fistulous pouches, draining veins, and surrounding venous structures were examined using cone beam CT.

Results

In 46.0% of laterals in normal controls, osseous venous structures were visualized within the jugular tubercle superomedially to the hypoglossal canal. We named these structures the jugular tubercle venous complex (JTVC). The JTVC was always continuous with the anterior condylar vein and was sometimes connected to surrounding venous channels. We detected nine fistulous pouches in the seven patients with AC-DAVFs. The fistulous pouches were in the JTVC (33.3%), anterior condylar vein (33.3%), and other venous channels within the exoccipital region (33.3%).

Conclusion

Although the JTVC is a venous structure frequently found in normal people, it had not been investigated until now. The venous channel between the anterior condylar vein and JTVC is a common origin site for AC-DAVFs, and it was associated with 66.6% of the AC-DAVF cases in the current study.



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Editorial Board

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Publication date: March 2018
Source:Journal of Environmental Radioactivity, Volume 183





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Sequential analyses of actinides in large-size soil and sediment samples with total sample dissolution

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Publication date: Available online 6 February 2018
Source:Journal of Environmental Radioactivity
Author(s): Maoyi Luo, Shan Xing, Yonggang Yang, Lijuan Song, Yan Ma, Yadong Wang, Xiongxin Dai, Steffen Happel
There is a growing demand for the determination of actinides in soil and sediment samples for environmental monitoring and tracing, radiological protection, and nuclear forensic reasons. A total sample dissolution method based on lithium metaborate fusion, followed by sequential column chromatography separation, was developed for simultaneous determination of Pu, Am and Cm isotopes in large-size environmental samples by alpha spectrometry and mass spectrometric techniques. The overall recoveries of both Pu and Am for the entire procedure were higher than 70% for large-size soil samples. The method was validated using 20 g of soil samples spiked with known amounts of 239Pu and 241Am as well as the certified reference materials IAEA-384 (Fangataufa Lagoon sediment) and IAEA-385 (Irish Sea sediment). All the measured results agreed very well with the expected values.



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Comparison of dosimetric parameters derived from whole organ and wall contours for bladder and rectum in cervical cancer patients treated with intracavitary and interstitial brachytherapy

For volumes up to 2 cm3 of the bladder and possibly up to 5 cm3 of the rectum, doses computed from the whole organ were good estimates of the doses in the wall in cervix brachytherapy, and there were no significant differences between patients treated with or without interstitial needles.

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Traffic University: How Small Changes in Lifestyle Can Change Your Life

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Publication date: March–April 2018
Source:Current Problems in Diagnostic Radiology, Volume 47, Issue 2
Author(s): Puneet Bhargava




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head and neck; +131 new citations

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

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



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IJMS, Vol. 19, Pages 481: The Impact of Aging on Cardio and Cerebrovascular Diseases

IJMS, Vol. 19, Pages 481: The Impact of Aging on Cardio and Cerebrovascular Diseases

International Journal of Molecular Sciences doi: 10.3390/ijms19020481

Authors: Carmine Izzo Albino Carrizzo Antonia Alfano Nicola Virtuoso Mario Capunzo Mariaconsiglia Calabrese Eros De Simone Sebastiano Sciarretta Giacomo Frati Marco Oliveti Antonio Damato Mariateresa Ambrosio Francesco De Caro Paolo Remondelli Carmine Vecchione

A growing number of evidences report that aging represents the major risk factor for the development of cardio and cerebrovascular diseases. Understanding Aging from a genetic, biochemical and physiological point of view could be helpful to design a better medical approach and to elaborate the best therapeutic strategy to adopt, without neglecting all the risk factors associated with advanced age. Of course, the better way should always be understanding risk-to-benefit ratio, maintenance of independence and reduction of symptoms. Although improvements in treatment of cardiovascular diseases in the elderly population have increased the survival rate, several studies are needed to understand the best management option to improve therapeutic outcomes. The aim of this review is to give a 360° panorama on what goes on in the fragile ecosystem of elderly, why it happens and what we can do, right now, with the tools at our disposal to slow down aging, until new discoveries on aging, cardio and cerebrovascular diseases are at hand.



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IJMS, Vol. 19, Pages 484: Long Chain Omega-3 Polyunsaturated Fatty Acid Supplementation Protects Against Adriamycin and Cyclophosphamide Chemotherapy-Induced Bone Marrow Damage in Female Rats

IJMS, Vol. 19, Pages 484: Long Chain Omega-3 Polyunsaturated Fatty Acid Supplementation Protects Against Adriamycin and Cyclophosphamide Chemotherapy-Induced Bone Marrow Damage in Female Rats

International Journal of Molecular Sciences doi: 10.3390/ijms19020484

Authors: Chia-Ming Fan Yu-Wen Su Peter Howe Cory Xian

Although bone marrow and bone toxicities have been reported in breast cancer survivors, preventative strategies are yet to be developed. Clinical studies suggest consumption of long chain omega-3 polyunsaturated fatty acids (LCn3PUFA) can attenuate age-related bone loss, and recent animal studies also revealed benefits of LCn3PUFA in alleviating bone marrow and bone toxicities associated with methotrexate chemotherapy. Using a female rat model for one of the most commonly used anthracycline-containing breast cancer chemotherapy regimens (adriamycin + cyclophosphamide) (AC) chemotherapy, this study investigated potential effects of daily LCn3PUFA consumption in preserving bone marrow and bone microenvironment during chemotherapy. AC treatment for four cycles significantly reduced bone marrow cellularity and increased marrow adipocyte contents. It increased trabecular bone separation but no obvious changes in bone volume or bone cell densities. LCn3PUFA supplementation (375 mg/100 g/day) attenuated AC-induced bone marrow cell depletion and marrow adiposity. It also partially attenuated AC-induced increases in trabecular bone separation and the cell sizes and nuclear numbers of osteoclasts formed ex vivo from bone marrow cells isolated from AC-treated rats. This study suggests that LCn3PUFA supplementation may have beneficial effects in preventing bone marrow damage and partially protecting the bone during AC cancer chemotherapy.



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IJMS, Vol. 19, Pages 483: Genome-Wide Analysis of the NF-YB Gene Family in Gossypium hirsutum L. and Characterization of the Role of GhDNF-YB22 in Embryogenesis

IJMS, Vol. 19, Pages 483: Genome-Wide Analysis of the NF-YB Gene Family in Gossypium hirsutum L. and Characterization of the Role of GhDNF-YB22 in Embryogenesis

International Journal of Molecular Sciences doi: 10.3390/ijms19020483

Authors: Yanli Chen Zhaoen Yang Yanqing Xiao Peng Wang Ye Wang Xiaoyang Ge Chaojun Zhang Xianlong Zhang Fuguang Li

Members of the NF-YB transcription factor gene family play important roles in diverse processes related to plant growth and development, such as seed development, drought tolerance, and flowering time. However, the function of NF-YB genes in cotton remains unclear. A total of 23, 24, and 50 NF-YB genes were identified in Gossypium arboreum (G. arboreum), Gossypium raimondii (G. raimondii), and G. hirsutum, respectively. A systematic phylogenetic analysis was carried out in G. arboretum, G. raimondii, G. hirsutum, Arabidopsis thaliana, cacao, rice and, sorghum, where the 150 NF-YB genes were divided into five groups (α–ε). Of these groups, α is the largest clade, and γ contains the LEC1 type NF-YB proteins. Syntenic analyses revealed that paralogues of NF-YB genes in G. hirsutum exhibited good collinearity. Owing to segmental duplication within the A sub-genome (At) and D sub-genome (Dt), there was an expanded set of NF-YB genes in G. hirsutum. Furthermore, we investigated the structures of exons, introns, and conserved motifs of NF-YB genes in upland cotton. Most of the NF-YB genes had only one exon, and the genes from the same clade exhibited a similar motif pattern. Expression data show that most NF-YB genes were expressed ubiquitously, and only a few genes were highly expressed in specific tissues, as confirmed by quantitative real-time PCR (qRT-PCR) analysis. The overexpression of GhDNF-YB22 gene, predominantly expressed in embryonic tissues, indicates that GhDNF-YB22 may affect embryogenesis in cotton. This study is the first comprehensive characterization of the GhNF-YB gene family in cotton, and showed that NF-YB genes could be divided into five clades. The duplication events that occurred over the course of evolution were the major impetus for NF-YB gene expansion in upland cotton. Collectively, this work provides insight into the evolution of NF-YB in cotton and further our knowledge of this commercially important species.



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IJMS, Vol. 19, Pages 482: Telomere Length Dynamics and the Evolution of Cancer Genome Architecture

IJMS, Vol. 19, Pages 482: Telomere Length Dynamics and the Evolution of Cancer Genome Architecture

International Journal of Molecular Sciences doi: 10.3390/ijms19020482

Authors: Kez Cleal Kevin Norris Duncan Baird

Telomeres are progressively eroded during repeated rounds of cell division due to the end replication problem but also undergo additional more substantial stochastic shortening events. In most cases, shortened telomeres induce a cell-cycle arrest or trigger apoptosis, although for those cells that bypass such signals during tumour progression, a critical length threshold is reached at which telomere dysfunction may ensue. Dysfunction of the telomere nucleoprotein complex can expose free chromosome ends to the DNA double-strand break (DSB) repair machinery, leading to telomere fusion with both telomeric and non-telomeric loci. The consequences of telomere fusions in promoting genome instability have long been appreciated through the breakage–fusion–bridge (BFB) cycle mechanism, although recent studies using high-throughput sequencing technologies have uncovered evidence of involvement in a wider spectrum of genomic rearrangements including chromothripsis. A critical step in cancer progression is the transition of a clone to immortality, through the stabilisation of the telomere repeat array. This can be achieved via the reactivation of telomerase, or the induction of the alternative lengthening of telomeres (ALT) pathway. Whilst telomere dysfunction may promote genome instability and tumour progression, by limiting the replicative potential of a cell and enforcing senescence, telomere shortening can act as a tumour suppressor mechanism. However, the burden of senescent cells has also been implicated as a driver of ageing and age-related pathology, and in the promotion of cancer through inflammatory signalling. Considering the critical role of telomere length in governing cancer biology, we review questions related to the prognostic value of studying the dynamics of telomere shortening and fusion, and discuss mechanisms and consequences of telomere-induced genome rearrangements.



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IJMS, Vol. 19, Pages 485: Integrins in T Cell Physiology

IJMS, Vol. 19, Pages 485: Integrins in T Cell Physiology

International Journal of Molecular Sciences doi: 10.3390/ijms19020485

Authors: Alessandra Bertoni Oscar Alabiso Alessandra Galetto Gianluca Baldanzi

From the thymus to the peripheral lymph nodes, integrin-mediated interactions with neighbor cells and the extracellular matrix tune T cell behavior by organizing cytoskeletal remodeling and modulating receptor signaling. LFA-1 (αLβ2 integrin) and VLA-4 (α4β1 integrin) play a key role throughout the T cell lifecycle from thymocyte differentiation to lymphocyte extravasation and finally play a fundamental role in organizing immune synapse, providing an essential costimulatory signal for the T cell receptor. Apart from tuning T cell signaling, integrins also contribute to homing to specific target organs as exemplified by the importance of α4β7 in maintaining the gut immune system. However, apart from those well-characterized examples, the physiological significance of the other integrin dimers expressed by T cells is far less understood. Thus, integrin-mediated cell-to-cell and cell-to-matrix interactions during the T cell lifespan still represent an open field of research.



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Airway inflammation after epicutaneous sensitization of mice requires protease activity of low-dose allergen inhalation

Epicutaneous exposure to allergens through the skin is considered to be an important route of sensitization.1,2 Allergen sources, such as mites, insects, fungi, and pollen, contain proteases, which are frequently allergens themselves.3 Recent studies using murine models of sensitization via skin4 or airways5-7 revealed that the protease activity of a model protease allergen, papain, is essential to the induction of inflammation at the sensitization sites and serum IgE/IgG1 responses. However, the role of allergen protease activity in effector-phase responses against low-dose antigen encounters after epicutaneous sensitization currently remains unknown.

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Why Don't Babies Smile From Birth?

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Their facial muscles work fine, but the neural networks that let them recognize the feeling of happiness take a while to develop 

-- Read more on ScientificAmerican.com
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Perivascular Epicardial Fat Stranding at Coronary CT Angiography: A Marker of Acute Plaque Rupture and Spontaneous Coronary Artery Dissection.

Perivascular Epicardial Fat Stranding at Coronary CT Angiography: A Marker of Acute Plaque Rupture and Spontaneous Coronary Artery Dissection.

Radiology. 2018 Feb 05;:171568

Authors: Hedgire S, Baliyan V, Zucker EJ, Bittner DO, Staziaki P, Takx RAP, Scholtz JE, Meyersohn N, Hoffmann U, Ghoshhajra B

Abstract
Purpose To evaluate the frequency and implications of perivascular fat stranding on coronary computed tomography (CT) angiograms obtained for suspected acute coronary syndrome (ACS). Materials and Methods This retrospective registry study was approved by the institutional review board. The authors reviewed the medical records and images of 1403 consecutive patients (796 men, 607 women; mean age, 52.8 years) who underwent coronary CT angiography at the emergency department from February 2012 to March 2016. Fat attenuation, length and number of circumferential quadrants of the affected segment, and attenuation values in the unaffected epicardial and subcutaneous fat were measured. "Cases" were defined as patients with perivascular fat stranding. Patients with significant stenosis but without fat stranding were considered control subjects. Baseline imaging characteristics, ACS frequency, and results of subsequent downstream testing were compared between cases and control subjects by using two-sample t, Mann-Whitney U, and Fisher tests. Results Perivascular fat stranding was seen in 11 subjects, nine with atherosclerotic lesions and two with spontaneous coronary artery dissections, with a mean fat stranding length of 19.2 mm and circumferential extent averaging 2.9 quadrants. The mean attenuation of perivascular fat stranding, normal epicardial fat, and normal subcutaneous fat was 17, -93.2, and -109.3 HU, respectively (P < .001). Significant differences (P < .05) between cases and control subjects included lower Agatston score, presence of wall motion abnormality, and initial elevation of serum troponin level. ACS frequency was 45.4% in cases and 3.8% in control subjects (P = .001). Conclusion Recognition of perivascular fat stranding may be a helpful additional predictor of culprit lesion and marker of risk for ACS in patients with significant stenosis or spontaneous coronary artery dissection. © RSNA, 2018 Online supplemental material is available for this article.

PMID: 29401041 [PubMed - as supplied by publisher]



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Imaging Follow-up of Low-Risk Incidental Pancreas and Kidney Findings: Effects of Patient Age and Comorbidity on Projected Life Expectancy.

Imaging Follow-up of Low-Risk Incidental Pancreas and Kidney Findings: Effects of Patient Age and Comorbidity on Projected Life Expectancy.

Radiology. 2018 Feb 05;:171701

Authors: Raphel TJ, Weaver DT, Berland LL, Herts BR, Megibow AJ, Knudsen AB, Pandharipande PV

Abstract
Purpose To determine the effects of patient age and comorbidity level on life expectancy (LE) benefits associated with imaging follow-up of Bosniak IIF renal cysts and pancreatic side-branch (SB) intraductal papillary mucinous neoplasms (IPMNs). Materials and Methods A decision-analytic Markov model to evaluate LE benefits was developed. Hypothetical cohorts with varied age (60-80 years) and comorbidities (none, mild, moderate, or severe) were evaluated. For each finding, LE projections from two strategies were compared: imaging follow-up and no imaging follow-up. Under follow-up, it was assumed that cancers associated with the incidental finding were successfully treated before they spread. For patients without follow-up, mortality risks from Bosniak IIF cysts (renal cell carcinoma) and SBIPMNs (pancreatic ductal adenocarcinoma) were incorporated. Model assumptions and parameter uncertainty were evaluated in sensitivity analysis. Results In the youngest, healthiest cohorts (age, 60 years; no comorbidities), projected LE benefits from follow-up were as follows: Bosniak IIF cyst, 6.5 months (women) and 5.8 months (men); SBIPMN, 6.4 months (women) and 5.3 months (men). Follow-up of Bosniak IIF cysts in 60-year-old women with severe comorbidities yielded a LE benefit of 3.9 months; in 80-year-old women with no comorbidities, the benefit was 2.8 months, and with severe comorbidities the benefit was 1.5 months. Similar trends were observed in men and for SBIPMN. Results were sensitive to the performance of follow-up for cancer detection; malignancy risks; and stage at presentation of malignant, unfollowed Bosniak IIF cysts. Conclusion With progression of age and comorbidity level, follow-up of low-risk incidental findings yields increasingly limited benefits for patients. © RSNA, 2018 Online supplemental material is available for this article.

PMID: 29401040 [PubMed - as supplied by publisher]



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RT @AnticancerOrgUK : New @Anticancerfund video on the potential of drug repurposing:https://t.co/inyOHYGF7p

RT @AnticancerOrgUK : New @Anticancerfund video on the potential of drug repurposing: https://t.co/inyOHYGF7p

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Asthma in inner city children: recent insights United States

Purpose of review Children living in US inner cities experience disparate burdens of asthma, especially in severity, impairment, exacerbations, and morbidity. Investigations seeking to better understand the factors and mechanisms underlying asthma prevalence, severity, and exacerbation in children living in these communities can lead to interventions that can narrow asthma disparities and potentially benefit all children with asthma. This update will focus on recent (i.e. late 2016–2017) advances in the understanding of asthma in US inner city children. Recent findings Studies published in the past year expand understanding of asthma prevalence, severity, exacerbation, and the outcomes of guidelines-based management of these at-risk children, including: asthma phenotypes in US inner city children that are severe and difficult-to-control; key environmental determinants and mechanisms underlying asthma severity and exacerbations (e.g. allergy-mediated exacerbation susceptibility to rhinovirus); the importance of schools as a place for provocative exposures (e.g. mouse allergen, nitrogen dioxide) as well as a place where asthma care and outcomes can be improved; and the development and validation of clinically useful indices for gauging asthma severity and predicting exacerbations. Summary These recent studies provide a trove of actionable findings that can improve asthma care and outcomes for these at-risk children. Correspondence to Andrew H. Liu, MD, Children's Hospital Colorado and University of Colorado School of Medicine, 13123 East 16th Avenue, Box B395, Aurora, CO 80045, USA. Tel: +1 720 777 2127; e-mail: Andrew.liu@childrenscolorado.org Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Asthma exacerbation prediction: recent insights

Purpose of review Asthma attacks are frequent in children with asthma and can lead to significant adverse outcomes including time off school, hospital admission and death. Identifying children at risk of an asthma attack affords the opportunity to prevent attacks and improve outcomes. Recent findings Clinical features, patient behaviours and characteristics, physiological factors, environmental data and biomarkers are all associated with asthma attacks and can be used in asthma exacerbation prediction models. Recent studies have better characterized children at risk of an attack: history of a severe exacerbation in the previous 12 months, poor adherence and current poor control are important features which should alert healthcare professionals to the need for remedial action. There is increasing interest in the use of biomarkers. A number of novel biomarkers, including patterns of volatile organic compounds in exhaled breath, show promise. Biomarkers are likely to be of greatest utility if measured frequently and combined with other measures. To date, most prediction models are based on epidemiological data and population-based risk. The use of digital technology affords the opportunity to collect large amounts of real-time data, including clinical and physiological measurements and combine these with environmental data to develop personal risk scores. These developments need to be matched by changes in clinical guidelines away from a focus on current asthma control and stepwise escalation in drug therapy towards inclusion of personal risk scores and tailored management strategies including nonpharmacological approaches. Summary There have been significant steps towards personalized prediction models of asthma attacks. The utility of such models needs to be tested in the ability not only to predict attacks but also to reduce them. Correspondence to Dr Louise Fleming, MB ChB, MD, Clinical Senior Lecturer, Paediatric Respiratory Consultant, Department of Respiratory Paediatrics, Royal Brompton Hospital, Sydney Street, London SW3 6NP. Tel: +02073528121; e-mail: l.fleming@rbht.nhs.uk Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Precision medicine in the treatment of primary immunodeficiency diseases

Purpose of the review Since the 1990s with the advances in molecular biology, a number of genetic defects have been described. The International Union of Immunological Sciences has recently updated the classification of genetic defects associated with primary immune deficiencies that now number 354. With the ever-expanding list of new monogenic disorders and a better understanding of the immunobiology and function of these defective genes, new therapies have emerged particularly aimed at the autoimmune and inflammatory conditions that plague these patients. Recent findings Immune deficiencies associated with gain-of-function (GOF) mutations are a potential category for targeted therapies to control the GOF activities of the mutated gene. In addition to the increased susceptibility to infections these patients have autoimmune and inflammatory diseases that are difficult to control with conventional therapies. The dysregulated immune functions of the activated phospholipase-3-kinase δ syndrome, cytotoxic T lymphocyte-associated antigen-4 haploinsufficiency, lipopolysaccharide-responsive beige-like anchor deficiency, the GOF mutations of signal transducer and activator of transcription 1 and 3 immune deficiencies will be reviewed. The targeted therapies for each of these immune deficiencies using small molecule kinase inhibitors and fusion protein biologic modifiers will be described. Summary In this review, we explore the recent advances in precision medicine treatment of several primary immunodeficiency syndromes in which immune dysregulation is a key feature. Understanding the immunobiology associated with these GOF mutations has led to the use of biologic therapies to better control the associated autoimmune and inflammatory manifestations. Correspondence to Mark Ballow, MD, Morsani College of Medicine, Tampa; Division of Allergy and Immunology, Department of Pediatrics, Children's Research Institute (4th floor), 140 7th Ave South, St Petersburg, Florida 33701-4899, USA. E-mail: mballow@health.usf.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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IJERPH, Vol. 15, Pages 276: Comment on Tomaskova et al. Mortality in Miners with Coal-Workers’ Pneumoconiosis in the Czech Republic in the Period 1992–2013. Int. J. Environ. Res. Public Health, 2017, 14, 269

IJERPH, Vol. 15, Pages 276: Comment on Tomaskova et al. Mortality in Miners with Coal-Workers’ Pneumoconiosis in the Czech Republic in the Period 1992–2013. Int. J. Environ. Res. Public Health, 2017, 14, 269

International Journal of Environmental Research and Public Health doi: 10.3390/ijerph15020276

Authors: Mei Yong

With interest, I read the recent analysis by Tomaskova and co-workers (2017) about mortality from coal workers’ pneumoconiosis (CWP). The research question remains unclear whether coal workers’ pneumoconiosis (CWP) resulting from exposure to respirable coal dust containing crystalline silica accelerates the development of lung cancer or whether it is an intermediate stage in the pathway. I made several points of considerations with respect to (1) qualified data; (2) alternate measures for excessive risks; and (3) methodological flaws that should be avoided.



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IJERPH, Vol. 15, Pages 275: Does Walkability Contribute to Geographic Variation in Psychosocial Distress? A Spatial Analysis of 91,142 Members of the 45 and Up Study in Sydney, Australia

IJERPH, Vol. 15, Pages 275: Does Walkability Contribute to Geographic Variation in Psychosocial Distress? A Spatial Analysis of 91,142 Members of the 45 and Up Study in Sydney, Australia

International Journal of Environmental Research and Public Health doi: 10.3390/ijerph15020275

Authors: Darren Mayne Geoffrey Morgan Bin Jalaludin Adrian Bauman

Walkability describes the capacity of the built environment to promote walking, and has been proposed as a potential focus for community-level mental health planning. We evaluated this possibility by examining the contribution of area-level walkability to variation in psychosocial distress in a population cohort at spatial scales comparable to those used for regional planning in Sydney, Australia. Data on psychosocial distress were analysed for 91,142 respondents to the 45 and Up Study baseline survey between January 2006 and April 2009. We fit conditional auto regression models at the postal area level to obtain smoothed “disease maps” for psychosocial distress, and assess its association with area-level walkability after adjusting for individual- and area-level factors. Prevalence of psychosocial distress was 7.8%; similar for low (7.9%), low-medium (7.9%), medium-high (8.0%), and high (7.4%) walkability areas; and decreased with reducing postal area socioeconomic disadvantage: 12.2% (most), 9.3%, 7.5%, 5.9%, and 4.7% (least). Unadjusted disease maps indicated strong geographic clustering of psychosocial distress with 99.0% of excess prevalence due to unobserved and spatially structured factors, which was reduced to 55.3% in fully adjusted maps. Spatial and unstructured variance decreased by 97.3% and 39.8% after adjusting for individual-level factors, and another 2.3% and 4.2% with the inclusions of area-level factors. Excess prevalence of psychosocial distress in postal areas was attenuated in adjusted models but remained spatially structured. Postal area prevalence of high psychosocial distress is geographically clustered in Sydney, but is unrelated to postal area walkability. Area-level socioeconomic disadvantage makes a small contribution to this spatial structure; however, community-level mental health planning will likely deliver greatest benefits by focusing on individual-level contributors to disease burden and inequality associated with psychosocial distress.



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Role of IL-13Rα2 in modulating IL-13 induced MUC5AC and ciliary changes in healthy and CRSwNP mucosa

Abstract

Background

The IL-13 receptor α2 (IL-13Rα2) is a receptor for IL-13 which has conflicting roles in mediating IL-13 responses in the lower airway; with little known about its impact on upper airway diseases. We sought to investigate the expression of IL-13 receptors, IL-13Rα1 and IL-13Rα2, in chronically inflamed nasal epithelium, and explore IL-13 induced signaling pathways in an in vitro model of human nasal epithelial cells (hNECs).

Methods

The protein and mRNA expression levels of IL-13 and its receptors in nasal biopsies of patients with nasal polyps (NP) and healthy controls were evaluated. We investigated goblet cell stimulation with mucus hypersecretion induced by IL-13 (10 ng/mL, 72 hours) treatment in hNECs using a pseudo-stratified epithelium in air-liquid interface (ALI) culture.

Results

There were significant increases in IL-13, IL-13Rα1 and IL-13Rα2 mRNA and protein levels in NP epithelium with healthy controls as baseline. MUC5AC mRNA positively correlated with IL-13Rα2 (r=0.5886, p=0.002) but not with IL-13Rα1 in primary hNECs. IL-13 treatment resulted in a significant increase in mRNA and protein levels of IL-13Rα2 only in hNECs.. IL-13 treatment induced an activation of extracellular signal-regulated kinases (ERK)1/2 and an upregulation of C-JUN; where the IL-13 induced effects on hNECs could be attenuated by ERK1/2 inhibitor (50 μMol/L) or dexamethasone (10-4-10-7 Mol/L) treatment.

Conclusions

IL-13Rα2 has a potential role in IL-13 induced MUC5AC and ciliary changes through ERK1/2 signal pathway in the nasal epithelium. IL-13Rα2 may contribute to airway inflammation and aberrant remodeling which are the main pathological features of CRSwNP.

This article is protected by copyright. All rights reserved.



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Refractory thyroid carcinoma: which systemic treatment to use?

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Refractory thyroid carcinoma: which systemic treatment to use?

Ther Adv Med Oncol. 2018;10:1758834017752853

Authors: Faugeras L, Pirson AS, Donckier J, Michel L, Lemaire J, Vandervorst S, D'Hondt L

Abstract
The incidence of thyroid cancer has increased markedly in recent decades, but has been stable in terms of mortality rates. For the most part, these cancers are treated with surgery, which may or may not be followed by radioactive iodine depending on the tumor subtype. Still, many of these cancers will recur and may be treated with radioactive iodine or another surgery. It is unclear what treatment is best for cases of locally advanced or metastatic thyroid cancer that are refractory to radioactive iodine. Chemotherapy has a very low response rate. However, in the past few years, several systemic therapies, primarily targeted, have emerged to improve the overall survival of these patients. Alternative treatments are also of interest, namely peptide receptor radionuclide therapy or immunotherapy.

PMID: 29399055 [PubMed]



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Prorenin receptor acts as a potential molecular target for pancreatic ductal adenocarcinoma diagnosis.

http:--www.impactjournals.com-oncotarget https:--www.ncbi.nlm.nih.gov-corehtml-pm Related Articles

Prorenin receptor acts as a potential molecular target for pancreatic ductal adenocarcinoma diagnosis.

Oncotarget. 2016 Aug 23;7(34):55437-55448

Authors: Arundhathi A, Chuang WH, Chen JK, Wang SE, Shyr YM, Chen JY, Liao WN, Chen HW, Teng YM, Pai CC, Wang CH

Abstract
Recent studies have implicated the prorenin receptor (PRR) is associated with pancreatic tumorigenesis. We therefore investigated the role of PRR in pancreatic tumorigenesis and assessed whether PRR can serve as a target for imaging diagnosis at early stages of PDAC. Here we show that aberrant expression of PRR in premalignant PanIN lesions, and human PDAC samples, and PDAC cell lines, particularly in Panc-1 cells. Interestingly, PRR expression was positively associated with PDAC progression. Moreover, overexpression of human PRR resulted in increased cell proliferation and decreased apoptosis, while knockdown of human PRR caused decreased cell proliferation and enhanced apoptosis in pancreatic cancer cells. We also observed that overexpression of human PRR enhanced MAPK and PI3K/Akt signaling pathways in PDAC cells, while knockdown of human PRR suppressed both of pathways. The confocal imaging analysis showed that human PRR was highly expressed in Panc-1, ASPC, and Miapaca cells, whereas BXPC-3, and HPAC cells had a significantly lower fluorescent signals. Consistently, the single-photon emission computed tomography (SPET/CT) showed that the uptake of anti-PRR labelled with 125I was higher in Panc-1 and ASPC tumors-bearing mice after 96 hours injection. Importantly, tumors in pancreas of Pdx1-cre; LSL-KrasG12D mice had a significant increased PRR expression and accumulation of radioactivity at 96 h after injection. These data suggest that 125I-anti-PRR can detect the orthotopic tumors in Pdx1-cre; LSL-KrasG12D mice. Therefore, anti-PRR labelled with 125I is a promising radiotracer for imaging diagnosis at early stages of pancreatic cancer.

PMID: 28874965 [PubMed - indexed for MEDLINE]



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Effect of pH and pulsed electric field process parameters on the aflatoxin reduction in model system using response surface methodology

Abstract

The presence of aflatoxin, a carcinogenic and toxigenic secondary metabolite produced by Aspergillus species, in food matrix has been a major worldwide problem for years now. Food processing methods such as roasting, extrusion, etc. have been employed for effective destruction of aflatoxins, which are known for their thermo-stable nature. The high temperature treatment, adversely affects the nutritive and other quality attributes of the food, leading to the necessity of application of non-thermal processing techniques such as ultrasonication, gamma irradiation, high pressure processing, pulsed electric field (PEF), etc. The present study was focused on analysing the efficacy of the PEF process in the reduction of the toxin content, which was subsequently quantified using HPLC. The process parameters of different pH model system (potato dextrose agar) artificially spiked with aflatoxin mix standard was optimized using the response surface methodology. The optimization of PEF process effects on the responses aflatoxin B1 and total aflatoxin reduction (%) by pH (4–10), pulse width (10–26 µs) and output voltage (20–65%), fitted 2FI model and quadratic model respectively. The response surface plots obtained for the processes were of saddle point type, with the absence of minimum or maximum response at the centre point. The implemented numerical optimization showed that the predicted and actual values were similar, proving the adequacy of the fitted models and also proved the possible application of PEF in toxin reduction.



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IJMS, Vol. 19, Pages 480: CircSMARCA5 Inhibits Migration of Glioblastoma Multiforme Cells by Regulating a Molecular Axis Involving Splicing Factors SRSF1/SRSF3/PTB

IJMS, Vol. 19, Pages 480: CircSMARCA5 Inhibits Migration of Glioblastoma Multiforme Cells by Regulating a Molecular Axis Involving Splicing Factors SRSF1/SRSF3/PTB

International Journal of Molecular Sciences doi: 10.3390/ijms19020480

Authors: Davide Barbagallo Angela Caponnetto Matilde Cirnigliaro Duilia Brex Cristina Barbagallo Floriana D’Angeli Antonio Morrone Rosario Caltabiano Giuseppe Barbagallo Marco Ragusa Cinzia Di Pietro Thomas Hansen Michele Purrello

Circular RNAs (circRNAs) have recently emerged as a new class of RNAs, highly enriched in the brain and very stable within cells, exosomes and body fluids. To analyze their involvement in glioblastoma multiforme (GBM) pathogenesis, we assayed the expression of twelve circRNAs, physiologically enriched in several regions of the brain, through real-time PCR in a cohort of fifty-six GBM patient biopsies and seven normal brain parenchymas. We focused on hsa_circ_0001445 (circSMARCA5): it was significantly downregulated in GBM biopsies as compared to normal brain tissues (p-value &lt; 0.00001, student’s t-test), contrary to its linear isoform counterpart that did not show any differential expression (p-value = 0.694, student’s t-test). Analysis of a public dataset revealed a negative correlation between the expression of circSMARCA5 and glioma’s histological grade, suggesting its potential negative role in the progression to malignancy. Overexpressing circSMARCA5 in U87MG cells significantly decreased their migration, but not their proliferation rate. In silico scanning of circSMARCA5 sequence revealed an enrichment in binding motifs for several RNA binding proteins (RBPs), specifically involved in splicing. Among them, serine and arginine rich splicing factor 1 (SRSF1), a splicing factor known to be a positive controller of cell migration and known to be overexpressed in GBM, was predicted to bind circSMARCA5 by three different prediction tools. Direct interaction between circSMARCA5 and SRSF1 is supported by enhanced UV crosslinking and immunoprecipitation (eCLIP) data for SRSF1 in K562 cells from Encyclopedia of DNA Elements (ENCODE). Consistently, U87MG overexpressing circSMARCA5 showed an increased expression of serine and arginine rich splicing factor 3 (SRSF3) RNA isoform containing exon 4, normally skipped in a SRSF1-dependent manner, resulting in a non-productive non-sense mediated decay (NMD) substrate. Interestingly, SRSF3 is known to interplay with two other splicing factors, polypyrimidine tract binding protein 1 (PTBP1) and polypyrimidine tract binding protein 2 (PTBP2), that positively regulate glioma cells migration. Collectively, our data show circSMARCA5 as a promising druggable tumor suppressor in GBM and suggest that it may exert its function by tethering the RBP SRSF1.



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We shouldn’t hide the gory details of how meat reaches our plate

ggmbx5-800x533.jpg

Eating animals is a choice we are all entitled to make but we should at least do so with consideration of their lives and deaths

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Ghostly images show the history of X-ray tubes

44-contest17-800x533.jpg

Some of the first machines ever built to emit X-rays have been given a taste of their own medicine - and these ghostly images are the result

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There could be entire stars and planets made out of dark matter

gettyimages-859670200-800x533.jpg

Mystery dark matter may not just form halos around galaxies. It could clump together like ordinary matter to make dark planets or stars

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Rare wooden tools show that Neanderthals got creative with fire

161788.jpg

Wooden tools are hardly ever preserved, but a cache found in Italy suggests Neanderthals made them with fire and used them to dig up foods like tubers

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Weird ice found on Neptune and Uranus has now been made on Earth

unknown-800x533.jpg

Bizarre ice that forms under intense pressure and high temperatures may cause Neptune’s and Uranus’s odd magnetic fields. Now, we’ve made this stuff on Earth

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Some people with epilepsy can learn to stop their own seizures

c0235760-brain_activity_in_epilepsy_spec

Alertness training seems to help some people with epilepsy to stop themselves from having seizures, and has been linked to changes in their brain structure

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DeepMind’s virtual psychology lab seeks flaws in digital minds

gettyimages-652667182-800x533.jpg

Google’s AI company has released a simulated 3D environment in which machines can pit themselves against cognitive tests designed for humans

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A Study of Clinicopathological Profile of Salivary Gland Swellings

Abstract

Salivary gland diseases usually present as a swelling of the affected gland. These lesions are commonly encountered in day to day practice. A salivary gland swelling can present in a variety of locations, depending on the salivary gland affected. The purpose of the study is to know the incidence of salivary gland swellings and the usefulness of FNAC in evaluating these swellings. The present study is a time bound prospective study of fifty consecutive cases of salivary gland swellings admitted in our hospital during the period November 2014–August 2016. Most of the patients underwent pre-operative work up with FNAC and patients indicated for surgery underwent surgery and HPE. Salivary gland swelling occurred more commonly in 3rd decade of life and equal number of cases were seen in both genders. Most of the patients presented with salivary gland swelling (98%). 21 (42%) were non neoplastic, 29 (58%) were neoplastic swellings, 18 (36%) were benign of which pleomorphic adenoma was the most common and 11 (22%) were malignant of which adenoid cystic carcinoma was the most common. Parotid gland was the most common gland involved. Fine needle aspiration cytology was highly sensitive for benign tumours and highly specific for malignant tumours. FNAC should be first choice of investigation in evaluating the salivary gland pathologies. Early diagnosis and subsequent appropriate management carries good prognosis.



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health technology; +401 new citations

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

health technology

These pubmed results were generated on 2018/02/06

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



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We shouldn’t hide the gory details of how meat reaches our plate

Eating animals is a choice we are all entitled to make but we should at least do so with consideration of their lives and deaths

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Ghostly images show the history of X-ray tubes

Some of the first machines ever built to emit X-rays have been given a taste of their own medicine - and these ghostly images are the result

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There could be entire stars and planets made out of dark matter

Mystery dark matter may not just form halos around galaxies. It could clump together like ordinary matter to make dark planets or stars

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Rare wooden tools show that Neanderthals got creative with fire

Wooden tools are hardly ever preserved, but a cache found in Italy suggests Neanderthals made them with fire and used them to dig up foods like tubers

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Weird ice found on Neptune and Uranus has now been made on Earth

Bizarre ice that forms under intense pressure and high temperatures may cause Neptune’s and Uranus’s odd magnetic fields. Now, we’ve made this stuff on Earth

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Some people with epilepsy can learn to stop their own seizures

Alertness training seems to help some people with epilepsy to stop themselves from having seizures, and has been linked to changes in their brain structure

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DeepMind’s virtual psychology lab seeks flaws in digital minds

Google’s AI company has released a simulated 3D environment in which machines can pit themselves against cognitive tests designed for humans

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head and neck; +131 new citations

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

head and neck

These pubmed results were generated on 2018/02/06

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



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InforMD: a new initiative to raise public awareness about breast density - promoting dialogue between government, h… https://t.co/ucaI6HV9Mr

InforMD: a new initiative to raise public awareness about breast density - promoting dialogue between government, h… https://t.co/ucaI6HV9Mr

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Monoclonal antibodies for the treatment of chronic rhinosinusitis with nasal polyposis: a systematic review.

Related Articles

Monoclonal antibodies for the treatment of chronic rhinosinusitis with nasal polyposis: a systematic review.

Rhinology. 2018 Feb 03;:

Authors: Tsetsos N, Goudakos JK, Daskalakis D, Konstantinidis I, Markou K

Abstract
BACKGROUND: Monoclonal antibodies have been proposed as a novel therapy in patients suffering from chronic rhinosinusitis with nasal polyposis (CRSwNP). The purpose of this systematic review was to evaluate their efficacy and safety.
METHODOLOGY: A literature search was performed in MEDLINE, Web of Science, the Cochrane Library and multiple trial registries followed by extensive hand-searching for the identification of relevant studies. Only randomized controlled trials (RCTs) comparing the use of monoclonal antibodies with placebo or another therapy in adult patients with CRSwNP were included.
RESULTS: Anti-immunoglobin E (IgE) therapy with omalizumab was assessed in two studies, anti-interleukin (IL)-5 therapy in three studies (1 reslizumab, 2 mepolizumab) and finally anti-IL-4 and anti-IL-13 therapy in only one. With the exception of one study, biologic therapy was proved to be effective in reducing total nasal endoscopic polyp score (TPS) in treatment as compared to placebo groups. Monoclonal antibodies brought about improvement in several other outcomes, such as opacification in computed tomography (CT), quality of life measures, nasal airflow, olfaction and type 2 helper T-cell (Th2) associated biomarkers. Overall, the use of these agents was deemed safe and well-tolerated.
CONCLUSIONS: This is the first systematic review showing encouraging results for the use of all three main categories of monoclonal antibodies in CRSwNP patients and highlights the need for further well-designed and with larger sample sizes RCTs.

PMID: 29396960 [PubMed - as supplied by publisher]



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Mucocele formation after frontal sinus obliteration.

Related Articles

Mucocele formation after frontal sinus obliteration.

Rhinology. 2018 Feb 03;:

Authors: Hansen FS, van der Poel NA, Freling NJM, Fokkens WJ

Abstract
BACKGROUND: A possible complication of frontal sinus obliteration with fat is the formation of mucoceles. We studied the prevalence of mucoceles as well as and the need for revision surgery.
METHODS: Retrospective case review of forty consecutive patients undergoing frontal sinus obliteration from September 1995 to February 2012 for chronic rhinosinusitis (26), frontal mucocele (12) or frontal osteoma (2) with an average follow up of 80 months (range 15-218). MRI of the paranasal sinuses was performed in all. Outcome measures included MRI signs of mucocele formation in the obliterated frontal sinus, revision surgery, symptom burden.
RESULTS: Magnetic resonance imaging (MRI) showed potential postoperative frontal sinus mucoceles in 6/40 patients. In 3 patients (7.5%) a revision operation was performed, revealing mucoceles in two cases. A wait and scan-policy in the other 3 patients confirmed the presence of a mucocele in 1 of these patients. The majority of patients (33/40, 83%) was asymptomatic at the last follow up.
CONCLUSION: The prevalence of mucoceles and revision rate in this series was 7.5% (3/40). MRI can improve detection rate and reduce / avoid unnecessary revision surgery after frontal sinus obliteration.

PMID: 29396959 [PubMed - as supplied by publisher]



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Higher prevalence of nasal polyposis among textile workers: an endoscopic based and controlled study.

Related Articles

Higher prevalence of nasal polyposis among textile workers: an endoscopic based and controlled study.

Rhinology. 2018 Feb 03;:

Authors: Veloso-Teles R, Cerejeira R, Roque-Farinha R, von Buchwald C

Abstract
BACKGROUND: There is a deficit of reliable epidemiologic studies exploring the prevalence of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Recent data suggests that occupational dust exposure may be involved in its physiopathology.
OBJECTIVES: To compare the prevalence of nasal polyposis (NP) in a group of workers with occupational dust exposure (textile workers) and in a control group (retail store workers).
METHODS: Cross-sectional study with a random sample of textile and retail store employees. Clinical data was gathered through a systematic interview, which included RhinoQOL and CAT questionnaires. A systematic endoscopic nasal examination was performed using a 0 degree rigid endoscope. Lund-Kennedy endoscopic score was determined for each participant. Statistical analysis was performed with SPSS.
RESULTS: 316 participants were included in the study, i.e. 215 textile workers and 101 retail store workers. NP was found in 19 subjects among textile workers and none in the control group. The prevalence of NP increased by age strata and by years of dust exposition. Polypoid degeneration of the middle turbinate was more prevalent in the exposed group with Lund-Kennedy scoring also higher. RhinoQOL and CAT questionnaires had both significantly higher scores among textile employees. Previous medical diagnosis of atopic diseases or chronic lower airway diseases did not differ between exposed and control groups or even between subjects with and without NP.
CONCLUSIONS: These results point to an important correlation between occupational dust exposure and NP occurrence.

PMID: 29396958 [PubMed - as supplied by publisher]



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Study of the relation between medial orbitofrontal artery and anterior skull base performed by computed tomography angiography.

Related Articles

Study of the relation between medial orbitofrontal artery and anterior skull base performed by computed tomography angiography.

Rhinology. 2018 Feb 03;:

Authors: Patricio HC, Felippu A, Pinheiro-Neto CD, Sennes LU

Abstract
BACKGROUND: The aims of this study were to analyze the relationships between the medial orbitofrontal artery (MOFA) and the anterior skull base (ASB) including anatomical endonasal landmarks using computed tomography angiography (CTA).
METHODS: We studied 52 CTAs using OsiriX software. All CTAs were placed in the same anatomical position. MOFA was identified in the sagittal and coronal plane and its correlation with ASB was analyzed. The distance between the MOFA and landmarks for endonasal surgery were obtained, determining the high risk areas for its injury.
RESULTS: After arising from the anterior cerebral artery, the MOFA dives inferiorly towards the ASB, close to the midline (average distance of 1.5 mm), approaching the planum sphenoidale (average distance of 1.8 mm) and then ascends away from the ASB as it runs anteriorly, with an average distance of 4.4 mm in the region of the anterior wall of the sphenoid sinus and 12 mm in the region of the anterior ethmoid artery.
CONCLUSIONS: The MOFA has an intimate relationship with the ASB and nasal cavity; the regions with the highest risk of surgical trauma are between the posterior ethmoid and the planum sphenoidale.

PMID: 29396957 [PubMed - as supplied by publisher]



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Fabrication of paclitaxel hybrid nanomicelles to treat resistant breast cancer via oral administration

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Nanosilver: new ageless and versatile biomedical therapeutic scaffold

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ASCO GU 2018: Apalutamide delays prostate cancer metastases by more than two years

Findings from the phase III placebo-controlled SPARTAN trial suggest that apalutamide is an effective treatment for men with non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk for developing metastatic disease, and for whom...

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ASCO GU 2018: Adding immunotherapy to standard treatment slows growth of advanced kidney cancer, with fewer side effects

In a phase III clinical trial of people with previously untreated metastatic renal cell cancer (mRCC), combining immunotherapy atezolizumab with targeted therapy bevacizumab delayed cancer growth by about three months longer than sunitinib, another...

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A novel genotoxin-specific qPCR array based on the metabolically competent human HepaRG ™ cell line as a rapid and reliable tool for improved in vitro hazard assessment

Abstract

Although the value of the regulatory accepted batteries for in vitro genotoxicity testing is recognized, they result in a high number of false positives. This has a major impact on society and industries developing novel compounds for pharmaceutical, chemical, and consumer products, as afflicted compounds have to be (prematurely) abandoned or further tested on animals. Using the metabolically competent human HepaRG cell line and toxicogenomics approaches, we have developed an upgraded, innovative, and proprietary gene classifier. This gene classifier is based on transcriptomic changes induced by 12 genotoxic and 12 non-genotoxic reference compounds tested at sub-cytotoxic concentrations, i.e., IC10 concentrations as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The resulting gene classifier was translated into an easy-to-handle qPCR array that, as shown by pathway analysis, covers several different cellular processes related to genotoxicity. To further assess the predictivity of the tool, a set of 5 known positive and 5 known negative test compounds for genotoxicity was evaluated. In addition, 2 compounds with debatable genotoxicity data were tested to explore how the qPCR array would classify these. With an accuracy of 100%, when equivocal results were considered positive, the results showed that combining HepaRG cells with a genotoxin-specific qPCR array can improve (geno)toxicological hazard assessment. In addition, the developed qPCR array was able to provide additional information on compounds for which so far debatable genotoxicity data are available. The results indicate that the new in vitro tool can improve human safety assessment of chemicals in general by basing predictions on mechanistic toxicogenomics information.



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Environmental effects of ozone depletion, UV radiation and interactions with climate change: UNEP Environmental Effects Assessment Panel, update 2017

GA?id=C7PP90043K

Photochem. Photobiol. Sci., 2018, Advance Article
DOI: 10.1039/C7PP90043K, Perspective
A. F. Bais, R. M. Lucas, J. F. Bornman, C. E. Williamson, B. Sulzberger, A. T. Austin, S. R. Wilson, A. L. Andrady, G. Bernhard, R. L. McKenzie, P. J. Aucamp, S. Madronich, R. E. Neale, S. Yazar, A. R. Young, F. R. de Gruijl, M. Norval, Y. Takizawa, P. W. Barnes, T. M. Robson, S. A. Robinson, C. L. Ballare, S. D. Flint, P. J. Neale, S. Hylander, K. C. Rose, S.-A. Wangberg, D.-P. Hader, R. C. Worrest, R. G. Zepp, N. D. Paul, R. M. Cory, K. R. Solomon, J. Longstreth, K. K. Pandey, H. H. Redhwi, A. Torikai, A. M. Heikkila
The present 2017 Update Report assesses some of the highlights about the interactive nature of the direct and indirect effects of UV radiation, atmospheric processes, and climate change.
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry


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IJMS, Vol. 19, Pages 478: Modulation of Telomerase Activity in Cancer Cells by Dietary Compounds: A Review

IJMS, Vol. 19, Pages 478: Modulation of Telomerase Activity in Cancer Cells by Dietary Compounds: A Review

International Journal of Molecular Sciences doi: 10.3390/ijms19020478

Authors: Takahiro Eitsuka Kiyotaka Nakagawa Shunji Kato Junya Ito Yurika Otoki Soo Takasu Naoki Shimizu Takumi Takahashi Teruo Miyazawa

Telomerase is expressed in ~90% of human cancer cell lines and tumor specimens, whereas its enzymatic activity is not detectable in most human somatic cells, suggesting that telomerase represents a highly attractive target for selective cancer treatment. Accordingly, various classes of telomerase inhibitors have been screened and developed in recent years. We and other researchers have successfully found that some dietary compounds can modulate telomerase activity in cancer cells. Telomerase inhibitors derived from food are subdivided into two groups: one group directly blocks the enzymatic activity of telomerase (e.g., catechin and sulfoquinovosyldiacylglycerol), and the other downregulates the expression of human telomerase reverse transcriptase (hTERT), the catalytic subunit of human telomerase, via signal transduction pathways (e.g., retinoic acid and tocotrienol). In contrast, a few dietary components, including genistein and glycated lipid, induce cellular telomerase activity in several types of cancer cells, suggesting that they may be involved in tumor progression. This review summarizes the current knowledge about the effects of dietary factors on telomerase regulation in cancer cells and discusses their molecular mechanisms of action.



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IJMS, Vol. 19, Pages 477: Changes in DNA Methylation from Age 18 to Pregnancy in Type 1, 2, and 17 T Helper and Regulatory T-Cells Pathway Genes

IJMS, Vol. 19, Pages 477: Changes in DNA Methylation from Age 18 to Pregnancy in Type 1, 2, and 17 T Helper and Regulatory T-Cells Pathway Genes

International Journal of Molecular Sciences doi: 10.3390/ijms19020477

Authors: Sabrina Iqbal Gabrielle Lockett John Holloway S. Arshad Hongmei Zhang Akhilesh Kaushal Sabarinath Tetali Nandini Mukherjee Wilfried Karmaus

To succeed, pregnancies need to initiate immune biases towards T helper 2 (Th2) responses, yet little is known about what establishes this bias. Using the Illumina 450 K platform, we explored changes in DNA methylation (DNAm) of Th1, Th2, Th17, and regulatory T cell pathway genes before and during pregnancy. Female participants were recruited at birth (1989), and followed through age 18 years and their pregnancy (2011–2015). Peripheral blood DNAm was measured in 245 girls at 18 years; from among these girls, the DNAm of 54 women was repeatedly measured in the first (weeks 8–21, n = 39) and second (weeks 22–38, n = 35) halves of pregnancy, respectively. M-values (logit-transformed β-values of DNAm) were analyzed: First, with repeated measurement models, cytosine–phosphate–guanine sites (CpGs) of pathway genes in pregnancy and at age 18 (nonpregnant) were compared for changes (p ≤ 0.05). Second, we tested how many of the 348 pathway-related CpGs changed compared to 10 randomly selected subsets of all other CpGs and compared to 10 randomly selected subsets of other CD4+-related CpGs (348 in each subset). Contrasted to the nonpregnant state, 27.7% of Th1-related CpGs changed in the first and 36.1% in the second half of pregnancy. Among the Th2 pathway CpGs, proportions of changes were 35.1% (first) and 33.8% (second half). The methylation changes suggest involvement of both Th1 and Th2 pathway CpGs in the immune bias during pregnancy. Changes in regulatory T cell and Th17 pathways need further exploration.



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IJMS, Vol. 19, Pages 479: The Role of Trio, a Rho Guanine Nucleotide Exchange Factor, in Glomerular Podocytes

IJMS, Vol. 19, Pages 479: The Role of Trio, a Rho Guanine Nucleotide Exchange Factor, in Glomerular Podocytes

International Journal of Molecular Sciences doi: 10.3390/ijms19020479

Authors: Mirela Maier Cindy Baldwin Lamine Aoudjit Tomoko Takano

Nephrotic syndrome is a kidney disease featured by heavy proteinuria. It is caused by injury to the specialized epithelial cells called “podocytes” within the filtration unit of the kidney, glomerulus. Previous studies showed that hyperactivation of the RhoGTPase, Rac1, in podocytes causes podocyte injury and glomerulosclerosis (accumulation of extracellular matrix in the glomerulus). However, the mechanism by which Rac1 is activated during podocyte injury is unknown. Trio is a guanine nucleotide exchange factor (GEF) known to activate Rac1. By RNA-sequencing, we found that Trio mRNA is abundantly expressed in cultured human podocytes. Trio mRNA was also significantly upregulated in humans with minimal change disease and focal segmental glomerulosclerosis, two representative causes of nephrotic syndrome. Reduced expression of Trio in cultured human podocytes decreased basal Rac1 activity, cell size, attachment to laminin, and motility. Furthermore, while the pro-fibrotic cytokine, transforming growth factor β1 increased Rac1 activity in control cells, it decreases Rac1 activity in cells with reduced Trio expression. This was likely due to simultaneous activation of the Rac1-GTPase activation protein, CdGAP. Thus, Trio is important in the basal functions of podocytes and may also contribute to glomerular pathology, such as sclerosis, via Rac1 activation.



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02/05/18 PHD comic: 'Stipend Percentages'

Piled Higher & Deeper by Jorge Cham
www.phdcomics.com
Click on the title below to read the comic
title: "Stipend Percentages" - originally published 2/5/2018

For the latest news in PHD Comics, CLICK HERE!



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Molecular characterization of hepatitis B virus X gene in HIV-positive South Africans

Abstract

Hepatitis B virus (HBV) infection is a major public health problem worldwide and the major cause of hepatocellular carcinoma (HCC) in South Africa. The role of HBV in HCC is not well understood, although the HBV X gene has been implicated as a critical factor. Data on the HBV X gene in HIV-positive South Africans are limited; thus, we investigated X gene variability in 24 HIV-infected treatment-naïve patients at Dr George Mukhari Academic Hospital. Quantitative and qualitative HBV DNA tests were conducted using real-time and in-house polymerase chain reaction (PCR) assays, respectively, targeting the complete HBV X gene. In-house PCR-positive samples were cloned using the P-Gem T-easy vector System II and sequenced. By phylogenetic analysis, X gene sequences were classified as subgenotype A1 (n = 15), A2 (n = 4), and D1 (n = 4), and one dual infection with subgenotypes as A1 and C. The basal core promoter mutations T1753C, A1762T, and G1764A were identified in the majority of sequences. Genotype D sequences had a 6-nucleotide insertion. In conclusion, subgenotype A1 was predominant, and a rare dual infection of HBV genotype A and C was detected. The 6-nucleotide insertion could represent a unique variant in the region and highlights the need for functional studies of HBV X gene variants, particularly from resource-limited settings.



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Increased mortality in octogenarians treated for lifestyle limiting claudication

Abstract

Objective

Treatment for lifestyle limiting claudication (LLC) that is due to infra-inguinal peripheral artery disease relies on either bypass, angioplasty, and/or stenting. Given the enthusiasm and shift toward more endovascular therapy for treatment of LLC, we sought to analyze whether octogenarians benefit from infra-inguinal interventions in the same manner as their younger counterparts.

Methods

We identified all patients admitted for elective treatment of LLC from the Nationwide Inpatient Sample from 2003 to 2012, who received open surgical or endovascular intervention for infra-inguinal peripheral arterial disease. These patients were divided into two groups including those between the ages 60–80 years (younger cohort) and those older than 80 years (octogenarians). Primary end-points included morbidity and mortality and the secondary end-points were length of hospital stay (LOS) and disposition after dismissal.

Results

Among 59,323 discharges identified in the dataset, 34,658 (58%) were males. There were 50,323 (85%) patients in the younger cohort and 9,000 (15%) octogenarians. The mean age was 69.9 ± 5.7 years and 84.2 ± 3.0 years for the younger cohort and octogenarians, respectively. The mean Charlson comorbidity index (CCI) was higher in our younger cohort (2.1 ± 1.1, P < 0.001). Octogenarians mainly treated with open surgery prior to 2004 are now treated endovascularly and this trend has remained stable. The younger cohort's treatment modality has fluctuated through the study period and most recently is treated mainly with open surgery. The rate of acute kidney injury, exacerbation of congestive heart failure and mortality was higher in octogenarians (P < 0.001). The rate of infectious wound complications was higher in the younger cohort (P < 0.05). Octogenarians have longer LOS and are dismissed in higher percentage to a skilled nursing facility (P < 0.001). On binary logistic regression analysis, age over 80 years, female sex, higher CCI and having an open as opposed to an endovascular procedure are independent predictors of in-hospital mortality.

Conclusions

Although endovascular techniques seem to dominate the care for octogenarians with LLC, the overall morbidity and mortality rates are significantly higher in this patient population. Other options such as medical management and/or supervised exercise therapy should be explored in this patient group.



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Transcatheter pledget-assisted suture tricuspid annuloplasty (PASTA) to create a double-orifice valve

Abstract

Objectives

Pledget-assisted suture tricuspid valve annuloplasty (PASTA) is a novel technique using marketed equipment to deliver percutaneous trans-annular sutures to create a double-orifice tricuspid valve.

Background

Tricuspid regurgitation is a malignant disease with high surgical mortality and no commercially available transcatheter solution in the US.

Methods

Two iterations of PASTA were tested using trans-apical or trans-jugular access in swine. Catheters directed paired coronary guidewires to septal and lateral targets on the tricuspid annulus under fluoroscopic and echocardiographic guidance. Guidewires were electrified to traverse the annular targets and exchanged for pledgeted sutures. The sutures were drawn together and knotted, apposing septal and lateral targets, creating a double orifice tricuspid valve.

Results

Twenty-two pigs underwent PASTA. Annular and chamber dimensions were reduced (annular area, 10.1 ± 0.8 cm2 to 3.8 ± 1.5 cm2 (naïve) and 13.1 ± 1.5 cm2 to 6.2 ± 1.0 cm2 (diseased); septal-lateral diameter, 3.9 ± 0.3 mm to 1.4 ± 0.6 mm (naïve) and 4.4 ± 0.4 mm to 1.7 ± 1.0 mm (diseased); and right ventricular end-diastolic volume, 94 ± 13 ml to 85 ± 14 ml (naïve) and 157 ± 25 ml to 143 ± 20 ml (diseased)). MRI derived tricuspid regurgitation fraction fell from 32 ± 12% to 4 ± 5%. Results were sustained at 30 days. Pledget pull-through force was five-fold higher (40.6 ± 11.7N vs 8.0 ± 2.6N, P < .01) using this strategy compared to single puncture techniques used to anchor current investigational devices. Serious complications were related to apical access.

Conclusions

PASTA reduces annular dimensions and tricuspid regurgitation in pigs. It may be cautiously applied to selected patients with severe tricuspid regurgitation and no options. This is the first transcatheter procedure, to our knowledge, to deliver standard pledgeted sutures to repair cardiac pathology.



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Fractional flow reserve guided percutaneous coronary intervention results in reduced ischemic myocardium and improved outcomes

Abstract

Objectives

To determine if fractional flow reserve guided percutaneous coronary intervention (FFR-guided PCI) is associated with reduced ischemic myocardium compared with angiography-guided PCI.

Background

Although FFR-guided PCI has been shown to improve outcomes, it remains unclear if it reduces the extent of ischemic myocardium at risk compared with angiography-guided PCI.

Methods

We evaluated 380 patients (190 FFR-guided PCI cases and 190 propensity-matched controls) who underwent PCI from 2009 to 2014. Clinical, laboratory, angiographic, stress testing, and major adverse cardiac events [MACE] (all-cause mortality, recurrence of MI requiring PCI, stroke) data were collected.

Results

Mean age was 63 ± 11 years; the majority of patients were males (76%) and Caucasian (77%). Median duration of follow up was 3.4 [Range: 1.9, 5.0] years. Procedural complications including coronary dissection (2% vs. 0%, P = .12) and perforation (0% vs. 0%, P = 1.00) were similar between FFR-guided and angiography-guided PCI patients. FFR-guided PCI patients had lower unadjusted (14.7% vs. 23.2%, P = .04) and adjusted [OR = 0.58 (95% CI: 0.34–0.98)] risk of repeat revascularization at one year. FFR-guided PCI patients were less likely (23% vs. 32%, P = .02) to have ischemia and had lower (5.9% vs. 21.1%, P < .001) ischemic burden (moderate-severe ischemia) on post-PCI stress testing. Presence of ischemia post-PCI remained a strong predictor of MACE [OR = 2.14 (95%CI: 1.28–3.60)] with worse survival compared to those without ischemia (HR = 1.63 (95% CI: 1.06–2.51).

Conclusion

Compared with angiography-guided PCI, FFR-guided PCI results in less repeat revascularization and a lower incidence of post PCI ischemia translating into improved survival, without an increase in complications.



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Tricuspid regurgitation as a complication of Edwards Sapien XT valve implantation in pulmonary position a problem to deal with

Abstract

Nowadays, percutaneous pulmonary valve implantation (PPVI) is a suitable alternative to surgical procedure in patients with right ventricle outflow tract dysfunction. Two valves are currently available for PPVI: the Melody valve and the Edwards Sapien valve. The following complications may occur: coronary artery compression, deformation of the aortic root, stent or valve embolization, damage of distal pulmonary arteries, access site injuries. Here, we report on three cases of severe tricuspid regurgitation due to valvular and subvalvular apparatus damage during Edwards Sapien XT valve implantation.



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Heparin use for diagnostic cardiac catheterization with a radial artery approach: An international survey of practice patterns

Abstract

Objectives

We aimed to describe global practice patterns of unfractionated heparin (UFH) use for diagnostic transradial cardiac catheterization.

Background

The use of the radial artery approach for cardiac catheterization is increasing globally. Limited contemporary data exist to support the use or optimal dosing of UFH to prevent radial artery occlusion (RAO) and other thromboembolic complications.

Methods

We performed a web-based international survey of 450 interventional cardiologists from 34 countries. We collected information regarding the experience and use of UFH for diagnostic transradial cardiac catheterization.

Results

The survey was conducted between June and July 2016 and was completed by 227 (50.4%) interventional cardiologists. Overall, 83.3% performed >75% of their coronary angiograms via a radial approach, with the plurality (41.9%) having 10–20 years of clinical experience. Of all respondents, 7.5% did not use UFH for routine diagnostic transradial heart catheterization. Of the 92.5% who did use UFH, it was preferentially administered intra-arterially by 60% and intravenously by 40%. The majority (62.6%) of interventionalists used a fixed UFH dose with 5,000 IU being the most common dose (used in 48%). For those using a weight-based UFH (50 IU/kg) dosing regimen for diagnostic procedures (36.1%), the administered UFH dose ranged from 2,000 up to 10,000 IU.

Conclusions

Despite the lack of firm evidence, the majority of interventional cardiologists who participated in the survey use UFH to prevent RAO for diagnostic transradial coronary angiography. However, there exist large practice disparities with regards to dose and route of administration. Given this knowledge gap, a dedicated randomized trial is warranted.



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Efficacy and safety of continuous every 2-week dosing of ixekizumab over 52 weeks in patients with moderate-to-severe plaque psoriasis in a randomized phase 3 trial (IXORA-P)

Abstract

Introduction

Ixekizumab is an interleukin-17A antagonist approved for treatment of moderate-to-severe plaque psoriasis with recommended 160-mg starting dose, then 80 mg every 2 weeks (Q2W) through Week 12, and every 4 weeks (Q4W) thereafter. This study evaluated continuous every 2-week dosing (Q2W) over 52 weeks.

Methods

In this Phase 3, multicentre, double-blinded, parallel-group trial, three ixekizumab dosing regimens were assessed for efficacy and safety at Week 52 in patients with moderate-to-severe plaque psoriasis randomized at a 2:1:1 ratio to continuous Q2W (N=611), continuous Q4W (N=310), or dose adjustment per protocol (Q4W/Q2W, N=306), each with a 160-mg starting dose. Dose adjustment was determined by predefined criteria to which investigators were blinded; 72 (23.5%) patients in the Q4W/Q2W group adjusted dose. Efficacy outcomes were evaluated using logistic regression.

Results

Co-primary endpoints were met at Week 52; Psoriasis Area and Severity Index 75 responses for Q2W and Q4W dose groups were 85.9% and 79.0%, respectively (p=0.006), and static Patient Global Assessment 0/1 responses for Q2W and Q4W dose groups were 78.6% and 70.6%, respectively (p=0.005). Treatment-emergent and serious adverse events were comparable across dose groups.

Conclusions

Ixekizumab Q2W had higher efficacy at Week 52 compared to Q4W, with no increase in safety events.

This article is protected by copyright. All rights reserved.



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Complement activation in hidradenitis suppurativa: a new pathway of pathogenesis?

Abstract

Objective

Despite the heavy purulence observed in hidradenitis suppurativa (HS), kinetics of complement anaphylatoxins acting to prime chemotaxis of neutrophils has never been studied. Complement activation was explored in HS.

Methods

Circulating concentrations of complement factor C5a as well as of membrane attack complex C5b-9 were determined in the plasma of 54 treatment naïve patients and of 14 healthy controls as well as in the pus of seven patients. Results were correlated with Hurley stage and iHS4 score of severity. Peripheral blood mononuclear cells (PBMCs) were isolated form seven Hurley III stage patients and seven healthy volunteers and stimulated in the presence of 25% of plasma for the production of tumor necrosis factor-alpha (TNFα).

Results

Circulating C5a and C5b-9 were significantly greater in patient than in control plasma; however concentrations in pus were very low. Circulating C5a levels exceeding 28 ng/ml were associated with specificity greater than 90% with occurrence of HS. Circulating C5a and C5b-9 were greater among the more severe patients. PBMCs of patients produced great TNFα concentrations only when growth medium was enriched with patient plasma; this was reversed with the addition of the C5a blocker IFX-1.

Conclusions

Systemic complement activation occurs in HS and may be used as a surrogate biomarker of HS. C5a stimulates over-production of TNFα and may be a future therapeutic target.

This article is protected by copyright. All rights reserved.



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IJMS, Vol. 19, Pages 476: Role of Zinc Homeostasis in the Pathogenesis of Diabetes and Obesity

IJMS, Vol. 19, Pages 476: Role of Zinc Homeostasis in the Pathogenesis of Diabetes and Obesity

International Journal of Molecular Sciences doi: 10.3390/ijms19020476

Authors: Ayako Fukunaka Yoshio Fujitani

Zinc deficiency is a risk factor for obesity and diabetes. However, until recently, the underlying molecular mechanisms remained unclear. The breakthrough discovery that the common polymorphism in zinc transporter SLC30A8/ZnT8 may increase susceptibility to type 2 diabetes provided novel insights into the role of zinc in diabetes. Our group and others showed that altered ZnT8 function may be involved in the pathogenesis of type 2 diabetes, indicating that the precise control of zinc homeostasis is crucial for maintaining health and preventing various diseases, including lifestyle-associated diseases. Recently, the role of the zinc transporter ZIP13 in the regulation of beige adipocyte biogenesis was clarified, which indicated zinc homeostasis regulation as a possible therapeutic target for obesity and metabolic syndrome. Here we review advances in the role of zinc homeostasis in the pathophysiology of diabetes, and propose that inadequate zinc distribution may affect the onset of diabetes and metabolic diseases by regulating various critical biological events.



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IJMS, Vol. 19, Pages 475: Alterations of Subchondral Bone Progenitor Cells in Human Knee and Hip Osteoarthritis Lead to a Bone Sclerosis Phenotype

IJMS, Vol. 19, Pages 475: Alterations of Subchondral Bone Progenitor Cells in Human Knee and Hip Osteoarthritis Lead to a Bone Sclerosis Phenotype

International Journal of Molecular Sciences doi: 10.3390/ijms19020475

Authors: Daniel Bianco Atanas Todorov Tomislav Čengić Geert Pagenstert Stefan Schären Cordula Netzer Thomas Hügle Jeroen Geurts

Subchondral bone tissue plays a key role in the initiation and progression of human and experimental osteoarthritis and has received considerable interest as a treatment target. Elevated bone turnover and remodeling leads to subchondral bone sclerosis that is characterized by an increase in bone material that is less mineralized. The aim of this study was to investigate whether perturbations in subchondral bone-resident progenitor cells might play a role in aberrant bone formation in osteoarthritis. Colony formation assays indicated similar clonogenicity of progenitor cells from non-sclerotic and sclerotic subchondral trabecular bone tissues of osteoarthritic knee and hip joints compared with controls from iliac crest bone. However, the osteogenic potential at the clonal level was approximately two-fold higher in osteoarthritis than controls. An osteogenic differentiation assay indicated an efficient induction of alkaline phosphatase activity but blunted in vitro matrix mineralization irrespective of the presence of sclerosis. Micro-computed tomography and histology demonstrated the formation of de novo calcified tissues by osteoblast-like cells in an ectopic implantation model. The expression of bone sialoprotein, a marker for osteoblast maturation and mineralization, was significantly less in sclerotic progenitor cells. Perturbation of resident progenitor cell function is associated with subchondral bone sclerosis and may be a treatment target for osteoarthritis.



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Brain Sciences, Vol. 8, Pages 28: Electric Field Comparison between Microelectrode Recording and Deep Brain Stimulation Systems—A Simulation Study

Brain Sciences, Vol. 8, Pages 28: Electric Field Comparison between Microelectrode Recording and Deep Brain Stimulation Systems—A Simulation Study

Brain Sciences doi: 10.3390/brainsci8020028

Authors: Fabiola Alonso Dorian Vogel Johannes Johansson Karin Wårdell Simone Hemm

The success of deep brain stimulation (DBS) relies primarily on the localization of the implanted electrode. Its final position can be chosen based on the results of intraoperative microelectrode recording (MER) and stimulation tests. The optimal position often differs from the final one selected for chronic stimulation with the DBS electrode. The aim of the study was to investigate, using finite element method (FEM) modeling and simulations, whether lead design, electrical setup, and operating modes induce differences in electric field (EF) distribution and in consequence, the clinical outcome. Finite element models of a MER system and a chronic DBS lead were developed. Simulations of the EF were performed for homogenous and patient-specific brain models to evaluate the influence of grounding (guide tube vs. stimulator case), parallel MER leads, and non-active DBS contacts. Results showed that the EF is deformed depending on the distance between the guide tube and stimulating contact. Several parallel MER leads and the presence of the non-active DBS contacts influence the EF distribution. The DBS EF volume can cover the intraoperatively produced EF, but can also extend to other anatomical areas. In conclusion, EF deformations between stimulation tests and DBS should be taken into consideration as they can alter the clinical outcome.



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Editorial Board

Publication date: 10 February 2018
Source:Journal of Controlled Release, Volume 271





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