Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

Αρχειοθήκη ιστολογίου

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Κυριακή 23 Ιουλίου 2017

Privacy matters: updating human rights for the digital society

Abstract

Privacy matters because everyone needs some portion of their intimate space - whether it is their bodies, their families and relationships, their property or information about them - to remain hidden and secure from unwanted or unexpected external interferences. Privacy is a prerequisite for the enjoyment of other hard-fought freedoms like free speech and non-discrimination on grounds of sex, race, sexual orientation and political and religious beliefs. This universal truism is being questioned in an age where humans are submitting large quantities of traces of themselves, increasingly unwittingly, and as a by-product or condition of their participation in digital life. However, as participation in digital society and the economy becomes all-pervasive, and in effect compulsory, privacy cannot become the preserve of those who can afford it. As memories of the man-made cataclysms of the twentieth century recede, there has never been a greater need for safeguards against unjustified intrusions into people's personal space by powerful state actors and corporations. Convergence between political malevolence and technological omnipotence is a 'real and present' danger. This article summarises the case for privacy and emerging legal principles such as accountability and individual control over data about them. It argues for a Global Friends of Privacy comprising willing regulators, academics and civil society to patrol more vigilantly and to contest more forcefully attempts to 'salami-slice' away precious liberties of populations.



http://ift.tt/2vQsq41

Distinct histopathologic features of radiation-induced chronic sinusitis

Background

Chronic rhinosinusitis (CRS) is a commonly observed sequela after radiation therapy to the paranasal sinuses. The histopathologic features of radiation-induced CRS have yet to be determined and may have major implications in disease management.

Methods

A structured histopathology report was utilized to analyze sinus tissue removed during functional endoscopic sinus surgery (FESS). Histopathology variables, Lund-Mackay score (LMS), and 22-item Sino-Nasal Outcome Test (SNOT-22) scores were compared among patients with radiation-induced CRS (CRSr), CRS without nasal polyps (CRSsNP), and CRS with nasal polyps (CRSwNP).

Results

Fifteen CRSr, 43 CRSsNP, and 56 CRSwNP patients who underwent FESS were analyzed. Compared with CRSsNP, CRSr cases had increased squamous metaplasia (40.0% vs 9.3%, p < 0.013) and subepithelial edema (53.3% vs. 2.3%, p < 0.001). Compared with CRSwNP, CRSr cases had fewer eosinophils per high-power field (20.0% vs 50.0%, p < 0.034), less basement membrane thickening (33.3% vs 76.8%, p < 0.002), and fewer eosinophil aggregates (0.0% vs 30.4%, p < 0.009). CRSr had significantly greater mean LMS (13.47 ± 5.13 vs 7.07 ± 4.79, p < 0.001) compared with CRSsNP.

Conclusion

Radiation-induced CRS patients exhibited greater squamous metaplasia and subepithelial edema when compared with a cohort of patients with CRSsNP, and decreased eosinophilia and basement membrane thickening compared with a cohort of CRSwNP patients. CRSr cases demonstrated no difference in eosinophilia or neutrophilia compared with CRSsNP, and decreased eosinophilia compared with CRSwNP, lending further credence to the unique nature of radiation in the development of CRS in this patient group. These findings may have major implications with regard to extent of surgical intervention and medical management.



http://ift.tt/2tSKIQt

Distinct histopathologic features of radiation-induced chronic sinusitis

Background

Chronic rhinosinusitis (CRS) is a commonly observed sequela after radiation therapy to the paranasal sinuses. The histopathologic features of radiation-induced CRS have yet to be determined and may have major implications in disease management.

Methods

A structured histopathology report was utilized to analyze sinus tissue removed during functional endoscopic sinus surgery (FESS). Histopathology variables, Lund-Mackay score (LMS), and 22-item Sino-Nasal Outcome Test (SNOT-22) scores were compared among patients with radiation-induced CRS (CRSr), CRS without nasal polyps (CRSsNP), and CRS with nasal polyps (CRSwNP).

Results

Fifteen CRSr, 43 CRSsNP, and 56 CRSwNP patients who underwent FESS were analyzed. Compared with CRSsNP, CRSr cases had increased squamous metaplasia (40.0% vs 9.3%, p < 0.013) and subepithelial edema (53.3% vs. 2.3%, p < 0.001). Compared with CRSwNP, CRSr cases had fewer eosinophils per high-power field (20.0% vs 50.0%, p < 0.034), less basement membrane thickening (33.3% vs 76.8%, p < 0.002), and fewer eosinophil aggregates (0.0% vs 30.4%, p < 0.009). CRSr had significantly greater mean LMS (13.47 ± 5.13 vs 7.07 ± 4.79, p < 0.001) compared with CRSsNP.

Conclusion

Radiation-induced CRS patients exhibited greater squamous metaplasia and subepithelial edema when compared with a cohort of patients with CRSsNP, and decreased eosinophilia and basement membrane thickening compared with a cohort of CRSwNP patients. CRSr cases demonstrated no difference in eosinophilia or neutrophilia compared with CRSsNP, and decreased eosinophilia compared with CRSwNP, lending further credence to the unique nature of radiation in the development of CRS in this patient group. These findings may have major implications with regard to extent of surgical intervention and medical management.



http://ift.tt/2tSKIQt

Comparison of ultraviolet absorbance and NO-chemiluminescence for ozone measurement in wildfire plumes at the Mount Bachelor Observatory

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Publication date: October 2017
Source:Atmospheric Environment, Volume 166
Author(s): Honglian Gao, Daniel A. Jaffe
The goal of this paper is to evaluate the accuracy of the commonly used ozone (O3) instrument (the ultraviolet (UV) photometer) against a Federal Reference Method (Nitric Oxide –chemiluminescence) for ozone measurement in wildfire smoke plumes. We carried out simultaneous ozone measurement with two UV O3 photometers and one nitric oxide–chemiluminescence (NO-CL) ozone detectors during wildfire season (Aug. 1–Sept. 30) in 2015 at the Mount Bachelor Observatory (MBO, 2763 m above mean sea level, Oregon, USA). The UV O3 shows good agreement and excellent correlation to NO-CL O3, with linear regression slopes close to unity and R2 of 0.92 for 1-h average data and R2 of 0.93 for O3 daily maximum 8-h average (MDA8). During this two-month period we identified 35 wildfire events. Ozone enhancements in those wildfire plumes measured by NO-CL O3 and UV O3 monitors also show good agreement and excellent linear correlation, with a slope and R2 of 1.03 and 0.86 for O3 enhancements (ΔO3) and 1.00 and 0.98 for carbon monoxide (CO)-normalized ozone enhancement ratios (ΔO3/ΔCO), respectively. Overall, the UV O3 was found to have a positive bias of 4.7 ± 2.8 ppbv compared to the NO-CL O3. The O3 bias between NO-CL O3 and UV O3 is independent of wildfire plume tracers such as CO, particulate matter (PM1), aerosol scattering, and ultrafine particles. The results demonstrate that the UV O3 absorbance method is reliable, even in highly concentrated wildfire plumes.



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Variations of aerosol size distribution, chemical composition and optical properties from roadside to ambient environment: A case study in Hong Kong, China

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Publication date: October 2017
Source:Atmospheric Environment, Volume 166
Author(s): Qian Zhang, Zhi Ning, Zhenxing Shen, Guoliang Li, Junke Zhang, Yali Lei, Hongmei Xu, Jian Sun, Leiming Zhang, Dane Westerdahl, Nirmal Kumar Gali, Xuesong Gong
This study investigated the "roadside-to-ambient" evolution of particle physicochemical and optical properties in typical urban atmospheres of Hong Kong through collection of chemically-resolved PM2.5 data and PM2.5 size distribution at a roadside and an ambient site. Roadside particle size distribution showed typical peaks in the nuclei mode (30–40 nm) while ambient measurements peaked in the Aitken mode (50–70 nm), revealing possible condensation and coagulation growth of freshly emitted particles during aging processes. Much higher levels of anthropogenic chemical components, i.e. nitrate, sulfate, ammonium, organic carbon (OC) and elemental carbon (EC), but lower levels of OC/EC and secondary inorganic aerosols (SIA)/EC ratios appeared in roadside than ambient particles. The high OC/EC and SIA/EC ratios in ambient particles implied high contributions from secondary aerosols. Black carbon (BC), a strong light absorbing material, showed large variations in optical properties when mixed with other inorganic and organic components. Particle-bound polycyclic aromatic hydrocarbons (p-PAHs), an indicator of brown carbon (BrC), showed significant UV-absorbing ability. The average BC and p-PAHs concentrations were 3.8 and 87.6 ng m−3, respectively, at the roadside, but were only 1.5 and 18.1 ng m−3 at the ambient site, suggesting BC and p-PAHs concentrations heavily driven by traffic emissions. In contrast, PM2.5 UV light absorption coefficients (babs-BrC,370nm) at the ambient site (4.2 Mm−1) and at the roadside site (4.1 Mm−1) were similar, emphasizing that particle aging processes enhanced UV light-absorbing properties, a conclusion that was also supported by the finding that the Absorption Ångström coefficient (AAC) value at UV wavelengths (AAC_UV band) at the ambient site were ∼1.7 times higher than that at the roadside. Both aqueous reaction and photochemically produced secondary organic aerosol (SOA) for ambient aerosols contributed to the peak values of babs-BrC,370nm in ambient particles at midnight and around noon, highlighting that secondary BrC had different sources and particle aging in the atmosphere affected BrC and BC properties and related aerosol light absorption.



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Diagnosing Tibetan pollutant sources via volatile organic compound observations

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Publication date: October 2017
Source:Atmospheric Environment, Volume 166
Author(s): Hongyan Li, Qiusheng He, Qi Song, Laiguo Chen, Yongjia Song, Yuhang Wang, Kui Lin, Zhencheng Xu, Min Shao
Atmospheric transport of black carbon (BC) from surrounding areas has been shown to impact the Tibetan environment, and clarifying the geographical source and receptor regions is crucial for providing guidance for mitigation actions. In this study, 10 trace volatile organic compounds (VOCs) sampled across Tibet are chosen as proxies to diagnose source regions and related transport of pollutants to Tibet. The levels of these VOCs in Tibet are higher than those in the Arctic and Antarctic regions but much lower than those observed at many remote and background sites in Asia. The highest VOC level is observed in the eastern region, followed by the southern region and the northern region. A positive matrix factorization (PMF) model found that three factors—industry, biomass burning, and traffic—present different spatial distributions, which indicates that different zones of Tibet are influenced by different VOC sources. The average age of the air masses in the northern and eastern regions is estimated to be 3.5 and 2.8 days using the ratio of toluene to benzene, respectively, which indicates the foreign transport of VOC species to those regions. Back-trajectory analyses show that the Afghanistan-Pakistan-Tajikistan region, Indo-Gangetic Plain (IGP), and Meghalaya-Myanmar region could transport industrial VOCs to different zones of Tibet from west to east. The agricultural bases in northern India could transport biomass burning-related VOCs to the middle-northern and eastern zones of Tibet. High traffic along the unique national roads in Tibet is associated with emissions from local sources and neighboring areas. Our study proposes international joint-control efforts and targeted actions to mitigate the climatic changes and effects associated with VOCs in Tibet, which is a climate sensitive region and an important source of global water.



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Case of tumoral melanosis with a massive infiltration of CD163+ and CD68+ macrophages



http://ift.tt/2gVVB2T

Dermatoscopy of palmar wart with falooda seed appearance



http://ift.tt/2eGQT8u

A rare case of lues maligna with ocular involvement presenting as an unmasking immune reconstitution inflammatory syndrome in a patient with HIV infection



http://ift.tt/2gVVzrN

HTLV-1 carrier psoriasis patients treated by anti-IL-23/IL-17



http://ift.tt/2eGQR0m

Dermatoscopy of palmar wart with falooda seed appearance



http://ift.tt/2eGQT8u

A rare case of lues maligna with ocular involvement presenting as an unmasking immune reconstitution inflammatory syndrome in a patient with HIV infection



http://ift.tt/2gVVzrN

HTLV-1 carrier psoriasis patients treated by anti-IL-23/IL-17



http://ift.tt/2eGQR0m

Effectiveness of weekly azathioprine pulse in the treatment of chronic plaque psoriasis: an open-label study: reply to author



http://ift.tt/2uONwCQ

Updating and identifying a novel mutation in the PMVK gene in classic porokeratosis of Mibelli



http://ift.tt/2vA0odv

Papules on the arms and renal cell carcinoma



http://ift.tt/2uNXX9W

HRAS mutation in phacomatosis pigmentokeratotica without extracutaneous disease



http://ift.tt/2vAvYrx

Plasmacytoid dendritic cells and type I interferon in the immunological response against warts

Summary

Background

Plasmacytoid dendritic cells (pDCs) are the most potent producers of type I interferons (IFNs), and are involved in the pathogenesis of several cutaneous infectious (especially viral), inflammatory/autoimmune and neoplastic entities. Their role in the pathogenesis and regression of human papilloma virus (HPV)-induced skin lesions has not been well studied.

Aim

To investigate pDC occurrence and activity in HPV-induced skin lesions, including inflamed and uninflamed warts as well as epidermodysplasia verruciformis (EDV)-associated lesions.

Methods

In total 20 inflamed and 20 uninflamed HPV-induced skin lesions (including 7 EDV lesions) were retrieved from our database, and the tissue was immunohistochemically tested for pDC occurrence and activity using anti-BDCA-2 and anti-MxA antibodies, respectively.

Results

pDCs were present in all 20 inflamed warts and absent from all 20 uninflamed cases. MxA expression was also diffuse and strong in 75% (15/20) inflamed warts, but not in any of the uninflamed warts.

Conclusions

pDCs constitute a central component of the inflammatory host response in inflamed warts, possibly contributing to their regression through production of type I interferons.



http://ift.tt/2uOGr57

Effectiveness of weekly azathioprine pulse in the treatment of chronic plaque psoriasis: an open-label study: reply to author



http://ift.tt/2uONwCQ

Updating and identifying a novel mutation in the PMVK gene in classic porokeratosis of Mibelli



http://ift.tt/2vA0odv

Papules on the arms and renal cell carcinoma



http://ift.tt/2uNXX9W

HRAS mutation in phacomatosis pigmentokeratotica without extracutaneous disease



http://ift.tt/2vAvYrx

Plasmacytoid dendritic cells and type I interferon in the immunological response against warts

Summary

Background

Plasmacytoid dendritic cells (pDCs) are the most potent producers of type I interferons (IFNs), and are involved in the pathogenesis of several cutaneous infectious (especially viral), inflammatory/autoimmune and neoplastic entities. Their role in the pathogenesis and regression of human papilloma virus (HPV)-induced skin lesions has not been well studied.

Aim

To investigate pDC occurrence and activity in HPV-induced skin lesions, including inflamed and uninflamed warts as well as epidermodysplasia verruciformis (EDV)-associated lesions.

Methods

In total 20 inflamed and 20 uninflamed HPV-induced skin lesions (including 7 EDV lesions) were retrieved from our database, and the tissue was immunohistochemically tested for pDC occurrence and activity using anti-BDCA-2 and anti-MxA antibodies, respectively.

Results

pDCs were present in all 20 inflamed warts and absent from all 20 uninflamed cases. MxA expression was also diffuse and strong in 75% (15/20) inflamed warts, but not in any of the uninflamed warts.

Conclusions

pDCs constitute a central component of the inflammatory host response in inflamed warts, possibly contributing to their regression through production of type I interferons.



http://ift.tt/2uOGr57

Dynamic nuclear polarization for sensitivity enhancement in modern solid-state NMR

Publication date: Available online 23 July 2017
Source:Progress in Nuclear Magnetic Resonance Spectroscopy
Author(s): Aany Sofia Lilly Thankamony, Johannes J. Wittmann, Monu Kaushik, Björn Corzilius
The field of dynamic nuclear polarization has undergone tremendous developments and diversification since its inception more than 6 decades ago. In this review we will provide an in-depth overview of the relevant topics involved in DNP-enhanced MAS NMR spectroscopy. This includes the theoretical description of DNP mechanisms as well as of the polarization transfer pathways that can lead to a uniform or selective spreading of polarization between nuclear spins. Furthermore, we will cover historical and state-of-the art aspects of dedicated instrumentation, polarizing agents, and optimization techniques for efficient MAS DNP. Finally, we present an extensive overview on applications in the fields of structural biology and materials science, that underlines that MAS DNP has moved far beyond the proof-of-concept stage and has become an important tool for research in these fields.Edited by Geoffrey Bodenhausen and Beat Meier

Graphical abstract

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Cutaneous squamous cell carcinoma of the scalp extending to the skull: A case report and review of the literature

Summary

Squamous cell carcinoma (SCC) of the scalp has increased prevalence in older patients and often presents later in life. Mohs micrographic surgery remains the most effective treatment in most cases. Delayed presentation may result in localized bony invasion or distant metastases. We present a case of an elderly woman presenting with extension of SCC into the parietal bone of the skull.



http://ift.tt/2tCEKbo

Cutaneous squamous cell carcinoma of the scalp extending to the skull: A case report and review of the literature

Summary

Squamous cell carcinoma (SCC) of the scalp has increased prevalence in older patients and often presents later in life. Mohs micrographic surgery remains the most effective treatment in most cases. Delayed presentation may result in localized bony invasion or distant metastases. We present a case of an elderly woman presenting with extension of SCC into the parietal bone of the skull.



http://ift.tt/2tCEKbo

Alternative splicing: A thermometer controlling gene expression



http://ift.tt/2uqYiwi

Genome organization: Tracking chromosomal conformation through the cell cycle



http://ift.tt/2uOkXW4

Dissecting evolution and disease using comparative vertebrate genomics

The last 25 years has seen a revolution in sequencing, with more than 100 vertebrate genome sequences now available. In this Review, Meadows and Lindblad-Toh discuss how the genomics of non-human organisms can provide insights into vertebrate biology and conservation, and how they can contribute to the understanding of human health and disease.

http://ift.tt/2uqMbiY

Naturally occurring immunomodulators with antitumor activity: An insight on their mechanisms of action.

Related Articles

Naturally occurring immunomodulators with antitumor activity: An insight on their mechanisms of action.

Int Immunopharmacol. 2017 Jul 19;50:291-304

Authors: Mohamed SIA, Jantan I, Haque MA

Abstract
Natural products with immunomodulatory activity are widely used in treatment of many diseases including autoimmune diseases, inflammatory disorders in addition to cancer. They gained a great interest in the last decades as therapeutic agents since they provide inexpensive and less toxic products than the synthetic chemotherapeutic agents. Immunomodulators are the agents that have the ability to boost or suppress the host defense response that can be used as a prophylaxis as well as in combination with other therapeutic modalities. The anticancer activity of these immunomodulators is due to their anti-inflammatory, antioxidant, and induction of apoptosis, anti-angiogenesis, and anti-metastasis effect. These natural immunomodulators such as genistein, curcumin, and resveratrol can be used as prophylaxis against the initiation of cancer besides the inhibition of tumor growth and proliferation. Whereas, immunostimulants can elicit and activate humoral and cell-mediated immune responses against the tumor that facilitate the recognition and destruction of the already existing tumor. This review represents the recent studies on various natural immunomodulators with antitumor effects. We have focused on the relationship between their anticancer activity and immunomodulatory mechanisms. The mechanisms of action of various immunomodulators such as polyphenolic compounds, flavonoids, organosulfur compounds, capsaicin, vinca alkaloids, bromelain, betulinic acid and zerumbone, the affected cancerous cell lines in addition to the targeted molecules and transcriptional pathways have been review and critically analyzed.

PMID: 28734166 [PubMed - as supplied by publisher]



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Induction of accelerated senescence by the microtubule-stabilizing agent peloruside A.

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Induction of accelerated senescence by the microtubule-stabilizing agent peloruside A.

Invest New Drugs. 2017 Jul 22;:

Authors: Chan A, Gilfillan C, Templeton N, Paterson I, Northcote PT, Miller JH

Abstract
Chemotherapeutic agents can induce accelerated senescence in tumor cells, an irreversible state of cell cycle arrest. Paclitaxel, a microtubule-stabilizing agent used to treat solid tumors of the breast, ovary, and lung and discodermolide, another stabilizing agent from a marine sponge, induce senescence in cultured cancer cells. The aim of this study was to determine if the microtubule-stabilizing agent peloruside A, a polyketide natural product from a marine sponge, can induce accelerated senescence in a breast cancer cell line MCF7. Doxorubicin, a DNA-damaging agent, paclitaxel, and discodermolide were used as positive controls. Senescence-associated-β-galactosidase activity was increased by peloruside A, similar to paclitaxel, discodermolde, and doxorubicin, with a potency heirarchy of doxorubicin > paclitaxel > discodermolide > peloruside, based on IC25 concentrations that inhibit proliferation. Clonogenic survival was significantly decreased by peloruside A, similar to doxorubicin and the two other microtubule-stabilizing agents. The tumor suppressor protein p53 increased after treatment, whereas pRb decreased in response to all four compounds. It was concluded that in addition to apoptosis, peloruside A causes accelerated senescence in a subpopulation of MCF7 cells that contributes to its potential anticancer activity in a breast cancer cell line.

PMID: 28733703 [PubMed - as supplied by publisher]



http://ift.tt/2uXutGZ

MOlecular Screening for CAncer Treatment Optimization (MOSCATO-01) in pediatric patients: A single institutional prospective molecular stratification trial.

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MOlecular Screening for CAncer Treatment Optimization (MOSCATO-01) in pediatric patients: A single institutional prospective molecular stratification trial.

Clin Cancer Res. 2017 Jul 21;:

Authors: Harttrampf AC, Lacroix L, Deloger M, Deschamps F, Puget S, Auger N, Vielh P, Varlet P, Balogh Z, Abbou S, Allorant A, Valteau-Couanet D, Sarnacki S, Galmiche L, Meurice G, Minard-Colin V, Grill J, Brugières L, Dufour C, Gaspar N, Michiels S, Vassal G, Soria JC, Geoerger B

Abstract
PURPOSE: This single institutional feasibility study prospectively characterized genomic alterations in recurrent or refractory solid tumors of pediatric patients in order to select a targeted therapy.<br /><br />Experimental Design: Following treatment failure patients with signed consent and aged above 6 months, underwent tumor biopsy or surgical resection of primary or metastatic tumor site.  These newly acquired samples were analyzed by comparative genomic hybridization array, next generation sequencing for 75 target genes, whole exome and RNA sequencing.  Biological significance of the alterations and suggestion of most relevant targeted therapies available were discussed in a multidisciplinary tumor board.<br /><br />Results: From December 2012 to January 2016, 75 patients were included, 73 patients underwent 79 interventions, 56 of which were research biopsies with a low complication rate.  All patients were pretreated, 37.0% had a brain tumor and 63.0% an extra-cranial solid tumor.  Median tumor cell content was 70% (range 0-100%).  Successful molecular analysis in 69 patients detected in 60.9% of patients an actionable alteration in various oncogenic pathways (42.4% with copy number change, 33.3% with mutation, 2.1% with fusion), and change in diagnosis in three patients.  Fourteen patients received 17 targeted therapies; two had received a matched treatment prior to inclusion.<br /><br />Conclusions: Research biopsies are feasible in advanced pediatric malignancies that exhibit a considerable amount of potentially actionable alterations.  Genetic events affecting different cancer hallmarks and limited access to targeted agents within pediatric clinical trials remain the main obstacles that are addressed in our two subsequent precision medicine studies MAPPYACTS and AcSé-ESMART.

PMID: 28733441 [PubMed - as supplied by publisher]



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Design, synthesis and in vitro anticancer activity of novel quinoline and oxadiazole derivatives of ursolic acid.

Related Articles

Design, synthesis and in vitro anticancer activity of novel quinoline and oxadiazole derivatives of ursolic acid.

Bioorg Med Chem Lett. 2017 Jul 12;:

Authors: Gu W, Jin XY, Li DD, Wang SF, Tao XB, Chen H

Abstract
A series of new quinoline derivatives of ursolic acid were designed and synthesized in an attempt to develop potential anticancer agents. The structures of these compounds were identified by (1)H NMR, (13)C NMR, IR and ESI-MS spectra analysis. The target compounds were evaluated for their in vitro cytotoxicity against three human cancer cell lines (MDA-MB-231, Hela and SMMC-7721). From the results, compounds 3a-d displayed significant antitumor activity against three cancer cell lines. Especially, compound 3b was found to be the most potent derivative with IC50 values of 0.61±0.07, 0.36±0.05, 12.49±0.08μM against MDA-MB-231, HeLa and SMMC-7721 cells, respectively, stronger than positive control etoposide. Furthermore, the Annexin V-FITC/PI dual staining assay revealed that compound 3b could significantly induce the apoptosis of MDA-MB-231 cells in a dose-dependent manner. The cell cycle analysis also indicated that compound 3b could cause cell cycle arrest of MDA-MB-231 cells at G0/G1 phase.

PMID: 28733083 [PubMed - as supplied by publisher]



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Encompassment of Benzyl Isothiocyanate in cyclodextrin using ultrasonication methodology to enhance its stability for biological applications.

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Encompassment of Benzyl Isothiocyanate in cyclodextrin using ultrasonication methodology to enhance its stability for biological applications.

Ultrason Sonochem. 2017 Nov;39:25-33

Authors: Uppal S, Kaur K, Kumar R, Kahlon NK, Singh R, Mehta SK

Abstract
The use of methodical and innovative sonication method has been explored for the fabrication of inclusion complex of Benzyl Isothiocyanate, a potential anticancer and -antimicrobial agent. The advancement involved investigation of inclusion behaviour, characterisation and an in-depth study of thermal and UV stability of Benzyl Isothiocyanate with cyclodextrins; β-CD and hp-β-CD. The sonication driven encompassment in cyclodextrins helped to overcome the hindrance of low solubility and high volatility. Investigations of physical and thermodynamic parameters using UV-visible spectroscopy, FTIR, XRD, TGA etc confirmed stability of inclusion complexes. Both β-CD and hp-β-CD based inclusion complexes retained the antimicrobial property of the free Benzyl Isothiocyanate, indicating their potential utility as antimicrobial agents. Haematological safety and cellular uptake data gives direction to in-depth analysis for its exploitation of anti-tumour activity.

PMID: 28732943 [PubMed - in process]



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Assessment of the potential impact of dose rounding parenteral chemotherapy agents on cost savings and drug waste minimization.

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Assessment of the potential impact of dose rounding parenteral chemotherapy agents on cost savings and drug waste minimization.

J Oncol Pharm Pract. 2017 Jan 01;:1078155217722205

Authors: Chillari KA, Southward J, Harrigan N

Abstract
Background Fiscally responsible utilization of anticancer treatments is necessary to combat their continually increasing cost. Dose rounding is one strategy that has been explored to minimize cost and waste without losing clinical effectiveness. Objectives To determine if dose rounding chemotherapy agents is a feasible cost-containment strategy at an institution with a small oncology clinic. Methods This study is a retrospective chart review of all body surface area dosed parenteral chemotherapy prescribed for an oncological diagnosis over a 12-month period (1 October 2015-30 September 2016). Chemotherapy doses were rounded down by 5%. Doses for patients with metastatic diagnoses were also rounded down by 10%. Rounded doses were evaluated for a potential decrease in vial size. Cost was represented as dollar/milligram of drug. Potential for drug waste minimization was also calculated. Results There were 877 total doses of chemotherapy administered to 70 unique patients throughout the 12-month duration of the study. When doses were rounded down by 5%, 140 doses qualified for a decrease in vial number. The potential for cost savings was $22,849 with 83,802 mg saved from wastage. A 10% decrease resulted in the reduction of vials for 248 doses, a potential savings of $30,911 with 129,011 milligrams saved. The targeted agents accounted for the majority of savings, $16,920 of the $22,849 with 5% rounding and $20,086 of the $30,911 with 10% rounding. Conclusion Dose rounding has the potential to be an effective cost-containment strategy in low volume oncology clinics.

PMID: 28732452 [PubMed - as supplied by publisher]



http://ift.tt/2vzDdQB

Mast cells in calcific aortic stenosis

Publication date: Available online 23 July 2017
Source:Pathology - Research and Practice
Author(s): Ivo Šteiner, Václav Stejskal, Pavel Žáček
In developed countries, calcific aortic stenosis (CAS) has become the most common acquired valvular disease and reason for aortic valve replacement. It is considered a form of atherosclerosis and, like the latter, of inflammatory origin, with presence in the calcified aortic valves of blood vessels, lymphatics, lymphocytes, plasma cells, histiocytes, and sometimes also of metaplastic bone tissue. This study is aimed at examining the presence of CD117 − positive mast cells in CAS. In 56 examined calcified aortic valves excised by cardiac surgery, mast cells were constantly present as a part of the polymorphous cellular infiltrate; in individual cases, their numbers were 1–90 (median 24). The numbers were significantly higher in the congenitally malformed/bicuspid valves (median 40) than in the tricuspid ones (median 20). In valves with presence of metaplastic bone, mast cells were significantly more numerous (median 42) than in those without metaplasia (median 20). In 12 normal aortic valves obtained at autopsies, the numbers of mast cells were 4–21 (median 11). Discussed is a possible role of mast cells in pathogenesis of CAS.



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Analysis of CD15, CD57 and HIF-1α in biopsies of patients with peri-implantitis

Publication date: Available online 23 July 2017
Source:Pathology - Research and Practice
Author(s): Márcia Fernandes de Araújo, Renata Margarida Etchebehere, Marcelo Luiz Ribeiro de Melo, Marcela Beghini, Viviane Oliveira Severino, Eliângela de Castro Côbo, Denise Bertulucci Rocha Rodrigues, Sanívia Aparecida de Lima Pereira
Peri-implantitis is an infectious disease characterized by inflammation of the tissues surrounding the implant, bleeding on probing with or without suppuration, and bone loss. Peri-implant lesions contain a leukocyte infiltrate of plasma cells, lymphocytes, macrophages and neutrophils. A survey of the literature did not show any studies reporting an association between hypoxia and peri-implantitis. The aim of the present cross-sectional study was to evaluate histological changes and immunostaining for CD15, CD57 and HIF-1α in the peri-implant mucosa of patients with and without peri-implantitis. Mucosal biopsies were obtained from 18 patients with peri-implantitis and 10 control subjects without peri-implantitis at a private health care center between 2010 and 2012. The sections were fixed in 10% buffered formalin, processed and embedded in paraffin for histopathological and immunohistochemical study. Acanthosis, spongiosis and exocytosis were observed in both groups, with no significant difference between them. The peri-implantitis group showed increased immunostaining for CD15, a neutrophil marker, and HIF-1α, a tissue hypoxia marker, but no significant difference in immunostaining for CD57, a Natural Killer cell marker. The increase in neutrophil (CD15) and hypoxia (HIF-1α) markers in patients with peri-implantitis suggests an active participation of neutrophils and hypoxia in the pathogenesis of this disease. Since the present study was the first to evaluate the expression of CD15, CD57 and HIF-1α in peri-implant tissues, further studies should be performed to better understand the role of these molecules in peri-implantitis.



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Granulomas within renal epithelial neoplasms in patients with sarcoidosis: A causal association?

Publication date: Available online 23 July 2017
Source:Pathology - Research and Practice
Author(s): Nasma K. Majeed, Andres M. Acosta, Andre Kajdacsy-Balla, Suman Setty, Nathan A. Aardsma
Sarcoidosis is a chronic granulomatous disease that can involve virtually every organ system, but most commonly presents as lung, skin, or lymph node disease. Although kidney involvement is usually clinically silent, granulomatous interstitial nephritis − the hallmark of renal sarcoidosis − can lead to functional impairment and organ failure. Also, recent studies have suggested an association between sarcoidosis and an increased risk of developing kidney tumors. While a sarcoid-like granulomatous reaction (SLGR) to renal epithelial neoplasms in patients without sarcoidosis has been well documented, direct involvement of the tumor parenchyma by sarcoidosis has been reported only rarely. Here we present two additional renal epithelial tumors directly involved by sarcoidosis with a common pattern of distribution of non-caseating granulomas.



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Clinicopathologic and molecular characterization of mammary analogue secretory carcinoma of salivary gland origin

Publication date: Available online 23 July 2017
Source:Pathology - Research and Practice
Author(s): F. Baghai, F. Yazdani, A. Etebarian, A. Garajei, A. Skalova
BackgroundMammary analogue secretory carcinoma (MASC) is a newly recognized salivary gland tumor that harbors a characteristic balanced chromosomal translocation t (12; 15) (p13; q25) resulting in an ETV6-NTRK3 fusion gene.MethodsRetrospective study of 111 salivary gland carcinomas revealed 37 cases with secretory features and growth pattern resembling secretory carcinoma of breast. These 37 cases were originally diagnosed as acinic cell carcinoma, adenocarcinoma not otherwise specified and cystadenocarcinoma. Positive immunostaining for S-100 protein and mammaglobin, followed by detection of ETV6 gene rearrangement by FISH and/or ETV6-NTRK3 fusion transcript by RT-PCR were used to identify MASCs.ResultsIn the cohort of 37 salivary carcinomas with secretory features we have identified 10 cases of MASC. All 10 MASCs were positive for mammaglobin, S-100 protein and SOX10, while staining for DOG1 and p63 protein were mostly absent. In 7/10 cases, both FISH and RT-PCR were positive while three remaining cases showed break of ETV6 gene by FISH and RT-PCR was negative. Clinical follow-up data were obtained in 6 out of 10 patients with MASC. In 3 patients cervical lymph node metastases developed, one patient with high grade transformed MASC died with multiple distant bone metastases, and local recurrence was observed in three patients.ConclusionOur clinicopathological data are in keeping with previous studies; in most cases, MASC is a low-grade malignancy with overall favorable prognosis. In rare cases, however, MASC with high-grade transformation may behave aggressively, and these patients could benefit from targeted biological treatment using tyrosine kinase inhibitors.



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Forkhead box protein A2, a pioneer factor for hepatogenesis, is involved in the expression of hepatic phenotype of alpha-fetoprotein-producing adenocarcinoma

Publication date: Available online 23 July 2017
Source:Pathology - Research and Practice
Author(s): Nobuhisa Yamamura, Kazunori Fugo, Takashi Kishimoto
Alpha-fetoprotein (AFP)-producing adenocarcinoma is a high-malignant variant of adenocarcinoma with a hepatic or fetal-intestinal phenotype. The number of cases of AFP-producing adenocarcinomas is increasing, but the molecular mechanism underlying the aberrant production of AFP is unclear. Here we sought to assess the role of Forkhead box A (FoxA)2, which is a pioneer transcription factor in the differentiation of hepatoblasts. FoxA2 expression was investigated in five cases of AFP-producing gastric adenocarcinomas by immunohistochemistry, and all cases showed FoxA2 expression. Chromatin immunoprecipitation revealed the DNA binding of FoxA2 on the regulatory element of AFP gene in AFP-producing adenocarcinoma cells. The inhibition of FoxA2 expression with siRNA reduced the mRNA expression of liver-specific proteins, including AFP, albumin, and transferrin. The inhibition of FoxA2 also reduced the expressions of liver-enriched nuclear factors, i.e., hepatocyte nuclear factor (HNF) 4α and HNF6, although the expressions of HNF1α and HNF1β were not affected. The same effect as FoxA2 knockdown in AFP producing adenocarcinoma cells was also observed in hepatocellular carcinoma cells. Our results suggest that FoxA2 plays a key role in the expression of hepatic phenotype of AFP-producing adenocarcinomas.



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Low SIRT3 expression contributes to tumor progression, development and poor prognosis in human pancreatic carcinoma

Publication date: Available online 23 July 2017
Source:Pathology - Research and Practice
Author(s): Shanshan Huang, Xiong Chen, Jiawei Zheng, Yufang Huang, Li Song, Yin Yin, Jianping Xiong
SIRT3, an important mitochondrial protein, may act as either an oncogene or tumor suppressor depending on the tumor-type. The aim of this study was to investigate the expression of SIRT3 in pancreatic carcinoma (PC) and its clinical association in PC patients. Immunohistochemistry was adopted to investigate the expression of SIRT3 in cancer and corrresponding adjacent non-cancer tissues across 79 patients with PC. The log-rank test and Cox hazard model were used to estimate the relationship between SIRT3 expression and prognosis. The staining results revealed that SIRT3 negative expression was more common in cancer tissues than in adjacent non-cancer tissues (P<0.001). Chi-square tests indicated that the expression of SIRT3 correlated with T status (p<0.001) and tumor stage (p=0.013). Kaplan-Meier analysis showed that negative SIRT3 expression is linked to a poor prognosis in PC patients. Multivariate analysis identified SIRT3 expression as an independent predictor for PC outcome both in the whole cohort and several subgroups of PC patients. Our results indicate that down-regulated SIRT3 may contribute to tumor progression and gloomy prognosis in PC patients and may sever as a novel prognostic marker.



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The antidepressant effect of melatonin and fluoxetine in diabetic rats is associated with a reduction of the oxidative stress in the prefrontal and hippocampal cortices

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Publication date: Available online 23 July 2017
Source:Brain Research Bulletin
Author(s): Redouane Rebai, Luc Jasmin, Abdennacer Boudah
In the past few years possible mechanisms that link diabetes and depression have been found. One of these mechanisms is the increase in lipid peroxidation and decrease in antioxidant activity in the hippocampal and prefrontal cortices, which are brain areas involved in mood. The goal of the present study was to evaluate the effect of an antidepressant and of an antioxidant on behavior and oxidative activity in brains of diabetic rats. Rats rendered diabetic after a treatment with streptozotocin (STZ) (60mg/kg) were treated with fluoxetine (15mg/kg), melatonin (10mg/kg), or vehicle for 4 weeks. All animals were tested for signs of depression and anxiety using the elevated plus maze (EPM), open field test (OFT) and the forced swim test (FST). Four groups were compared: (1) normoglycemic, (2) hyperglycemic vehicle treated, and hyperglycemic (3) fluoxetine or (4) melatonin treated rats. On the last day of the study, blood samples were obtained to determine the levels of hemoglobin A1c (HbA1c). Also, brain samples were collected to measure the oxidative stress in the hippocampal and prefrontal cortices using the thiobarbituric acid reactive substances (TBARS) assay. The activity of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST) were also measured on the brain samples.The results show that both fluoxetine and melatonin decrease the signs of depression and anxiety in all tests. Concomitantly, the levels of HbA1c were reduced in drug treated rats, and to a greater degree in the fluoxetine group. In the cerebral cortex of diabetic rats, TBARS was increased, while the activity of CAT, GPx and GST were decreased. Fluoxetine and melatonin treatments decreased TBARS in both cortices. In the prefrontal cortex, fluoxetine and melatonin restored the activity of CAT, while only melatonin improved the activity of GPx and GST. In the hippocampus, the activity of GPx alone was restored by melatonin, while fluoxetine had no effect.These results suggest that antidepressants and antioxidants can counter the mood and oxidative disorders associated with diabetes. While these effects could result from a decreased production of reactive oxygen species (ROS) remains to be established.



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Stimulation of RNA Polymerase II ubiquitination and degradation by yeast mRNA 3′-end processing factors is a conserved DNA damage response in eukaryotes

Publication date: Available online 23 July 2017
Source:DNA Repair
Author(s): Jason N. Kuehner, James W. Kaufman, Claire Moore
The quality and retrieval of genetic information is imperative to the survival and reproduction of all living cells. Ultraviolet (UV) light induces lesions that obstruct DNA access during transcription, replication, and repair. Failure to remove UV-induced lesions can abrogate gene expression and cell division, resulting in permanent DNA mutations. To defend against UV damage, cells utilize transcription-coupled nucleotide excision repair (TC-NER) to quickly target lesions within active genes. In cases of long-term genotoxic stress, a slower alternative pathway promotes degradation of RNA Polymerase II (Pol II) to allow for global genomic nucleotide excision repair (GG-NER). The crosstalk between TC-NER and GG-NER pathways and the extent of their coordination with other nuclear events has remained elusive. We aimed to identify functional links between the DNA damage response (DDR) and the mRNA 3′-end processing complex. Our labs have previously shown that UV-induced inhibition of mRNA processing is a conserved DDR between yeast and mammalian cells. Here we have identified mutations in the yeast mRNA 3′-end processing cleavage factor IA (CFIA) and cleavage and polyadenylation factor (CPF) that confer sensitivity to UV-type DNA damage. In the absence of TC-NER, CFIA and CPF mutants show reduced UV tolerance and an increased frequency of UV-induced genomic mutations, consistent with a role for RNA processing factors in an alternative DNA repair pathway. CFIA and CPF mutants impaired the ubiquitination and degradation of Pol II following DNA damage, but the co-transcriptional recruitment of Pol II degradation factors Elc1 and Def1 was undiminished. Overall these data are consistent with yeast 3′-end processing factors contributing to the removal of Pol II stalled at UV-type DNA lesions, a functional interaction that is conserved between homologous factors in yeast and human cells.

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Differential expression of glucagon-like peptide-2 (GLP-2) is involved in pancreatic islet cell adaptations to stress and beta-cell survival

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Publication date: Available online 23 July 2017
Source:Peptides
Author(s): Dawood Khan, Srividya Vasu, R. Charlotte Moffett, Nigel Irwin, Peter R. Flatt
Recent studies have confirmed that locally released proglucagon derived gene products, other than glucagon, have a major influence on pancreatic endocrine function. We assessed the impact of glucagon-like peptide-2 (GLP-2) on beta-cell secretory function, proliferation and apoptosis, as well as glucose tolerance, feeding behaviour and islet adaptions to chemically-induced insulin deficiency and resistance. The GLP-2 receptor was evidenced on cultured rodent and human beta-cells, rodent alpha-cells and isolated mouse islets. GLP-2 had no effect on insulin secretion from beta-cells, or isolated mouse islets. In vivo, GLP-2 administration significantly (P<0.05 to P<0.01) decreased food intake in mice. Conversely, GLP-2 had no discernible effects on glucose disposal or insulin secretion. As expected, streptozotocin treatment decreased and hydrocortisone increased beta-cell mass in mice. GLP-2 was visualised in mouse islets and intestinal L-cells. Islet GLP-2 co-localisation with glucagon was significantly decreased (P<0.01) by both streptozotocin and hydrocortisone. In contrast, both interventions increased (P<0.05) co-localisation of GLP-2 with somatostatin. Interestingly, GLP-2 positive cells were reduced (P<0.05) in the intestines of streptozotocin, but not hydrocortisone, treated mice. Further in vitro investigations revealed that GLP-2 protected rodent and human 1.1B4 beta-cells against streptozotocin induced DNA damage. Furthermore, GLP-2 augmented (P<0.05) BRIN BD11 beta-cell proliferation, but was less efficacious in 1.1B4 cells. These data highlight the involvement of GLP-2 receptor signalling in the adaptations to pancreatic islet cell stress.



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Factor structure of DSM-5 PTSD symptoms in trauma-exposed adolescents: Examining stability across time

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Publication date: Available online 23 July 2017
Source:Journal of Anxiety Disorders
Author(s): Li Wang, Xing Cao, Chengqi Cao, Ruojiao Fang, Haibo Yang, Jon D. Elhai
This study investigated the latent structure of DSM-5 PTSD symptoms using two-wave longitudinal data collected from a sample of adolescents exposed to an explosion accident. Two waves of surveys were conducted approximately 3 and 8 months after the accident, respectively. A total of 836 students completed the baseline survey, and 762 students completed the follow-up survey. The results of confirmatory factor analyses(CFA) indicated that a seven-factor hybrid model composed of intrusion, avoidance, negative affect, anhedonia, externalizing behaviors, anxious arousal and dysphoric arousal factors yielded significantly better data fit at both waves than the other models including the DSM-5 four-factor model, the six-factor anhedonia and externalizing behaviors models. Furthermore, the results of CFA invariance tests supported the longitudinal invariance of the model. Implications and limitations in terms of these results are discussed.



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Demand/withdraw communication in the context of intimate partner violence: Implications for psychological outcomes

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Publication date: Available online 22 July 2017
Source:Journal of Anxiety Disorders
Author(s): Alison M. Pickover, Alexandra J. Lipinski, Thomas S. Dodson, Han N. Tran, Matthew J. Woodward, J.Gayle Beck
Intimate partner violence (IPV) is associated with symptoms of posttraumatic stress disorder (PTSD) and generalized anxiety disorder (GAD). To clarify the influence of a dyadic conflict pattern that has previously been shown to accompany violence in romantic relationships (partner demand/self withdraw) on these mental health outcomes, we examined the associations between three forms of IPV (physical, emotional-verbal, dominance-isolation), partner demand/self withdraw, and PTSD and GAD symptoms, in a sample of 284 IPV-exposed women. Using structural equation modeling, we found significant associations between dominance-isolation IPV, partner demand/self withdraw, and clinician-assessed GAD symptoms. Associations between emotional-verbal IPV and partner demand/self withdraw were also significant. Associations for physical IPV, partner demand/self withdraw, and clinician-assessed PTSD symptoms were not statistically significant. These results underscore the need for research on the mental health outcomes associated with specific forms of IPV and the long-term psychological consequences of the conflict patterns that uniquely characterize violent relationships.



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Multi-informant assessment of siblings of youth with autism spectrum disorder: Parent-child discrepancies in at-risk classification

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Publication date: September 2017
Source:Research in Developmental Disabilities, Volume 68
Author(s): James A. Rankin, Theodore S. Tomeny, Tammy D. Barry
BackgroundThe behavioral and emotional functioning of typically-developing (TD) siblings of youth with autism spectrum disorder (ASD) has been frequently assessed in the literature; however, these assessments typically include only one informant, rarely considering differences between parent and self-reports of sibling adjustment.AimsThis study examined parent-youth reported informant discrepancies in behavioral and emotional functioning, including whether parent and youth reports yielded the same conclusions regarding TD sibling risk status.Methods, procedures, and resultsAmong 113 parents and TD siblings of youth with ASD, TD siblings self-reported more overall, conduct, hyperactivity, and peer problems (compared to parent reports). Although few siblings were considered at-risk, those who were identified were not usually identified as at-risk on both informants' reports. Moreover, ASD symptoms, broader autism phenotype symptoms, parent mental health concerns, and social support from parents were all related to differences in at-risk classification between parent- and sibling self-report.Conclusions and implicationsThis paper highlights the necessity of multi-informant reporting when considering TD sibling psychological functioning.What this paper addsThis study helps to address gaps in the literature on assessment of emotional and behavioral functioning of TD siblings of youth with ASD. The results highlight the importance of utilizing both parent- and self-report when identifying TD siblings at-risk for maladjustment. Although few siblings were considered at-risk, those who were identified were not usually identified as such on both informants' reports, and a variety of sibling- and parent-factors were associated with differences in at-risk classification. Thus, inclusion and examination of both parent- and self-report of TD sibling psychological functioning is vital for accurately identifying numbers of TD siblings at-risk of maladjustment.



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Surgical management of temporal bone osteoradionecrosis: Single surgeon experience of 47 cases

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Publication date: Available online 23 July 2017
Source:American Journal of Otolaryngology
Author(s): Sameep Kadakia, Arvind Badhey, Jared Inman, Moustafa Mourad, Yadranko Ducic
PurposeTo report the outcomes of 47 patients with temporal bone osteoradionecrosis treated primarily with surgical resection in order to analyze whether flap type and hyperbaric oxygen use affect wound breakdown.Materials and methodsBetween January 1998 and January 2016, 47 patients were treated for temporal bone osteoradionecrosis with surgery. Some patients were also treated with hyperbaric oxygen. Resection of grossly necrotic temporal bone was followed by immediate reconstruction with local, regional, or free flaps. Minimum follow-up was 6months. If patients had breakdown of their initial reconstructions, secondary reconstruction was performed with either a regional or free flap. During the post-operative period, wound breakdown, flap complications, and patient survival were noted.Results30 patients developed ORN from primary radiotherapy while 17 had post-operative radiation. It was found that wound breakdown was significantly associated with type of flap reconstruction (p=0.02) with local flap reconstruction portending a poorer prognosis. Hyperbaric oxygen was not associated with decreased wound breakdown (p=0.5).ConclusionsSurgical treatment can be an effective treatment for temporal bone osteoradionecrosis, without hyperbaric oxygen providing any additional benefit. Reconstruction with regional or free flaps may be a more reliable method to resurface defects compared to local flaps.



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Mycobacterium tuberculosis PPE44 (Rv2770c) is involved in response to multiple stresses and promotes the macrophage expression of IL-12 p40 and IL-6 via the p38, ERK, and NF-κB signaling axis

Publication date: September 2017
Source:International Immunopharmacology, Volume 50
Author(s): Zhaoxiao Yu, Chenhui Zhang, Mingliang Zhou, Qiming Li, Hui Li, Wei Duan, Xue Li, Yonghong Feng, Jianping Xie
Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a formidable threat to global public health. The successful intracellular persistence of M. tuberculosis significantly contributes to the intractability of tuberculosis. Proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) are mycobacterial exclusive protein families that widely reported to be involved in the bacterial virulence, physiology and interaction with host. Rv2770c (PPE44), a predicted virulence factor, was up-regulated upon the infected guinea pig lungs. To investigate the role of Rv2770c, we heterologously expressed the PPE44 in the nonpathogenic fast-growing M. smegmatis strain. Subcellular location analysis demonstrated that Rv2770c is a cell wall associated protein, suggestive of a potential candidate involved in host-pathogen interaction. The Rv2770c can enhance M. smegmatis survival within macrophages and under stresses such as H2O2, SDS, diamide exposure, and low pH condition. M. smegmatis expressing Rv2770c is more virulent as testified by the increased death of macrophages and the increased expression of interlukin-6 (IL-6) and interlukin-12p40 (IL-12p40). Moreover, Rv2770c altered the secretion of IL-6 and IL-12p40 of macrophages via NF-κB, ERK1/2 and p38 MAPK axis. Taken together, this study implicated that Rv2770c was a virulent factor actively engaged in the interaction with host macrophage.



http://ift.tt/2uNEKVC

Surgical management of temporal bone osteoradionecrosis: Single surgeon experience of 47 cases

To report the outcomes of 47 patients with temporal bone osteoradionecrosis treated primarily with surgical resection in order to analyze whether flap type and hyperbaric oxygen use affect wound breakdown.

http://ift.tt/2vOdenH

Surgical management of temporal bone osteoradionecrosis: Single surgeon experience of 47 cases

To report the outcomes of 47 patients with temporal bone osteoradionecrosis treated primarily with surgical resection in order to analyze whether flap type and hyperbaric oxygen use affect wound breakdown.

http://ift.tt/2vOdenH

Clinical outcomes after interstitial brachytherapy for early-stage nasal squamous cell carcinoma

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Publication date: Available online 23 July 2017
Source:Brachytherapy
Author(s): Warren Bacorro, Alexandre Escande, Stéphane Temam, Isabelle Dumas, Emilie Routier, Marie-Catherine Gensse, Pierre Blanchard, François Janot, Christine Mateus, Yungan Tao, Caroline Robert, Eric Deutsch, Christine Haie-Meder, Cyrus Chargari
PurposeRadiotherapy of nasal carcinomas results in cure rates comparable to surgery, with anatomic preservation and good cosmesis. Brachytherapy (BT) overcomes difficulties with dosimetric coverage and affords a localized and highly conformal irradiation. We report our experience of BT for early-stage nasal squamous cell carcinomas (SCCs).Methods and MaterialsClinical data, BT parameters, and outcome of consecutive patients treated by interstitial BT in our institute between December 1982 and April 2015 for a localized nasal SCC were examined. A total of 34 patients with newly diagnosed T1-2N0-1 nasal skin (n = 22) or nasal cavity (n = 12) SCC were identified. Implantation and dosimetry were done according to the Paris system rules. Low-dose-rate (n = 30) or pulsed-dose-rate (n = 4) techniques were used. Median dose was 70 Gy (64–75 Gy). Sites of tumor recurrence, toxicity rates, and cosmesis outcome were examined.ResultsMedian followup time was 89 months. All patients achieved complete response. Five patients experienced local failure, with a median interval of 9 months (range, 5–12 months). Grade 3 acute reactions were reported in 2 patients (6%). Most delayed complications were mild to moderate, and good or fair cosmesis was achieved in 97%. Estimated local failure-free survival and disease-free survival rates at 5 year were 85% (95% CI = 68–94%) and 76% (95% CI = 58–88%), respectively.ConclusionsInterstitial BT is effective for selected nasal SCCs, with durable local control, acceptable toxicity, and good cosmesis.



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Functional brain outcomes of L2 speech learning emerge during sensorimotor transformation

Publication date: 1 October 2017
Source:NeuroImage, Volume 159
Author(s): Daniel Carey, Marc E. Miquel, Bronwen G. Evans, Patti Adank, Carolyn McGettigan
Sensorimotor transformation (ST) may be a critical process in mapping perceived speech input onto non-native (L2) phonemes, in support of subsequent speech production. Yet, little is known concerning the role of ST with respect to L2 speech, particularly where learned L2 phones (e.g., vowels) must be produced in more complex lexical contexts (e.g., multi-syllabic words). Here, we charted the behavioral and neural outcomes of producing trained L2 vowels at word level, using a speech imitation paradigm and functional MRI. We asked whether participants would be able to faithfully imitate trained L2 vowels when they occurred in non-words of varying complexity (one or three syllables). Moreover, we related individual differences in imitation success during training to BOLD activation during ST (i.e., pre-imitation listening), and during later imitation. We predicted that superior temporal and peri-Sylvian speech regions would show increased activation as a function of item complexity and non-nativeness of vowels, during ST. We further anticipated that pre-scan acoustic learning performance would predict BOLD activation for non-native (vs. native) speech during ST and imitation. We found individual differences in imitation success for training on the non-native vowel tokens in isolation; these were preserved in a subsequent task, during imitation of mono- and trisyllabic words containing those vowels. fMRI data revealed a widespread network involved in ST, modulated by both vowel nativeness and utterance complexity: superior temporal activation increased monotonically with complexity, showing greater activation for non-native than native vowels when presented in isolation and in trisyllables, but not in monosyllables. Individual differences analyses showed that learning versus lack of improvement on the non-native vowel during pre-scan training predicted increased ST activation for non-native compared with native items, at insular cortex, pre-SMA/SMA, and cerebellum. Our results hold implications for the importance of ST as a process underlying successful imitation of non-native speech.



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Dragonfly wing nodus: a one-way hinge contributing to the asymmetric wing deformation

Publication date: Available online 22 July 2017
Source:Acta Biomaterialia
Author(s): H. Rajabi, N. Ghoroubi, K. Stamm, E. Appel, S.N. Gorb
Dragonfly wings are highly specialized locomotor systems, which are formed by a combination of several structural components. The wing components, also known as structural elements, are responsible for the various aspects of the wing functionality. Considering the complex interactions between the wing components, modelling of the wings as a whole is only possible with inevitable huge oversimplifications. In order to overcome this difficulty, we have recently proposed a new approach to model individual components of complex wings comparatively. Here, we use this approach to study nodus, a structural element of dragonfly wings which has been less studied to date. Using a combination of several imaging techniques including scanning electron microscopy (SEM), wide-field fluorescence microscopy (WFM), confocal laser scanning microscopy (CLSM) and micro-computed tomography (micro-CT) scanning, we aim to characterize the spatial morphology and material composition of fore- and hindwing nodi of the dragonfly Brachythemis contaminata. The microscopy results show the presence of resilin in the nodi, which is expected to help the deformability of the wings. The computational results based on three-dimensional (3D) structural data suggest that the specific geometry of the nodus restrains its displacements when subjected to pressure on the ventral side. This effect, resulting from an interlocking mechanism, is expected to contribute to the dorso-ventral asymmetry of wing deformation and to provide a higher resistance to aerodynamic forces during the downstroke. Our results provide an important step towards better understanding of the structure-property-function relationship in dragonfly wings.Statement of significanceIn this study, we investigate the wing nodus, a specialized wing component in dragonflies. Using a combination of modern imaging techniques, we demonstrate the presence of resilin in the nodus, which is expected to facilitate the wing deformability in flight. The specific geometry of the nodus, however, seems to restrain its displacements when subjected to pressure on the ventral side. This effect, resulting from an interlocking mechanism, is suggested to contribute to dorso-ventral asymmetry of wing deformations and to provide a higher resistance to aerodynamic forces during the downstroke. Our results provide an important step towards better understanding of the structure-property-function relationship in dragonfly wings and might help to design more efficient wings for biomimetic micro-air vehicles.

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Corrigendum to “Non-invasive tracking of hydrogel degradation using upconversion nanoparticles” [Acta Biomater. 55 (2017) 410–419]

Publication date: Available online 22 July 2017
Source:Acta Biomaterialia
Author(s): Yuqing Dong, Guorui Jin, Changchun Ji, Rongyan He, Min Lin, Xin Zhao, Ang Li, Tian Jian Lu, Feng Xu




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Carbon nano-onions: unique carbon nanostructures with fascinating properties and their potential applications

Publication date: Available online 22 July 2017
Source:Inorganica Chimica Acta
Author(s): Olena Mykhailiv, Halyna Zubyk, Marta E. Plonska-Brzezinska
This article presents a short review of the knowledge concerning carbon nano-onions, also known as onion-like carbon or multi-layered fullerenes. Currently, these nanostructures are some of the most fascinating carbon forms. We can only find approximately 2,000 articles under the entry of "carbon onion" in the Web of Science. Surprisingly, there have been ∼40,000 citations since their discovery, and the interest in these nanostructures is still growing. In the last three years, 5,000 citations per year have been reported. This means that researchers have noted the unusual nature of these carbon nanostructures. In this article, we review the most important literature reports in this area, which in a condensed way, present these nanostructures, their production methods, their unusual physical and chemical properties and their potential uses.

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Icosahedral nanocrystals of noble metals: Synthesis and applications

Publication date: Available online 22 July 2017
Source:Nano Today
Author(s): Helan Wang, Shan Zhou, Kyle D. Gilroy, Zaisheng Cai, Younan Xia
Icosahedral nanocrystals of noble metals have received ever increasing interests in recent years owing to their unique features such as the size-dependent distribution of strain fields and the presence of a large number of twin boundaries. In this review, we start with a brief introduction to the strain field distribution on an icosahedral nanocrystal and then we discuss the size-dependent structural thermodynamics, together with remarks on the synthetic approaches to icosahedral nanocrystals of various noble metals in high purity. The recent breakthroughs in synthesis can be attributed to a strong correlation between the kinetics of reduction and the way atoms are assembled in nuclei during homogenous nucleation. We aim to provide a brief account of new developments while highlighting the key experimental parameters that give rise to icosahedral nanocrystals. We focus on monometallic systems based on Au, Ag, Pd, Pt, and Rh, along with some bimetallic systems. At the end, we showcase the performance of icosahedral nanocrystals towards catalytic and photonic applications, and offer some perspectives on future directions.

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Glassy carbon proves strong under pressure

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Publication date: Available online 22 July 2017
Source:Nano Today





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Holey graphene promises better energy storage

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Publication date: Available online 22 July 2017
Source:Nano Today





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Boosting the capacitance and voltage of aqueous supercapacitors via redox charge contribution from both electrode and electrolyte

Publication date: Available online 22 July 2017
Source:Nano Today
Author(s): Jee Y. Hwang, Maher F. El-Kady, Mengping Li, Cheng-Wei Lin, Matthew Kowal, Xu Han, Richard B. Kaner
Supercapacitors are evolving into an important component in energy storage technology with the capability for storing and discharging energy very quickly and effectively. State-of-the-art supercapacitors feature activated carbon electrodes impregnated with a non-aqueous electrolyte (typically acetonitrile) that operate at voltages between 2.2–2.7V. Unfortunately, activated carbons have low specific capacitance (100–120Fg−1) in organic electrolytes which severely limits the energy density of supercapacitors. In addition, organic solvents are often flammable leading to safety and environmental concerns. Aqueous electrolytes, on the other hand, are safer, cheaper and have higher ionic conductivity, promising higher capacitance electrodes. However, the low voltage window enforced by the low decomposition voltage of water around 1.23V is a major challenge. Here, we demonstrate symmetric supercapacitors operating at an ultrahigh voltage of 1.8V that can provide specific electrode capacitances up to 716Fg−1, which is higher than traditional activated carbon electrodes. This is possible through designing both the electrode and electrolyte to work synergistically towards improving not only the capacitance of the electrodes, but also the voltage and cycling stability of the supercapacitor. We also demonstrate by using a simple laser technique the possibility of fabricating micro-supercapacitors with great potential for miniaturized electronics. This work provides an effective strategy for designing and fabricating aqueous supercapacitors that hold promise for a sustainable energy future.

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Vitamin D endocrinology of bone mineralization

Publication date: 15 September 2017
Source:Molecular and Cellular Endocrinology, Volume 453
Author(s): Marjolein van Driel, Johannes P.T.M. van Leeuwen
Bone is a dynamic tissue that is strongly influenced by endocrine factors to restore the balance between bone resorption and bone formation. Bone formation involves the mineralization of the extracellular matrix formed by osteoblasts. In this process the role of vitamin D (1α,25(OH)2D3) is both direct and indirect. The direct effects are enabled via the Vitamin D Receptor (VDR); the outcome is dependent on the presence of other factors as well as origin of the osteoblasts, treatment procedures and species differences. Vitamin D stimulates mineralization of human osteoblasts but is often found inhibitory for mineralization of murine osteoblasts.In this review we will overview the current knowledge of the role of the vitamin D endocrine system in controlling the mineralization process in bone.



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The endocrine vitamin D system in the gut

Publication date: 15 September 2017
Source:Molecular and Cellular Endocrinology, Volume 453
Author(s): Antonio Barbáchano, Asunción Fernández-Barral, Gemma Ferrer-Mayorga, Alba Costales-Carrera, María Jesús Larriba, Alberto Muñoz
The active vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) has important regulatory actions in the gut through endocrine and probably also intracrine, autocrine and paracrine mechanisms. By activating the vitamin D receptor (VDR), which is expressed at a high level in the small intestine and colon, 1,25(OH)2D3 regulates numerous genes that control gut physiology and homeostasis. 1,25(OH)2D3 is a major responsible for epithelial barrier function and calcium and phosphate absorption, and the host's defense against pathogens and the inflammatory response by several types of secretory and immune cells. Moreover, recent data suggest that 1,25(OH)2D3 has a regulatory effect on the gut microbiota and stromal fibroblasts. Many studies have linked vitamin D deficiency to inflammatory bowel diseases (ulcerative colitis and Crohn's disease) and to an increased risk of colorectal cancer, and the possible use of VDR agonists to prevent or treat these diseases is receiving increasing interest.



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Nitric oxide (NO) inhibition of meiotic G2-M1 transition in Anabas testudineus oocytes: Participation of cAMP-dependent protein kinase (PKA) in regulation of intra-oocyte signaling events

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Publication date: Available online 23 July 2017
Source:Molecular and Cellular Endocrinology
Author(s): Poulomi Nath, Debabrata Das, Soumojit Pal, Sudipta Maitra
Nitric oxide (NO) regulation of ovarian function in mammals has been studied extensively. However, relatively less information is available on NO action on meiotic G2-M1 transition in teleost oocytes. In the present study using follicle-enclosed oocytes of Anabas testudineus, NO regulation of intra-oocyte signaling events during meiotic G2-M1 transition were examined. Priming with NO donor, sodium nitroprusside (SNP) prevented 17α,20β-dihydroxy-4-pregenen-3-one (17,20β-P)-induced germinal vesicle break down (GVBD) in dose- and duration-dependent manner. Impaired GVBD response in SNP-treated groups corroborated well with reduced p34Cdc2 (Thr161) phosphorylation. Immunoblot analysis revealed that congruent with elevated cAMP-dependent protein kinase (PKA) phosphorylation (activation), NO inhibition of meiotic maturation involves down regulation of Cdc25 activation, Mos synthesis and MAPK3/1 (p-ERK1/2) phosphorylation. However, priming with PKA inhibitor (H89) could reverse SNP attenuation of oocyte GVBD significantly. Collectively our results indicate that negative influence of NO on meiotic G2-M1 transition in perch oocytes might involve PKA activation.



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The molecular complexity of primary ovarian insufficiency aetiology and the use of massively parallel sequencing

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Publication date: Available online 23 July 2017
Source:Molecular and Cellular Endocrinology
Author(s): Paul Laissue
Primary ovarian insufficiency (POI) is a frequently occurring pathology, leading to infertility. Genetic anomalies have been described in POI and mutations in numerous genes have been definitively related to the pathogenesis of the disease. Some studies based on next generation sequencing (NGS) have been successfully undertaken as they have led to identify new mutations associated with POI aetiology.The purpose of this review is to present the most relevant molecules involved in diverse complex pathways, which may contribute towards POI. The main genes participating in bipotential gonad formation, sex determination, meiosis, folliculogenesis and ovulation are described to enable understanding how they may be considered putative candidates involved in POI. Considerations regarding NGS technical aspects such as design and data interpretation are mentioned. Successful NGS initiatives used for POI studying and future challenges are also discussed.



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Psoriasis: a mixed autoimmune and autoinflammatory disease

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Publication date: December 2017
Source:Current Opinion in Immunology, Volume 49
Author(s): Yun Liang, Mrinal K Sarkar, Lam C Tsoi, Johann E Gudjonsson
In recent years marked progress has been made in our understanding of the critical biologic and immunologic pathways involved in psoriasis. Genetic studies have demonstrated that susceptibility to psoriasis involves components of both the adaptive and innate immune system and not surprisingly activation of both of these arms of the immune system is found in psoriatic skin. While adaptive immune responses predominate in chronic plaque psoriasis, innate and autoinflammatory responses dominate in pustular forms of psoriasis, with other clinical subtypes extending on a spectrum between plaque and pustular psoriasis. This makes psoriasis a unique disease where both autoimmune and autoinflammatory responses co-exist, with the balance between the two being critical in shaping its clinical presentation.



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Definition: Source Monitoring

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Publication date: Available online 22 July 2017
Source:Cortex
Author(s): Karen J. Mitchell




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Neural Processes Underlying the Orienting of Attention without Awareness

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Publication date: Available online 22 July 2017
Source:Cortex
Author(s): Charles M. Giattino, Zaynah M. Alam, Marty G. Woldorff
Despite long being of interest to both philosophers and scientists, the relationship between attention and perceptual awareness is not well understood, especially to what extent they are even dissociable. Previous studies have shown that stimuli of which we are unaware can orient spatial attention and affect behavior. Yet, relatively little is understood about the neural processes underlying such unconscious orienting of attention, and how they compare to conscious orienting. To directly compare the cascade of attentional processes with and without awareness of the orienting stimulus, we employed a spatial-cueing paradigm and used object-substitution masking to manipulate subjects' awareness of the cues. We recorded EEG during the task, from which we extracted hallmark event-related-potential (ERP) indices of attention. Behaviorally, there was a 61 ms validity effect (invalidly minus validly cued target RTs) on cue-aware trials. On cue-unaware trials, subjects also had a robust validity effect of 20 ms, despite being unaware of the cue. An N2pc to the cue, a hallmark index of the lateralized orienting of attention, was observed for cue-aware but not cue-unaware trials, despite the latter showing a clear behavioral validity effect. Finally, the sensory P1 to the targets was larger when validly vs. invalidly cued, even when subjects were unaware of the preceding cue, demonstrating enhanced sensory processing of targets following subliminal cues. These results suggest that subliminal stimuli can orient attention and lead to subsequent enhancements to both stimulus sensory processing and behavior, but through different neural mechanisms than stimuli we perceive, such as via a subcortical pathway.



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Multicenter randomized double-blind, placebo-controlled trial GORTEC 2009-01 evaluating the effect of the regenerating agent RGTA on radiodermatitis of head and neck cancer patients

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Publication date: Available online 22 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Yungan Tao, Anne Auperin, Christian Sire, Michel Martin, Marie-Gabrielle Saliou, Etienne Bardet, Xu Shan Sun, Thierry Chatellier, Clotilde Morand, Alexandre Cornely, Moussa Angokai, Alessia Di Rito, Ketty Kichenin, Pierre Blanchard, Ida D'Onofrio, Jean Bourhis
BackgroundConcomitant cetuximab and radiotherapy could induce severe radiodermatitis in patients with head and neck cancer (HNC). The OTD70DERM®, a Regenerating Agent (RGTA) is structural and functional analogue of glycosaminoglycans. Pre-clinical studies showed that topical RGTA could markedly reduce radiation-induced mucosal and cutaneous toxicities without tumor protection. This study aimed to transfer this observation in patients to evaluate the effect of topical RGTA on radiodermatitis in a clinical situation for which radio-induced skin reactions are frequent and/or severe i.e. in patients with HNC receiving radiotherapy and cetuximab. The primary endpoint was the incidence of grade ≥2 radiodermatitis.Patients and MethodsA multicenter, randomized, double-blind, placebo-controlled trial was performed on newly diagnosed HNC patients receiving conventionally fractionated RT (70 Gy/ 35 fractions) and weekly cetuximab. Patients were randomized 1:1 to receive topical OTD70DERM® or placebo on irradiated skin once daily. The criteria NCI-CTCAE 3.0 was used for radiodermatitis (photography of radiation zone); and the Dermatology Life Quality Index (DLQI) score was evaluated. All the skin reactions obtained from photographs were scored independently of investigators by two experts.ResultsIn 76 randomized patients (38 in each arm), 72 patients were available for final radiodermatitis evaluation (37 in RGTA arm and 35 in placebo arm). No significant difference was observed concerning the incidence or duration of grade ≥2 radiodermatitis between the two arms (81% for RGTA versus 80% placebo, p = 0.9); no significant difference between two arms regarding grade ≥2 radiodermatitis evaluated by experts regarding the photographs analyzed for 68 patients (76% vs 74%, p = 0.78); and no significant difference of DLQI score was observed (score > 10: 15% vs 20%, p = 0.45).ConclusionDespite a good pre-clinical rationale, RGTA did not reduce the incidence and severity of radiodermatitis in patients with HNC..

Teaser

Pre-clinical studies showed that topical OTD70DERM®, a Regenerating Agent functional analogue of glycosaminoglycans could markedly reduce radiation-induced mucosal and cutaneous toxicities. This hypothesis was tested in a randomized, placebo-controlled trial performed in 76 HNC patients receiving radiotherapy plus cetuximab. No significant difference was observed concerning the incidence or duration of grade ≥2 radiodermatitis between the arms. Despite a good pre-clinical rationale, OTD70DERM® did not reduce the incidence and severity of radiodermatitis.


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Conventional versus hypofractionated radiotherapy in localized or locally advanced prostate cancer: A systematic review and meta-analysis along with therapeutic implications

Publication date: Available online 22 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Niloy R. Datta, Emanuel Stutz, Susanne Rogers, Stephan Bodis
PurposeA systematic review and meta-analysis was conducted to evaluate the therapeutic outcomes of conventional (CRT) and hypofractionated radiotherapy (HRT) in localized or locally advanced prostate cancers (LLPCa).Material and methods599 abstracts were extracted from five databases and screened as per the PRISMA guidelines. Only phase III trials randomized between CRT and HRT in LLPCa with a minimum of 5-year follow-up were considered. The evaluated endpoints were - biochemical failure (BF), biochemical and/or clinical failure (BCF), overall mortality (OM), prostate cancer-specific mortality (PCaSM), both acute and late gastrointestinal (GI) and genitourinary (GU) (grade >2) toxicities.ResultsTen trials from nine publications, totaling 8,146 patients (CRT: 3,520; HRT: 4,626; one study compared two HRT schedules with a common CRT regime) were included in the evaluation. There were no significant differences in patient characteristics between the two arms. However, the radiotherapy treatment parameters differed significantly between CRT and HRT (all p<0.001). Use of androgen deprivation therapy (ADT) varied from 0-100% in both groups, (mean + SD: 43.3% + 43.6; CRT vs. HRT: p:ns). The odds ratio (OR), risk ratio (RR) and risk difference (RD) between CRT and HRT for BF, BCF, OM, PCaSM, acute GU, late GU and GI toxicities were all nonsignificant. Nevertheless, acute GI toxicities were 9.1% less with CRT (RD=0.091, OR=1.687, RR=1.470, all p<0.001). On subgroup analysis, patient groups with < vs.>66.8% ADT (RD: 0.052 vs. 0.136; p=0.008) and < vs.>76% full seminal vesicles in clinical target volume (RD: 0.034 vs. 0.108; p<0.001) were found to significantly influence the acute GI toxicity with HRT.ConclusionsHRT provides similar therapeutic outcomes to CRT in LLPCa except for a significantly higher risk of acute GI toxicity. HRT enables a reduction in overall treatment time and offers patient convenience. However variables contributing to an increased acute GI toxicity need careful consideration.



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Radiation therapy for optic pathway and hypothalamic low-grade gliomas in children

Publication date: Available online 23 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Derek S. Tsang, Erin S. Murphy, Thomas E. Merchant
BackgroundThe long-term survival of pediatric patients with optic pathway or hypothalamic low-grade glioma (LGG) who receive radiation therapy (RT) has not been previously assessed.MethodsA retrospective study was performed of all patients with optic-hypothalamic pediatric LGG treated with RT at a single institution. Eligible patients were aged 21 years or younger at the time of RT and had localized LGG diagnosed by neuroimaging or histology. The median RT dose was 54 Gy, delivered in 30 fractions. Event-free survival (EFS) was defined as survival without progression or secondary high-grade glioma. Days were counted from the first day of RT.ResultsEighty-nine patients were included in the study, with a median follow-up of 12.5 years. Fourteen of the patients had neurofibromatosis type 1 (NF-1). The 10-year EFS was 61.9% (95% CI 31.2–82.1) for patients with NF-1 and 67.5% (95% CI 54.8–77.3) for those without NF-1. The 10-year overall survival (OS) was 92.3% (95% CI 56.6–98.9) for patients with NF-1 and 98.4% (95% CI 89.1–99.8) for those without NF-1. Pre-RT chemotherapy (which was more commonly given to younger patients) was associated with reduced EFS, whereas younger age was associated with reduced OS. Eight patients, including four with NF-1, developed possible radiation-induced neoplasms. The 10-year cumulative incidence of clinically-significant vasculopathy was 7.1% (95% CI 2.9–13.9); no child older than 10 years at the commencement of RT developed vasculopathy.Conclusion(s)Radiation is an effective treatment for optic-hypothalamic LGG. Older children without NF-1 have a low risk of late toxicity. RT can be considered for selected younger patients or individuals with NF-1 as a salvage treatment after progression.

Teaser

Radiation therapy for pediatric optic pathway or hypothalamic low-grade glioma establishes long-term disease control in most patients, with 10-year event-free survival (EFS) of greater than 60% and 10-year overall survival (OS) of greater than 90%. The presence of NF-1 did not affect EFS or OS. No child older than 10 years developed vasculopathy after receiving RT. Radiation is thus an effective treatment for optic-hypothalamic LGG, and older children without NF-1 have a low risk of late toxicity.


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Recent time trends and predictors of heart dose from breast radiotherapy in a large quality consortium of radiation oncology practices

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Publication date: Available online 22 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Lori J. Pierce, Mary Feng, Kent A. Griffith, Reshma Jagsi, Thomas Boike, Daniel Dryden, Gregory S. Gustafson, Lisa Benedetti, Martha M. Matuszak, Teamour S. Nurushev, Joe Haywood, Jeffrey D. Radawski, Corey Speers, Eleanor M. Walker, James A. Hayman, Jean M. Moran
IntroductionLimited data exist regarding the range of heart doses received in routine practice following radiotherapy (RT) for breast cancer (BC) in the United States today and the potential impact of continual assessment of cardiac dose on practice patterns.Methods and MaterialsFrom 2012-2015, 4688 patients with BC treated with whole breast RT at 20 sites participating in a state-wide consortium were enrolled into a registry. The importance of limiting cardiac dose has been emphasized in the consortium since 2012 and mean heart dose (MHD) has been reported to each institution since 2014. Effects on MHD were estimated for both conventional fractionation (CF) and accelerated fractionation (AF) using regression models with technique (intensity modulated RT, IMRT vs. three-dimensional conformal RT, 3DCRT), deep-inspiration breath hold (DIBH) use, position (supine vs. prone), nodal RT (if delivered) and boost (yes/no) as covariates.ResultsFor left-sided BC treated with CF, median MHD in 2012 was 2.19 Gy compared to 1.65 Gy in 2015 (p<0.001). Factors which significantly increased MHD for CF were increasing separation relative to 22 cm (1.5%/cm) ; supra-/infraclavicular node RT (17.1%); internal mammary node RT (40.7%); use of boost (20.9%); treatment per year prior to 2015 (7.7%); and IMRT (20.8%). For left-sided BC treated with AF, the median MHD in 2012 was 1.70 Gy versus 1.22 Gy in 2015 (p<0.001). Factors that significantly increased MHD following AF were separation (1.7% /cm); use of boost (20.0%); year prior to 2015 (8.5%); and IMRT (19.2%). Factors for both CF and AF that significantly reduced MHD were use of DIBH and prone positioning.ConclusionsMHD for left-sided cancers has decreased over a recent 4-year period coincident with increased focus on cardiac sparing in the radiation oncology community in general and within a state-wide consortium specifically. These data suggest a positive impact of systematically monitoring heart dose delivered.

Teaser

With recent focus on minimizing radiation dose to the heart following adjuvant therapy for breast cancer, it is important to understand the current state of cardiac sparing and predictors of heart dose. In a large U.S. state-wide registry, we evaluated recent time trends in mean heart dose, adjusting for planned target dose and treatment technique. Our findings indicate mean heart dose decreased significantly for left-sided breast cancers over a 4-year period using ongoing monitoring of cardiac dose by institution.


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Stem Cell Therapy for Abrogating Stroke-Induced Neuroinflammation and Relevant Secondary Cell Death Mechanisms

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Publication date: Available online 23 July 2017
Source:Progress in Neurobiology
Author(s): Connor Stonesifer, Sydney Corey, Shaila Ghanekar, Zachary Diamandis, Sandra A. Acosta, Cesar V. Borlongan
Ischemic stroke is a leading cause of death worldwide. A key secondary cell death mechanism mediating neurological damage following the initial episode of ischemic stroke is the upregulation of endogenous neuroinflammatory processes to levels that destroy hypoxic tissue local to the area of insult, induce apoptosis, and initiate a feedback loop of inflammatory cascades that can expand the region of damage. Stem cell therapy has emerged as an experimental treatment for stroke, and accumulating evidence supports the therapeutic efficacy of stem cells to abrogate stroke-induced inflammation. In this review, we investigate clinically relevant stem cell types, such as hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), very small embryonic-like stem cells (VSELs), neural stem cells (NSCs), extraembryonic stem cells, adipose tissue-derived stem cells, breast milk-derived stem cells, menstrual blood-derived stem cells, dental tissue-derived stem cells, induced pluripotent stem cells (iPSCs), teratocarcinoma-derived Ntera2/D1 neuron-like cells (NT2N), c-mycER(TAM) modified NSCs (CTX0E03), and notch-transfected mesenchymal stromal cells (SB623), comparing their potential efficacy to sequester stroke-induced neuroinflammation and their feasibility as translational clinical cell sources. To this end, we highlight that MSCs, with a proven track record of safety and efficacy as a transplantable cell for hematologic diseases, stand as an attractive cell type that confers superior anti-inflammatory effects in stroke both in vitro and in vivo. That stem cells can mount a robust anti-inflammatory action against stroke complements the regenerative processes of cell replacement and neurotrophic factor secretion conventionally ascribed to cell-based therapy in neurological disorders.



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Nanomaterial Applications for Neurological Diseases and Central Nervous System Injury

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Publication date: Available online 22 July 2017
Source:Progress in Neurobiology
Author(s): Lijie Huang, Jiangnan Hu, Shengwei Huang, Brian Wang, Felix Siaw-Debrah, Mark Nyanzu, Yu Zhang, Qichuan Zhuge
The effectiveness of noninvasive treatment for neurological disease is generally limited by the poor entry of therapeutic agents into the central nervous system (CNS). Most CNS drugs cannot permeate into the brain parenchyma because of the blood-brain barrier thus, overcoming this problem has become one of the most significant challenges in the development of neurological therapeutics. Nanotechnology has emerged as an innovative alternative for treating neurological diseases. In fact, rapid advances in nanotechnology have provided promising solutions to this challenge. This review highlights the applications of nanomaterials in the developing neurological field and discusses the evidence for their efficacies.



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Tyr42 phosphorylation of RhoA GTPase promotes tumorigenesis through nuclear factor (NF)-κB

Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Jae-Gyu Kim, Kyoung-Chan Choi, Chang-Won Hong, Hwee-Seon Park, Eun-Kyoung Choi, Yong-Sun Kim, Jae-Bong Park
Dysregulation of reactive oxygen species (ROS) levels is implicated in the pathogenesis of several diseases, including cancer. However, the molecular mechanisms for ROS in tumorigenesis have not been well established. In this study, hydrogen peroxide activated nuclear factor-κB (NF-κB) and RhoA GTPase. In particular, we found that hydrogen peroxide lead to phosphorylation of RhoA at Tyr42 via tyrosine kinase Src. Phospho-Tyr42 (p-Tyr42) residue of RhoA is a binding site for Vav2, a guanine nucleotide exchange factor (GEF), which then activates p-Tyr42 form of RhoA. P-Tyr42 RhoA then binds to IκB kinase γ (IKKγ), leading to IKKβ activation. Furthermore, RhoA WT and phospho-mimic RhoA, RhoA Y42E, both promoted tumorigenesis, whereas the dephospho-mimic RhoA, RhoA Y42F suppressed it. In addition, hydrogen peroxide induced NF-κB activation and cell proliferation, along with expression of c-Myc and cyclin D1 in the presence of RhoA WT and RhoA Y42E, but not RhoA Y42F. Indeed, levels of p-Tyr42 Rho, p-Src, and p-65 are significantly increased in human breast cancer tissues and show correlations between each of the two components. Conclusively, the posttranslational modification of as RhoA p-Tyr42 may be essential for promoting tumorigenesis in response to generation of ROS.

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Editorial Board

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Publication date: September 2017
Source:Free Radical Biology and Medicine, Volume 110





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Insights into the differential toxicological and antioxidant effects of 4-phenylchalcogenil-7-chloroquinolines in Caenorhabditis elegans

Publication date: September 2017
Source:Free Radical Biology and Medicine, Volume 110
Author(s): Willian G. Salgueiro, Bruna S. Goldani, Tanara V. Peres, Antonio Miranda-Vizuete, Michael Aschner, João Batista Teixeira da Rocha, Diego Alves, Daiana S. Ávila
Organic selenium and tellurium compounds are known for their broad-spectrum effects in a variety of experimental disease models. However, these compounds commonly display high toxicity and the molecular mechanisms underlying these deleterious effects have yet to be elucidated. Thus, the need for an animal model that is inexpensive, amenable to high-throughput analyses, and feasible for molecular studies is highly desirable to improve organochalcogen pharmacological and toxicological characterization. Herein, we use Caenorhabdtis elegans (C. elegans) as a model for the assessment of pharmacological and toxicological parameters following exposure to two 4-phenylchalcogenil-7-chloroquinolines derivatives (PSQ for selenium and PTQ for tellurium-containing compounds). While non-lethal concentrations (NLC) of PTQ and PSQ attenuated paraquat-induced effects on survival, lifespan and oxidative stress parameters, lethal concentrations (LC) of PTQ and PSQ alone are able to impair these parameters in C. elegans. We also demonstrate that DAF-16/FOXO and SKN-1/Nrf2 transcription factors underlie the mechanism of action of these compounds, as their targets sod-3, gst-4 and gcs-1 were modulated following exposures in a daf-16- and skn-1-dependent manner. Finally, in accordance with a disturbed thiol metabolism in both LC and NLC, we found higher sensitivity of trxr-1 worm mutants (lacking the selenoprotein thioredoxin reductase 1) when exposed to PSQ. Finally, our study suggests new targets for the investigation of organochalcogen pharmacological effects, reinforcing the use of C. elegans as a powerful platform for preclinical approaches.

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Réponse des auteurs à la lettre à propos de l’article : « Télédermatologie en milieu carcéral : étude rétrospective de 500 télé-expertises »

Publication date: Available online 22 July 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): B. Khatibi, A. Bambe, C. Chantalat, M. Resche-Rigon, A. Sanna, C. Fac, M. Bagot, F. Guibal




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Réponse des auteurs à la lettre à propos de l’article : « Télédermatologie en milieu carcéral : étude rétrospective de 500 télé-expertises »

Publication date: Available online 22 July 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): B. Khatibi, A. Bambe, C. Chantalat, M. Resche-Rigon, A. Sanna, C. Fac, M. Bagot, F. Guibal




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Should radiographic progression still be used as outcome in RA?

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Publication date: Available online 22 July 2017
Source:Clinical Immunology
Author(s): Désirée van der Heijde, Robert Landewé
Radiographs of hands and feet are traditionally the images that are used to assess structural damage progression in drug trials in patients with rheumatoid arthritis, aiming at proving the disease modifying capacity of a drug. Although treatment has largely improved over the past decade and consequently radiographic progression is limited in control arms in clinical trials, recent trials are still able to show inhibition of structural progression by new drugs. The requirements for the successful use of radiographic progression as an outcome in rheumatoid arthritis trials will be discussed in this paper.



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Should radiographic progression still be used as outcome in RA?

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Publication date: Available online 22 July 2017
Source:Clinical Immunology
Author(s): Désirée van der Heijde, Robert Landewé
Radiographs of hands and feet are traditionally the images that are used to assess structural damage progression in drug trials in patients with rheumatoid arthritis, aiming at proving the disease modifying capacity of a drug. Although treatment has largely improved over the past decade and consequently radiographic progression is limited in control arms in clinical trials, recent trials are still able to show inhibition of structural progression by new drugs. The requirements for the successful use of radiographic progression as an outcome in rheumatoid arthritis trials will be discussed in this paper.



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Density Functionalized [RuII(NO)(Salen)(Cl)] Complex: Computational Photodynamics and In Vitro Anticancer Facets

Publication date: Available online 22 July 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Jan Mohammad Mir, N. Jain, P.S. Jaget, R.C. Maurya
Photodynamic therapy (PDT) is a treatment that uses photosensitizing agents to kill cancer cells. Scientific community has been eager for decades in enduring curiosity to design an efficient PDT drug. Under such purview, the current report deals with the computational photodynamic behavior of ruthenium(II) nitrosyl complex containing N, N'-salicyldehyde-ethylenediimine (SalenH2), the synthesis and X-ray crystallography of which is already known [Ref. 36]. Gaussian 09W software package was employed to carry out the density functional (DFT) studies. DFT calculations with Becke-3–Lee–Yang–Parr (B3LYP)/Los Alamos National Laboratory 2 Double Z (LanL2DZ) specified for Ru atom and B3LYP/6-31G(d,p) combination for all other atoms were used using effective core potential method. Both, the ground and excited states of the complex were evolved. Some known photosensitizers were compared with the target complex. Pthalocyanine and porphyrin derivatives were the compounds selected for the respective comparative study. It is suggested that effective photoactivity was found due to the presence of ruthenium core in the model complex. In addition to the evaluation of theoretical aspects in vitro anticancer aspects against COLO-205 human cancer cells have also been carried out with regard to the complex. More emphasis was laid to extrapolate DFT to depict the chemical power of the target compound to release nitric oxide. A promising visible light triggered nitric oxide releasing power of the compound has been inferred. In vitro antiproliferative studies of [RuCl3(PPh3)3] and [Ru(NO)(Salen)(Cl)] have revealed the model complex as an excellent anticancer agent. From IC50 values of 40.031mg/mL in former and of 9.74mg/mL in latter, it is established that latter bears more anticancer potentiality. From overall study the DFT based structural elucidation and the efficiency of NO, Ru and Salen co-ligands has shown promising drug delivery property and a good candidacy for both chemotherapy as well as light therapy.

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Antimicrobial peptides human LL-37 and β-defensin-3 modulate the expression of nerve elongation factors in human epidermal keratinocytes

Publication date: Available online 23 July 2017
Source:Journal of Dermatological Science
Author(s): Yoshie Umehara, Yayoi Kamata, Mitsutoshi Tominaga, François Niyonsaba, Hideoki Ogawa, Kenji Takamori




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Sesame allergy in adults

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Publication date: Available online 23 July 2017
Source:Annals of Allergy, Asthma & Immunology
Author(s): Philip H. Li, Natasha Gunawardana, Iason Thomas, Kok Loong Ue, Leonard Siew, Timothy J. Watts, Keyna Bintcliffe, Rubaiyat Haque, Krzysztof Rutkowski, Isabel Skypala, Stephen J. Till




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