Clinicopathological features of thyroid cancer in the elderly compared to younger counterparts: single-center experience

Abstract

Purpose

The incidence of thyroid cancer is increased in elderly patients. It tends to be larger and have more aggressive characteristics in these patients. Our aim was to compare features of thyroid carcinoma in geriatric and non-geriatric patients.

Methods

In total, 933 patients with thyroid cancer were retrospectively reviewed. Thyroid functions, ultrasonography features of malignant nodules, cytological and histopathological findings and the rates of recurrence and persistence were compared in patients ≥65 and <65 years old.

Results

There were 153 malignant foci in 109 (11.7%) patients ≥65 and 1185 malignant foci in 824 (88.3%) patients <65 years old. Mean nodule diameter was significantly higher in geriatric patients (p = 0.008). Most of the ultrasonographical features of malignant nodules were similar in two groups. Hypoechoic halo was observed in 16.4 and 28.6% of malignant nodules in geriatric and non-geriatric group, respectively (p = 0.034). There was no significant difference in cytological diagnosis. Histopathologically, tumor diameter, rates of microcarcinomas and incidentality were similar. Of all cancer types, 88.8% in geriatric and 93.9% in non-geriatric group were papillary thyroid cancer (p = 0.028). Hurthle cell cancer constituted 3.9 and 1.1% of carcinomas in geriatric and non-geriatric patients, respectively (p = 0.015); 2.0 and 0.2% of tumors in geriatric and non-geriatric group were anaplastic, respectively (p = 0.012). Capsular and vascular invasion, extrathyroidal extension, persistence and recurrence rates were similar.

Conclusions

Rates of anaplastic cancer and Hurthle cell cancer which is known to have worser prognosis among other differentiated thyroid cancers are increased in geriatric ages. Cytological evaluation of thyroid nodules should strongly be considered due to increased tendency for aggressive tumor types in these patients.

http://ift.tt/2fJwL1b

The role of ficolin-like protein (PcFLP1) in the antibacterial immunity of red swamp crayfish (Procambarus clarkii)

Publication date: January 2017
Source:Molecular Immunology, Volume 81
Author(s): Yun-Jia Dai, Yu-Qing Wang, Ying-Hao Zhang, Yan Liu, Jin-quan Li, Shun Wei, Li-Juan Zhao, Yong-can Zhou, Li Lin, Jiang-Feng Lan
In invertebrates, ficolin-like proteins (FLPs) play important roles in innate immunity against pathogens. Previous studies primarily investigated the functions of FLPs in immune recognition, activation, and regulation. However, limited research has examined the functions of FLPs as immune effectors. In this work, a ficolin-like protein was identified in red swam crayfish (Procambarus clarkii) and designated as PcFLP1. Quantitative RT-PCR and western blot were employed to analyze the distribution and expression profiles of PcFLP1 in the tissues of the crayfish. The results indicated that PcFLP1 was present in all tested tissues, including hemocytes, heart, hepatopancreas, gill, stomach, and mid-intestine. The expression level of PcFLP1 was up-regulated in hemocytes, hepatopancreas and mid-intestines of the crayfish challenged with Vibrio parahaemolyticus. Further study demonstrated that PcFLP1 could protect the hepatopancreatic cells of crayfish from V. parahaemolyticus infection. The recombinant PcFLP1 enhanced bacterial elimination in crayfish, whereas the antibacterial action was inhibited after PcFLP1 was knocked down. Furthermore, PcFLP1 could bound to bacteria and inhibited bacterial replication. These results demonstrated that PcFLP1 plays an important role in the anti-Vibrio immunity of red swamp crayfish.



http://ift.tt/2fVVYbw

Characterization of peritoneal leukemia-associated macrophages in Notch1-induced mouse T cell acute lymphoblastic leukemia

Publication date: January 2017
Source:Molecular Immunology, Volume 81
Author(s): Shayan Chen, Xiao Yang, Wenli Feng, Feifei Yang, Rong Wang, Chong Chen, Lina Wang, Yongmin Lin, Qian Ren, Guoguang Zheng
Macrophages, which have remarkable plasticity, are indispensable cellular components and play essential roles in both innate and adaptive immune responses. Peritoneal macrophages show unique gene expression profile and peritoneal cavity is also involved in leukemia. However, the characteristics of peritoneal leukemia-associated macrophages (Per LAMs) have not been established. Here we studied the phenotype of Per LAMs, their subpopulations in Notch1-induced acute lymphoblastic leukemia mice and compared with LAMs from BM or spleen in the same model. Peritoneal macrophages and Per LAMs simultaneously expressed high level iNOS and Arg1, which was not commonly observed in macrophages from different origins. Furthermore, LAMs from peritoneal, BM and spleen expressed lower level CSF-1, TGF-β1 and VEGF-A than tumor-associated macrophages (TAMs). Moreover, diverse responses in the expression of some phenotype-associated genes to leukemia microenvironments were detected among those LAMs. In addition, Per LAMs can be sub-divided into CD206⁺ and CD206⁻ sub-populations, which expressed both M1- and M2-associated genes. These results revealed the unique phenotype of Per macrophages and Per LAMs and contributed to better understanding of macrophage plasticity and their pathological roles in leukemia.



http://ift.tt/2fVWJBy

Treponema pallidum flagellin FlaA2 induces IL-6 secretion in THP-1 cells via the Toll-like receptor 2 signaling pathway

Publication date: January 2017
Source:Molecular Immunology, Volume 81
Author(s): Yafeng Xie, Man Xu, Yongjian Xiao, Zhuoran Liu, Chuanhao Jiang, Xingxing Kuang, Chuan Wang, Haiying Wu, Jing Peng, Chun Li, Yu Wang, Huaming Liu, Bin Liu, Xiaotuan Zhang, Feijun Zhao, Tiebing Zeng, Shuangquan Liu, Yimou Wu
Treponema pallidum subsp. pallidum membrane proteins are considered as potent inducers in the initiation and development of inflammation. In the present study, the mechanism that leads to the production of interleukin 6 (IL-6), one of the key proinflammatory cytokines, by human monocytic THP-1 cells when these cells are treated with T. pallidum flagellin FlaA2 was investigated. Stimulation with flagellin FlaA2 can induce IL-6 expression in human monocytes and augment the phosphorylation of ERK, p38, and NF-κB, but has no effect on the phosphorylation of JNK. Likewise, FlaA2-induced IL-6 production was found to be attenuated by inhibitors for ERK, p38, and NF-κB, but not by JNK inhibitor. Immunofluorescence analysis showed that flagellin FlaA2 could stimulate the translocation of IκBα from the cytosol to the nucleus, and this phenomenon could be inhibited by the specific inhibitor BAY11-7082. FlaA2–induced IL-6 expression was also proved to be abrogated by transfection with dominant negative (DN) plasmid of MyD88. We further demonstrated that transfection with DN-TLR2 was sufficient to attenuate IL-6 expression and the phosphorylation of ERK, p38, and IκBα. These results suggest that flagellin FlaA2 induces IL-6 production via signaling pathways involving TLR2, MyD88, ERK, p38, and NF-κB in monocytes, which could contribute to the pathogenesis of T. pallidum.



http://ift.tt/2fJru9X

Circadian Homeostasis of Liver Metabolism Suppresses Hepatocarcinogenesis

Publication date: Available online 23 November 2016
Source:Cancer Cell
Author(s): Nicole M. Kettner, Horatio Voicu, Milton J. Finegold, Cristian Coarfa, Arun Sreekumar, Nagireddy Putluri, Chinenye A. Katchy, Choogon Lee, David D. Moore, Loning Fu
Chronic jet lag induces spontaneous hepatocellular carcinoma (HCC) in wild-type mice following a mechanism very similar to that observed in obese humans. The process initiates with non-alcoholic fatty liver disease (NAFLD) that progresses to steatohepatitis and fibrosis before HCC detection. This pathophysiological pathway is driven by jet-lag-induced genome-wide gene deregulation and global liver metabolic dysfunction, with nuclear receptor-controlled cholesterol/bile acid and xenobiotic metabolism among the top deregulated pathways. Ablation of farnesoid X receptor dramatically increases enterohepatic bile acid levels and jet-lag-induced HCC, while loss of constitutive androstane receptor (CAR), a well-known liver tumor promoter that mediates toxic bile acid signaling, inhibits NAFLD-induced hepatocarcinogenesis. Circadian disruption activates CAR by promoting cholestasis, peripheral clock disruption, and sympathetic dysfunction.

Graphical abstract

Teaser

Kettner et al. show that experimental chronic jet lag induces persistent deregulation of liver gene expression and metabolism, culminating in the development of hepatocellular carcinoma. The bile acid receptor FXR and xenobiotic receptor CAR play an important role in this process.


http://ift.tt/2fvvcGd

NUP98 Fusion Proteins Interact with the NSL and MLL1 Complexes to Drive Leukemogenesis

Publication date: Available online 23 November 2016
Source:Cancer Cell
Author(s): Haiming Xu, Daria G. Valerio, Meghan E. Eisold, Amit Sinha, Richard P. Koche, Wenhuo Hu, Chun-Wei Chen, S. Haihua Chu, Gerard L. Brien, Christopher Y. Park, James J. Hsieh, Patricia Ernst, Scott A. Armstrong
The nucleoporin 98 gene (NUP98) is fused to a variety of partner genes in multiple hematopoietic malignancies. Here, we demonstrate that NUP98 fusion proteins, including NUP98-HOXA9 (NHA9), NUP98-HOXD13 (NHD13), NUP98-NSD1, NUP98-PHF23, and NUP98-TOP1 physically interact with mixed lineage leukemia 1 (MLL1) and the non-specific lethal (NSL) histone-modifying complexes. Chromatin immunoprecipitation sequencing illustrates that NHA9 and MLL1 co-localize on chromatin and are found associated with Hox gene promoter regions. Furthermore, MLL1 is required for the proliferation of NHA9 cells in vitro and in vivo. Inactivation of MLL1 leads to decreased expression of genes bound by NHA9 and MLL1 and reverses a gene expression signature found in NUP98-rearranged human leukemias. Our data reveal a molecular dependency on MLL1 function in NUP98-fusion-driven leukemogenesis.

Graphical abstract

Teaser

Xu et al. reveal a key role for MLL1 in NUP98 fusion leukemias and show that NUP98 fusion proteins interact with MLL1 and NSL histone modifiers on chromatin to drive expression of both Hoxa and Hoxb cluster genes important for sustaining leukemia.


http://ift.tt/2fvpAMr

Phototherapy with Narrow-Band UVB in Adult Guttate Psoriasis: Results and Patient Assessment

Background: Acute guttate psoriasis (AGP) is a distinctive clinical entity with good response to treatment with narrow-band ultraviolet B (NB-UVB). Objective: To investigate the results of NB-UVB phototherapy in adult patients with adult guttate psoriasis. Material and Methods: We carried out a prospective, open, and observational study. Patients over 18 years with more than 5% of body surface area affected were included. The PASI was assessed prior to and after treatment. The follow-up period was 18 months. After treatment, patients completed a simple questionnaire to assess their overall impression of the treatment. Results: The 67 adult patients with AGP included in this study had an initial PASI of 8.55 (SD 5.03). Patients were treated with a mean of 19.9 sessions (SD 13.5) and mean doses of 14 mJ/cm² (SD 10.5). Of the 67 patients, 52 achieved PASI90 with 96.15% of PASI reduction, and of these, 46 (88%) maintained PASI90 during the 18 months of follow-up. Patients were very satisfied with the treatment. Discussion: AGP is a defined clinical entity with a variable course. Phototherapy with NB-UVB appears to be a very good option for treatment of AGP because of the good results obtained and patient satisfaction.
Dermatology

http://ift.tt/2gkkUGP

The role of ficolin-like protein (PcFLP1) in the antibacterial immunity of red swamp crayfish (Procambarus clarkii)

Publication date: January 2017
Source:Molecular Immunology, Volume 81
Author(s): Yun-Jia Dai, Yu-Qing Wang, Ying-Hao Zhang, Yan Liu, Jin-quan Li, Shun Wei, Li-Juan Zhao, Yong-can Zhou, Li Lin, Jiang-Feng Lan
In invertebrates, ficolin-like proteins (FLPs) play important roles in innate immunity against pathogens. Previous studies primarily investigated the functions of FLPs in immune recognition, activation, and regulation. However, limited research has examined the functions of FLPs as immune effectors. In this work, a ficolin-like protein was identified in red swam crayfish (Procambarus clarkii) and designated as PcFLP1. Quantitative RT-PCR and western blot were employed to analyze the distribution and expression profiles of PcFLP1 in the tissues of the crayfish. The results indicated that PcFLP1 was present in all tested tissues, including hemocytes, heart, hepatopancreas, gill, stomach, and mid-intestine. The expression level of PcFLP1 was up-regulated in hemocytes, hepatopancreas and mid-intestines of the crayfish challenged with Vibrio parahaemolyticus. Further study demonstrated that PcFLP1 could protect the hepatopancreatic cells of crayfish from V. parahaemolyticus infection. The recombinant PcFLP1 enhanced bacterial elimination in crayfish, whereas the antibacterial action was inhibited after PcFLP1 was knocked down. Furthermore, PcFLP1 could bound to bacteria and inhibited bacterial replication. These results demonstrated that PcFLP1 plays an important role in the anti-Vibrio immunity of red swamp crayfish.



http://ift.tt/2fVVYbw

Characterization of peritoneal leukemia-associated macrophages in Notch1-induced mouse T cell acute lymphoblastic leukemia

Publication date: January 2017
Source:Molecular Immunology, Volume 81
Author(s): Shayan Chen, Xiao Yang, Wenli Feng, Feifei Yang, Rong Wang, Chong Chen, Lina Wang, Yongmin Lin, Qian Ren, Guoguang Zheng
Macrophages, which have remarkable plasticity, are indispensable cellular components and play essential roles in both innate and adaptive immune responses. Peritoneal macrophages show unique gene expression profile and peritoneal cavity is also involved in leukemia. However, the characteristics of peritoneal leukemia-associated macrophages (Per LAMs) have not been established. Here we studied the phenotype of Per LAMs, their subpopulations in Notch1-induced acute lymphoblastic leukemia mice and compared with LAMs from BM or spleen in the same model. Peritoneal macrophages and Per LAMs simultaneously expressed high level iNOS and Arg1, which was not commonly observed in macrophages from different origins. Furthermore, LAMs from peritoneal, BM and spleen expressed lower level CSF-1, TGF-β1 and VEGF-A than tumor-associated macrophages (TAMs). Moreover, diverse responses in the expression of some phenotype-associated genes to leukemia microenvironments were detected among those LAMs. In addition, Per LAMs can be sub-divided into CD206⁺ and CD206⁻ sub-populations, which expressed both M1- and M2-associated genes. These results revealed the unique phenotype of Per macrophages and Per LAMs and contributed to better understanding of macrophage plasticity and their pathological roles in leukemia.



http://ift.tt/2fVWJBy

Treponema pallidum flagellin FlaA2 induces IL-6 secretion in THP-1 cells via the Toll-like receptor 2 signaling pathway

Publication date: January 2017
Source:Molecular Immunology, Volume 81
Author(s): Yafeng Xie, Man Xu, Yongjian Xiao, Zhuoran Liu, Chuanhao Jiang, Xingxing Kuang, Chuan Wang, Haiying Wu, Jing Peng, Chun Li, Yu Wang, Huaming Liu, Bin Liu, Xiaotuan Zhang, Feijun Zhao, Tiebing Zeng, Shuangquan Liu, Yimou Wu
Treponema pallidum subsp. pallidum membrane proteins are considered as potent inducers in the initiation and development of inflammation. In the present study, the mechanism that leads to the production of interleukin 6 (IL-6), one of the key proinflammatory cytokines, by human monocytic THP-1 cells when these cells are treated with T. pallidum flagellin FlaA2 was investigated. Stimulation with flagellin FlaA2 can induce IL-6 expression in human monocytes and augment the phosphorylation of ERK, p38, and NF-κB, but has no effect on the phosphorylation of JNK. Likewise, FlaA2-induced IL-6 production was found to be attenuated by inhibitors for ERK, p38, and NF-κB, but not by JNK inhibitor. Immunofluorescence analysis showed that flagellin FlaA2 could stimulate the translocation of IκBα from the cytosol to the nucleus, and this phenomenon could be inhibited by the specific inhibitor BAY11-7082. FlaA2–induced IL-6 expression was also proved to be abrogated by transfection with dominant negative (DN) plasmid of MyD88. We further demonstrated that transfection with DN-TLR2 was sufficient to attenuate IL-6 expression and the phosphorylation of ERK, p38, and IκBα. These results suggest that flagellin FlaA2 induces IL-6 production via signaling pathways involving TLR2, MyD88, ERK, p38, and NF-κB in monocytes, which could contribute to the pathogenesis of T. pallidum.



http://ift.tt/2fJru9X

Intranasal insulin boosts gustatory sensitivity

Abstract

Intranasal insulin had been in the spotlight not only for enhancing memory processes but also for its anorexic effects, as well as its effects on olfactory sensitivity. Here, the influence of intranasal insulin on gustatory sensitivity was investigated using intranasal applications of insulin or placebo in a double-blind manner alongside a control condition without any application.

We hypothesized that intranasal insulin, as it mediates satiety, alters gustatory sensitivity whereas placebo application and control should not alter gustatory sensitivity. We did not expect the sensitivity to the different taste solutions to differ. Sweet, salty, bitter and sour liquids in four different concentrations were sprayed on the tongue of healthy male subjects. Additionally, non-tasting water was applied to be able to calculate taste sensitivity referring to the parameter d prime (d') of the signal detection theory (SDT). The task of the subject was to identify the quality of the respective tastant. Gustatory sensitivity as well as blood parameters were evaluated using repeated-measures ANOVAs.

Gustatory sensitivity, implying all tastants, improved significantly following intranasal insulin application compared to application of placebo, but did not reach significance compared to the control condition. Subjects performed best in detecting the sweet taste and worst in detecting the bitter taste. The blood parameters glucose, insulin, HOMA and leptin did not differ with respect to insulin or placebo condition, nor did they differ regarding measurements preceding or following intranasal application, proving peripheral euglycaemia during the experiment. Thus, it can be concluded that application of intranasal insulin in comparison to placebo led to an improved gustatory sensitivity.

This article is protected by copyright. All rights reserved.

http://ift.tt/2glrUXr

Markers of Islet Endothelial Dysfunction Occur in Male db/db Mice and May Contribute to Reduced Insulin Release

Endocrinology, Early Release.


http://ift.tt/2gxnKfG

Exploring value from the patient’s perspective between modern radiation therapy modalities for localized prostate cancer

Publication date: Available online 24 November 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Narek Shaverdian, Darlene Verruttipong, Pin-Chieh Wang, Amar U. Kishan, D Jeffrey Demanes, Susan McCloskey, Patrick Kupelian, Michael L. Steinberg, Christopher R. King
PurposeThe patient's perspective on their treatment experience has not been compared between modern radiation modalities for localized prostate cancer (PCa). We evaluated treatment regret and patient perceptions of their treatment experience to better inform our understanding of a treatment's value.Methods and MaterialsPatients with localized PCa treated with SBRT, IMRT or HDR Brachytherapy (HDR) between 2008-14 with at least one year of follow-up were surveyed. The questionnaire explored the decision-making experience, expectations of toxicities vs. the reality, and treatment regret via a validated tool.Results329 consecutive patients were surveyed with an 86% response rate (IMRT, n=74; SBRT, n=108; HDR, n=94). The median patient age and post-treatment follow-up was 68 years and 47 months, respectively. 82% of patients had T1c disease with either Gleason 6 (42%) or Gleason 7 (58%) pathology and a median iPSA of 5.8 ng/ml. 13% expressed regret with their treatment. Among patients with regret, 71% now wish they had elected for active surveillance. Incidence of regret was significantly different between treatment modalities: 5% of patients treated with SBRT expressed regret vs. 18% with HDR and 19% with IMRT (p<0.01). On multivariable logistic regression, patients treated with HDR vs. SBRT were 7.42 times more likely to have regret, and patients treated with IMRT vs. SBRT were 11.11 times more likely to have regret (p<0.01 and p<0.01, respectively). Significantly more patients treated with SBRT selected that their actual long-term toxicities were significantly less than originally expected compared with IMRT and HDR patients (SBRT 43% vs. IMRT 20% vs HDR 10%, p<0.01).ConclusionsWe found significant differences in the patient experience between SBRT, IMRT and HDR, with significantly less treatment regret and less toxicity than expected among SBRT patients. The majority of patients with regret would now opt for active surveillance, and therefore pre-treatment counseling is essential.



http://ift.tt/2fsGTKI

The Significance of Co-Expression of Epidermal Growth Factor Receptor (EGFR) and Ki67 on Clinical Outcome in Patients with Anal Cancer Treated with Chemoradiotherapy: An Analysis of Study XXXX

Publication date: Available online 23 November 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Corinne M. Doll, Jennifer Moughan, Alexander Klimowicz, Clement K. Ho, Elizabeth N. Kornaga, Susan P. Lees-Miller, Jaffer A. Ajani, Christopher H. Crane, Lisa A. Kachnic, Gordon S. Okawara, Lawrence B. Berk, Kevin S. Roof, Mark J. Becker, David L. Grisell, Robert J. Ellis, Paul Sperduto, Gerald Marsa, Chandan Guha, Anthony Magliocco
PurposeTo measure co-expression of EGFR and Ki67 proteins in pre-treatment tumor biopsies of anal cancer patients enrolled on Study XXXX, a phase III trial comparing 5FU/MMC/RT (Arm A) vs. 5FU/cisplatin/RT (Arm B), and to correlate expression with clinical outcome.Materials/MethodsEGFR and Ki67 co-expression was measured after constructing a tissue microarray using fluorescence immunohistochemistry and automated quantitative image analysis (AQUA). Ki67 score within EGFR high vs. low areas (Ki67ratio in EGFRhigh:low) in each tumor core was analyzed at the median, quartiles and as a continuous variable. Associations between the tumor markers and clinical endpoints [overall and disease-free survival (OS, DFS), loco-regional and colostomy failure (LRF, CF), and distant metastases (DM] were explored.Results282 pre-treatment tumors were analyzed from Study XXXX. Of evaluated specimens, 183 (65%, n=89, Arm A; n=94, Arm B) were eligible and analyzable. There were no significant differences in baseline characteristics or outcomes between analyzable and unanalyzable patient cases. Median follow-up was 6.0 years. On multivariate analysis, after adjusting for gender, patients with Ki67ratio in EGFRhigh:low ≥ median had worse OS (HR=2.41, 95% C.I. = [1.38, 4.19], p=0.0019). After adjusting for N stage and largest tumor dimension, patients with Ki67ratio in EGFRhigh:low ≥ median had a higher risk of a disease-free failure (HR=1.85, 95% C.I. = [1.18, 2.92], p=0.0078). Technical validation with an independent anal cancer patient cohort was performed and shows a very similar biomarker score distribution.ConclusionsHigh Ki67ratio in EGFRhigh:low is associated with worse clinical outcome in this subset of patients with anal cancer treated with chemoradiation on Study XXXX. Evaluation within a clinical trial will be required to determine whether patients with these tumor characteristics may specifically benefit from an EGFR targeted therapeutic agent.

Teaser

Co-expression of EGFR and Ki67 was measured in pre-treatment tumor biopsies of anal cancer patients enrolled on Study XXXX. It was determined those patients whose tumors had Ki67ratio in EGFRhigh:low ≥ median had worse overall survival and disease-free survival. This suggests that proliferative dysregulation in EGFR high expressing tumor cells is a potential marker of aggressiveness.


http://ift.tt/2glsyEf

Bone Marrow-Sparing Intensity Modulated Radiation Therapy with Concurrent Cisplatin for Stage Ib-Iva Cervical Cancer: An International Multi-Center Phase Ii Clinical Trial (Intertecc-2)

Publication date: Available online 23 November 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Loren K. Mell, Igor Sirák, Lichun Wei, Rafal Tarnawski, Umesh Mahantshetty, Catheryn M. Yashar, Michael T. McHale, Ronghui Xu, Gordon Honerkamp-Smith, Ruben Carmona, Mary Wright, Casey W. Williamson, Linda Kasaová, Nan Li, Stephen Kry, Jeff Michalski, Walter Bosch, William Straube, Julie Schwarz, Jessica Lowenstein, Steve B. Jiang, Cheryl C. Saenz, Steve Plaxe, John Einck, Chonlakiet Khorprasert, Paul Koonings, Terry Harrison, Mei Shi, A.J. Mundt
PurposeTo test the hypothesis that intensity modulated radiation therapy (IMRT) reduces acute hematologic and gastrointestinal (GI) toxicity for patients with locoregionally advanced cervical cancer.MethodsWe enrolled patients with stage IB-IVA cervical carcinoma on a single-arm phase II trial involving eight centers internationally. All patients received weekly cisplatin concurrently with once-daily IMRT, followed by intracavitary brachytherapy as indicated. The primary endpoint was the occurrence of either acute grade ≥ 3 neutropenia or clinically significant GI toxicity within 30 days of completing chemoradiotherapy. A pre-planned subgroup analysis tested the hypothesis that positron emission tomography (PET)-based image-guided IMRT (IG-IMRT) lowers the risk of acute neutropenia. We also longitudinally assessed changes in quality of life.ResultsFrom October 2011 to April 2015, 83 patients met eligibility criteria and initiated protocol therapy. Median follow-up was 26.0 months. The incidence of any primary event was 26.5% (95% CI, 18.2-36.9%), significantly lower than the 40% incidence hypothesized a priori from historical data (p=0.012). The incidences of grade ≥ 3 neutropenia and clinically significant GI toxicity were 19.3% (95% CI, 12.2-29.0%) and 12.0% (95% CI, 6.7-20.8%), respectively. Compared to patients treated without IG-IMRT (N=48), patients treated with IG-IMRT (N=35) had significantly lower grade ≥ 3 neutropenia (8.6% vs. 27.1%, 2-sided chi-square p=0.035), and non-significantly lower grade ≥ 3 leukopenia (25.7% vs. 41.7%, p=0.13) and any grade ≥ 3 hematologic toxicity (31.4% vs. 43.8%, p=0.25).ConclusionIMRT reduces acute hematologic and GI toxicity compared to standard treatment, with promising therapeutic outcomes. PET-guided IMRT reduces acute neutropenia.

Teaser

This was an international phase II trial to test the hypothesis that IMRT reduces acute toxicity for locoregionally advanced cervical cancer. In 83 patients enrolled, acute gastrointestinal was significantly reduced with both IMRT and PET-guided bone marrow sparing IMRT (IG-IMRT) compared to historical controls. Neutropenia was significantly reduced in patients treated with IG-IMRT. We conclude that IMRT reduces acute toxicity compared to standard treatment in this population, and that IG-IMRT warrants testing in randomized trials.


http://ift.tt/2fsy8QM

Large scale retrospective Monte Carlo dosimetric study for permanent implant prostate brachytherapy

Publication date: Available online 23 November 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): N. Miksys, E. Vigneault, A.G. Martin, L. Beaulieu, R.M. Thomson
PurposeTo retrospectively compare water-based and full tissue model Monte Carlo dose calculations in a large cohort of permanent implant prostate brachytherapy (PIPB) patients.Methods and MaterialsFor 613 patients, EGSnrc BrachyDose dose calculations are performed in two virtual patient models: TG43sim (simulated AAPM TG-43 conditions) and MCref (CT derived heterogeneous tissue model with interseed effects). A sensitivity analysis is performed in a patient subset (25 with and 25 without prostatic calcifications) to explore dose calculation dependence on organ-at-risk (OAR) and calcification tissue elemental compositions and modelling approach.ResultsIn the target volume, average D90 (V100) is lower with MCref than TG43sim by 5.9 ± 1.6% (2.6 ± 1.7%). Patients with prostatic calcifications can have substantial under-dosed volumes due to calcification shielding, lowering D90 up to 25%. In the urethra, average D5 (D30) is lower with MCref than TG43sim by 4.4 ± 1.8% (4.7 ± 1.9%). In the rectum (bladder) average D0.1cc is lower (higher) with MCref than TG43sim by 5.2 ± 1.8% (1.3 ± 1.8%). Doses to target and OARs can increase or decrease by several percent depending on the assumed tissue elemental composition. In patients with calcifications, differences between approaches to model calcifications can vary target and OAR dose metrics by upwards of 10%.ConclusionsTG43sim typically overestimates target and OAR doses by several percent, on average, compared to MCref. The considerable variation in relative TG43sim and MCref doses between patients, and the larger dose differences for calcified patients, suggests that clinical adoption of Monte Carlo dose calculations for PIPB should be pursued. The substantial sensitivity of Monte Carlo dose calculations to patient modelling approach supports the adoption of a consensus modelling scheme, such as MCref described herein, to assure consistency of practice.



http://ift.tt/2glsDYz

A Randomized Phase II Trial of Prophylactic Manuka Honey for the Reduction of Chemoradiation Therapy Induced Esophagitis During the Treatment of Lung Cancer: Results of Trial ****

Publication date: Available online 23 November 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Shannon Fogh, Snehal Deshmukh, Lawrence B. Berk, Amylou C. Dueck, Kevin Roof, Sherif Yacoub, Thomas Gergel, Kevin Stephans, Andreas Rimner, Albert DeNittis, John Pablo, Justin Rineer, Terence M. Williams, Deborah Bruner
PurposeRandomized trials have shown that honey is effective for prevention of radiation-induced mucositis in head and neck cancer patients. Because there is no efficacious preventative for radiation esophagitis in lung cancer patients, this trial compared liquid honey, honey lozenges, and standard supportive care for radiation esophagitis.MethodsPatients were stratified by percentage of esophagus receiving specific radiation dose (V60Gy esophagus < or ≥ 30%), then randomized between supportive care, 10 ml of liquid Manuka honey four times a day or 2 lozenges (10 ml of dehydrated Manuka honey) four times a day during concurrent chemotherapy and radiotherapy. The primary endpoint was patient-reported pain on swallowing utilizing an eleven point (0-10) scale at 4 weeks (Numerical Rating Pain Scale, NRPS). The study was designed to detect 15% relative reduction of change in NRPS score. Secondary endpoints were trend of pain over time, opioid use, clinically-graded and patient-reported adverse events, weight loss, dysphagia, nutritional status and quality of life.Results53 patients were randomized to supportive care, 54 randomized to liquid honey and 56 to lozenge honey. There was no significant difference in the primary endpoint of change in the NRPS at 4 weeks between arms. There were no differences in any of the secondary endpoints except for opioid use at 4 weeks during treatment between the supportive care and liquid honey arms which was found to be significant (p=0.03) with more patients on the supportive care arm taking opioids.ConclusionHoney as prescribed within this protocol was not superior to best supportive care in preventing radiation esophagitis. Further testing of other types of honey and research into the mechanisms of action are needed.

Teaser

As there is currently no efficacious preventative for radiation esophagitis in lung cancer patients, this trial compared liquid honey, honey lozenges, and standard supportive care for radiation esophagitis. Honey prescribed within this protocol was not superior to best supportive care in preventing radiation esophagitis.Further studies are warranted to better understand if the link between honey microbiota, bacteriostatic properties and/or immune response to honey may demonstrate clinical benefit, and whether honey use can reduce opioid use during treatment.Manuka Honey for Esophagitis


http://ift.tt/2fsIVdD

*ASCENDE-RT: An Analysis of Survial Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- And Intermediate-Risk Prostate Cancer

Publication date: Available online 24 November 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): W. James Morris, Scott Tyldesley, Sree Rodda, Ross Halperin, Howard Pai, Michael McKenzie, Graeme Duncan, Gerard Morton, Jeremy Hamm, Nevin Murray
PurposeTo report the primary endpoint of biochemical progression free survival (b-PFS) and secondary survival endpoints for a randomized trial comparing two methods of dose escalation for intermediate- and high-risk prostate cancer.Materials and MethodsThe trial enrolled 398 men, median age 68; 69% (N =276) had high-risk disease. After stratification by risk group, subjects were randomized to either a standard arm with 12 months of androgen deprivation therapy (ADT), pelvic irradiation to 46 Gy followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. Two hundred trial subjects were assigned to DE-EBRT boost and 198 to LDR-PB boost. Median follow-up is 6.5 years.ResultsIn an intent-to-treat analysis, men randomized to DE-EBRT were twice as likely to experience biochemical failure (MVA HR: 2.04, p =0.004). The 5-, 7-, and 9-year Kaplan-Meier b-PFS estimates were 89%, 86% and 83% for those randomized to LDR-PB boost versus 84%, 75% and 62% for DE-EBRT boost (log rank p <0.001). The LDR-PB boost benefited both intermediate- and high-risk patients. Since the b-PFS curves for the treatment arms diverge sharply after 4 years, the relative advantage of the LDR-PB should increase with longer follow up.In MVA, the only variables correlated with reduced overall survival (OS) were age (MVA HR: 1.06/year, p =0.004) and biochemical failure (MVA HR: 6.30, p <0.001). Although biochemical failure was associated with increased mortality and randomization to DE-EBRT doubled the rate of biochemical failure, no significant OS difference was observed between arms (MVA HR 1.13, p =0.62).ConclusionsCompared to 78 Gy EBRT, men randomized to LDR-PB boost were twice as likely to be free of biochemical failure at 6.5 years median follow-up.



http://ift.tt/2fbRs9W

Positive Regulation of Lyn Kinase by CD148 Is Required for B Cell Receptor Signaling in B1 but Not B2 B Cells

Publication date: Available online 23 November 2016
Source:Immunity
Author(s): Katarzyna M. Skrzypczynska, Jing W. Zhu, Arthur Weiss
B1 and B2 B cells differ in their ability to respond to T-cell-independent (TI) antigens. Here we report that the Src-family kinase (SFK) regulator CD148 has a unique and critical role in the initiation of B1 but not B2 cell antigen receptor signaling. CD148 loss-of-function mice were found to have defective B1 B-cell-mediated antibody responses against the T-cell-independent antigens NP-ficoll and Pneumovax 23 and had impaired selection of the B1 B cell receptor (BCR) repertoire. These deficiencies were associated with a decreased ability of B1 B cells to induce BCR signaling downstream of the SFK Lyn. Notably, Lyn appeared to be selectively regulated by CD148 and loss of this SFK resulted in opposite signaling phenotypes in B1 and B2 B cells. These findings reveal that the function and regulation of Lyn during B1 cell BCR signaling is distinct from other B cell subsets.

Graphical abstract

Teaser

In conventional B cell BCR signaling, CD45 and CD148 are redundant positive regulators of SFKs. Skrzypczynska and colleagues demonstrate a unique requirement for CD148 in B1 B cells due to its selective activation of the SFK Lyn, which appears to have a critical positive regulatory role in B1 BCR signaling.


http://ift.tt/2gqacjg

Long term reduction in food allergy susceptibility in mice by combining breastfeeding-induced tolerance and TGF-β enriched formula after weaning

Abstract

Background

Oral tolerance induction in early life is a promising approach for food allergy prevention. Its success requires the identification of factors necessary for its persistence.

Objectives

We aimed to assess in mice duration of allergy prevention by breastfeeding-induced oral tolerance and whether oral TGF-β supplementation after weaning would prolong it.

Methods

We quantified ovalbumin (OVA) and OVA specific immunoglobulins levels by ELISA in milk from the EDEN birth cohort. Since OVA specific Ig were found in all samples, we assessed whether OVA-immunized mice exposed to OVA during lactation could prevent allergic diarrhea in their 6 and 13-week-old progeny. In some experiments, a TGF-β enriched formula was given after weaning.

Results

At 6 weeks, only 13% and 34% of mice breastfed by OVA-exposed mothers exhibited diarrhea after 6 and 7 OVA challenges versus 44% and 72% in mice breastfed by naïve mothers (p=0.02 and 0.01). Protection was associated with decreased levels of MMCP1 and OVA specific IgE (p<0.0001). At 13 weeks, although OVA specific IgE remained low (p=0.001), diarrhea occurrence increased to 32% and 46% after 6 and 7 OVA challenges in mice breastfed by OVA-exposed mothers. MMCP1 levels were not significantly inhibited. Supplementation with TGF-β after weaning induced a strong protection in 13-week-old mice breastfed by OVA-exposed mothers compared to mice breastfed by naive mothers (0%, 13% and 32% of diarrhea at the 5th, 6th and 7th challenges versus 17, 42 and 78%; p=0.05, 0.0043 and 0.0017). MMCP1 levels decreased by half compared to control mice (p=0.02). Prolonged protection was only observed in mice rendered tolerant by breastfeeding and was associated with an improved gut barrier.

Conclusions

In mice, prevention of food allergy by breastfeeding-induced tolerance is of limited duration. Nutritional intervention by TGF-β supplementation after weaning could prolong beneficial effects of breast milk on food allergy prevention.

This article is protected by copyright. All rights reserved.

http://ift.tt/2gEv4Gw

Genome-wide association study of peanut allergy reproduces association with amino acid polymorphisms in HLA-DRB1

Abstract

Background

Genetic variants for IgE-mediated peanut allergy are yet to be fully characterized and to date only one genome-wide association study (GWAS) has been published.

Objective

To identify genetic variants associated with challenge proven peanut allergy.

Methods

We carried out a GWAS comparing 73 infants with challenge-proven IgE-mediated peanut allergy against 148 non-allergic infants (all ~ 1 year old). We tested a total of 3.8 million single nucleotide polymorphism (SNPs), as well as imputed HLA alleles and amino acids. Replication was assessed by de novo genotyping in a panel of additional 117 cases and 380 controls, and in silico testing in two independent GWAS cohorts.

Results

We identified 21 independent associations at P ≤ 5x10^-5 but were unable to replicate these. The most significant HLA association was the previously reported amino acid variant located at position 71, within the peptide-binding groove of HLA-DRB1 (P = 2x10^-4). Our study therefore reproduced previous findings for the association between peanut allergy and HLA-DRB1 in this Australian population.

Conclusions & Clinical Relevance

Genetic determinants for challenge proven peanut allergy include alleles at the HLA-DRB1 locus.

This article is protected by copyright. All rights reserved.

http://ift.tt/2gk7Pgr

Individually dosed omalizumab: an effective treatment for severe peanut allergy

Abstract

Background

Treatment with omalizumab has shown a positive effect on food allergies, but no dosages are established. Basophil allergen threshold sensitivity (CD-sens) can be used to objectively measure omalizumab treatment efficacy and correlates with the outcome of Double Blind Placebo Controlled Food Challenge to peanut.

Objective

To evaluate if individualized omalizumab treatment monitored by CD-sens could be an effective intervention for suppression of allergic reactions to peanut.

Methods

Severely peanut allergic adolescents (n=23) were treated with omalizumab for 8 weeks and CD-sens was analysed before and after. Based on whether CD-sens was suppressed after 8 weeks, the patients either were subject to a peanut challenge or received 8 more weeks with increased dose of omalizumab, followed by peanut challenge or another 8-week cycle of omalizumab. IgE and IgE-antibodies to peanut and its components were analysed before treatment.

Results

After individualized omalizumab-treatment (8-24 weeks) all patients continued with an open peanut challenge with no (n=18) or mild (n=5) objective allergic symptoms. Patients (n=15) needing an elevated omalizumab-dose (ED) to supress CD-sens, had significantly higher CD-sens values at baseline 1.49 (0.44-20.5) compared to those (n=8) who managed with normal dose (ND) 0.32 (0.24-5.5) (p<0.01). Median ratios for Ara h 2 IgE-ab/IgE were significantly higher in the ED group (17%) compared to the ND group (11%).

Conclusions and Clinical Relevance

Individually dosed omalizumab, monitored by CD-sens, is an effective and safe treatment for severe peanut allergy. The ratio of IgE-ab to storage protein Ara h 2/IgE as well as CD-sens to peanut may predict the need of a higher omalizumab dose. Clinical trials numbers: EudraCT; 2012-005625-78, ClinicalTrials. gov; NCT02402231

This article is protected by copyright. All rights reserved.

http://ift.tt/2gEuJDy

Diagnosing occupational asthma

Summary

Making an accurate diagnosis of occupational asthma (OA) is, generally, important. The condition has not only significant health consequences for affected workers, but also substantial socio-economic impacts for workers, their employers and wider society. Missing a diagnosis of OA may lead to continued exposure to a causative agent and progressive worsening of disease; conversely, diagnosing OA when it is not present may lead to inappropriate removal from exposure and unnecessary financial and social consequences. While the most accurate investigation is specific inhalation challenge in an experienced centre, this is a scarce resource and in many cases reliance is on other tests. This review provides a technical dossier of the diagnostic value of the available methods which include an appropriate clinical history, the use of specific immunology and measurement of inflammatory markers, and various methods of relating functional changes in airway calibre to periods at work. It is recommended that these approaches are used iteratively and in judicious combination, in cognisance of the individual patient's circumstances and requirements. Based on available evidence, a working diagnostic algorithm is proposed that can be adapted to the suspected agent, purpose of diagnosis, and available resources. For better or worse, many of the techniques – and their interpretation – are available only in specialised centres and where there is room for doubt, referral to such a centre is probably wise. Accordingly, the implementation or development of such specialised centres with appropriate equipment and expertise should greatly improve the diagnostic evaluation of work-related asthma.

This article is protected by copyright. All rights reserved.

http://ift.tt/2gk5kuN

Neutrophil autophagy and extracellular DNA traps contribute to airway inflammation in severe asthma

Abstract

Background

Autophagy and neutrophil extracellular DNA traps (NETs) are implicated in asthma; however, their roles in asthma pathogenesis have not been elucidated.

Objectives

We compared autophagy and NET production levels from peripheral blood neutrophils (PBNs) of patients with severe asthma (SA) and non-severe asthma (NSA). Additionally, we investigated the inflammatory effects of NETs on human airway epithelial cells (AECs) and peripheral blood eosinophils (PBEs).

Methods

PBNs from patients with SA (n=30) and NSA (n=38) were treated with interleukin (IL)-8 (100 ng/ml). Autophagy (light chain 3-II expression) and NET production levels were evaluated by western blot, immunofluorescence microscopy, and PicoGreen assay. The effects of NETs on AECs were assessed by investigating cell death, cell detachment, expression of occludin and claudin-1, and IL-8 production; the effects of NETs on PBEs were examined by investigating the activation and release of eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN).

Results

Untreated and IL-8-treated PBNs from the SA group produced higher autophagy and NET levels compared with those from the NSA group (P<0.01). IL-8 increased autophagy and NET levels in PBNs from the SA group but not from the NSA group. NET levels were correlated with autophagy levels in PBNs (P<0.001). IL-8-induced NET production levels negatively were correlated with FEV1/FVC (r = 0.700, P = 0.016). NETs induced cell death, detachment, degradation of occludin and claudin-1, and IL-8 production from AECs. Higher levels of NET-induced ECP and EDN were released from PBEs in SA compared with NSA groups.

Conclusions & Clinical Relevance

Neutrophil autophagy and NETs could enhance asthma severity by damaging airway epithelium and triggering inflammatory responses of AECs and PBEs. Modulating neutrophil autophagy and NET production may be a new target therapy for SA.

This article is protected by copyright. All rights reserved.

http://ift.tt/2gEunNn

Intravenous ketamine for subacute treatment of refractory chronic migraine: a case series

Refractory migraine is a challenging condition with great impact on health related quality of life. Intravenous (IV) ketamine has been previously used to treat various refractory pain conditions. We present a ...

http://ift.tt/2gq9baV

Long term reduction in food allergy susceptibility in mice by combining breastfeeding-induced tolerance and TGF-β enriched formula after weaning

Abstract

Background

Oral tolerance induction in early life is a promising approach for food allergy prevention. Its success requires the identification of factors necessary for its persistence.

Objectives

We aimed to assess in mice duration of allergy prevention by breastfeeding-induced oral tolerance and whether oral TGF-β supplementation after weaning would prolong it.

Methods

We quantified ovalbumin (OVA) and OVA specific immunoglobulins levels by ELISA in milk from the EDEN birth cohort. Since OVA specific Ig were found in all samples, we assessed whether OVA-immunized mice exposed to OVA during lactation could prevent allergic diarrhea in their 6 and 13-week-old progeny. In some experiments, a TGF-β enriched formula was given after weaning.

Results

At 6 weeks, only 13% and 34% of mice breastfed by OVA-exposed mothers exhibited diarrhea after 6 and 7 OVA challenges versus 44% and 72% in mice breastfed by naïve mothers (p=0.02 and 0.01). Protection was associated with decreased levels of MMCP1 and OVA specific IgE (p<0.0001). At 13 weeks, although OVA specific IgE remained low (p=0.001), diarrhea occurrence increased to 32% and 46% after 6 and 7 OVA challenges in mice breastfed by OVA-exposed mothers. MMCP1 levels were not significantly inhibited. Supplementation with TGF-β after weaning induced a strong protection in 13-week-old mice breastfed by OVA-exposed mothers compared to mice breastfed by naive mothers (0%, 13% and 32% of diarrhea at the 5th, 6th and 7th challenges versus 17, 42 and 78%; p=0.05, 0.0043 and 0.0017). MMCP1 levels decreased by half compared to control mice (p=0.02). Prolonged protection was only observed in mice rendered tolerant by breastfeeding and was associated with an improved gut barrier.

Conclusions

In mice, prevention of food allergy by breastfeeding-induced tolerance is of limited duration. Nutritional intervention by TGF-β supplementation after weaning could prolong beneficial effects of breast milk on food allergy prevention.

This article is protected by copyright. All rights reserved.

http://ift.tt/2gEv4Gw

Genome-wide association study of peanut allergy reproduces association with amino acid polymorphisms in HLA-DRB1

Abstract

Background

Genetic variants for IgE-mediated peanut allergy are yet to be fully characterized and to date only one genome-wide association study (GWAS) has been published.

Objective

To identify genetic variants associated with challenge proven peanut allergy.

Methods

We carried out a GWAS comparing 73 infants with challenge-proven IgE-mediated peanut allergy against 148 non-allergic infants (all ~ 1 year old). We tested a total of 3.8 million single nucleotide polymorphism (SNPs), as well as imputed HLA alleles and amino acids. Replication was assessed by de novo genotyping in a panel of additional 117 cases and 380 controls, and in silico testing in two independent GWAS cohorts.

Results

We identified 21 independent associations at P ≤ 5x10^-5 but were unable to replicate these. The most significant HLA association was the previously reported amino acid variant located at position 71, within the peptide-binding groove of HLA-DRB1 (P = 2x10^-4). Our study therefore reproduced previous findings for the association between peanut allergy and HLA-DRB1 in this Australian population.

Conclusions & Clinical Relevance

Genetic determinants for challenge proven peanut allergy include alleles at the HLA-DRB1 locus.

This article is protected by copyright. All rights reserved.

http://ift.tt/2gk7Pgr

Individually dosed omalizumab: an effective treatment for severe peanut allergy

Abstract

Background

Treatment with omalizumab has shown a positive effect on food allergies, but no dosages are established. Basophil allergen threshold sensitivity (CD-sens) can be used to objectively measure omalizumab treatment efficacy and correlates with the outcome of Double Blind Placebo Controlled Food Challenge to peanut.

Objective

To evaluate if individualized omalizumab treatment monitored by CD-sens could be an effective intervention for suppression of allergic reactions to peanut.

Methods

Severely peanut allergic adolescents (n=23) were treated with omalizumab for 8 weeks and CD-sens was analysed before and after. Based on whether CD-sens was suppressed after 8 weeks, the patients either were subject to a peanut challenge or received 8 more weeks with increased dose of omalizumab, followed by peanut challenge or another 8-week cycle of omalizumab. IgE and IgE-antibodies to peanut and its components were analysed before treatment.

Results

After individualized omalizumab-treatment (8-24 weeks) all patients continued with an open peanut challenge with no (n=18) or mild (n=5) objective allergic symptoms. Patients (n=15) needing an elevated omalizumab-dose (ED) to supress CD-sens, had significantly higher CD-sens values at baseline 1.49 (0.44-20.5) compared to those (n=8) who managed with normal dose (ND) 0.32 (0.24-5.5) (p<0.01). Median ratios for Ara h 2 IgE-ab/IgE were significantly higher in the ED group (17%) compared to the ND group (11%).

Conclusions and Clinical Relevance

Individually dosed omalizumab, monitored by CD-sens, is an effective and safe treatment for severe peanut allergy. The ratio of IgE-ab to storage protein Ara h 2/IgE as well as CD-sens to peanut may predict the need of a higher omalizumab dose. Clinical trials numbers: EudraCT; 2012-005625-78, ClinicalTrials. gov; NCT02402231

This article is protected by copyright. All rights reserved.

http://ift.tt/2gEuJDy

Diagnosing occupational asthma

Summary

Making an accurate diagnosis of occupational asthma (OA) is, generally, important. The condition has not only significant health consequences for affected workers, but also substantial socio-economic impacts for workers, their employers and wider society. Missing a diagnosis of OA may lead to continued exposure to a causative agent and progressive worsening of disease; conversely, diagnosing OA when it is not present may lead to inappropriate removal from exposure and unnecessary financial and social consequences. While the most accurate investigation is specific inhalation challenge in an experienced centre, this is a scarce resource and in many cases reliance is on other tests. This review provides a technical dossier of the diagnostic value of the available methods which include an appropriate clinical history, the use of specific immunology and measurement of inflammatory markers, and various methods of relating functional changes in airway calibre to periods at work. It is recommended that these approaches are used iteratively and in judicious combination, in cognisance of the individual patient's circumstances and requirements. Based on available evidence, a working diagnostic algorithm is proposed that can be adapted to the suspected agent, purpose of diagnosis, and available resources. For better or worse, many of the techniques – and their interpretation – are available only in specialised centres and where there is room for doubt, referral to such a centre is probably wise. Accordingly, the implementation or development of such specialised centres with appropriate equipment and expertise should greatly improve the diagnostic evaluation of work-related asthma.

This article is protected by copyright. All rights reserved.

http://ift.tt/2gk5kuN

Neutrophil autophagy and extracellular DNA traps contribute to airway inflammation in severe asthma

Abstract

Background

Autophagy and neutrophil extracellular DNA traps (NETs) are implicated in asthma; however, their roles in asthma pathogenesis have not been elucidated.

Objectives

We compared autophagy and NET production levels from peripheral blood neutrophils (PBNs) of patients with severe asthma (SA) and non-severe asthma (NSA). Additionally, we investigated the inflammatory effects of NETs on human airway epithelial cells (AECs) and peripheral blood eosinophils (PBEs).

Methods

PBNs from patients with SA (n=30) and NSA (n=38) were treated with interleukin (IL)-8 (100 ng/ml). Autophagy (light chain 3-II expression) and NET production levels were evaluated by western blot, immunofluorescence microscopy, and PicoGreen assay. The effects of NETs on AECs were assessed by investigating cell death, cell detachment, expression of occludin and claudin-1, and IL-8 production; the effects of NETs on PBEs were examined by investigating the activation and release of eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN).

Results

Untreated and IL-8-treated PBNs from the SA group produced higher autophagy and NET levels compared with those from the NSA group (P<0.01). IL-8 increased autophagy and NET levels in PBNs from the SA group but not from the NSA group. NET levels were correlated with autophagy levels in PBNs (P<0.001). IL-8-induced NET production levels negatively were correlated with FEV1/FVC (r = 0.700, P = 0.016). NETs induced cell death, detachment, degradation of occludin and claudin-1, and IL-8 production from AECs. Higher levels of NET-induced ECP and EDN were released from PBEs in SA compared with NSA groups.

Conclusions & Clinical Relevance

Neutrophil autophagy and NETs could enhance asthma severity by damaging airway epithelium and triggering inflammatory responses of AECs and PBEs. Modulating neutrophil autophagy and NET production may be a new target therapy for SA.

This article is protected by copyright. All rights reserved.

http://ift.tt/2gEunNn

Cosmetics Use-Related Adverse Events and Determinants Among Jigjiga Town Residents, Eastern Ethiopia

Abstract

Introduction

Non-medicated cosmetics use is very common among the Ethiopian population. However, little is known about these products' related adverse events. The aim of this study was to assess the prevalence and determinants of cosmetics-related adverse events among Jigjiga Town residents, Eastern Ethiopia.

Methods

A community-based cross-sectional study design was conducted in May and June 2014. Semi-structured interviews were used to collect cosmetics use pattern and related adverse events. For assessing determinants, logistic regression was used and statistical significance was set at p < 0.05.

Results

Overall, 600 participants were approached with a 93% response rate. Ninety-three percent (n = 521) of them reported the use of cosmetics at least once within 2 weeks prior to this study, and of these, 229 (44%) used traditional herbal cosmetics along with modern cosmetics. A total of 342 (61%) reported experiencing adverse events of which the most common reported were: allergic reactions, 149 (36%); the appearance of acne, 66 (16%); and hirsutism, 52 (12.5%). The occurrence of cosmetics-related adverse events were significantly associated with the number of cosmetics used per day, the frequency of use, mixing of different types of cosmetics together, and mixing of cosmetics with water or saliva.

Conclusion

A higher proportion of cosmetic users reported experiencing at least one adverse event. The number of cosmetic products and frequency of use were important predictors for experiencing adverse events. This implies the need to consider safety concerns related to cosmetic use. Approaches to address such issues may include awareness creation programs and promoting the concept of cosmetovigilance among cosmetic sellers, users, and other stakeholders.

http://ift.tt/2gEwCQT

The association between dentition status and sarcopenia in Japanese adults aged ≥75 years

Abstract

Background

Sarcopenia is an age-related loss of muscle mass and muscle strength or physical performance. There are limited data on the association between oral health and sarcopenia.

Objective

To test the hypothesis that impaired dentition status was associated with sarcopenia, we conducted a cross-sectional study.

Methods

A total of 272 community-dwelling Japanese adults aged ≥75 years for whom data were available from comprehensive health examinations conducted in 2015 were included in this study. During dental examination, the number of natural teeth and occluding pairs of natural teeth was counted. In denture wearers, the fit of the removable dentures was also evaluated. The criteria proposed by the Asian Working Group for Sarcopenia were used to define sarcopenia. A multivariable logistic regression model was used to evaluate the association between dentition status and the presence of sarcopenia.

Results

The prevalence of sarcopenia was 25.7% (70/272). Compared to individuals with ≥10 occluding pairs of natural teeth, those with no occluding pairs of natural teeth had significantly higher risk of having sarcopenia (adjusted odds ratio, 3.37; 95% confidence interval, 1.07–10.61), after adjusting for possible confounders. In addition, compared to individuals with well-fitting dentures, those with ill-fitting dentures had significantly higher risk of having sarcopenia (adjusted odds ratio, 5.07; 95% confidence interval, 1.59–16.19).

Conclusions

Our findings suggest that impaired dentition status is significantly associated with sarcopenia among community-dwelling Japanese adults aged ≥75 years. Future longitudinal studies with larger, more diverse populations are necessary to validate our findings.

This article is protected by copyright. All rights reserved.

http://ift.tt/2gEnF9U

Tongue to palate resistance training improves tongue strength and oropharyngeal swallowing function in subacute stroke survivors withdysphagia

Abstract

Tongue function can affect both the oral and pharyngeal stages of the swallowing process, and proper tongue strength are vital for safe oropharyngeal swallowing. This trial investigated the effect of tongue to palate resistance training (TPRT) on tongue strength and oropharyngeal swallowing function in stroke with dysphagia patients. This trial was performed using a 4-week, 2-group, pre-post design. Participants were allocated to the experimental group (n=18) or the control group (n=17). The experimental group was performed TPRT for 4 wks/, 5 day/wk) and traditional dysphagia therapy, whereas the control group performed traditional dysphagia therapy on the same schedule. Tongue strength was measured by using the Iowa Oral Performance Instrument. Swallowing function was measured by using the videofluoroscopic dysphagia scale (VDS) and penetration-aspiration scale (PAS) based on a videofluoroscopic swallowing study. Experimental group showed more improved in the tongue strength (both anterior and posterior region, p = 0.009, 0.015). In addition, the experimental group showed more improved scores on the oral and pharyngeal phase of VDS (p = 0.029, 0.007), but not on the PAS (p = 0.471), compared with the control group. This study demonstrated the effectiveness of TPRT in increasing tongue muscle strength and improving swallowing function in patients with poststroke dysphagia. Therefore, we recommend TPRT as an easy and simple rehabilitation strategy for improving swallowing in patients with dysphagia.

This article is protected by copyright. All rights reserved.

http://ift.tt/2gk83Ev

Editorial Board

Publication date: November 2016
Source:Acta Oecologica, Volume 77





http://ift.tt/2gk3Ctq

A cryptic mitochondrial DNA link between North European and West African dogs

Publication date: Available online 24 November 2016
Source:Journal of Genetics and Genomics
Author(s): Adeniyi C. Adeola, Sheila C. Ommeh, Jiao-Jiao Song, Olaogun S. Charles, Oscar J. Sanke, Ting-Ting Yin, Guo-Dong Wang, Shi-Fang Wu, Zhong-Yin Zhou, Jacqueline K. Lichoti, Bernard R. Agwanda, Philip M. Dawuda, Robert W. Murphy, Min-Sheng Peng, Ya-Ping Zhang
Domestic dogs have an ancient origin and a long history in Africa. Nevertheless, the timing and sources of their introduction into Africa remain enigmatic. Herein, we analyse variation in mitochondrial DNA (mtDNA) D-loop sequences from 345 Nigerian and 37 Kenyan village dogs plus 1530 published sequences from dogs from other parts of Africa, Europe and West Asia. All Kenyan dogs can be assigned to one of three haplogroups (matrilines; clades): A, B, C, while Nigerian dogs can be assigned to one of four haplogroups A, B, C, and D. None of the African dogs exhibits a matrilineal contribution from the African wolf (Canis lupus lupaster). The genetic signal of a recent demographic expansion is detected in Nigerian dogs from West Africa. The analyses of mitochondrial genomes reveal a maternal genetic link between modern West African and North European dogs indicated by sub-haplogroup D1 (but not the entire haplogroup D) coalescing around 12,000 years ago. Incorporating molecular anthropological evidence, we propose that sub-haplogroup D1 in West African dogs could be traced back to the late-glacial dispersals, potentially associated with human hunter-gatherer migration from southwestern Europe.



http://ift.tt/2gjVM2Q

Grifolin derivatives from Albatrellus ovinus as TRPV1 receptor blockers for cosmetic applications

Abstract

Objective

Blocking the TRPV1 receptor is an interesting approach for the treatment of sensitive skin. Here we investigated the potential of grifolin derivatives from Albatrellus ovinus to act as TRPV1 receptor blockers and their potential to serve as cosmetic active ingredients.

Methods

Binding characteristics of grifolin derivatives from Albatrellus ovinus were determined in competitive and functional in vitro assays to achieve IC₅₀ values. The TRPV1 receptor was activated in vivo with capsaicin and noxious heat to investigate skin reddening, microcirculation, skin sensations and heat pain thresholds.

Results

Grifolin derivatives extracted from Albatrellus ovinus proved to inhibit the TRPV1 receptor in vitro and in vivo. Besides suppression of the TRPV1 receptor activity upon chemical stimulation with capsaicin, thermal activation was shown to be inhibited as well by application of cosmetic formulations containing 3% Albatrellus ovinus extract. The reduction of stinging and burning sensations as well as reduction of reddening and microcirculation upon irritation with capsaicin or thermal stress proved efficacy in vivo.

Conclusion

Grifolin derivatives from Albatrellus ovinus are able to serve as fungal derived TRPV1 receptor blockers with capability to serve as a cosmetic active ingredient on sensitive skin.

This article is protected by copyright. All rights reserved.

http://ift.tt/2fJ9Y5s

Blood Oxidative Stress (BLOS) is a Secondary Host Defense System Responding Normally to Anaerobic Wound Infection and Inadvertently to Dietary Ultra-Exogenous Sulfide Formation (USF)

Publication date: Available online 23 November 2016
Source:Medical Hypotheses
Author(s): Peter G. Stroot
Blood oxidative stress (BLOS) is the presence of white blood cells and platelets that are generating high levels of reactive oxygen species (ROS). A mathematical model links the level of BLOS or BLOS# and plasma sulfide concentration. An increase in the BLOS# reduces the plasma sulfide concentration. The reported maximum plasma sulfide concentration for defined health conditions were used to calculate the minimum BLOS#. Elevated BLOS generates high plasma concentration of ROS, which triggers multiple responses in the body that protect the host. First, insulin production by the pancreas is inhibited, which results in elevated blood glucose levels. This results in advanced glycation end products (AGE), which thicken the blood vessel wall. Elevated blood glucose levels also increases urination, which reduces the availability of substrates for infectious bacteria. Second, one or more signaling molecules are stimulated to produce vascular hypertrophy resulting in hypertension. Third, the initial stage of atherosclerosis thickens the blood vessel wall while also protecting the inner surface of the blood vessels from localized infection. The first three mechanisms provide added protection against pathogen migration through the blood vessel wall and reduce the cross-sectional area of blood vessels, which increases the retention time (RT) for improved ROS inactivation of pathogens. Fourth, genes expressed in the liver, which are associated with drug oxidation and uptake transport, are inhibited. This inhibition protects the host from any toxins produced by an anaerobic infection. Elevated BLOS also reduces plasma sulfide concentration, which inhibits wound healing and extends aerobic conditions of the wound. The normal induction of BLOS offers a short-term, cascade of several primary mechanisms for secondary defense against anaerobic infection of a wound. Normal induction of BLOS is due to ultra-exogenous sulfide formation (USF) generated by a local anaerobic infection of a wound in the natural environment. The presence of BLOS without infection is indicative of inadvertent dietary induction. Long-term dietary BLOS results in many severe inflammatory diseases and cancers that are common in an ageing population. Glands were identified as more susceptible to cancers caused by long-term dietary BLOS. Variable BLOS levels in patients of clinical trials may also be reducing effectiveness of experimental drugs and causing drug toxicity. If BLOS is confirmed as a secondary defense against infection that is inadvertently triggered by diet, then a large number of common health problems may be treated and managed by apheresis and dietary changes.



http://ift.tt/2gEmMhD

How long does the volumizing effect of a zingiber officinale-based lip plumper last?

The vermilion zone of the lips (also called red lip or zone of Klein) has peculiar characteristics, different from the surrounding skin, which make it one of the most important parts of the lips. It can be considered a tactile organ, with an essential role in the body's anatomy and functions. Together with the lips, the vermilion zone represents one of the typical characteristics of mammals and its evolutionary appearance seems to be linked to the source of nutrition of these animals (especially breastfeeding), to the articulation of sounds, to their facial expression and to their sexual function. The vermilion is actually an erogenous zone, which not only generates sexual feelings when touched or stimulated, but also sends symbolic signals through the transmission of sensual and sexual information.

This article is protected by copyright. All rights reserved.

http://ift.tt/2fJ7OTt

Cognitive eloquence in neurosurgery: Insight from graph theoretical analysis of complex brain networks

Publication date: Available online 23 November 2016
Source:Medical Hypotheses
Author(s): Stefan Lang
The structure and function of the brain can be described by complex network models, and the topological properties of these models can be quantified by graph theoretical analysis. This has given insight into brain regions, known as hubs, which are critical for integrative functioning and information transfer, both fundamental aspects of cognition. In this manuscript a hypothesis is put forward for the concept of cognitive eloquence in neurosurgery; that is regions (cortical, subcortical and white matter) of the brain which may not necessarily have readily identifiable neurological function, but if injured may result in disproportionate cognitive morbidity. To this end, the effects of neurosurgical resection on cognition is reviewed and an overview of the role of complex network analysis in the understanding of brain structure and function is provided. The literature describing network, behavioural, and cognitive effects resulting from lesions to, and disconnections of, centralized hub regions will be emphasized as evidence for the espousal of the concept of cognitive eloquence.



http://ift.tt/2gjXVM6

Mitotic Nuclear Envelope Breakdown and Spindle Nucleation Are Controlled by Interphase Contacts between Centromeres and the Nuclear Envelope

Publication date: Available online 23 November 2016
Source:Developmental Cell
Author(s): Alfonso Fernández-Álvarez, Cécile Bez, Eileen T. O'Toole, Mary Morphew, Julia Promisel Cooper
Faithful genome propagation requires coordination between nuclear envelope (NE) breakdown, spindle formation, and chromosomal events. The conserved linker of nucleoskeleton and cytoskeleton (LINC) complex connects fission yeast centromeres and the centrosome, across the NE, during interphase. During meiosis, LINC connects the centrosome with telomeres rather than centromeres. We previously showed that loss of telomere-LINC contacts compromises meiotic spindle formation. Here, we define the precise events regulated by telomere-LINC contacts and address the analogous possibility that centromeres regulate mitotic spindle formation. We develop conditionally inactivated LINC complexes in which the conserved SUN-domain protein Sad1 remains stable but severs interphase centromere-LINC contacts. Strikingly, the loss of such contacts abolishes spindle formation. We pinpoint the defect to a failure in the partial NE breakdown required for centrosome insertion into the NE, a step analogous to mammalian NE breakdown. Thus, interphase chromosome-LINC contacts constitute a cell-cycle control device linking nucleoplasmic and cytoplasmic events.

Graphical abstract

Teaser

The role of interphase centromere-LINC contacts has been a longstanding intractable mystery. Fernández-Álvarez et al. generate a mutation that severs these centromere-LINC contacts, leading to failed nuclear envelope breakdown and, in turn, failed spindle assembly. Thus, centromere-LINC contacts couple chromosomal events with cytoplasmic events that propel the cell cycle.


http://ift.tt/2gEl27Z

The Red Light Receptor Phytochrome B Directly Enhances Substrate-E3 Ligase Interactions to Attenuate Ethylene Responses

Publication date: Available online 23 November 2016
Source:Developmental Cell
Author(s): Hui Shi, Xing Shen, Renlu Liu, Chang Xue, Ning Wei, Xing Wang Deng, Shangwei Zhong
Plants germinating under subterranean darkness assume skotomorphogenesis, a developmental program strengthened by ethylene in response to mechanical pressure of soil. Upon reaching the surface, light triggers a dramatic developmental transition termed de-etiolation that requires immediate termination of ethylene responses. Here, we report that light activation of photoreceptor phyB results in rapid degradation of EIN3, the master transcription factor in the ethylene signaling pathway. As a result, light rapidly and efficiently represses ethylene actions. Specifically, phyB directly interacts with EIN3 in a light-dependent manner and also physically associates with F box protein EBFs. The light-activated association of phyB, EIN3, and EBF1/EBF2 proteins stimulates robust EIN3 degradation by SCF^EBF1/EBF2 E3 ligases. We reveal that phyB manipulates substrate-E3 ligase interactions in a light-dependent manner, thus directly controlling the stability of EIN3. Our findings illustrate a mechanistic model of how plants transduce light information to immediately turn off ethylene signaling for de-etiolation initiation.

Graphical abstract

Teaser

Exposure of plants to sunshine upon emergence from the soil causes dramatic developmental changes, including inhibition of ethylene signaling. Shi, Shen et al. now show that the light-activated photoreceptor phyB contributes to this acute transition by mediating an interaction between the ethylene signaling regulator EIN3 and an E3 ubiquitin ligase.


http://ift.tt/2gEhToG

Fetal Valproate Syndrome with Limb Defects: An Indian Case Report

Epilepsy is a common disorder and exposure to antiepileptic drugs during pregnancy increases the risk of teratogenicity. Older AEDs such as valproate and phenobarbital are associated with a higher risk of major malformations in the fetus than newer AEDs like lamotrigine and levetiracetam. Exposure to valproic acid during first trimester can result in fetal valproate syndrome (FVS), comprising typical facial features, developmental delay, and a variety of malformations such as neural tube defects, cardiac and genitourinary malformations, and limb defects. We are presenting an Indian case of FVS with major limb defects.

http://ift.tt/2fVAqfk

Torsion of a Communicating Hydrocele Presented as Acute Scrotum: A Case Report and Literature Review

Torsion of a communicating hydrocele is extremely rare, and the cause is unclear. We report the case of a 3-year-old boy referred to us with acute scrotum. Operative findings revealed torsion of a communicating hydrocele with a 360-degree rotation of the distal end. We performed surgical excision of the necrotic cystic mass and high ligation of the peritoneal communication. A high index of suspicion is required for the correct diagnosis and treatment of this condition, which should be included among the causes of acute scrotum in childhood.

http://ift.tt/2fberSn

A Natural Language Processing-based Model to Automate MRI Brain Protocol Selection and Prioritization

Publication date: Available online 23 November 2016
Source:Academic Radiology
Author(s): Andrew D. Brown, Thomas R. Marotta
Rationale and ObjectivesIncorrect imaging protocol selection can contribute to increased healthcare cost and waste. To help healthcare providers improve the quality and safety of medical imaging services, we developed and evaluated three natural language processing (NLP) models to determine whether NLP techniques could be employed to aid in clinical decision support for protocoling and prioritization of magnetic resonance imaging (MRI) brain examinations.Materials and MethodsTo test the feasibility of using an NLP model to support clinical decision making for MRI brain examinations, we designed three different medical imaging prediction tasks, each with a unique outcome: selecting an examination protocol, evaluating the need for contrast administration, and determining priority. We created three models for each prediction task, each using a different classification algorithm—random forest, support vector machine, or k-nearest neighbor—to predict outcomes based on the narrative clinical indications and demographic data associated with 13,982 MRI brain examinations performed from January 1, 2013 to June 30, 2015. Test datasets were used to calculate the accuracy, sensitivity and specificity, predictive values, and the area under the curve.ResultsOur optimal results show an accuracy of 82.9%, 83.0%, and 88.2% for the protocol selection, contrast administration, and prioritization tasks, respectively, demonstrating that predictive algorithms can be used to aid in clinical decision support for examination protocoling.ConclusionsNLP models developed from the narrative clinical information provided by referring clinicians and demographic data are feasible methods to predict the protocol and priority of MRI brain examinations.



http://ift.tt/2gEcwGb

Enterocyte Purge and Rapid Recovery Is a Resilience Reaction of the Gut Epithelium to Pore-Forming Toxin Attack

Publication date: Available online 23 November 2016
Source:Cell Host & Microbe
Author(s): Kwang-Zin Lee, Matthieu Lestradet, Catherine Socha, Stefanie Schirmeier, Antonin Schmitz, Caroline Spenlé, Olivier Lefebvre, Céline Keime, Wennida M. Yamba, Richard Bou Aoun, Samuel Liegeois, Yannick Schwab, Patricia Simon-Assmann, Frédéric Dalle, Dominique Ferrandon
Besides digesting nutrients, the gut protects the host against invasion by pathogens. Enterocytes may be subjected to damage by both microbial and host defensive responses, causing their death. Here, we report a rapid epithelial response that alleviates infection stress and protects the enterocytes from the action of microbial virulence factors. Intestinal epithelia exposed to hemolysin, a pore-forming toxin secreted by Serratia marcescens, undergo an evolutionarily conserved process of thinning followed by the recovery of their initial thickness within a few hours. In response to hemolysin attack, Drosophila melanogaster enterocytes extrude most of their apical cytoplasm, including damaged organelles such as mitochondria, yet do not lyse. We identify two secreted peptides, the expression of which requires CyclinJ, that mediate the recovery phase in which enterocytes regain their original shape and volume. Epithelial thinning and recovery constitute a fast and efficient response to intestinal infections, with pore-forming toxins acting as alarm signals.

Graphical abstract

Teaser

Bacterial pore-forming toxins damage host cells. Lee, Lestradet et al. find that enterocytes exposed to these toxins extrude much of their apical cytoplasm, purging themselves of damaged components and bacteria. The thinned epithelium recovers its original shape within hours via a process that requires CyclinJ-dependent signaling between enterocytes.


http://ift.tt/2g7PbJl

Noncanonical Fungal Autophagy Inhibits Inflammation in Response to IFN-γ via DAPK1

Publication date: Available online 23 November 2016
Source:Cell Host & Microbe
Author(s): Vasilis Oikonomou, Silvia Moretti, Giorgia Renga, Claudia Galosi, Monica Borghi, Marilena Pariano, Matteo Puccetti, Carlo A. Palmerini, Lucia Amico, Alessandra Carotti, Lucia Prezioso, Angelica Spolzino, Andrea Finocchi, Paolo Rossi, Andrea Velardi, Franco Aversa, Valerio Napolioni, Luigina Romani
Defects in a form of noncanonical autophagy, known as LC3-associated phagocytosis (LAP), lead to increased inflammatory pathology during fungal infection. Although LAP contributes to fungal degradation, the molecular mechanisms underlying LAP-mediated modulation of inflammation are unknown. We describe a mechanism by which inflammation is regulated during LAP through the death-associated protein kinase 1 (DAPK1). The ATF6/C/EBP-β/DAPK1 axis activated by IFN-γ not only mediates LAP to Aspergillus fumigatus but also concomitantly inhibits Nod-like receptor protein 3 (NLRP3) activation and restrains pathogenic inflammation. In mouse models and patient samples of chronic granulomatous disease, which exhibit defective autophagy and increased inflammasome activity, IFN-γ restores reduced DAPK1 activity and dampens fungal growth. Additionally, in a cohort of hematopoietic stem cell-transplanted patients, a genetic DAPK1 deficiency is associated with increased inflammation and heightened aspergillosis susceptibility. Thus, DAPK1 is a potential drugable player in regulating the inflammatory response during fungal clearance initiated by IFN-γ.

Graphical abstract

Teaser

Defects in noncanonical autophagy increase inflammatory pathology during fungal infection. Oikonomou et al. find that the kinase DAPK1 induced by IFN-γ promotes both noncanonical autophagy and NLRP3 inflammasome proteasomal degradation in response to Aspergillus fumigatus. By restoring DAPK1, IFN-γ may assist fungal clearance while restraining inflammation in mice and humans.


http://ift.tt/2g7Roos

Detection the Mycoplasma pneumonia in synovial fluid of children with negative culture arthritis: A cross sectional study in Tehran, Iran.

Related Articles

Detection the Mycoplasma pneumonia in synovial fluid of children with negative culture arthritis: A cross sectional study in Tehran, Iran.

Infect Disord Drug Targets. 2016 Nov 21;

Authors: Noorbakhsh S, Shokrollahi MR, Taj FE, Zarabi V, Tabatabaei A

Abstract
BACKGROUND: arthritis could be caused by different etiologies ranging from rheumatologic diseases to infectious conditions. Therefore, early diagnosis of etiology and treatment is important. The purpose of this study was to determine the the M.pneumonia in synovial fluid of children with arthritis by 2 methods (serology and qualitative PCR). Methods & materials: this trial was carried out as a cross sectional study in pediatric and orthopedic ward of Rasoul-e Akram hospital in Tehran, Iran. Seventy three patients (39 boys and 34 girls) with mean age of 11± 3.9 y/o were selected by continuous sampling After synovial fluid aspiration, all samples were evaluated by direct smear, culture and latex tests. Septic arthritis diagnosed in 18 patients( 25.4%). PCR and serology tests for M.pneumonia (specific IgM and IgG) were performed in 50 cases with negative culture.The results were compared by Independent T test.
RESULTS: According to physical examination and culture 18 patients (25.4%) was diagnosed with septic arthritis,50 patients with non-septic arthritis studied. Seventeen patients (33.3%) were IgG positive and 2 patients (4%) were IgM positive. Only 2 patients (4%) showed weakly positive results on PCR which did not demonstrate any association with serology.
CONCLUSION: Positive PCR in SF (4%) definitely indicates active infection and M.pneumonia induced arthiritis..Although positive SF -IgM (4%) suggests either a current or a very recent M.pneumonia infection but not for SF-IgG ( previous infection ). So, we can summate that PCR, though being the best and most accurate method to detect M.pneumonia infection arthritis, is not considered a practical one due to costs and availability issues. Hence it can be safely replaced by serology test ( Specific IgM ) in SF for diagnosis of M. pneumonia arthritis, is available in most hospitals and is much more economic compared to PCR.

PMID: 27875955 [PubMed - as supplied by publisher]

http://ift.tt/2gkYo3Z

Osseointegrated implants into a variety of composite free flaps: A comparative analysis.

Osseointegrated implants into a variety of composite free flaps: A comparative analysis.

Head Neck. 2016 Nov 23;:

Authors: Burgess M, Leung M, Chellapah A, Clark JR, Batstone MD

Abstract
BACKGROUND: Significant oral function is often lost after surgical therapy for head and neck cancer. The use of osseointegrated implants for reconstruction in patients with head and neck surgery has shown to significantly improve the quality of life for these patients. Variable success rates range from 99% to 70%.
METHODS: A retrospective audit of patient records was performed looking at cumulative survival of implants. Inclusion criteria were patients who were treated at 1 of 2 designated Australian Head and Neck Units and received oral osseointegrated implants.
RESULTS: Fifty-nine patients were included for analysis. One hundred ninety-nine implants were placed into vascularized bone grafts (VBGs). There were 11 implant failures with an overall success rate of 94.5%. There was 1 significant adverse outcome with a pathological fracture of a flap after implant placement. Implant success in scapula and iliac crest flaps was comparable to fibula flaps.
CONCLUSION: Implants placed into VBGs have a reasonable success rate in well-selected patients. © 2016 Wiley Periodicals, Inc. Head Neck, 2016.

PMID: 27880030 [PubMed - as supplied by publisher]

http://ift.tt/2gjeyqZ

Inhibition of epithelial-mesenchymal transition by cetuximab via the EGFR-GEP100-Arf6-AMAP1 pathway in head and neck cancer.

Inhibition of epithelial-mesenchymal transition by cetuximab via the EGFR-GEP100-Arf6-AMAP1 pathway in head and neck cancer.

Head Neck. 2016 Nov 23;:

Authors: Matsumoto Y, Sakurai H, Kogashiwa Y, Kimura T, Matsumoto Y, Shionome T, Asano M, Saito K, Kohno N

Abstract
BACKGROUND: Despite improved survival by the addition of a monoclonal antibody against epidermal growth factor receptor (EGFR), cetuximab, to chemotherapy or radiotherapy for squamous cell carcinoma of the head and neck (SCCHN), cetuximab by itself is not a potent antiproliferative agent against SCCHN. We aimed to elucidate working mechanism of cetuximab in SCCHN.
METHODS: The effect of cetuximab on the proliferation, migration, invasion, epithelial-mesenchymal transition, and signaling events downstream of the EGFR were investigated in 4 SCCHN cell lines. The in vivo efficacy of cetuximab was evaluated in a xenotransplant model.
RESULTS: Cetuximab inhibited migration, invasion, epithelial-mesenchymal transition, and lymph node metastasis by suppressing EGFR-GEP100-Arf6-AMAP1 pathway, but it did not inhibit cancer cell proliferation.
CONCLUSION: The improved survival by the addition of cetuximab is likely to be attributable to the antiepithelial-mesenchymal transition action of cetuximab via inhibiting EGFR-GEP100-Arf6-AMAP1 pathway. © 2016 Wiley Periodicals, Inc. Head Neck, 2016.

PMID: 27880014 [PubMed - as supplied by publisher]

http://ift.tt/2fuAXEa

Head and neck surgical subspecialty training in Africa: Sustainable models to improve cancer care in developing countries.

Head and neck surgical subspecialty training in Africa: Sustainable models to improve cancer care in developing countries.

Head Neck. 2016 Nov 23;:

Authors: Fagan JJ, Zafereo M, Aswani J, Netterville JL, Koch W

Abstract
BACKGROUND: Cancer poses a health crisis in the developing world where surgery is the mainstay of treatment for head and neck cancers. However, a shortage of surgeons with appropriate skills exists. How do we train head and neck surgeons in developing countries and avoid a brain drain? The ideal model provides appropriate affordable training leading to establishment of head and neck cancer centers that teach and train others.
METHODS: Different head and neck surgery training models are presented based on the personal experiences of the authors. Surgical exposure of head and neck fellows in Cape Town and (potentially) in Nairobi is benchmarked against programs in the United States.
RESULTS: Surgical exposure in Cape Town is equivalent to that in the United States, but more appropriate to a developing world setting.
CONCLUSION: Training can be achieved in a number of ways, which may be complimentary. Fellowship training is possible in developing countries. © 2016 Wiley Periodicals, Inc. Head Neck, 2016.

PMID: 27880008 [PubMed - as supplied by publisher]

http://ift.tt/2g7iAnd