Status and progress of treatment methods for root caries in the last decade: a literature review

Abstract

The aim of this literature review is to explore the treatment methods for root caries in laboratory and clinical research in the last decade. A systematic search of publications in PubMed and Web of Science databases was performed. The time-span was limited to the last 10 years and English language. Further retrieval was conducted using the search terms of specific therapies or treatments. Titles and abstracts of identified publications were screened. Reviews; case reports; conference abstracts; letters to editor; dissertation and theses; non-English articles; epidemiological studies, diagnostic methods or decision-making process for root caries treatment without assessment of its efficacy; deep carious lesions with inflamed pulp and require pulp capping or endodontic treatment and research on root cementum were excluded. The remaining papers were retrieved with full-texts. Cross-referencing was performed to identify other relevant articles in addition to manual screening of the bibliographies of the remaining papers. Eighty-two articles were included in this systematic review and full texts were retrieved. Types of studies included laboratory studies and clinical trials. Therapeutic approaches for root caries without risk of pulp exposure can be categorised into non-invasive and restorative treatment. Non-invasive treatments which targeted different causative factors of root caries have been developed in the last decade. Accordingly, several artificial caries model systems have been proposed for the study of root caries in the laboratory. Carious tissue excavation techniques and restorative materials and procedures have been modified to improve the prognosis of invasive treatment. It is of importance to determine the most appropriate therapy for root caries and further clinical trials are needed to draw firm conclusions concerning the efficacy and consistency of the various treatment methods proposed.

This article is protected by copyright. All rights reserved.

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Effect of anchovy by-product protein coating incorporated with thyme essential oil on the shelf life of anchovy ( Engraulis encrasicolus L.) fillets

Abstract

The effects of anchovy by-product protein coatings incorporated with thyme essential oil (TEO) on the shelf life of anchovy (Engraulis encrasicolus L.) fillets stored at 4 ± 1 °C were investigated. We grouped fillets in three categories: untreated fillets, fillets treated in coating solution alone, and fillets treated in coating solution containing 1.5% TEO and analyzed on 0, 3, 6, and 9 days of storage. It was observed that the total volatile basic nitrogen (TVB-N) and pH of all the fillet groups increased under cold storage conditions; however, this increase was much slow in both the coated anchovy fillets. Both coating applications slowed down the lipid oxidation but the coating containing TEO exhibited better effect than coating alone. The coating application alone or with essential oil had limited effect on microbial growth but positively affected the sensory quality. These results revealed that anchovy by-product protein coating mixed with TEO may prolong anchovy fillets' shelf life stored under cold condition.

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Comparative characteristics of rice wine fermentations using Monascus koji and rice nuruk

Abstract

Wine fermentations using rice media containing either Monascus koji or rice nuruk were performed and fermentative characteristics based on the koji type were investigated. Cultivations were performed in a 20 °C room in a 20 L bottle with the rice media that included Monascus rice koji at both 20 and 30%, or rice nuruk at 20%. After 22 days of cultivation, the ethanol yield reached 14.2–14.6% (v/v) for M. koji and 16.5% (v/v) for rice nuruk. This lower yield with use of M. koji was thought to be due to rapid cell concentration decreases in the later stage. Total amounts of organic acids and volatile compounds in fermentations using M. koji were 166–172 and 1779–1874 mg/L, respectively, being 8.7–12.9% and 46.3–54.1% higher than with use of rice nuruk. With M. koji, a high quality rice wine was produced with high levels of volatile compounds and monacolin K.

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Antioxidant and hepatoprotective activity of kaempferol 3- O -β- d - (2,6-di- O -α- l -rhamnopyranosyl)galactopyronoside against carbon tetrachloride-induced liver injury in mice

Abstract

This study aims to investigate the antioxidant and hepatoprotective effects of kaempferol 3-O-β-d- (2,6-di-O-α-l-rhamnopyranosyl)galactopyronoside (KG) isolated from unripe soybean leaves. Carbon tetrachloride (CCl₄)-induced hepatotoxic ddY mice were used in the study. The mice were divided into three groups, namely the control group, the CCl₄ group (CCl₄, CCl₄ injected), and the KG group (KG, CCl₄ injected with KG administration). Hepatic injury markers of serum and liver were analyzed. The results show that serum ALT, AST activities, hepatic glutathione, superoxide dismutase, catalase, and glutathione peroxidase activities were normalized in mice pretreated with KG. Furthermore, the liver thiobarbituric acid reactive substances levels were found to be improved by pretreatment with KG, indicating that KG is available to alleviate liver injury, this may be due to its antioxidant properties. This study suggests that unripe soy leaves could be used as functional food materials.

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Effects of aronia extract on lifespan and age-related oxidative stress in Drosophila melanogaster

Abstract

The effects of aronia extract (AE) supplementation on the lifespan and age-associated oxidative stress was investigated in the fruit fly Drosophila melanogaster. Supplementation with 2.5 mg/mL of AE (AE 2.5) extended the mean lifespan in D. melanogaster by 18%. AE supplementation significantly improved locomotor activity at both 10 and 40 days. In 40-days-old flies, reactive oxygen species production was significantly lower and accumulation of the lipid oxidation product malondialdehyde had markedly decreased by 49.3% in the AE 2.5 group. The extended longevity and improved locomotion in the AE 2.5 group were probably because of increases in the level of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) and expression of stress resistance genes (Hsp68, l(2)efl, and Jafrac1). Present study provides the evidence that dietary supplementation with AE extended lifespan and ameliorated age-related oxidative damages in D. melanogaster.

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Masthead

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Table of contents

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Screening is not a viable tool for detecting cancer in India: Dr. Sachin Almel - ETHealthworld.com

Screening is not a viable tool for detecting cancer in India: Dr. Sachin Almel ETHealthworld.com Likewise, the highest number of men suffering from prostate cancer and the incidence is increasing in our country. The difference is that cancer of the prostate is not the leading cancer in our country. In our country, we still have cancers of the ... and more »

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An Evaluation of the Evidence Relating to Physical Inactivity, Sedentary Behavior, and Cancer Incidence and Mortality

Abstract

Purpose of Review

This review provides an up-to-date overview of the evidence relating to physical inactivity, sedentary behavior, and cancer, both in terms of risk and mortality. A summary of the postulated biological mechanisms underpinning these associations is also presented.

Recent Findings

Epidemiologic evidence suggests that physical activity is inversely associated with cancers of the esophagus (adenocarcinoma), liver, lung, kidney, gastric cardia, endometrium, colon, rectum, head and neck, bladder, and breast, as well as myeloid leukemia and myeloma. Physical activity prior to a cancer diagnosis is related to decreased risk of all-cancer mortality, and pre- and postdiagnosis physical activities are both related to lower risk of breast cancer-specific and colorectal cancer-specific mortality. Prolonged sedentary behavior is associated with an increased risk of colorectal, endometrial, lung, and breast cancer. Pre-diagnosis sedentary behavior is associated with increased risk of all-cancer mortality and colorectal cancer-specific mortality. Postulated biological mechanisms underpinning the associations of physical inactivity and sedentary behavior with cancer include body composition (most evidence relates to adiposity), sex hormones, metabolic hormones, and chronic inflammation.

Summary

Relatively small behavioral changes at a population level would likely decrease cancer-related burden of disease and associated health expenditure. At the individual level, the optimal frequency, duration, and intensity of physical activity or sedentary behavior required for significant risk reduction or increase remain unclear. Future research should integrate objective activity monitoring with multiple assessment time points into large cohort studies for improved assessment of physical activity and sedentary behavior. Such data will help inform more robust and detailed recommendations for cancer control.

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The core planar cell polarity gene, Vangl2, maintains apical-basal organisation of the corneal epithelium

Abstract

The role of the core planar cell polarity (PCP) pathway protein, Vangl2, was investigated in the corneal epithelium of the mammalian eye, a paradigm anatomical model of planar cell migration. The gene was conditionally knocked out in vivo and knocked down by siRNA, followed by immunohistochemical, behavioural and morphological analysis of corneal epithelial cells. The primary defects observed in vivo were of apical-basal organisation of the corneal epithelium, with abnormal stratification throughout life, mislocalisation of the cell membrane protein, Scribble, to the basal side of cells, and partial loss of the epithelial basement membrane. Planar defects in migration after wounding and in the presence of an applied electric field were noted. However, knockdown of Vangl2 also retarded cell migration in individual cells that had no contact with their neighbours, which precluded a classic PCP mechanism. It is concluded that some of the planar polarity phenotypes in PCP mutants may arise from disruption of apical-basal polarity.

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Association between serum osteocalcin and body mass index: a systematic review and meta-analysis

Abstract

Purpose

Osteocalcin is considered as a bone-derived hormone affecting on the body fat distribution and body mass index. Several cross-sectional studies have investigated the association between serum osteocalcin and body mass index. The aim of this study was to summarize the evidence on the relationship between serum osteocalcin and body mass index.

Methods

We conducted a complete search up to November 2016 in PubMed and SCOPUS and reviewed reference list of all relevant articles and reviews. The DerSimonian–Laird method were used to pool effect sizes of eligible studies. The potential sources of heterogeneity were assessed using the standard χ ² test.To find possible the sources of between-study heterogeneity, we carried out subgroup analyses based on sex, and type of study population.

Results

There was a significant inverse association in the overall result of this study between serum osteocalcin levels and BMI(r = −0.161; 95% CI: −0.197, −0.124, p < 0.000). In the subgroup analysis to find the sources of significant heterogeneity between-study, we observed that the type of the study population may be the source of between-study heterogeneity and the most correlation was seen in metabolic syndrome studies (r = −0.265; p = 0.000).

Conclusion

Findings from the available data indicated an overall significant inverse association between serum osteocalcin and body mass index. Further studies based on the type of study population are needed to better clarify these associations.

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Effect of application sequence of fluoride and CPP-ACP on remineralization of white spot lesions in primary teeth: An in-vitro study

Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Ola B. Al-Batayneh, Reem A. Jbarat, Susan N. Al-Khateeb
ObjectiveTo explore how application sequence of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and fluoride influences remineralization of enamel white spot lesions (WSL) in primary teeth.DesignIn this in-vitro study, artificial WSLs were created in 130 primary teeth. Teeth were divided into 4 groups (n=27) and a control group (n=22) and exposed to one of the following remineralization regimens for 10 weeks: Group-1; 500ppm fluoride dentifrice; Group-2; 10% w/v CPP-ACP; Group-3; fluoride applied first, then CPP-ACP; Group-4; CPP-ACP applied first, then fluoride, and Group-5 was control. All groups were kept in a remineralizing solution. Mineral changes (ΔF) were quantified weekly using quantitative light-induced fluorescence. Statistical analysis was done using Statistical Package for the Social Sciences (SPSS version 20.0).ResultsRemineralization occurred in all groups to different degrees; changes from baseline were significant in groups 1–4 (P≤0.05). Group-4 showed the earliest significant remineralization (after 2 weeks) among groups, (P<0.001). Group-4 showed maximum changes in ΔF among groups; however, only differences with Groups 1 and 5 were significant (P<0.05 and P<0.01, respectively). Group-3 showed better remineralization than Groups 1, 2 and 5; however, the difference was only significant with Group-5 (P<0.001). There were no significant differences between Group 1and 2, however, only Group 2 showed better remineralization than Group 5, (P<0.01).ConclusionCombined treatment with CPP-ACP followed by fluoride exhibited the best remineralization of white spot lesions in primary teeth in this study. Combined treatment with fluoride followed by CPP-ACP showed a tendency towards better remineralization than fluoride or CPP-ACP alone.



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Amelogenin induces M2 macrophage polarisation via PGE2/cAMP signalling pathway

Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Kensuke Yamamichi, Takao Fukuda, Terukazu Sanui, Kyosuke Toyoda, Urara Tanaka, Yuki Nakao, Karen Yotsumoto, Hiroaki Yamato, Takaharu Taketomi, Takeshi Uchiumi, Fusanori Nishimura
ObjectivesAmelogenin, the major component of the enamel matrix derivative (EMD), has been suggested as a bioactive candidate for periodontal regeneration. Apart from producing a regenerative effect on periodontal tissues, amelogenin has also been reported to have an anti-inflammatory effect. However, the precise molecular mechanisms underlying these effects remain unclear. In the present study, we examined the immunomodulatory effects of amelogenin on macrophages.DesignHuman phorbol 12-myristate 13-acetate (PMA)-differentiated U937 macrophages and CD14+ peripheral blood-derived monocytes (PBMC)-derived macrophages were stimulated with recombinant amelogenin (rM180). After performing a detailed microarray analysis, the effects of rM180 on macrophage phenotype and signal transduction pathways were evaluated by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, confocal microscopy and flow cytometry.ResultsThe microarray analysis demonstrated that rM180 increased the expression of anti-inflammatory genes in lipopolysaccharide (LPS)-challenged macrophages after 24h, while it temporarily up-regulated inflammatory responses at 4h. rM180 significantly enhanced the expression of M2 macrophage markers (CD163 and CD206). rM180-induced M2 macrophage polarisation was associated with morphological changes as well as vascular endothelial growth factor (VEGF) production. rM180 enhanced prostaglandin E2 (PGE2) expression, and the activation of the cAMP/cAMP-responsive element binding (CREB) signaling pathway was involved in amelogenin-induced M2 macrophage polarisation. Blocking of PGE2 signaling by indomethacin specifically abrogated rM180 with or without LPS-induced M2 shift in PBMC-derived macrophages.ConclusionAmelogenin could reprogram macrophages into the anti-inflammatory M2 phenotype. It could therefore contribute to the early resolution of inflammation in periodontal lesions and provide a suitable environment for remodeling-periodontal tissues.



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Treatment of Hansen’s Disease (Leprosy)

Abstract

Purpose of review

Because leprosy (Hansen's Disease, HD) is rare, details of treatment of this infection and of its complications are not familiar to many physicians. The basic treatment of Mycobacterium leprae infection, prevention of associated disabilities, and management of its complications have therefore been reviewed.

Recent findings

Multi-drug therapy (MDT) for HD is highly effective, but lengthy (12–24 months). Drug resistance and relapse of infection are rare. New anti-mycobacterial agents are being tested to try to reduce the duration of treatment. The major challenge in HD is the management of immunologically mediated complications called reactions, and of the neuritis and neuropathy that may result. Reactions are often perceived—incorrectly—as "treatment failure," relapse, or an adverse drug reaction. They occur before, during, or after completion of MDT, triggered by M. leprae antigens. Reactions are medical emergencies because they can precipitate severe, rapid peripheral nerve injury.

Summary

Anti-mycobacterial treatment of HD is highly successful; shortening the duration of treatment is a major goal. Reactions require prompt treatment with moderate to high doses of corticosteroids. One type of reaction (ENL) responds to thalidomide, but this is expensive and can induce severe birth defects. Other immunosuppressive agents are being studied for their benefit in managing reactions. Basic and clinical research are focused upon developing short-duration drug regimens, improving treatment of reactions, and preventing or limiting nerve injury.

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Hiccups

Hiccups: A hiccup is an extraordinary type of respiratory movement involving a sudden inspiration (intake of air) due to an involuntary contraction of the diaphragm accompanied by closure of the glottis (the vocal apparatus of the larynx).

The abrupt inspiration is the result of a sudden contraction of the diaphragm. Closure of the glottis then halts the incoming air. The column of air strikes the closed glottis to produce the characteristic sound: a hiccup.

Hiccups are often rhythmic. They are usually just a minor nuisance, but prolonged hiccups can become a major medical problem.

The word "hiccup" was in use by 1530. It is an instance of onomatopoeia, the imitation of natural sounds by words. Alternative forms of "hiccups" include "hiccough" and "hickup."

MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
We Bring Doctors' Knowledge To You

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Cancer survivor gives back - liherald.com

liherald.com

Cancer survivor gives back liherald.com For a decade and a half, thyroid cancer survivor Abby Melendez, of Baldwin, has run a support group for people with the disease. Since the group began, more than 100 people have come to through it, seeking the understanding, consolation and validation ...

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RNA-transfection of γ/δ T cells with a chimeric antigen receptor or an α/β T-cell receptor: a safer alternative to genetically engineered α/β T cells for the immunotherapy of melanoma

Adoptive T-cell therapy relying on conventional T cells transduced with T-cell receptors (TCRs) or chimeric antigen receptors (CARs) has caused substantial tumor regression in several clinical trials. However,...

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MicroRNA-29a regulates lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophages through the Akt1/ NF-κB pathway

Publication date: Available online 12 August 2017
Source:Experimental Cell Research
Author(s): Bufu Tang, Xingchen Li, Yanling Ren, Jing Wang, Di Xu, Yiru Hang, Tingting Zhou, Feng li, Ling Wang
Akt activation in macrophages enhances lipopolysaccharide (LPS)-induced inflammatory responses through upregulation of the NF-κB signal pathway. Akt phosphorylation via microRNA (miR) caused the downregulation of Akt1. Here, we evaluated the role of miR-29a in LPS-triggered inflammatory responses. LPS stimulation of primary macrophages and RAW264.7 cells gradually increased the levels of miR-29a and was dependent on the LPS concentration. Overexpression of miR-29a in macrophages enhanced the expression of proinflammatory cytokines including IL-1β and IL-6, but not TNF-α. Conversely, knockdown of miR-29a diminished cytokine expression. Bioinformatics analyses indicated that Akt1 was a potential target of miR-29a through its interaction with the CDS region of Akt1. The miR-29a also enhanced LPS-induced NF-κB signaling through increased NF-κB transcriptional activity and phosphorylation of p65, and through binding to Akt1. Moreover, Akt1 silencing promoted the LPS-induced expression of IL-1β and IL-6, and upregulated the NF-κB pathway. Taken together, our results suggested that miR-29a participates in the regulation of inflammatory responses in LPS-stimulated macrophages by promoting NF-κB activation through targeting Akt1.



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MRTF-A-miR-206-WDR1 form feedback loop to regulate breast cancer cell migration

Publication date: Available online 17 August 2017
Source:Experimental Cell Research
Author(s): Yuan Xiang, Xing-Hua Liao, Ao Yao, Huan Qin, Li-Juan Fan, Jia-Peng Li, Peng Hu, Hui Li, Wei Guo, Jun-Yan Li, Chao-Jiang Gu, Le-Yuan Bao, Tong-Cun Zhang
Breast cancer is the leading cause of cancer death in women worldwide which is closely related to metastasis. Our previous study has shown that MRTF-A promote the migration of MDA-MB-231 cells and WDR1 promotes breast cancer cell migration. But the exact molecular mechanism on metastasis is still not fully understood, we now report that WDR1 enhanced the effect of MRTF-A induced-MDA-MB-231 cell migration by promoting the expression of the EMT markers and migration markers via RhoA-MRTF-A signaling pathway. Importantly, WDR1 promoted the nuclear importion of MRTF-A by affecting the expression of nuclear transport protein importin. But WDR1 did not affect the expression of MRTF-A. Interestingly, MRTF-A promoted the expression of miR-206 via its promoter CArG box but miR-206 inhibits the migration of breast cancer cells through suppressing the expression of WDR1 and MRTF-A via targeted their 3'UTR. Our data thus provide important and novel insights into MRTF-A-miR-206-WDR1 form feedback loop to regulate breast cancer cell migration.



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Rheological properties of washed and unwashed tilapia ( Oreochromis mossambicus ) fish meat: effect of sucrose and sorbitol

Abstract

In the present study, the dynamic viscoelastic behavior (DVB) and flow behavior of fresh tilapia (Oreochromis mossambicus) meat containing cryoprotectants were evaluated with and without water washing. The DVB profile of washed meat with 4% sucrose and sorbitol indicated the maximum structure buildup reaction up to 56.8 °C; thereafter, hydrophobic interactions leading to decreased gelation were suppressed. In both the samples, there was no clear indication of the sol–gel transition temperature. In flow-profile measurements, the presence of cryoprotectants gave rise to the minimum thixotropic area, indicating a low level of impairment in structure. The shear-stress sweep of water-washed tilapia proteins added with cryoprotectants did not reveal significant changes at 28 and 40 °C. In texture-profile analysis, the hardness values were lower in fresh meat than cooked meat. The findings of this study will be helpful in the formulation and design of various mince-based products and in determining the appropriate use of cryoprotectants and water washing in the processing of minced meat.

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Optimization of bayberry juice spray drying process using response surface methodology

Abstract

In this study, thirteen different runs according to the central composite design-response surface methodology were used to optimize the quality parameters of spray-dried bayberry juice powder. The independent variables were different levels of inlet air temperature (145.8–174.1 °C) and maltodextrin concentration (22.9–37.0%). The responses were process yield, moisture content, hygroscopicity, glass transition temperature (Tg), total color difference (ΔE), redness, retention of phenolics and anthocyanins, and antioxidant capacity. The optimum operation conditions for the highest Tg, redness, anthocyanins retention and antioxidant capacity with the lowest ΔE and hygroscopicity were obtained at inlet drying temperature of 150 °C and maltodextrin concentration of 31%. This study revealed that by applying these optimal conditions, bayberry juice powder with a 74.16% yield, 3.15% moisture content, 10.25% hygroscopicity, 41.15 °C Tg, 24.74 ΔE, 27.45 Hunter a redness, 89.55% anthocyanins retention, 77.71% phenolics retention, and 30.19 mmol Trolox equivalents/g antioxidant capacity was produced.

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Composite Scaffolds of Mineralized Natural Extracellular Matrix on True Bone Ceramic Induce Bone Regeneration Through Smad1/5/8 and ERK1/2 Pathways

Tissue Engineering Part A , Vol. 0, No. 0.


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Early Immunomodulatory Effects of Implanted Human Perivascular Stromal Cells During Bone Formation

Tissue Engineering Part A , Vol. 0, No. 0.


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CXCR4 blockade with AMD3100 enhances Taxol chemotherapy to limit ovarian cancer cell growth.

The standard of care for ovarian cancer includes initial treatment with chemotherapy. Despite initial efficacy, over 70% of patients develop recurrence; thus, there is a need to identify novel approaches that can improve therapeutic outcomes. We evaluated AMD3100 (Plerixafor), an FDA-approved CXCR4 inhibitor, as a potential adjunctive therapy for low-dose Taxol (Paclitaxel) by assessing the impact on in-vitro ovarian cancer cell proliferation. Proliferation was a measure for both human TOV-112D and murine ID8 ovarian cancer cells incubated with AMD3100 and Taxol, either individually or in combination. Impact of treatment was first determined for the simultaneous administration of AMD3100 and Taxol. We next assessed a sequential application of AMD3100 pretreatment, followed by AMD3100, Taxol, or a combination to test for sensitization to Taxol. In addition, we measured the impact of AMD3100 and Taxol, individually and in combination, on colony formation, an in-vitro model assay of tumor growth. Expression data, as measured by flow cytometry, show that both ID8 and TOV-112D cells are positive for CXCR4, CXCR7, and CXCL12. Combination treatment with AMD3100 (

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PA-MSHA induces apoptosis and suppresses metastasis by tumor associated macrophages in bladder cancer cells

The aim of the present study was to investigate effects of Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA) on the inhibition of the proliferation of bladder cancer cell lines and to further defin...

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Necrotic mucosal CD30-positive ulcer on the oral mucosa: a self-healing lymphoma

Publication date: Available online 12 August 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): A. Molinari, I.S. Prabhu




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Trapezoidal mandibular osteotomy for augmentation of the airway in sleep apnoea

Publication date: Available online 14 August 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): J.T. Carneiro, E.L. de Souza Cruz, A.K. da Silva Tabosa, P.H. de Moraes




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Postoperative complications after head and neck operations that require free tissue transfer- prevalence, morbidity, and cost

Publication date: Available online 12 August 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): J. McMahon, T.P.B. Handley, A. Bobinskas, M. Elsapagh, H.S. Anwar, P.V. Ricciardo, A. McLaren, R. Davis, N. Syyed, C. MacIver, C. Wales, W.S. Hislop, E. Thomson, S. Thomson, K. Fitzpatrick, A. Rae, R. Campbell
To understand and reduce the impact of postoperative complications, we studied 568 patients who had had operations over 72 months in our hospital. Multivariate analysis indicated that factors indicative of coexisting conditions (including activated systemic inflammation) and the complexity of the operation are primary determinants of postoperative complications. The enhanced recovery after surgery (ERAS) care pathway did not have an effect on their occurrence or severity. Systematic study of patients' toleration of major head and neck operations is required, as optimal perioperative care pathways remain elusive.



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Successful treatment of metastatic alveolar rhabdomyosarcoma with MGMT gene promoter methylation by temozolomide-based combination chemotherapy

Abstract

A 3-year-old male presented with a large retroperitoneal mass and multiple metastases. Biopsy results suggested alveolar rhabdomyosarcoma bearing a methylated O6-methylguanine-DNA methyltransferase (MGMT) gene promoter. Serum microRNA-206 levels were elevated and remained high after three cycles of vincristine, dactinomycin, and cyclophosphamide (VAC). Replacement of vincristine, irinotecan, and temozolomide (VIT) for VAC induced a marked tumor reduction and normalization of the miR-206 levels. The patient completed 14 cycles of VIT with local radiotherapy and has been in remission for 31 months. Temozolomide could be effective for tumors with a methylated MGMT gene promoter. Individualized therapy is warranted for such patients.

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History of parvovirus B19 infection is associated with silent cerebral infarcts

Abstract

Background

The relationship between silent cerebral infarcts (SCIs) and history of parvovirus B19 (B19V) has not been systematically evaluated. As an ancillary study from the Silent Cerebral Infarct Trial (SIT) (NCT00072761), we tested the hypothesis that a history of B19V infection is associated with an increased prevalence of SCIs in children with sickle cell anemia.

Procedure

We used a retrospective cross-sectional cohort study design; each participant underwent a brain magnetic resonance imaging (MRI) scan and medical record review for prior B19V infection (n = 958).

Results

SCI was present in 30% (287 of 958) of participants and 17% (165 of 958) had a history of B19V infection. Based on prior evidence that low baseline hemoglobin (Hgb) levels are associated with increased odds of SCI, Hgb levels were divided into tertiles (<7.6 g/dl, ≥7.6–≤8.5 g/dl, ≥8.6 g/dl) and multivariable analysis was used to determine the relationship between the joint effect of prior B19V infection, Hgb levels, and SCI. Prior B19V infection and the lowest Hgb tertile were associated with increased risk of SCI (odds ratio [OR] 2.12; 95% CI, 1.17–3.84; P = 0.013); no prior B19V infection and the highest Hgb tertile were associated with a decreased risk (OR 0.56; 95% CI, 0.38–0.84; P = 0.004).

Conclusions

Efforts to decrease the incidence of B19V infection, such as the development of a B19V vaccine, may decrease SCI prevalence.

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Lack of mortality in 22 children with sickle cell anemia and severe malarial anemia

Abstract

Retrospective studies suggest that there is high mortality in children with sickle cell anemia (SCA) and severe malaria. We assessed mortality in Ugandan children with severe malarial anemia (SMA, n = 232) or cerebral malaria (CM, n = 267) by sickle cell hemoglobin genotype. Admission and 2-year follow-up mortality did not differ among children with SMA who had homozygous form of sickle cell hemoglobin (HbSS) versus normal form of adult hemoglobin (admission, 0/22, 0%, vs. 1/208, 0.5%; follow-up, 1/22, 4.5%; 7/207, 3.4%, respectively; all P > 0.6). The single child with CM and HbSS survived. The study findings highlight the need for large prospective studies of malaria-related mortality in children with SCA.

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Comment on: Acquired monosomy 7 myelodysplastic syndrome in a child with clinical features of dyskeratosis congenita and IMAGe association

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Determinants of thermostability in the cytochrome P450 fold

Publication date: Available online 17 August 2017
Source:Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
Author(s): Kurt L. Harris, Raine E.S. Thomson, Silja J. Strohmaier, Yosephine Gumulya, Elizabeth M.J. Gillam
Cytochromes P450 are found throughout the biosphere in a wide range of environments, serving a multitude of physiological functions. The ubiquity of the P450 fold suggests that it has been co-opted by evolution many times, and likely presents a useful compromise between structural stability and conformational flexibility. The diversity of substrates metabolized and reactions catalyzed by P450s makes them attractive starting materials for use as biocatalysts of commercially useful reactions. However, process conditions impose different requirements on enzymes to those in which they have evolved naturally. Most natural environments are relatively mild, and therefore most P450s have not been selected in Nature for the ability to withstand temperatures above ~40°C, yet industrial processes frequently require extended incubations at much higher temperatures. Thus, there has been considerable interest and effort invested in finding or engineering thermostable P450 systems. Numerous P450s have now been identified in thermophilic organisms and analysis of their structures provides information as to mechanisms by which the P450 fold can be stabilized. In addition, protein engineering, particularly by directed or artificial evolution, has revealed mutations that serve to stabilize particular mesophilic enzymes of interest. Here we review the current understanding of thermostability as it applies to the P450 fold, gleaned from the analysis of P450s characterized from thermophilic organisms and the parallel engineering of mesophilic forms for greater thermostability. We then present a perspective on how this information might be used to design stable P450 enzymes for industrial application.



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In vitro characterization of CYP102G4 from Streptomyces cattleya: A self-sufficient P450 naturally producing indigo

Publication date: Available online 15 August 2017
Source:Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
Author(s): Joonwon Kim, Pyung-gang Lee, Eun-ok Jung, Byung-Gee Kim
Self-sufficient CYP102As possess outstanding hydroxylating activity to fatty acids such as myristic acid. Other CYP102 subfamily members share substrate specificity of CYP102As, but, occasionally, unusual characteristics of its own subfamily have been found. In this study, only one self-sufficient cytochrome P450 from Streptomyces cattleya was renamed from CYP102A_scat to CYP102G4, purified and characterized. UV–Vis spectrometry pattern, FAD/FMN analysis, and protein sequence comparison among CYP102s have shown that CYP102 from Streptomyces cattleya belongs to CYP102G subfamily. It showed hydroxylation activity toward fatty acids generating ω-1, ω-2, and ω-3-hydroxyfatty acids, which is similar to the general substrate specificity of CYP102 family. Unexpectedly, however, expression of CYP102G4 showed indigo production in LB medium batch flask culture, and high catalytic activity (kcat/Km) for indole was measured as 6.14±0.10min⁻¹mM⁻¹. Besides indole, CYP102G4 was able to hydroxylate aromatic compounds such as flavone, benzophenone, and chloroindoles. Homology model has shown such ability to accept aromatic compounds is due to its bigger active site cavity. Unlike other CYP102s, CYP102G4 did not have biased cofactor dependency, which was possibly determined by difference in NAD(P)H binding residues (Ala984, Val990, and Tyr1064) compared to CYP102A1 (Arg966, Lys972 and Trp1046). Overall, a self-sufficient CYP within CYP102G subfamily was characterized using purified enzymes, which appears to possess unique properties such as an only prokaryotic CYP naturally producing indigo.



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The transmembrane domain of the p75 neurotrophin receptor stimulates phosphorylation of the TrkB tyrosine kinase receptor [Cell Biology]

The function of protein products generated from intramembraneous cleavage by the γ-secretase complex is not well defined. The γ-secretase complex is responsible for the cleavage of several transmembrane proteins, most notably the amyloid precursor protein which results in Aβ, a transmembrane (TM) peptide. Another protein that undergoes a very similar γ-secretase cleavage is the p75 neurotrophin receptor. However, the fate of the cleaved p75 TM domain is unknown. p75 neurotrophin receptor is highly expressed during early neuronal development and regulates survival and process formation of neurons. Here, we report that the p75 TM can stimulate the phosphorylation of the tyrosine kinase receptor B (TrkB). In vitro phosphorylation experiments indicated that a peptide representing p75 TM increases TrkB phosphorylation in a dose- and time- dependent manner. Moreover, mutagenesis analyses revealed that a valine residue at position 264 in the rat p75 neurotrophin receptor is necessary for the ability of p75 TM to induce TrkB phosphorylation. Since this residue is immediately after the γ-secretase cleavage site, we then examined if the p75(αγ) peptide, which is a product of both α- and γ- cleavage events, could also induce TrkB phosphorylation. Experiments using TM domains from other receptors, EGFR and FGFR1, failed to stimulate TrkB phosphorylation. Co-immunoprecipitation and biochemical fractionation data suggested that p75 TM stimulates TrkB phosphorylation at the cell membrane. Altogether our results suggest that TrkB activation by p75(αγ) peptide may be enhanced in situations where the levels of the p75 receptor are increased, such as during brain injury, Alzheimers disease, and epilepsy.

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Mammalian haploid cells present problems during mitosis that limit their viability; the removal of the p53 tumor ... - Science Daily

Mammalian haploid cells present problems during mitosis that limit their viability; the removal of the p53 tumor ... Science Daily The Genomic Instability Group at the Spanish National Cancer Research Centre (CNIO) has offered an explanation of this phenomenon and proposes a way to overcome it. This work has been published this week in the journal, Proceedings of the National ...

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Young Age and Male Sex Are Predictors of Large-Volume Central Neck Lymph Node Metastasis in Clinical N0 Papillary Thyroid Microcarcinomas

Thyroid , Vol. 0, No. 0.


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Sexual dimorphism of the pulmonary transcriptome in neonatal hyperoxic lung injury: identification of angiogenesis as a key pathway

Bronchopulmonary dysplasia (BPD) is characterized by impaired alveolar secondary septation and vascular growth. Exposure to high concentrations of oxygen (hyperoxia) contributes to the development of BPD. Male sex is considered an independent risk factor for the development of BPD. The reasons underlying sexually dimorphic outcomes in premature neonates are not known. We hypothesized that sex-specific modulation of biological processes in the lung under hyperoxic conditions, contributes to sex-based differences. Neonatal male and female mice (C57BL/6) were exposed to hyperoxia (95% FiO2, post-natal day (PND) 1-5: saccular stage of lung development) and euthanized on PND 7 or 21. Pulmonary gene expression was studied using RNA-Seq on the Illumina HiSeq 2500 platform. Analysis of the pulmonary transcriptome revealed differential sex-specific modulation of crucial pathways such as: angiogenesis, response to hypoxia, inflammatory response and p53 pathway. Candidate genes from these pathways were validated at the mRNA level by qPCR. Analysis also revealed sex-specific differences in the modulation of crucial transcription factors. Focusing on the differential modulation of the angiogenesis pathway, we also show sex-specific differential activation of Hif-1α regulated genes using ChIP-qPCR and differences in expression of crucial genes (Vegf, VegfR2, and Phd2) modulating angiogenesis. We demonstrate the translational relevance of our findings by showing that our murine sex-specific differences in gene expression correlate with those from a pre-existing human BPD dataset. In conclusion, we provide novel molecular insights into differential sex-specific modulation of the pulmonary transcriptome in neonatal hyperoxic lung injury and highlight angiogenesis as one of the crucial differentially modulated pathways.

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Fra-2 negatively regulates postnatal alveolar septation by modulating myofibroblast function

Mice that globally over-express the transcription factor, Fos-related antigen-2 (Fra-2), develop extensive pulmonary fibrosis and pulmonary vascular remodeling. To determine if these phenotypes are a consequence of ectopic Fra-2 expression in vascular smooth muscle cells and myofibroblasts, we generated mice that over-express Fra-2 specifically in these cells types (α-SMA-rtTA; tetO-Fra-2). Surprisingly, these mice did not develop vascular remodeling or pulmonary fibrosis, but developed a spontaneous emphysema-like phenotype characterized by alveolar enlargement. Secondary septa formation is an important step in the normal development of lung alveoli and α-SMA expressing fibroblasts (myofibroblasts) play a crucial role in this process. The mutant mice showed reduced numbers of secondary septa at P7 and enlarged alveolar size starting at P12, suggesting that the process of secondary septa formation was impaired. Lineage tracing using α-SMA-rtTA mice crossed to a floxed TdTomato reporter revealed that embryonic expression of α-SMA cre marked a population of cells that gave rise to nearly all alveolar myofibroblasts. Comprehensive transcriptome analyses (RNA sequencing) demonstrated that the overwhelming majority of genes whose expression was significantly altered by over-expression of Fra-2 in myofibroblasts encoded secreted proteins, components of the extracellular matrix (ECM) and cell adhesion associated genes, including coordinate upregulation of pairs of integrins and their principal ECM ligands. In addition, primary myofibroblasts isolated from the mutant mice showed reduced migration capacity. These findings suggest that Fra-2 over-expression might impair myofibroblast functions crucial for secondary septation, such as myofibroblast migration across alveoli, by perturbing interactions between integrins and locally produced components of the ECM.

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Erratum to: A novel tubulin polymerization inhibitor, MPT0B206, downregulates Bcr-Abl expression and induces apoptosis in imatinib-sensitive and imatinib-resistant CML cells

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Peristomal leakage of enteroatmospheric fistulas treated with lipotransfer combined to minimal-invasive scar release technique

Abstract

Lipografting is emerging as a "rescue" treatment for postoperative sequelae, soft tissue volume defects and refractory fistulas. After complicated laparotomies or colostomies, also peristomal soft tissue volume deficiencies and scarring can occur and lead to severe care problems. Currently, no satisfactory treatment is available for these sequelae resulting in general surgery. In this case report, we applied the operative approach by means of a minimal-invasive scar release combined to waterjet-assisted lipotransfer and sculpturing on the abdominal wall as a treatment of peristomal irregularities. We applied one procedure on a patient with insufficient stoma sealing on large enteroatmospheric fistulas in "frozen" open abdomen (Björk 4 classification). Clinical and aesthetic outcome were measured and evaluated via digital photographs and CT scan pre- and postoperatively. Size reduction, complete sealing of the stoma appliance and total healing of the peristomal skin damage were accomplished within 5 weeks.

Level of Evidence: Level V, therapeutic study.

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Prevalence and its associated psychological variables of symptoms of depression and anxiety among ovarian cancer patients in China: a cross-sectional study

It is well known that cancer patients tend to have high levels of perceived stress and symptoms of depression and anxiety. However, there is less study on the association between perceived stress and symptoms ...

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A PILOT STUDY OF PD-1 AND PD-L1 EXPRESSION IN A SPECTRUM OF ORAL DYSPLASIAS AND ORAL SQUAMOUS CELL CARCINOMAS

Publication date: September 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 124, Issue 3
Author(s): S. GLASS, R. REICH, P. FREEDMAN




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CHITOSAN IN THE TREATMENT OF RADIOTHERAPY INDUCED ORAL MUCOSITIS IN HEAD AND NECK CANCER PATIENTS: A RANDOMISD CLINICAL TRIAL

Publication date: September 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 124, Issue 3
Author(s): ARVIND MUTHUKRISHNAN, G. SHANMUGHAPRIYA




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HISTOCHEMICAL ASSESSMENT FOR VASCULAR ENDOTHELIAL CELLS AND PERIVASCULAR CELLS DURING ENDOCHONDRAL OSSIFICATION

Publication date: September 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 124, Issue 3
Author(s): ERIKA TSUCHIYA, TOMOKA HASEGAWA, NORIO AMIZUKA, YOSHIMASA KITAGAWA




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16S METAGENOMIC ANALYSIS OF INTRATUMORAL BACTERIAL FLORA IN ORAL CANCER PATIENTS

Publication date: September 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 124, Issue 3
Author(s): RIE TESHIMA, TAKASHI MATSUMOTO, KENJI KAWANO, YOSHIO YAMAOKA




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Table of Contents

Publication date: September 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 124, Issue 3





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WILLINGNESS TO PAY, HEALTH UTILITY AND QUALITY OF LIFE IN ORAL LICHEN PLANUS – A COMPARATIVE STUDY ACROSS HEATH ECONOMIES

Publication date: September 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 124, Issue 3
Author(s): RICHEAL NI RIORDAIN, CHRISTINE MCCREARY, TIM HODGSON




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EXPRESSION ANALYSIS OF CANONICAL WNT PATHWAY GENES IN ORAL SQUAMOUS CELL CARCINOMA AND THEIR POSSIBLE ROLE AS BIOMARKERS

Publication date: September 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 124, Issue 3
Author(s): MADHULAXMI MARIMUTHU, P.U. ABDUL WAHAB, ANANDAN BALAKRISHNAN, SAMBANDHAM SHANMUGAM, VINOD NARAYANAN, M.R. MUTHUSEKHAR




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IMPACT OF SALIVARY FLOW RATE ON FUNGAL INFECTIONS ASSOCIATED WITH STEROID TREATMENT OF ORAL LICHEN PLANUS

Publication date: September 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 124, Issue 3
Author(s): MARY HIL EDENS, MICHAEL CARPENTER, JOEL NAPENAS, MICHAEL BRENNAN




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Oral health status and risk of bacteremia following allogeneic hematopoietic cell transplantation

Publication date: September 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 124, Issue 3
Author(s): Ahmed S. Sultan, Yvette Zimering, Gloria Petruzziello, Edwin P. Alyea, Joseph H. Antin, Robert J. Soiffer, Vincent T. Ho, Stephen T. Sonis, Sook-Bin Woo, Francisco M. Marty, Nathaniel S. Treister
ObjectivesThe aim of this study was to evaluate the impact of oral health status on bacteremia risk in a cohort of patients with acute myeloid leukemia (AML) who underwent chemotherapy followed by myeloablative allogeneic hematopoietic cell transplantation (allo-HCT).Study DesignA retrospective study was conducted in patients with AML from 2007 to 2011. Oral health status was determined from a pre–allo-HCT dental evaluation. Positive blood cultures were recorded from AML induction to post–allo-HCT day +60. Organisms that caused bacteremia were classified as "of possible oral source" by a blinded microbiologist. Two-sided Fisher's exact test was used to compare the oral health status of the entire cohort with that of patients with blood cultures of potential oral source.ResultsPre–allo-HCT dental evaluations were completed in 91 (99%) of 92 patients. Of these 91 patients, 13 (14%) with dental pathology (13 of 13 [100%]) completed all required dental treatment before allo-HCT. Bacteremias occurred in 63 of 92 patients (68%), and 12 (19%) of 63 patients had positive blood cultures of potential oral source. Of these, 1 of 12 patients developed bacteremia during AML induction, and 11 of 12 developed bacteremia during allo-HCT.ConclusionsOral health status was not associated with risk of bacteremia of potential oral source either at AML induction or consolidation or at allo-HCT.



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ALVEOLAR SOFT PART SARCOMA METASTATIC TO THE MANDIBLE: A REPORT AND REVIEW OF LITERATURE

Publication date: September 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 124, Issue 3
Author(s): S. PETERS, M. PERRINO, A. YOON, E. PHILIPONE




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Salivary and serum levels of tumor necrosis factor-alpha in oral lichen planus: a systematic review and meta-analysis study

Publication date: September 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 124, Issue 3
Author(s): Hamid Reza Mozaffari, Mazaher Ramezani, Mohammad Mahmoudiahmadabadi, Neda Omidpanah, Masoud Sadeghi
ObjectiveTumor necrosis factor-α (TNF-α) has a role in the progression of the oral lichen planus (OLP). The aim of this meta-analysis study was to evaluate the salivary and serum TNF-α levels in patients with OLP.Study DesignWe searched in the databases of PubMed/Medline, Science direct, Scopus, Web of Science, and Cochrane Library for studies reported from 1983 to 2016. All studies were checked for evaluation of salivary and serum levels of TNF-α in patients with OLP compared with healthy controls.ResultsTwelve studies were included in the meta-analysis. The mean difference of 7 studies reporting salivary TNF-α levels in patients with OLP versus healthy controls was 25.90 pg/mL (95% confidence interval [CI] 15.31-36.49; P < .00001) and 7 studies reporting serum TNF-α levels was 1.65 pg/mL (95% CI −0.82 to 4.11; P = .19).ConclusionsIn patients with OLP, the higher levels of TNF-α in saliva compared with serum suggest that measurement of this marker in saliva may be more useful than in serum for determining diagnostic and therapeutic aims.



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TINNITUS AND TEMPOROMANDIBULAR JOINT DISORDER SUBTYPES

Publication date: September 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 124, Issue 3
Author(s): SUSEE PRIYANKA RAVURI




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THE RELATIONSHIP BETWEEN RADIOGRAPHIC DENTAL ABNORMALITIES AND AGE AT INITIAL TREATMENT OF PEDIATRIC CANCER

Publication date: September 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 124, Issue 3
Author(s): VERA MONICA LIM, HALEY FREYMILLER, ADI SAX, ADEPITAN OWOSHO, JOSEPH HURYN, SAEHEE YOM, CHERRY ESTILO




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Combination of traditional chemotherapy, new drug kills rare cancer ... - EurekAlert (press release)

Combination of traditional chemotherapy, new drug kills rare cancer ... EurekAlert (press release) An experimental drug combined with the traditional chemotherapy drug cisplatin, when used in mice, destroyed a rare form of salivary gland tumor and ... and more »

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Effect of alisertib, an investigational aurora a kinase inhibitor on the QTc interval in patients with advanced malignancies

Summary

Aims A primary objective of this study was to investigate the effect of single and multiple doses of alisertib, an investigational Aurora A kinase inhibitor, on the QTc interval in patients with advanced malignancies. The dose regimen used was the maximum tolerated dose which was also the recommended phase 3 dose (50 mg twice daily [BID] for 7 days in 21-day cycles). Methods Patients received a single dose of alisertib (50 mg) on Day 1, and multiple doses of alisertib (50 mg BID) on Days 4 through to the morning of Day 10 of the first cycle of treatment. Triplicate ECGs were collected at intervals over 10 to 24 h via Holter recorders on Days −1 (baseline), 1 and 10. Changes from time-matched baseline values were calculated for various ECG parameters including QTc, heart rate, PR and QRS intervals. Alisertib pharmacokinetics were also assessed during the study, and an exposure-QTc analysis was conducted. Results Fifty patients were included in the QTc analysis. The upper bounds of the 95% confidence intervals for changes from time-matched baseline QTcF and QTcI values were <5 ms across all study days, time points and correction methods. Alisertib did not produce clinically relevant effects on heart rate, PR or QRS intervals. There was no evidence of a concentration-QTc effect relationship. Conclusions Alisertib does not cause QTc prolongation and can be concluded to not have any clinically relevant effects on cardiac repolarization or ECG parameters at the single agent maximum tolerated dose of 50 mg BID.

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Loss of the tumor suppressor STAG2 promotes telomere recombination and extends the replicative lifespan of normal human cells

Sister chromatids are held together by cohesin, a tripartite ring with a peripheral SA1/2 subunit, where SA1 is required for telomere cohesion and SA2 for centromere cohesion. The STAG2 gene encoding SA2 is often inactivated in human cancer, but not in in a manner associated with aneuploidy. Thus, how these tumors maintain chromosomal cohesion and how STAG2 loss contributes to tumorigenesis remain open questions. Here we show that, despite a loss in centromere cohesion, sister chromatids in STAG2 mutant tumor cells maintain cohesion in mitosis at chromosome arms and telomeres. Telomere maintenance in STAG2 mutant tumor cells occurred by either telomere recombination or telomerase activation mechanisms. Notably, these cells were refractory to telomerase inhibitors, indicating recombination can provide an alternative means of telomere maintenance. STAG2 silencing in normal human cells which lack telomerase led to increased recombination at telomeres, delayed telomere shortening and postponed senescence onset. Insofar as telomere shortening and replicative senescence prevent genomic instability and cancer by limiting the number of cell divisions, our findings suggest that extending the lifespan of normal human cells due to inactivation of STAG2 could promote tumorigenesis by extending the period during which tumor-driving mutations occur.

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PADI2-mediated citrullination promotes prostate cancer progression

Onset of castration-resistance prostate cancer (CRPC) after long-term androgen-deprivation therapy remains a major obstacle in the treatment of prostate cancer (PCa). The peptidylarginine deiminase PADI2 has been implicated in chronic inflammatory diseases and cancer. Here we show that PADI2 is an androgen-repressed gene and is upregulated in CRPC. PADI2 expression was required for survival and cell cycle progression of PCa cells, and PADI2 promoted proliferation of PCa cells under androgen-deprived or castration conditions in vitro and in vivo. Cytoplasmic PADI2 protected the androgen receptor (AR) against proteasome-mediated degradation and facilitated AR binding to its target genes after nuclear translocation and citrullination of histone H3 amino acid residue R26. By contrast, mutant PADI2 D180A failed to affect AR stability, nuclear translocation or transcriptional activity. PADI2 mediated AR control in a manner dependent on its enzymatic activity and nuclear localization, as correlated with increased histone H3 citrullination. Notably, co-administration of the PADI inhibitor Cl-amidine and the AR signaling inhibitor enzalutamide synergized in inhibiting CRPC cell proliferation in vitro and tumor growth in vivo. Overall, our results establish PADI2 as a key mediator for AR in PCa progression, especially CRPC, and they suggest PADI as novel therapeutic targets in this disease setting.

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Combination therapy with bispecific antibodies and PD-1 blockade enhances the antitumor potency of T cells

The DOCK-AND-LOCK (DNL®) method is a platform technology that combines recombinant engineering and site-specific conjugation to create multispecific, multivalent antibodies of defined composition with retained bioactivity. We have applied DNL® to generate a novel class of trivalent bispecific antibodies (bsAbs), each comprising an anti-CD3 scFv covalently conjugated to a stabilized dimer of different anti-tumor Fabs. Here we report the further characterization of two such constructs, (E1)-3s and (14)-3s, which activate T cells and target Trop-2- and CEACAM5-expressing cancer cells, respectively. (E1)-3s and (14)-3s, in the presence of human T cells, killed target cells grown as monolayers at subnanomolar concentrations, with a similar potency observed for drug-resistant cells. Antitumor efficacy was demonstrated for (E1)-3s co-administered with human peripheral blood mononuclear cells (PBMC) in NOD/SCID mice harboring xenografts of MDA-MB-231, a triple-negative breast cancer line constitutively expressing Trop-2 and PD-L1. Growth inhibition was observed following treatment with (E1)-3s or (14)-3s combined with human PBMC in 3D spheroids generated from target cell lines to mimic the in vivo behavior and microenvironment of these tumors. Moreover, addition of an antagonistic anti-PD-1 antibody increased cell death in 3D spheroids and extended survival of MDA-MB-231-bearing mice. These preclinical results emphasize the potential of combining T cell-redirecting bsAbs with antagonists or agonists that mitigate T cell inhibition within the tumor microenvironment to improve immunotherapy of solid cancers in patients. They also support the use of 3D spheroids as a predictive alternative to in vivo models for evaluating T cell functions.

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Therapeutic targeting of the CBP/p300 bromodomain blocks the growth of castration-resistant prostate cancer

Resistance invariably develops to anti-androgen therapies used to treat newly diagnosed prostate cancers, but effective treatments for castration-resistant disease remain elusive. Here we report that the transcriptional co-activator CBP/p300 is required to maintain the growth of castration-resistant prostate cancer. To exploit this vulnerability, we developed a novel small-molecule inhibitor of the CBP/p300 bromodomain that blocks prostate cancer growth in vitro and in vivo. Molecular dissection of the consequences of drug treatment revealed a critical role for CBP/p300 in histone acetylation required for the transcriptional activity of the androgen receptor and its target gene expression. Our findings offer a preclinical proof of concept for small molecule therapies to target the CBP/p300 bromodomain as a strategy to treat castration-resistant prostate cancer.

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Trastuzumab Increases HER2 Uptake and Cross-Presentation by Dendritic Cells

Early phase clinical trials evaluating CD8+ T cell-eliciting, HER2-derived peptide vaccines administered to HER2-positive breast cancer patients in the adjuvant setting suggest synergy between the vaccines and trastuzumab, the monoclonal antibody targeting the HER2 protein. Among 60 patients enrolled on clinical trials evaluating the E75+GM-CSF and GP2+GM-CSF vaccines, there have been no recurrences in patients vaccinated after receiving trastuzumab as part of standard therapy in the per treatment analyses conducted after a median follow-up of greater than 34 months. Here we describe a mechanism by which this synergy may occur. Flow cytometry showed that trastuzumab facilitated uptake of HER2 by dendritic cells (DC), which was mediated by the Fc receptor and was specific to trastuzumab. In vitro, increased HER2 uptake by DC increased cross-presentation of E75, the immunodominant epitope derived from the HER2 protein; an observation confirmed in two in vivo mouse models. This increased E75 cross-presentation, mediated by trastuzumab treatment, enabled more efficient expansion of E75-specific cytotoxic T cells (E75-CTL). These results demonstrate a mechanism by which trastuzumab links innate and adaptive immunity by facilitating activation of antigen-specific T cells. Based on these data, we conclude that HER2-positive breast cancer patients that have been treated with trastuzumab may experience a more robust antitumor immune response by restimulation of T cells with the E75 peptide vaccine, thereby accounting for the improved disease-free survival observed with combination therapy.

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MRE11 promotes tumorigenesis by facilitating resistance to oncogene-induced replication stress

Hypomorphic mutations in the genes encoding the MRE11/RAD50/NBS1 (MRN) DNA repair complex lead to cancer-prone syndromes. MRN binds DNA double strand breaks where it functions in repair and triggers cell cycle checkpoints via activation of the ataxia-telangiectasia mutated (ATM) kinase. To gain understanding of MRN in cancer, we engineered mice with B lymphocytes lacking MRN, or harboring MRN in which MRE11 lacks nuclease activities. Both forms of MRN deficiency led to hallmarks of cancer, including oncogenic translocations involving c-Myc and the immunoglobulin locus. These pre-neoplastic B lymphocytes did not progress to detectable B lineage lymphoma, even in the absence of p53. Moreover, Mre11 deficiencies prevented tumorigenesis in a mouse model strongly predisposed to spontaneous B cell lymphomas. Our findings indicate that MRN cannot be considered a standard tumor suppressor and instead imply that nuclease activities of MRE11 are required for oncogenesis. Inhibition of MRE11 nuclease activity increased DNA damage and selectively induced apoptosis in cells overexpressing oncogenes, suggesting MRE11 serves an important role in countering oncogene-induced replication stress. Thus, MRE11 may offer a target for cancer therapeutic development. More broadly, our work supports the idea that subtle enhancements of endogenous genome instability can exceed the tolerance of cancer cells and be exploited for therapeutic ends.

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Therapeutic effects of XPO1 inhibition in thymic epithelial tumors

Exportin 1 (XPO1) mediates nuclear export of many cellular factors known to play critical roles in malignant processes, and selinexor (KPT-330) is the first XPO1-selective inhibitor of nuclear export (SINE) compound in advanced clinical development phase for cancer treatment. We demonstrated here that inhibition of XPO1 drives nuclear accumulation of important cargo tumor suppressor proteins (TSP) including transcription factor FOXO3a and p53 in thymic epithelial tumor (TET) cells and induces p53-dependent and -independent antitumor activity in vitro. Selinexor suppressed the growth of TET xenograft tumors in athymic nude mice via inhibition of cell proliferation and induction of apoptosis. Loss of p53 activity or amplification of XPO1 may contribute to resistance to XPO1 inhibitor in TET. Using mass spectrometry-based proteomics analysis, we identified a number of proteins whose abundances in the nucleus and cytoplasm shifted significantly following selinexor treatment in the TET cells. Furthermore, we found that XPO1 was highly expressed in aggressive histotypes and advanced stages of human TET, and high XPO1 expression was associated with poorer patient survival. These results underscore an important role of XPO1 in the pathogenesis of TET and support clinical development of XPO1 inhibitor for the treatment of patients with this type of tumors.

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{beta}-adrenergic signaling in mice housed at standard temperatures suppresses an effector phenotype in CD8+ T cells and undermines checkpoint inhibitor therapy

The immune context of tumors has significant prognostic value and is predictive of responsiveness to several forms of therapy, including immunotherapy. We report here that CD8+ T cell frequency and functional orientation within the tumor microenvironment is regulated by β2-adrenergic receptor (β-AR) signaling in host immune cells. We used three strategies - physiologic (manipulation of ambient thermal environment), pharmacologic (β-blockers), and genetic (β2-adrenergic receptor knockout mice) to reduce adrenergic stress signaling in two widely studied preclinical mouse tumor models. Reducing β-AR signaling facilitated conversion of tumors to an immunologically active tumor microenvironment with increased intra-tumoral frequency of CD8+ T cells with an effector phenotype and decreased expression of PD-1, in addition to an elevated effector CD8+ T cell to CD4+ regulatory T cell ratio (IFN-γ+CD8+:Treg). Moreover, this conversion significantly increased the efficacy of anti-PD-1 checkpoint blockade. These data highlight the potential of adrenergic stress and norepinephrine-driven β-adrenergic receptor signaling to regulate the immune status of the tumor microenvironment and supports the strategic use of clinically available β-blockers in patients to improve responses to immunotherapy.

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Phenotypic Heterogeneity of Circulating Tumor Cells Informs Clinical Decisions between AR Signaling Inhibitors and Taxanes in Metastatic Prostate Cancer

The heterogeneity of an individual patient's tumor has been linked to treatment resistance, but quantitative biomarkers to rapidly and reproducibly evaluate heterogeneity in a clinical setting are currently lacking. Using established tools available in a CAP-accredited and CLIA-certified clinical laboratory, we quantified digital pathology features on 9,225 individual circulating tumor cells (CTCs) from 179 unique metastatic castration-resistant prostate cancer (mCRPC) patients to define phenotypically distinct cell types. Heterogeneity was quantified based on the diversity of cell types in individual patient samples using the Shannon index and associated with overall survival (OS) in the 145 specimens collected prior to initiation of second or later lines of therapy. Low CTC phenotypic heterogeneity was associated with better OS in patients treated with androgen receptor signaling inhibitors (ARSI), whereas high heterogeneity was associated with better OS in patients treated with taxane chemotherapy. Overall, the results show that quantifying CTC phenotypic heterogeneity can help inform the choice between ARSI and taxanes in mCRPC patients.

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Hepatoprotective and antioxidant effects of single clove garlic against CCl4-induced hepatic damage in rabbits

The increase in demand and consumption of single clove garlic or 'Solo garlic' (Allium sativum) has resulted in an increase in research on its therapeutic properties. The present study aims to evaluate the antiox...

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Neuroprotective properties of curcumin in toxin-base animal models of Parkinson’s disease: a systematic experiment literatures review

Curcumin (diferuloylmethane), a polyphenol extracted from the plant Curcuma longa, is widely used in Southeast Asia, China and India in food preparation and for medicinal purposes. Meanwhile, the neuroprotective ...

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Comparison of the trapezius and the adductor pollicis muscle as predictor of good intubating conditions: a randomized controlled trial

Adequate muscle relaxation is important for ensuring optimal conditions for intubation. Although acceleromyography of the adductor pollicis muscle is commonly used to assess conditions for intubation, we hypot...

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Biodiversity variability and metal accumulation strategies in plants spontaneously inhibiting fly ash lagoon, India

Abstract

Out of 29 plant species taken into consideration for biodiversity investigations, the present study screened out Cyperus rotundus L., Calotropis procera (Aiton) W.T. Aiton, Croton bonplandianus Baill., Eclipta prostrata (L.) L., and Vernonia cinerea (L.) Less. as the most suitable metal-tolerant plant species (high relative density and frequency) which can grow on metal-laden fly ash (FA) lagoon. Total (aqua-regia), residual (HNO₃) and plant available (CaCl₂) metal concentrations were assessed for the clean-up of metal-contaminated FA disposal site using naturally colonized plants. The total metal concentration (in mg kg⁻¹) in FA followed an order of Mn (229.8) > Ni (228.4) > Zn (89.4) > Cr (61.2) > Pb (56.6) > Cu (51.5) > Co (41.9) > Cd (9.7). The HNO₃- and CaCl₂-extracted metals were 0.57–15.68% and 0.03–7.82% of the total metal concentration, respectively. The concentration of Ni and Cr in FA in the present study was highest among the previously studied Indian and average world power plants and Cd, Ni, and Cr were above soil toxicity limit. The variation in total, residual, and plant-available metal (single extraction) concentration indicated the presence of different proportions of metals in FA lagoon which affects the metal uptake potential of the vegetation growing on it. It has been reported that plant-available metal extractant (CaCl₂) is the most suitable extractant for assessment of metal transfer from soil to plant. However in the present study, Spearman's correlation showed best significant correlation between total metal concentration in FA and shoot metal concentration (r = 0.840; p < 0.01) which suggest aqua-regia as the best extractant for understanding the bioavailability and transfer of metal, and in calculation of BCF for moderately contaminated site. It can be stated that plant-available extractant is not always suitable for understanding the availability of metal, but total metal concentration can provide a better insight especially for moderate or low metal-contaminated sites. Principle component analysis revealed that all the plants showed positive correlation with Co and Cd which suggest its subsequent uptake in root and shoot. The biological indices (BCF, BAF, and TF) revealed that E. prostrata (10 mg Cd kg⁻¹) and C. procera (3.5 mg Cd kg⁻¹) can be utilized efficiently for the phytoextraction of Cd and phytostabilization of other potentially toxic metals (Pb, Cr, and Co) from FA lagoon. All the plants were tolerant to Pb pollution (TF > 1, BAF > 1, and BCF > 1); hence, there was a negligible translocation of Pb to the aerial tissues of these plants which shows their suitability in phytostabilization. In addition, V. cinerea accumulated elevated concentration of potentially toxic Cr (50 mg Cr kg⁻¹) and Ni (67 mg Ni kg⁻¹) which could also help in the phytoremediation of FA lagoon.

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In situ remediation of chlorinated solvent-contaminated groundwater using ZVI/organic carbon amendment in China: field pilot test and full-scale application

Abstract

Chlorinated solvents in groundwater pose threats to human health and the environment due to their carcinogenesis and bioaccumulation. These problems are often more severe in developing countries such as China. Thus, methods for chlorinated solvent-contaminated groundwater remediation are urgently needed. This study presents a technique of in situ remediation via the direct-push amendment injection that enhances the reductive dechlorination of chlorinated solvents in groundwater in the low-permeability aquifer. A field-based pilot test and a following real-world, full-scale application were conducted at an active manufacturing facility in Shanghai, China. The chlorinated solvents found at the clay till site included 1,1,1-trichloroethane (1,1,1-TCA), 1,1-dichloroethane (1,1-DCA), 1,1-dichloroethylene (1,1-DCE), vinyl chloride (VC), and chloroethane (CA). A commercially available amendment (EHC^®, Peroxychem, Philadelphia, PA) combining zero-valent iron and organic carbon was used to treat the above pollutants. Pilot test results showed that direct-push EHC injection efficiently facilitated the in situ reductive remediation of groundwater contaminated with chlorinated solvents. The mean removal rates of 1,1,1-TCA, 1,1-DCA, and 1,1-DCE at 270 days post-injection were 99.6, 99.3, and 73.3%, respectively, which were obviously higher than those of VC and CA (42.3 and 37.1%, respectively). Clear decreases in oxidation-reduction potential and dissolved oxygen concentration, and increases in Fe²⁺ and total organic carbon concentration, were also observed during the monitoring period. These indicate that EHC promotes the anaerobic degradation of chlorinated hydrocarbons primarily via long-term biological reductive dechlorination, with instant chemical reductive dechlorination acting as a secondary pathway. The optimal effective time of EHC injection was 0–90 days, and its radius of influence was 1.5 m. In full-scale application, the maximum concentrations of 1,1,1-TCA and 1,1-DCA in the contaminate plume fell below the relevant Dutch Intervention Values at 180 days post-injection. Moreover, the dynamics of the target pollutant concentrations mirrored those of the pilot test. Thus, we have demonstrated that the direct-push injection of EHC successfully leads to the remediation of chlorinated solvent-contaminated groundwater in a real-world scenario. The parameters determined by this study (e.g., effectiveness, injection amount, injection depth, injection pressures, and radius of influence) are applicable to other low-permeability contaminated sites where in situ remediation by enhanced reductive dechlorination is required.

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Externalities: Pigouvian taxes

Print section Print Rubric:  Arthur Pigou thought that taxes could solve a common market failure. The fourth brief in our series on big economic ideas Print Headline:  The lives of others Print Fly Title:  Externalities UK Only Article:  standard article Issue:  How Trump has a feeble grasp of what it means to be president Fly Title:  Externalities Main image:  20170819_BBD001_0.jpg LOUD conversation in a train carriage that makes concentration impossible for fellow-passengers. A farmer spraying weedkiller that destroys his neighbour's crop. Motorists whose idling cars spew fumes into the air, polluting the atmosphere for everyone. Such behaviour might be considered thoughtless, anti-social or even immoral. For economists these spillovers are a problem to be solved. Markets are supposed to organise activity in a way that leaves everyone better off. But the ...

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The 12th Evidence Based Management Day on “Laryngeal Cancer” London, 3 November 2016

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Morphoproteomics, E6/E7 in-situ hybridization, and biomedical analytics define the etiopathogenesis of HPV-associated oropharyngeal carcinoma and provide targeted therapeutic options

Human papillomavirus (HPV) has been identified as an etiopathogenetic factor in oropharyngeal squamous cell carcinoma. The HPV E6 and E7 oncogenes are instrumental in promoting proliferation and blocking differen...

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6-Methoxyethylamino-numonafide inhibits hepatocellular carcinoma xenograft growth as a single agent and in combination with sorafenib [Research]

Hepatocellular carcinoma (HCC) is the third leading form of cancer worldwide, and its incidence is increasing rapidly in the United States, tripling over the past 3 decades. The current chemotherapeutic strategies against localized and metastatic HCC are ineffective. Here we report that 6-methoxyethylamino-numonafide (MEAN) is a potent growth inhibitor of murine xenografts of 2 human HCC cell lines. At the same dose and with the same treatment strategies, MEAN was more efficacious in inhibiting tumor growth in mice than sorafenib, the only approved drug for HCC. Treatment by MEAN at an effective dose for 6 wk was well tolerated by animals. Combined therapy using both sorafenib and MEAN enhanced tumor growth inhibition over monotherapy with either agent. Additional experiments revealed that MEAN inhibited tumor growth through mechanisms distinct from those of either its parent compound, amonafide or sorafenib. MEAN suppressed C-MYC expression and increased expression of several tumor suppressor genes, including Src homology region 2 domain-containing phosphatase-1 (SHP-1) and TXNIP (thioredoxin-interacting protein). As an encouraging feature for envisioned clinical application, the IC₅₀ of MEAN was not significantly changed in several drug-resistant cell lines with activated P-glycoprotein drug efflux pumps compared to drug-sensitive parent cells, demonstrating the ability of MEAN to be effective in cells resistant to existing chemotherapy regimens. MEAN is a promising candidate for clinical development as a single-agent therapy or in combination with sorafenib for the management of HCC.—Liu, Y., Lou, G., Norton, J. T., Wang, C., Kandela, I., Tang, S., Shank, N. I., Gupta, P., Huang, M., Avram, M. J., Green, R., Mazar, A., Appella, D., Chen, Z., Huang, S. 6-Methoxyethylamino-numonafide inhibits hepatocellular carcinoma xenograft growth as a single agent and in combination with sorafenib.

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Cell-autonomous cytotoxicity of type I interferon response via induction of endoplasmic reticulum stress [Research]

The interaction of IFN with specific membrane receptors that transduce death-inducing signals is considered to be the principle mechanism of IFN-induced cytotoxicity. In this study, the classic non–cell-autonomous cytotoxicity of IFN was augmented by cell-autonomous mechanisms that operated independently of the interaction of IFN with its receptors. Cells primed to produce IFN by 5-azacytidine (5-aza) underwent endoplasmic reticulum (ER) stress. The chemical chaperones tauroursodeoxycholate (TUDCA) and 4-phenylbutyrate (4-PBA), as well as the iron chelator ciclopirox (CPX), which reduces ER stress, alleviated the cytotoxicity of 5-aza. Ablation of CCAAT-enhancer-binding protein homologous protein (CHOP), the major ER stress–associated proapoptotic transcription factor, protected fibroblasts from 5-aza only when the cytotoxicity was examined cell autonomously. In a medium-transfer experiment in which the cell-autonomous effects of 5-aza was dissociated, CHOP ablation was incapable of modulating cytotoxicity; however, neutralization of IFN receptor was highly effective. Also the levels of caspase activation showed a distinct profile between the cell-autonomous and the medium-transfer experiments. We suggest that besides the classic paracrine mechanism, cell-autonomous mechanisms that involve induction of ER stress also participate. These results have implications in the development of anti-IFN-based therapies and expand the class of pathologic states that are viewed as protein-misfolding diseases.—Mihailidou, C., Papavassiliou, A. G., Kiaris, H. Cell-autonomous cytotoxicity of type I interferon response via induction of endoplasmic reticulum stress.

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Transcriptomic and epigenetic regulation of disuse atrophy and the return to activity in skeletal muscle [Research]

Physical inactivity and disuse are major contributors to age-related muscle loss. Denervation of skeletal muscle has been previously used as a model with which to investigate muscle atrophy following disuse. Although gene regulatory networks that control skeletal muscle atrophy after denervation have been established, the transcriptome in response to the recovery of muscle after disuse and the associated epigenetic mechanisms that may function to modulate gene expression during skeletal muscle atrophy or recovery have yet to be investigated. We report that silencing the tibialis anterior muscle in rats with tetrodotoxin (TTX)—administered to the common peroneal nerve—resulted in reductions in muscle mass of 7, 29, and 51% with corresponding reductions in muscle fiber cross-sectional area of 18, 42, and 69% after 3, 7, and 14 d of TTX, respectively. Of importance, 7 d of recovery, during which rodents resumed habitual physical activity, restored muscle mass from a reduction of 51% after 14 d TTX to a reduction of only 24% compared with sham control. Returning muscle mass to levels observed at 7 d TTX administration (29% reduction). Transcriptome-wide analysis demonstrated that 3714 genes were differentially expressed across all conditions at a significance of P ≤ 0.001 after disuse-induced atrophy. Of interest, after 7 d of recovery, the expression of genes that were most changed during TTX had returned to that of the sham control. The 20 most differentially expressed genes after microarray analysis were identified across all conditions and were cross-referenced with the most frequently occurring differentially expressed genes between conditions. This gene subset included myogenin (MyoG), Hdac4, Ampd3, Trim63 (MuRF1), and acetylcholine receptor subunit α1 (Chrna1). Transcript expression of these genes and Fboxo32 (MAFbx), because of its previously identified role in disuse atrophy together with Trim63 (MuRF1), were confirmed by real-time quantitative RT-PCR, and DNA methylation of their promoter regions was analyzed by PCR and pyrosequencing. MyoG, Trim63 (MuRF1), Fbxo32 (MAFbx), and Chrna1 demonstrated significantly decreased DNA methylation at key time points after disuse-induced atrophy that corresponded with significantly increased gene expression. Of importance, after TTX cessation and 7 d of recovery, there was a marked increase in the DNA methylation profiles of Trim63 (MuRF1) and Chrna1 back to control levels. This also corresponded with the return of gene expression in the recovery group back to baseline expression observed in sham-operated controls. To our knowledge, this is the first study to demonstrate that skeletal muscle atrophy in response to disuse is accompanied by dynamic epigenetic modifications that are associated with alterations in gene expression, and that these epigenetic modifications and gene expression profiles are reversible after skeletal muscle returns to normal activity.—Fisher, A. G., Seaborne, R. A., Hughes, T. M., Gutteridge, A., Stewart, C., Coulson, J. M., Sharples, A. P., Jarvis, J. C. Transcriptomic and epigenetic regulation of disuse atrophy and the return to activity in skeletal muscle.

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IL-17A deficiency mitigates bleomycin-induced complement activation during lung fibrosis [Research]

Interleukin 17A (IL-17A) and complement (C') activation have each been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). We have reported that IL-17A induces epithelial injury via TGF-β in murine bronchiolitis obliterans; that TGF-β and the C' cascade present signaling interactions in mediating epithelial injury; and that the blockade of C' receptors mitigates lung fibrosis. In the present study, we investigated the role of IL-17A in regulating C' in lung fibrosis. Microarray analyses of mRNA isolated from primary normal human small airway epithelial cells indicated that IL-17A (100 ng/ml; 24 h; n = 5 donor lungs) induces C' components (C' factor B, C3, and GPCR kinase isoform 5), cytokines (IL8, -6, and -1B), and cytokine ligands (CXCL1, -2, -3, -5, -6, and -16). IL-17A induces protein and mRNA regulation of C' components and the synthesis of active C' 3a (C3a) in normal primary human alveolar type II epithelial cells (AECs). Wild-type mice subjected to IL-17A neutralization and IL-17A knockout (il17a^–/–) mice were protected against bleomycin (BLEO)-induced fibrosis and collagen deposition. Further, BLEO-injured il17a^–/– mice had diminished levels of circulating Krebs Von Den Lungen 6 (alveolar epithelial injury marker), local caspase-3/7, and local endoplasmic reticular stress-related genes. BLEO-induced local C' activation [C3a, C5a, and terminal C' complex (C5b-9)] was attenuated in il17a^–/– mice, and IL-17A neutralization prevented the loss of epithelial C' inhibitors (C' receptor-1 related isoform Y and decay accelerating factor), and an increase in local TUNEL levels. RNAi-mediated gene silencing of il17a in fibrotic mice arrested the progression of lung fibrosis, attenuated cellular apoptosis (caspase-3/7) and lung deposition of collagen and C' (C5b-9). Compared to normals, plasma from IPF patients showed significantly higher hemolytic activity. Our findings demonstrate that limiting complement activation by neutralizing IL-17A is a potential mechanism in ameliorating lung fibrosis.—Cipolla, E., Fisher, A. J., Gu, H., Mickler, E. A., Agarwal, M., Wilke, C. A., Kim, K. K., Moore, B. B., Vittal, R. IL-17A deficiency mitigates bleomycin-induced complement activation during lung fibrosis.

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Dialogue wise as HPV-related oral cancer rates rise — APH - Sault Star

Sault Star

Dialogue wise as HPV-related oral cancer rates rise — APH Sault Star "I could tell everybody not to have sex, but I'm not sure if that's going to go over well," said Spruyt. Algoma Public Health's medical officer of health was responding to recent news that the number of oropharyngeal cancer cases have increased in ...

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Dr. Bauml on the Unmet Need in Head and Neck Cancer - OncLive

OncLive

Dr. Bauml on the Unmet Need in Head and Neck Cancer OncLive Because HPV-associated head and neck cancer is more common, the concept of survivorship needs to be developed, explains Bauml. Since patients with HPV-associated head and neck cancer tend to be younger, healthier patients, they receive more toxic ... and more »

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A two-year follow-up of surgical and non-surgical treatments in patients with masticatory muscle tendon-aponeurosis hyperplasia

This study re-examined the usefulness of surgery for the management of masticatory muscle tendon-aponeurosis hyperplasia (MMTAH) through a comparison of the outcomes between patients who underwent surgery and those who did not. The duration of follow-up was 2 years. Twenty-eight patients who attended the study hospital and were given a diagnosis of MMTAH were included. Nineteen patients underwent surgery (surgical group) and nine patients were instructed to open their mouths wide once a day and did not undergo surgery (non-surgical group).

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Marginal or segmental mandibulectomy: treatment modality selection for oral cancer: a systematic review and meta-analysis

Surgery is the most well established mode of initial definitive treatment for the majority of oral cancers. The most important decision in terms of tumour ablation in oral cancers when the jaws are potentially involved is the management of the mandible. The aim of this study was to explore the differences in survival rate and disease control between patients undergoing marginal mandibulectomy and patients undergoing segmental mandibulectomy using a systematic review and meta-analysis approach. A total of 15 cohort studies, including 1672 participants, were identified.

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Virtual quad zygoma implant placement using cone beam computed tomography: sufficiency of malar bone volume, intraosseous implant length, and relationship to the sinus according to the degree of alveolar bone atrophy

The objective of this study was to investigate the malar bone volume and length that a zygomatic implant can engage, and the relationship to the sinus according to the degree of alveolar bone atrophy. A three-dimensional evaluation was performed using cone beam computed tomography scans from 23 patients with a totally edentulous maxilla; quad zygoma implants were virtually placed. The predictor variable was the amount of malar bone volume and length that a zygomatic implant can engage. The primary outcome variable was the relationship to the sinus according to the degree of alveolar bone atrophy.

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Age-stratified analysis of tumor markers and tumor characteristics in adolescents and young women with mature cystic teratoma

Serum tumor markers are widely used for the preoperative evaluation of an adnexal mass. Elevations of cancer antigen (CA) 125 and CA 19-9 have been reported in patients with mature cystic teratoma (MCT). The aim of the study is to investigate the relation of serum tumor markers with tumor characteristics in young women with MCT.

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Does CT help in predicting preepiglottic space invasion in laryngeal carcinoma?

Publication date: Available online 12 August 2017
Source:Auris Nasus Larynx
Author(s): Gülpembe Bozkurt, Özlem Ünsal, İrfan Çelebi, Burak Ayhan, Umman Guliyev, Pınar Akova, Tülay Başak, Berna Uslu Coşkun
ObjectiveEvaluating preepiglottic space involvement in laryngeal cancer by CT may lead misinterpretation. We sought to understand the causes of misinterpretation in evaluating the preepiglottic space by CT and assessed the effects of misinterpretation in treatment plans of patients with laryngeal squamous cell carcinomas.MethodsSpecimen histopathology reports of 102 (99 male, 3 female) patients who underwent total or partial laryngectomy due to supraglottic and/or transglottic laryngeal carcinoma were reviewed. Neck CTs were also re‐assessed for preepiglottic space involvement by three radiologists. The initial surgical treatment choices were re-examined according to the current radiological evaluation in combination with pathological results of the specimens and physical examination findings in the patients. Interobserver agreement regarding image interpretation was based on a kappa analysis.ResultsThe interclass correlation coefficient in predicting preepiglottic space invasion was 0.74; this was considered 'good.' Among the three radiologists, sensitivity, specificity, accuracy of CT in detecting preepiglottic space involvement were 86–93%, 75–93%, and 77–93%, respectively, while the negative and positive predictive values were 97–98% and 38–50%, respectively. Given the previous treatments applied, false-positive diagnoses for PES involvement resulted in overtreatment in 2.9% of cases. False-negative diagnoses of PES involvement (1.9% of cases) did not result in any undertreatment.ConclusionsAlthough CT is a practical and inexpensive imaging tool for evaluating laryngeal carcinomas, the PPV of CT in assessing preepiglottic space invasion, especially in advanced tumors, is low and may lead to overtreatment.



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Clinical course of incidental parathyroidectomy: Single center experience

Publication date: Available online 12 August 2017
Source:Auris Nasus Larynx
Author(s): Sabri Özden, Ahmet Erdoğan, Besir Simsek, Baris Saylam, Baris Yıldız, Mesut Tez
ObjectiveThyroidectomy is a very common surgical procedure. Regardless of surgeon experience, incidental parathyroidectomy is a complication of thyroidectomy. The aim of this study was to identify the clinical course of incidental parathyroidectomies after thyroidectomy.MethodsPatients who underwent thyroidectomy between January 2010 and June 2014 were evaluated retrospectively. Pathology reports were reviewed for the presence of parathyroid tissue in the thyroidectomy pathology specimens. Information regarding demographic, laboratory variables, operative details, and postoperative complications were collected.ResultsIncidental parathyroidectomy was found in 178 out of 3022 patients who had thyroidectomy (5.8%). Types of surgeries performed for 178 patients were total thyroidectomy (TT) in 132(74.2%) cases, TT and central lymph node dissection(CLND) in 30 (16.9%) cases, lobectomy in seven cases (3.9%), completion thyroidectomy in five (2.8%) patients and modified cervical lymph node dissection in four (2.2%)patients. One and two parathyroid glands were accidentally removed in 152 (85.3%) and 26 (14.7%) patients, respectively.In the entire series, biochemical temporary postoperative hypocalcemia occurred in 75(42.1%) patients and permanent hypocalcemia occured in 12 (6.7%) patients with incidental parathyroidectomy. There was not a statistically significant difference regarding the occurrence of postoperative permanent hypocalcemia between the patients who had incidental parathyroidectomy of one gland and the patients with two incidental parathyroidectomies (p=0.114).ConclusionIncidental parathyroidectomy is not uncommon during thyroidectomy. No association between inadvertent parathyroidectomy and postoperative permanent hypocalcemia was found.



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