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

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Παρασκευή 23 Ιουνίου 2017

Model-based spike sorting with a mixture of drifting t-distributions

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Publication date: Available online 23 June 2017
Source:Journal of Neuroscience Methods
Author(s): Kevin Q. Shan, Evgueniy V. Lubenov, Athanassios G. Siapas
BackgroundChronic extracellular recordings are a powerful tool for systems neuroscience, but spike sorting remains a challenge. A common approach is to fit a generative model, such as a mixture of Gaussians, to the observed spike data. Even if non-parametric methods are used for spike sorting, such generative models provide a quantitative measure of unit isolation quality, which is crucial for subsequent interpretation of the sorted spike trains.New methodWe present a spike sorting strategy that models the data as a mixture of drifting t-distributions. This model captures two important features of chronic extracellular recordings—cluster drift over time and heavy tails in the distribution of spikes—and offers improved robustness to outliers.ResultsWe evaluate this model on several thousand hours of chronic tetrode recordings and show that it fits the empirical data substantially better than a mixture of Gaussians. We also provide a software implementation that can re-fit long datasets in a few seconds, enabling interactive clustering of chronic recordings.Comparison with existing methodsWe identify three common failure modes of spike sorting methods that assume stationarity and evaluate their impact given the empirically-observed cluster drift in chronic recordings. Using hybrid ground truth datasets, we also demonstrate that our model-based estimate of misclassification error is more accurate than previous unit isolation metrics.ConclusionsThe mixture of drifting t-distributions model enables efficient spike sorting of long datasets and provides an accurate measure of unit isolation quality over a wide range of conditions.



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Overcoming obstacles in the design of cancer anorexia/weight loss trials

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Publication date: Available online 24 June 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Jennifer G. Le-Rademacher, Jeffrey Crawford, William J. Evans, Aminah Jatoi
Most advanced cancer patients suffer loss of appetite (anorexia) and loss of weight. Despite the fact that cancer anorexia and weight loss are associated with a poor prognosis and detract from quality of life, no interventions have been demonstrated to palliate this syndrome in its entirety, particularly in patients with treatment-refractory malignancies. Recently, two registration trials − one with anamorelin and another with enobosarm − failed to reach their primary endpoints, thus raising questions. Were both these agents ineffective? Alternatively, did study design issues compromise the ability of these trials to identify effective agents? Thus, this review is timely insofar it serves as an introduction to study design, offers guidance on how to test promising agents for cancer anorexia/weight loss, and provides advice for overcoming trial design obstacles.



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UNRAVELLING THE COMPLEXITY OF SIGNALLING NETWORKS IN CANCER: A REVIEW OF THE INCREASING ROLE FOR COMPUTATIONAL MODELLING

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Publication date: Available online 23 June 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): John Garland
Cancer induction is a highly complex process involving hundreds of different inducers but whose eventual outcome is the same. Clearly, it is essential to understand how signalling pathways and networks generated by these inducers interact to regulate cell behaviour and create the cancer phenotype. While enormous strides have been made in identifying key networking profiles, the amount of data generated far exceeds our ability to understand how it all "fits together". The number of potential interactions is astronomically large and requires novel approaches and extreme computation methods to dissect them out. However, such methodologies have high intrinsic mathematical and conceptual content which is difficult to follow. This review explains how computation modelling is progressively finding solutions and also revealing unexpected and unpredictable nano-scale molecular behaviours extremely relevant to how signalling and networking are coherently integrated. It is divided into linked sections illustrated by numerous figures from the literature describing different approaches and offering visual portrayals of networking and major conceptual advances in the field. First, the problem of signalling complexity and data collection is illustrated for only a small selection of known oncogenes. Next, new concepts from biophysics, molecular behaviours, kinetics, organisation at the nano level and predictive models are presented. These areas include: visual representations of networking, Energy Landscapes and energy transfer/dissemination (entropy); diffusion, percolation; molecular crowding; protein allostery; quinary structure and fractal distributions; energy management, metabolism and re-examination of the Warburg effect. The importance of unravelling complex network interactions is then illustrated for some widely-used drugs in cancer therapy whose interactions are very extensive. Finally, use of computational modelling to develop micro- and nano- functional models ("bottom-up" research) is highlighted. The review concludes that computational modelling is an essential part of cancer research and is vital to understanding network formation and molecular behaviours that are associated with it. Its role is increasingly essential because it is unravelling the huge complexity of cancer induction otherwise unattainable by any other approach.



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Promoting healthier children's meals at quick-service and full-service restaurants: Results from a pilot and feasibility study

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Publication date: 1 October 2017
Source:Appetite, Volume 117
Author(s): Nanette V. Lopez, Sara C. Folta, Meaghan E. Glenn, Vanessa M. Lynskey, Anjali A. Patel, Stephanie Anzman-Frasca
High-calorie restaurant foods contribute to childhood overweight. Increased consumer demand for healthier kids' meals may motivate the restaurant industry to provide additional healthy options. This study pilot-tested a combination of four strategies (toy incentive, placemats, server prompts, signage) designed to increase demand for healthier kids' meals, which were defined as those eligible for the National Restaurant Association's Kids LiveWell program. Relative sales of healthier kids' meals were examined before (n = 3473 total kids' meal orders) and during Month 1 (n = 3546 total kids' meal orders) and Month 2 of implementation (n = 3645 total kids' meal orders) of an 8-week intervention in two locations each of a quick-service (QSR) and full-service (FSR) restaurant chain. Convenience samples of children (n = 27) and their parents (n = 28) were surveyed regarding parent and child perceptions of intervention components. Findings regarding the effectiveness and feasibility of the intervention were mixed. At the FSRs, the relative percentage of monthly sales from healthier kids' meals increased from 5.0% of kids' meal orders at baseline to 8.3% during Month 1, ending at 6.4% during Month 2. At the QSRs, the relative percentage of monthly sales from healthier kids' entrees decreased from 27.5% at baseline to 25.2% during Month 1, ending at 25.9% during Month 2. Implementation quality tracking showed that consistent implementation of intervention components was a challenge; parent- and child-reported awareness of intervention components supported this finding. Future directions are discussed, aiming to build upon these findings and maximize the feasibility, effectiveness, and sustainability of efforts to promote healthier eating in restaurants.



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Dining with dad: Fathers' influences on family food practices

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Publication date: 1 October 2017
Source:Appetite, Volume 117
Author(s): Priya Fielding-Singh
Scholars have documented multiple influences on family food practices. This article examines an overlooked contributor to family diet: fathers. Using 109 in-depth interviews with middle and upper-middle class mothers, adolescents, and fathers in the United States, I show how fathers can undermine mothers' efforts to provision a healthy diet. While family members perceive mothers as committed to provisioning a healthy diet, many fathers are seen as, at best, detached and, at worst, a threat to mothers' dietary aspirations. Fathers not only do little foodwork; they are also viewed as less concerned about their own and other family members' dietary health. When tasked with feeding, many fathers often turn to quick, unhealthy options explicitly avoided by mothers. Mothers report efforts to limit fathers' involvement in foodwork to ensure the healthiness of adolescents' diets, with variation across families by mothers' employment status. Fathers' dietary approaches reflect and reinforce traditional gender norms and expectations within families. In highlighting how and why fathers can undermine mothers' efforts to provision a healthy diet, this study deepens our understanding of the myriad dynamics shaping family food practices.



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Notalgia paresthetica: factors associated with its perceived severity, duration, side, and localization

Abstract

Background

Notalgia paresthetica (NP) is a disorder characterized by pruritus localized to the patient's back. Little is known about predictors of severity, duration, side, and localization.

Objective

To identify factors associated with perceived severity, duration, side, and localization of NP.

Methods

In a cross-sectional study, disease severity, duration, side, and localization were compared among the considered variables. Multivariate analysis was used to assess each variable contribution in predicting disease severity and its duration.

Results

Sixty-five patients were recruited. Disease involved more female than male patients (Female/Male: 1.6) and after adjusting for all potential confounders, it was perceived as more severe in females (OR = 7.3, 95% CI = 2–26.3, P < 0.01). NP was reported more frequently on the right side among patients sleeping on the left side and conversely (P < 0.05). A higher disease duration was significantly linked to a higher body mass index (OR = 4.8, 95% CI = 1.3–17.1, P < 0.05).

Conclusion

Our study linked female gender to worse disease severity, a higher body mass index to longer disease duration, and prevailing sleep position to NP side expression. The sleeping position should be considered a possible target for treating the disease.



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A novel heterocyclic compound improves working memory in the radial arm maze and modulates the dopamine receptor D1R in frontal cortex of the Sprague-Dawley rat

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Publication date: 14 August 2017
Source:Behavioural Brain Research, Volume 332
Author(s): Ahmed M. Hussein, Yogesh D. Aher, Predrag Kalaba, Nilima Y. Aher, Vladimir Dragačević, Bojana Radoman, Marija Ilić, Johann Leban, Tetyana Beryozkina, Abdel Baset M.A. Ahmed, Ernst Urban, Thierry Langer, Gert Lubec
A series of compounds have been shown to enhance cognitive function via the dopaminergic system and indeed the search for more active and less toxic compounds is continuing. It was therefore the aim of the study to synthetise and test a novel heterocyclic compound for cognitive enhancement in a paradigm for working memory. Specific and effective dopamine re-uptake inhibition DAT (IC50=4,1±0,8μM) made us test this compound in a radial arm maze (RAM) in the rat.CE-125 (4-((benzhydrylsulfinyl)methyl)-2-cyclopropylthiazole), was tested for dopamine (DAT), serotonin and norepinephrine re-uptake inhibition by a well-established system. The working memory index (WMI) was evaluated in male Sprague Dawley rats that were intraperitoneally injected with CE-125 (1 or 10mg/kg body weight). In order to evaluate basic neurotoxicity, the open field, elevated plus maze, rota rod studies and the forced swim test were carried out. Frontal cortex was taken at the last day of the RAM test and dopamine receptors D1R and D2R, DAT and phosphorylated DAT protein levels were determined.On the 10th day both doses were increasing the WMI as compared to the vehicle-treated group. In both, trained and treated groups, D1R levels were significantly reduced while D2R levels were unchanged. DAT levels were comparable between all groups while phosphorylated DAT levels were increased in the trained group treated with 1mg/kg body weight. CE-125 as a probably non-neurotoxic compound and specific reuptake inhibitor was shown to increase performance (WMI) and modulation of the dopaminergic system is proposed as a possible mechanism of action.



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Disturbances of novel object exploration and recognition in a chronic ketamine mouse model of schizophrenia

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Publication date: 14 August 2017
Source:Behavioural Brain Research, Volume 332
Author(s): Maria Jelena Hauser, Dirk Isbrandt, Jochen Roeper
Schizophrenia is a chronic and devastating disease with an overall lifetime risk of 1%. While positive symptoms of schizophrenia such as hallucinations and delusions are reduced by antipsychotic medication based on the inhibition of type 2 dopaminergic receptors (D2R), negative symptoms (e.g. reduced motivation) and cognitive symptoms (e.g. impaired working memory) of schizophrenia are not effectively treated by current medication. This dichotomy might arise in part because of our limited understanding of the pathophysiology of negative and cognitive symptoms in schizophrenia. In addition to genetic approaches, chronic systemic application of NMDA inhibitors such as ketamine have been used to generate rodent models, which displayed several relevant endophenotypes related to negative and cognitive symptoms and might thus facilitate mechanistic studies into the underlying pathophysiology. In this context, previous behavioral testing identified impairments in novel object recognition memory as a key feature in chronic NMDA-inhibitor schizophrenia rodent models. Using a chronic ketamine mouse model, we have however identified are more complex behavioral phenotype including deficits in novel space and novel object exploration in combination deficits in short-term novel object recognition memory. These impairments in novelty discrimination are in line with prefrontal and hippocampal reductions in parvalbumin-expression as well as reduced expression of the early immediate gene c-fos after novel-object exploration in hippocampal areas in our model. Our results indicate that adult C57Bl6N mice chronically treated with ketamine display combined impairments in novelty exploration and recognition, which might represent both motivational (negative) and cognitive symptoms of schizophrenia.



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Acquired bilateral telangiectasia macularis eruptiva perstans: A unique clinical feature of photodamaging rather than a subtype of cutaneous mastocytosis

Abstract

Telangiectasia macularis eruptiva perstans (TMEP) is a rare subtype of cutaneous mastocytosis, characterized by telangiectatic tan to brown macules on the trunk and extremities. Although TMEP has been descried as an uncommon disease in the literature, we often encounter patients with TMEP lesions in the outpatient clinic. We aimed to assess the clinical and histopathological characteristics of acquired bilateral TMEP, and the pathophysiological mechanism of acquired bilateral TMEP among these patients. We retrospectively reviewed 30 patients (28 men and 2 women) with acquired bilateral TMEP; multiple telangiectatic dark red to brown macules that were symmetrically distributed. The clinical characteristics and general histopathological findings of lesional skin were investigated. The number of mast cells was evaluated using immunohistochemical analysis with an antibody directed against c-kit (CD117). Acquired bilateral TMEP was predominantly localized on the sun-exposed area: the upper arm in 30 patients (100%), forearm in 19 patients (63.3%) and anterior chest in 15 patients (50%). A total of 16 patients (53.3%) showed at least one aggravating factor, including UV irradiation, alcohol use and heat exposure. Compared with the mast cell numbers in 19 age- and biopsy site-matched healthy controls (91 ± 29.0/mm2), the number of mast cells in the papillary dermal skin of acquired bilateral TMEP patients was significantly increased (159 ± 37.2/mm2, P < 0.01). In addition, a significant difference in vessel numbers in the papillary dermis was observed between acquired bilateral TMEP patients and healthy controls (10.5 ± 1.9 vs 5.4 ± 1.0/mm2, P < 0.01). Acquired bilateral TMEP is a relatively common disorder in middle-aged Asian men. An increased number of mast cells and dilated vessels might be a photoaging-related reactive process of chronic sun-exposure, which consequently leads to the formation of characteristic telangiectatic hyperpigmentary macules through certain melanogenic mediators.



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Terminalia bellirica (Gaertn.) Roxb. fruit mitigates CCl4 induced oxidative stress and hepatotoxicity in rats

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Jayesh Kuriakose, Helen Lal Raisa, Vysakh A., Binil Eldhose, Latha M.S.
Terminalia bellirica (Gaertn.) Roxb. is a medicinal plant used for the treatment of various ailments in the traditional system of medicine like Ayurveda where it has been prescribed as a rejuvenator and general health tonic. The fruit of the plant is one of the components of the age old ayurvedic formulation-'Triphala'. The present study evaluates curative effect of aqueous acetone extract of Terminalia bellirica fruits (AATB) against CCl4 induced oxidative stress and liver damage in an animal model. Two doses of the fruit extract (200mg/kg body weight and 400mg/kg body weight) were investigated for the beneficial effects. At the end of the treatment, liver function markers (ALT, AST, ALP, GGT, LDH, total bilirubin, total protein, albumin, globulin, albumin-globulin ratio) as well as hepatic oxidative stress markers (SOD, CAT, GSH) were evaluated. Treatment with AATB significantly restored the parameters towards normal level as compared to the elevated biochemical markers in the CCl4 treated animals. Reversal to normal tissue architecture was observed in histological evaluation. The results of AATB (400mg/kg) were found comparable with that of standard drug silymarin in all the parameters. The above findings suggest the therapeutic potential of the plant in alleviating hepatic oxidative stress and tissue damage, hence the traditional use of the plant in this regard stands justified.

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Structural evidence of quercetin multi-target bioactivity: A reverse virtual screening strategy

Publication date: 30 August 2017
Source:European Journal of Pharmaceutical Sciences, Volume 106
Author(s): Diego Carvalho, Margot Paulino, Fabio Polticelli, Florencia Arredondo, Robert J. Williams, Juan A. Abin-Carriquiry
The ubiquitous flavonoid quercetin is broadly recognized for showing diverse biological and health-promoting effects, such as anti-cancer, anti-inflammatory and cytoprotective activities. The therapeutic potential of quercetin and similar compounds for preventing such diverse oxidative stress-related pathologies has been generally attributed to their direct antioxidant properties. Nevertheless, accumulated evidence indicates that quercetin is also able to interact with multiple cellular targets influencing the activity of diverse signaling pathways. Even though there are a number of well-established protein targets such as phosphatidylinositol 3 kinase and xanthine oxidase, there remains a lack of a comprehensive knowledge of the potential mechanisms of action of quercetin and its target space. In the present work we adopted a reverse screening strategy based on ligand similarity (SHAFTS) and target structure (idTarget, LIBRA) resulting in a set of predicted protein target candidates. Furthermore, using this method we corroborated a broad array of previously experimentally tested candidates among the predicted targets, supporting the suitability of this screening approach. Notably, all of the predicted target candidates belonged to two main protein families, protein kinases and poly [ADP-ribose] polymerases. They also included key proteins involved at different points within the same signaling pathways or within interconnected signaling pathways, supporting a pleiotropic, multilevel and potentially synergistic mechanism of action of quercetin. In this context we highlight the value of quercetin's broad target profile for its therapeutic potential in diseases like inflammation, neurodegeneration and cancer.

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Development of IgY antibodies against anti-snake toxins endowed with highly lethal neutralizing activity

Publication date: 30 August 2017
Source:European Journal of Pharmaceutical Sciences, Volume 106
Author(s): David Gitirana da Rocha, Jorge Hernandez Fernandez, Cláudia Maria Costa de Almeida, Cláudia Letícia da Silva, Fábio Carlos Magnoli, Osmair Élder da Silva, Wilmar Dias da Silva
Snakebite envenoming is a major neglected disease related to poverty in developing countries. Treatment involves the administration of a specific antivenom serum and auxiliary therapies, if necessary. The improvement of antibodies is of great importance for the technological advancement of antivenom therapy and to reduce the morbidity and mortality associated with this medical burden. In the present study, adult hens were immunized nine times with 20μg of B. arietans or C. d. terrificus venoms at three-week intervals between immunizations. Developing antibodies presented increasing avidity and affinity to antigenic toxin epitopes along immunization, attaining a plateau after the seventh immunization. Pooled egg yolk-purified IgY antivenom antibodies, subjected to in vitro–in vivo lethality assay using Swiss adult mice, exhibited potent venom lethal neutralizing activity. Taken together, chickens under the described immunization schedule were considered alternative candidates for antivenom production. Lower maintenance costs, a simple antibody manufacturing process and immunization suffering restrictions are additional advantages.

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Silymarin prevents NLRP3 inflammasome activation and protects against intracerebral hemorrhage

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Raorao Yuan, Hengyi Fan, Shiqi Cheng, WeiWei Gao, Xin Xu, Shigang Lv, Minhua Ye, Miaojing Wu, Xingen Zhu, Yan Zhang
Inflammatory response mediates secondary injury during intracerebral hemorrhage (ICH). In the present study, we determined oxidative stress and involvement of NLRP3 in ICH injury and analyzed whether silymarin might offer protective effect against ICH injury. Post 24h after ICH injury there was increased oxidative stress markers (reactive oxygen species (ROS) and lipid peroxides) compared to sham group. Silymarin (200mg/kg) treatment 30 mins post ICH injury prevented increase in oxidative stress markers and up-regulated antioxidant status. Further, there was significant increase in nuclear levels of NF-κB-p65 and pro-inflammatory cytokine expressions post ICH injury. NLRP3 inflammasome activation and downstream targets such as caspase-1 and IL-1β expressions were significantly up regulated in ICH injury. Silymarin treatment significantly down regulated the inflammatory responses by suppressing NF-κB-p65 levels and inflammasome-mediated caspase-1/IL-1β expressions. Further, treatment with silymarin post ICH injury increased Nrf-2/HO-1 and thereby improved overall cytoprotection. These findings together show that silymarin acts as neuroprotective compound by preventing inflammatory activation and up regulating Nrf-2/HO-1 signaling post ICH injury.



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MicroRNA-493 suppresses hepatocellular carcinoma tumorigenesis through down-regulation of anthrax toxin receptor 1 (ANTXR1) and R-Spondin 2 (RSPO2)

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Yuqiang Xu, Kuikui Ge, Junhao Lu, Jinjiang Huang, Wei Wei, Qingshan Huang
Hepatocellular carcinoma (HCC) is known as a highly prevalent cancer with a poor prognosis and short survival time, despite intensive research and clinical efforts. Increasing numbers of studies have reported that microRNAs are involved in the malignant behavior of hepatocellular carcinoma cells via directly targeting multiple oncogenes or tumor suppressors. Here, we report that the expression of microRNA-493 (miR-493) is decreased in HCC cell lines and in tumor tissues. Overexpression of miR-493 in HCC cells dramatically inhibited cell proliferation and colony-formation in vitro and inhibited tumor formation of HCC cell xenografts in vivo. miR-493 also suppressed cell migration and invasion in HCC cell lines. Novel targets ANTXR1 and RSPO2 were confirmed to be suppressed by miR-493 directly, and overexpression of ANTXR1 and RSPO2 could restore tumorigenesis in miR-493 treated HCC cell. Moreover, Wnt/β-catenin signaling pathway, which was reported to be activated by ANTXR1 and RSPO2, was also inhibited by miR-493 overexpression and might be involved in anti-tumor function of miR-493. These findings suggest that miR-493 acts as a negative regulator in hepatocellular carcinoma progression and may be a potential therapeutic target for HCC.



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The many postures of noncanonical Wnt signaling in development and diseases

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Qian Xiao, Zhengxi Chen, Xiaozhuang Jin, Runyi Mao, Zhenqi Chen
Wnt signaling regulates many aspects of vertebrate development. Its dysregulation causes developmental defects and diseases including cancer. The signaling can be categorized in two pathways: canonical and noncanonical. Canonical pathway plays a key role in regulating proliferation and differentiation of cells whilst noncanonical Wnt signaling mainly controls cellular polarity and motility. During development, noncanonical Wnt signaling is required for tissue formation. Recent studies have shown that noncanonical Wnt signaling is involved in adult tissue development and cancer progression. In this review, we try to describe and discuss the mechanisms behind the biological effects of noncanonical Wnt signaling, diseases caused by its dysregulation, and implications in adult tissue development biology.



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Cardiaprotective effect of crocetin by attenuating apoptosis in isoproterenol induced myocardial infarction rat model

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Weili Zhang, Yuhui Li, Zhiming Ge
Given study evaluates the cardioprotective effect of crocetin in myocardial infracted (MI) rats. MI was produced by administering isoproterenol (90mg/kg/day, i.p.) in rats for two consecutive days. all the animals were divided in to four groups such as control group receives only saline; MI group which receives only isoproterenol and crocetin treated group which receives crocetin (50, 100 and 200mg/kg/day, p.o.) for the duration of 15 days. At the end of dosing left ventricular functions was assessed to estimate its effect on cardiac functions. Catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), creatine kinase (CK-MB), lactate dehydrogenase (LDH) and inflammatory cytokines were determined in the cardiac tissue homogenate. Histopathology study was also carried out using hematoxylin and eosin staining. Immunohistochemistry was done for the estimation of Caspase-3, Bcl-2, Bax and Nrf-2 level in the myocardial tissues of MI rats.Result of the study suggested that GSH, CAT, CK-MB, and LDH were (p<0.01) increased in the tissue homogenate of crocetin treated group than MI group. However crocetin significantly (p<0.01) decreases the level of MDA and activity of SOD in the tissue homogenate than MI group. It was observed that treatment with crocetin attenuates the level of inflammatory cytokines in the myocardial tissues of MI rats. Moreover level of caspase-3, Bax and Nrf-2 significantly reduced and Bcl-2 enhanced in the myocardial tissues of MI rats than MI group. The altered cellular architecture of heart tissue sections in the myocardial infracted rats were reversed by administration of crocetin treatment. Taking all these data together, it may be suggested that the crocetin act as a possible protective agent in myocardial infarction by decreasing oxidative stress and inflammatory cytokines and thereby attenuates the apoptosis of myocardial cells.



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Inducible nitric oxide synthase: Good or bad?

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Maggie Lind, Alan Hayes, Martin Caprnda, Daniel Petrovic, Luis Rodrigo, Peter Kruzliak, Anthony Zulli
Nitric oxide synthases (NOS) are a family of isoforms responsible for the synthesis of the potent dilator nitric oxide (NO). Expression of inducible NOS (iNOS) occurs in conditions of inflammation, and produces large amounts of NO. In pathological conditions iNOS is regarded as a harmful enzyme and is proposed to be a major contributor to diseases of the cardiovascular system such as atherosclerosis. In this review, we address the notion that iNOS is a detrimental enzyme in disease and discuss its potentially beneficial roles. Additionally, we describe other molecules associated with iNOS in diseases such as atherosclerosis, and current research on therapeutic inhibitors tested to reduced pathology associated with cardiovascular diseases (CVD).



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Alpinumisoflavone inhibits osteoclast differentiation and exerts anti-osteoporotic effect in ovariectomized mice

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Wei Cong, Chao Zhou, Jun Yin
Alpinumisoflavone (AIF), a naturally occurring flavonoid compound exacted from Derris eriocarpa, has been found to have a number of pharmacological activities. However, its role in bone disorder has not been investigated. The aim of this study is to evaluate the osteoprotective effect of AIF on ovariectomy-induced bone loss in mice model and related underlying mechanisms. Our study provides experimental evidence that AIF could regulate the remodeling process of bone and exert osteoprotective effect against ovariectomy-induced bone loss. Moreover, our results show that AIF suppresses osteoclast differentiation by attenuating RANKL-induced activation of p38, ERK and JNK pathways and consequently represses the expression of c-Fos and NFATc1.



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Evaluation of in vitro anticancer activity of 1,8-Cineole–containing n-hexane extract of Callistemon citrinus (Curtis) Skeels plant and its apoptotic potential

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Sowndarya Sampath, Vidhya Veeramani, Gopal Shankar Krishnakumar, Udhayakumar Sivalingam, Suguna Lakshmi Madurai, Rose Chellan
Plants are the source of a variety of secondary metabolites, which are often used in the anticancer activity. Discovering new anticancer drug from herbal source is more important in both biological and pharmacological activities. Hence, the objective of this study is to identify the anticancer agent in Callistemon citrinus (Curtis) Skeels (CC) for the treatment of cancer. Very recently we have reported an increased antioxidant activity in the ethanolic and methanolic extracts (EE and ME) of CC but significantly reduced activity (rather increased cytotoxicity), in the n-hexane extract (HE). In this study, the cytotoxicity of all the three solvent extracts was tested against A431, MG-63 and HaCaT cell lines by MTT assay. Interestingly HE has showed increased anti-proliferative effect against the cancer cells but was resisted by non-malignant cells. HPLC and GC–MS analysis revealed the presence of 1,8-Cineole as a predominant compound in HE, the semi-purified bioactive extract. Henceforth, this would be called HE-C and be used for further analyses to understand its mode of action on induced apoptosis/necrosis. Alamar blue assay of HE-C showed cytotoxicity and change in morphological characteristics, which was confirmed by AO/EB staining using fluorescence microscopy, ultra-structural features of apoptosis using SEM and TEM. HE-C induced cell death was also detected by FACS using FITC–labelled Annexin-V and Propidium iodide. ROS generation was monitored using DCF-DA by flow cytometry. The overall results suggested that the selective extract (HE-C) containing 1,8-Cineole has shown potential anti-cancer activity in a dose-dependent manner, and cell death was induced through ROS-mediated apoptosis. Our findings provide an insight into the potential of 1,8-Cineole as a novel drug for killing cancer cells.

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Tanshinone I alleviates insulin resistance in type 2 diabetes mellitus rats through IRS-1 pathway

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Ying Wei, Jiaqi Gao, Lingling Qin, Yunling Xu, Dongchao Wang, Haoxia Shi, Tunhai Xu, Tonghua Liu
Tanshinone I from tanshen has been used in traditional Chinese medicine for treating cardiovascular diseases and inflammatory diseases. Given the link between inflammation and Type 2 diabetes mellitus (T2DM), we suspect that tanshinone I may have a beneficial effect on T2DM. This study was to investigate the potential effects of tanshinone I on T2DM and its underlying mechanism. T2DM was thus induced in Sprague-Dawley (SD) rats using streptozotocin (STZ) and high-fat diet. It was observed that T2DM rats had higher levels of total cholesterol (TC), nonesterified fatty acids (NEFAs), total triglyceride (TG) and total low density lipoprotein cholesterol (LDL-C) compared with normal, healthy SD rats. Treatment with tanshinone I decreased these levels and lowered blood glucose level in T2DM rats. In addition, enzyme-linked immunosorbent assay (ELISA) analysis showed that T2DM rats had elevated levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Furthermore, Western blot analysis revealed that T2DM rats had enhanced nuclear translocation of NF-κB as well as elevated phosphorylation of Ser307 in IRS-1(insulin receptor substrate 1). Treatment by tanshinone I lowered the levels of IL-6 and TNF-α, decreased nuclear translocation of NF-κB as well as phosphorylation of Ser307 in IRS-1. These results demonstrated that tanshinone I could alleviate T2DM syndrome in rats.



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Individual differences in functional connectivity during naturalistic viewing conditions

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Publication date: 15 August 2017
Source:NeuroImage, Volume 157
Author(s): Tamara Vanderwal, Jeffrey Eilbott, Emily S. Finn, R. Cameron Craddock, Adam Turnbull, F. Xavier Castellanos
Naturalistic viewing paradigms such as movies have been shown to reduce participant head motion and improve arousal during fMRI scanning relative to task-free rest, and have been used to study both functional connectivity and stimulus-evoked BOLD-signal changes. These task-based hemodynamic changes are synchronized across subjects and involve large areas of the cortex, and it is unclear whether individual differences in functional connectivity are enhanced or diminished under such naturalistic conditions. This work first aims to characterize variability in BOLD-signal based functional connectivity (FC) across 2 distinct movie conditions and eyes-open rest (n=31 healthy adults, 2 scan sessions each). We found that movies have higher within- and between-subject correlations in cluster-wise FC relative to rest. The anatomical distribution of inter-individual variability was similar across conditions, with higher variability occurring at the lateral prefrontal lobes and temporoparietal junctions. Second, we used an unsupervised test-retest matching algorithm that identifies individual subjects from within a group based on FC patterns, quantifying the accuracy of the algorithm across the three conditions. The movies and resting state all enabled identification of individual subjects based on FC matrices, with accuracies between 61% and 100%. Overall, pairings involving movies outperformed rest, and the social, faster-paced movie attained 100% accuracy. When the parcellation resolution, scan duration, and number of edges used were increased, accuracies improved across conditions, and the pattern of movies>rest was preserved. These results suggest that using dynamic stimuli such as movies enhances the detection of FC patterns that are unique at the individual level.



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Neural representations of the concepts in simple sentences: Concept activation prediction and context effects

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Publication date: 15 August 2017
Source:NeuroImage, Volume 157
Author(s): Marcel Adam Just, Jing Wang, Vladimir L. Cherkassky
Although it has been possible to identify individual concepts from a concept's brain activation pattern, there have been significant obstacles to identifying a proposition from its fMRI signature. Here we demonstrate the ability to decode individual prototype sentences from readers' brain activation patterns, by using theory-driven regions of interest and semantic properties. It is possible to predict the fMRI brain activation patterns evoked by propositions and words which are entirely new to the model with reliably above-chance rank accuracy. The two core components implemented in the model that reflect the theory were the choice of intermediate semantic features and the brain regions associated with the neurosemantic dimensions. This approach also predicts the neural representation of object nouns across participants, studies, and sentence contexts. Moreover, we find that the neural representation of an agent-verb-object proto-sentence is more accurately characterized by the neural signatures of its components as they occur in a similar context than by the neural signatures of these components as they occur in isolation.



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Comparison of the spatial resolution of source imaging techniques in high-density EEG and MEG

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Publication date: 15 August 2017
Source:NeuroImage, Volume 157
Author(s): T. Hedrich, G. Pellegrino, E. Kobayashi, J.M. Lina, C. Grova
BackgroundThe present study aims at evaluating and comparing electrical and magnetic distributed source imaging methods applied to high-density Electroencephalography (hdEEG) and Magnetoencephalography (MEG) data. We used resolution matrices to characterize spatial resolution properties of Minimum Norm Estimate (MNE), dynamic Statistical Parametric Mapping (dSPM), standardized Low-Resolution Electromagnetic Tomography (sLORETA) and coherent Maximum Entropy on the Mean (cMEM, an entropy-based technique). The resolution matrix provides information of the Point Spread Functions (PSF) and of the Crosstalk functions (CT), this latter being also called source leakage, as it reflects the influence of a source on its neighbors.MethodsThe spatial resolution of the inverse operators was first evaluated theoretically and then with real data acquired using electrical median nerve stimulation on five healthy participants. We evaluated the Dipole Localization Error (DLE) and the Spatial Dispersion (SD) of each PSF and CT map.ResultscMEM showed the smallest spatial spread (SD) for both PSF and CT maps, whereas localization errors (DLE) were similar for all methods. Whereas cMEM SD values were lower in MEG compared to hdEEG, the other methods slightly favored hdEEG over MEG. In real data, cMEM provided similar localization error and significantly less spatial spread than other methods for both MEG and hdEEG. Whereas both MEG and hdEEG provided very accurate localizations, all the source imaging methods actually performed better in MEG compared to hdEEG according to all evaluation metrics, probably due to the higher signal-to-noise ratio of the data in MEG.ConclusionOur overall results show that all investigated methods provide similar localization errors, suggesting very accurate localization for both MEG and hdEEG when similar number of sensors are considered for both modalities. Intrinsic properties of source imaging methods as well as their behavior for well-controlled tasks, suggest an overall better performance of cMEM in regards to spatial resolution and spatial leakage for both hdEEG and MEG. This indicates that cMEM would be a good candidate for studying source localization of focal and extended generators as well as functional connectivity studies.



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Relay transport of aerosols to Beijing-Tianjin-Hebei region by multi-scale atmospheric circulations

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Publication date: September 2017
Source:Atmospheric Environment, Volume 165
Author(s): Yucong Miao, Jianping Guo, Shuhua Liu, Huan Liu, Gen Zhang, Yan Yan, Jing He
The Beijing-Tianjin-Hebei (BTH) region experiences heavy aerosol pollution, which is found to have close relationships with the synoptic- and local-scale atmospheric circulations. However, how and to what extent these multi-scale circulations interplay to modulate aerosol transport have not been fully understood. To this end, this study comprehensively investigated the impacts of these circulations on aerosol transport in BTH by focusing on an episode occurred on 1 June 2013 through combining both observations and three-dimensional simulations. It was found that during this episode, the Bohai Sea acted as a transfer station, and the high-pressure system over the Yellow Sea and sea-breeze in BTH took turns to affect the transport of aerosols. In the morning, influenced by the high-pressure system, lots of aerosols emitted from Shandong and Jiangsu provinces were first transported to the Bohai Sea. After then, these aerosols were brought to the BTH region in the afternoon through the inland penetration of sea-breeze, significantly exacerbating the air quality in BTH. The inland penetration of sea-breeze could be identified by the sharp changes in ground-based observed temperature, humidity, and wind when the sea-breeze front (SBF) passed by. Combining observations with model outputs, the SBF was found to be able to advance inland more than ∼150 km till reaching Beijing. This study has important implications for better understanding the aerosol transport in BTH, and improving the forecast of such aerosol pollution.



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Mass size distribution of particle-bound water

Publication date: September 2017
Source:Atmospheric Environment, Volume 165
Author(s): S. Canepari, G. Simonetti, C. Perrino
The thermal-ramp Karl-Fisher method (tr-KF) for the determination of PM-bound water has been applied to size-segregated PM samples collected in areas subjected to different environmental conditions (protracted atmospheric stability, desert dust intrusion, urban atmosphere). This method, based on the use of a thermal ramp for the desorption of water from PM samples and the subsequent analysis by the coulometric KF technique, had been previously shown to differentiate water contributes retained with different strength and associated to different chemical components in the atmospheric aerosol.The application of the method to size-segregated samples has revealed that water showed a typical mass size distribution in each one of the three environmental situations that were taken into consideration. A very similar size distribution was shown by the chemical PM components that prevailed during each event: ammonium nitrate in the case of atmospheric stability, crustal species in the case of desert dust, road-dust components in the case of urban sites.The shape of the tr-KF curve varied according to the size of the collected particles. Considering the size ranges that better characterize the event (fine fraction for atmospheric stability, coarse fraction for dust intrusion, bi-modal distribution for urban dust), this shape is coherent with the typical tr-KF shape shown by water bound to the chemical species that predominate in the same PM size range (ammonium nitrate, crustal species, secondary/combustion species - road dust components).

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The impact of household cooking and heating with solid fuels on ambient PM2.5 in peri-urban Beijing

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Publication date: September 2017
Source:Atmospheric Environment, Volume 165
Author(s): Jiawen Liao, Anna Zimmerman Jin, Zoë A. Chafe, Ajay Pillarisetti, Tao Yu, Ming Shan, Xudong Yang, Haixi Li, Guangqing Liu, Kirk R. Smith
Household cooking and space heating with biomass and coal have adverse impacts on both indoor and outdoor air quality and are associated with a significant health burden. Though household heating with biomass and coal is common in northern China, the contribution of space heating to ambient air pollution is not well studied. We investigated the impact of space heating on ambient air pollution in a village 40 km southwest of central Beijing during the winter heating season, from January to March 2013. Ambient PM2.5 concentrations and meteorological conditions were measured continuously at rooftop sites in the village during two winter months in 2013. The use of coal- and biomass-burning cookstoves and space heating devices was measured over time with Stove Use Monitors (SUMs) in 33 households and was coupled with fuel consumption data from household surveys to estimate hourly household PM2.5 emissions from cooking and space heating over the same period. We developed a multivariate linear regression model to assess the relationship between household PM2.5 emissions and the hourly average ambient PM2.5 concentration, and a time series autoregressive integrated moving average (ARIMA) regression model to account for autocorrelation. During the heating season, the average hourly ambient PM2.5 concentration was 139 ± 107 μg/m3 (mean ± SD) with strong autocorrelation in hourly concentration. The average primary PM2.5 emission per hour from village household space heating was 0.736 ± 0.138 kg/hour. The linear multivariate regression model indicated that during the heating season – after adjusting for meteorological effects – 39% (95% CI: 26%, 54%) of hourly averaged ambient PM2.5 was associated with household space heating emissions from the previous hour. Our study suggests that a comprehensive pollution control strategy for northern China, including Beijing, should address uncontrolled emissions from household solid fuel combustion in surrounding areas, particularly during the winter heating season.



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Cultural Competence.

Author: Reed, Cindy RN
Page: 13


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New Immunization Initiatives Show Promise.

Author: Sofer, Dalia
Page: 14


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Impact of LULCC on the emission of BVOCs during the 21st century

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Publication date: September 2017
Source:Atmospheric Environment, Volume 165
Author(s): Sebastian Szogs, Almut Arneth, Peter Anthoni, Jonathan C. Doelman, Florian Humpenöder, Alexander Popp, Thomas A.M. Pugh, Elke Stehfest
Land-use and land-cover change (LULCC) is one of the key drivers of anthropogenic climate change. In addition to greenhouse gases such as CO2 or CH4, LULCC affects also the emission of other carbon trace gases such as biogenic volatile organic compounds (BVOCs). We investigate the impact of changing LULCC on the emission of isoprene and monoterpenes during the 21st century using seven different land-use projections, applying the dynamic vegetation modelling framework LPJ-GUESS. Climate change, and atmospheric CO2-concentration are based on the RCP2.6 scenario. The different LULCC-scenarios explore the impact of different land-based climate change mitigation strategies (such as afforestation and avoided deforestation, or bioenergy). We show that the increase of land area under crops or grassland would lead to a significant decrease of BVOC emissions, with a strong negative correlation between the fraction of managed global land area and the emission of isoprene and monoterpenes. But the choice of crops is important, especially for the bioenergy scenarios in which increasing fractional cover leads to decreasing BVOC emissions in our simulations; use of woody bioenergy crops can reverse this decrease. The strong impact of LULCC on the global and regional emission of BVOCs implies the need to include the impact of these changes in projections of atmospheric composition and air quality.



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Mind the Facts.

Author: Kennedy, Maureen Shawn MA, RN, FAAN
Page: 7


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Forever Hold Your Peace: When Preprocedure Safety Concerns Are Missed.

Author: Crooks, Elizabeth Anne DNP, RN, CNE
Page: 11


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Monitoring Opioid-Induced Respiratory Depression.

Author: Hinds, Janice ADN, RN
Page: 13


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Monitoring Opioid-Induced Respiratory Depression.

Author: Gaines, Nicole RN
Page: 13


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Risk Tools vs. Nurse Perception.

Author: P., Cheri
Page: 13


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Risk Tools vs. Nurse Perception.

Author: D.T., Tanya
Page: 13


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Norepinephrine Shortage Led to Increased Deaths from Septic Shock.

Author: Stockwell, Serena
Page: 15


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From the Agencies.

Author:
Page: 15


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Nursing Protocol for Stroke Increases Survival, Reduces Disability.

Author: Stockwell, Serena
Page: 16


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NewsCAP: Kidney and eye events in diabetes decrease with intensive glucose control.

Author:
Page: 16


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NewsCAP: Trans fat restrictions are associated with decreased cardiovascular events.

Author:
Page: 16


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An Innovative Syringe Exchange Program.

Author: Potera, Carol
Page: 17


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NewsCAP: More states enact enhanced Nurse Licensure Compact (eNLC) legislation.

Author:
Page: 17


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NewsCAP: The presence of more certified wound care nurses is associated with fewer HAPIs.

Author:
Page: 17


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The Growing Trend of Medical Tourism.

Author: Nelson, Roxanne
Page: 18-19


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AJN On the Cover.

Author: Szulecki, Diane Editor
Page: 20


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AJN On the Web.

Author:
Page: 20


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Does Chewing Gum Promote Bowel Function After Cesarean Section?.

Author: Wilson, Amanda PhD, BA (Hons), RN, MCA
Page: 21


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Sedentary work and the risks of colon and rectal cancer by anatomical sub-site in the Canadian census health and environment cohort (CanCHEC)

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Publication date: August 2017
Source:Cancer Epidemiology, Volume 49
Author(s): Manisha Pahwa, M. Anne Harris, Jill MacLeod, Michael Tjepkema, Paul A. Peters, Paul A. Demers
BackgroundSedentary behaviour is a potential risk factor for colorectal cancer. We examined the association between sedentary work, based on body position, and colorectal cancer risk in Canadians.MethodsA working body position category (a. sitting; b. standing and walking; c. sitting, standing, and walking; d. other) was assigned to occupations reported by 1991 Canadian Census respondents based on national occupational counselling guidelines. Adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated for cancers of the colon (overall, proximal, and distal) and rectum in men and women newly diagnosed from 1992 to 2010.ResultsCompared to "sitting" jobs, men in occupations with "other" (non-sitting, −standing, or −walking) body positions had a weakly significant reduced colon cancer risk (HR=0.93, 95% CI: 0.89, 0.98) primarily attributed to protection at the distal site (HR=0.90, 95% CI: 0.84, 0.97). Men in "standing and walking" and "sitting, standing, and walking" jobs did not have significantly reduced colon cancer risks. No effects were observed for rectal cancer in men or colon and rectal cancer in women.ConclusionThe two significant findings of this analysis should be followed-up in further investigations with additional information on potential confounders. Null findings for rectal cancer were consistent with other studies.



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Opposite effects of catalase and MnSOD ectopic expression on stress induced defects and mortality in the desmin deficient cardiomyopathy model

Publication date: September 2017
Source:Free Radical Biology and Medicine, Volume 110
Author(s): Kleopatra Rapti, Antigoni Diokmetzidou, Ismini Kloukina, Derek J. Milner, Aimilia Varela, Constantinos H. Davos, Yassemi Capetanaki
Oxidative stress has been linked strongly to cell death and cardiac remodeling processes, all hallmarks of heart failure. Mice deficient for desmin (des-/-), the major muscle specific intermediate filament protein, develop dilated cardiomyopathy and heart failure characterized by mitochondrial defects and cardiomyocyte death. The cellular and biochemical alterations in the hearts of these mice strongly suggest that oxidative stress is one of the mechanisms contributing to the pathogenesis of the phenotype. Recently, we showed that indeed the desmin deficient cardiomyocytes are under increased oxidative stress. In order to verify these findings in vivo, we generated transgenic animals overexpressing SOD2 (MnSOD) and/or catalase in the heart and crossed them with des-/- mice, thus allowing us to evaluate the contribution of oxidative injury in inherited cardiomyopathies, as well as the therapeutic potential of antioxidant strategies. Moderate MnSOD and/or catalase overexpression in des-/- hearts leads to a marked decrease in intracellular reactive oxygen species (ROS), ameliorates mitochondrial and other ultrastructural defects, minimizes myocardial degeneration and leads to a significant improvement of cardiac function. Importantly, catalase overexpression increased the 50% survival rate of des-/- mice in an obligatory exercise to 100%. In contrast, MnSOD overexpression enhanced the lethality of des-/- mice, underscoring the importance of a fine balanced cellular redox status. Overall, the present study supports the contribution of oxidative stress in the development of des-/- cardiomyopathy and points to a well-considered antioxidant treatment as therapeutic for cardiomyopathies.

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Modulation of gap junction-associated Cx43 in neural stem/progenitor cells following traumatic brain injury

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Publication date: Available online 23 June 2017
Source:Brain Research Bulletin
Author(s): Kisha Greer, Jiang Chen, Thomas Brickler, Robert Gourdie, Michelle H Theus
Restoration of learning and memory deficits following traumatic brain injury (TBI) is attributed, in part, to enhanced neural stem/progenitor cell (NSPCs) function. Recent findings suggest gap junction (GJ)-associated connexin 43 (Cx43) plays a key role in the cell cycle regulation and function of NSPCs and is modulated following TBI. Here, we demonstrate that Cx43 is up-regulated in the dentate gyrus following TBI and is expressed on vimentin-positive cells in the subgranular zone. To test the role of Cx43 on NSPCs, we exposed primary cultures to the α-connexin Carboxyl Terminal (αCT1) peptide which selectively modulates GJ-associated Cx43. Treatment with αCT1 substantially reduced proliferation and increased caspase 3/7 expression on NSPCs in a dose-dependent manner. αCT1 exposure also reduced overall expression of Cx43 and phospho (p)-Serine368. These findings demonstrate that Cx43 positively regulates adult NPSCs; the modulation of which may influence changes in the dentate gyrus following TBI.



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Influence of social interaction on nociceptive-induced changes in locomotor activity in a mouse model of acute inflammatory pain: use of novel thermal assays

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Publication date: Available online 23 June 2017
Source:Brain Research Bulletin
Author(s): Branden A. Smeester, Jang-Hern Lee, Alvin J. Beitz
Most acute and chronic animal models of pain rely heavily on reflexive assays for evaluating levels of nociception, which involves removing the animal from its normal social environment. Here, we examine and characterize the influence of social interactions on inflammatory pain-evoked changes in movement in two different mouse strains. To produce inflammatory nociception, we injected CFA bilaterally into the hind paws of Balb/c and C3H mice and then recorded exploratory locomotor activity using an automated detector system to first evaluate the effects of social behavior on nociception. Secondly, we determined if carprofen administration altered the effects of social behavior on nociceptive-evoked movement. This methodology was expanded to create a novel thermal activity assay to objectively measure the effect of heat and cold on CFA-evoked animal movement in paired animals. Paired Balb/c and C3H mice exhibited significant hyper-locomotion that lasted for 3hours post-injection in Balb/c, but only 1hour post-injection in C3H. Single Balb/c mice only showed increased activity for 1hour post-injection, while single C3H mice showed no increase. This CFA-induced increase in activity in paired animals was highly inversely correlated with mechanical allodynia as measured using standard Von Frey filaments. Carprofen administration completely blocked this CFA-induced hyperlocomotor activity. Both heat and cold induced a significant increase in locomotor activity in paired mice injected with CFA, while having no effect on activity in control mice injected with saline. The results presented here indicate that social interactions greatly influence inflammatory pain-induced changes in locomotor activity and indicate that the use of movement-based assays to evaluate nociception in paired mice may provide an alternative and more sensitive method to quantify nociception and characterize novel analgesic effects over time in the context of social interactions in rodent models of pain.



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Age-dependent changes in autophosphorylation of alpha calcium/calmodulin dependent kinase II in hippocampus and amygdala after contextual fear conditioning

Publication date: Available online 23 June 2017
Source:Brain Research Bulletin
Author(s): Ton Fang, Kamillia Kasbi, Stephanie Rothe, Wajeeha Aziz, K. Peter Giese
The hippocampus and amygdala are essential brain regions responsible for contextual fear conditioning (CFC). The autophosphorylation of alpha calcium-calmodulin kinase II (αCaMKII) at threonine-286 (T286) is a critical step implicated in long-term potentiation (LTP), learning and memory. However, the changes in αCaMKII levels with aging and training in associated brain regions are not fully understood. Here, we studied how aging and training affect the levels of phosphorylated (T286) and proportion of phosphorylated:total αCaMKII in the hippocampus and amygdala. Young and aged mice, naïve (untrained) and trained in CFC, were analysed by immunohistochemistry for the levels of total and phosphorylated αCaMKII in the hippocampus and amygdala. We found that two hours after CFC training, young mice exhibited a higher level of phosphorylated and increased ratio of phosphorylated:total αCaMKII in hippocampal CA3 stratum radiatum. Furthermore, aged untrained mice showed a higher ratio of phosphorylated:total αCaMKII in the CA3 region of the hippocampus when compared to the young untrained group. No effect of training or aging were seen in the central, lateral and basolateral amygdala regions, for both phosphorylated and ratio of phosphorylated:total αCaMKII. These results show that aging impairs the training-induced upregulation of autophosphorylated (T286) αCaMKII in the CA3 stratum radiatum of the hippocampus. This indicates that distinct age-related mechanisms underlie CFC that may rely more heavily on NMDA receptor-dependent plasticity in young age.



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Evaluation of clinical process in osteosarcoma patients treated with chemotherapy including cisplatin, adriamycin, ifosfamide, and etoposide and determination of the treatment sequels in a long-term 11-year follow-up

Mozaffar Aznab, Maryam Hematti

Journal of Cancer Research and Therapeutics 2017 13(2):291-296

Aim: The aim of this study was to evaluate the effect of adding etoposide and ifosfamide chemotherapy drugs to treatment regimen of patients affected with osteosarcoma and to determine the clinical process and response to treatment during a follow-up period of 11 years. Materials and Methods: Forty patients with osteosarcoma participated in this study from July 2005 to 2016. Treatments were started based on the following schema and after initial examinations including biochemical profile, checking for lung metastasis by simple radiography, chest computed tomography scan, and bones scan. The initial chemotherapy which consisted of four cycles of cisplatin and adriamycin alternative with ifosfamide and etoposide was provided. Afterward, resection of the primary tumor and also the metastatic lesions was performed in patients with lung metastasis in case they had radiological evidence of response to the treatment. Results: The mean of follow-up duration in this study was 50 months. Thirty-four patients did not have metastasis and six were metastatic. Of 34 patients, 18 had relapse and 16 patients never had relapse. Five patients experienced only local relapse, nine had only systemic relapse, and two patients had simultaneous systemic and local relapses. Thirteen patients had died. The mean of overall survival in patients was 81 months. The mean of survival in patients with and without primary metastasis was 30 and 90 months, respectively. Conclusion: Favorable response to the treatment was obtained with an appropriate multiple disciplinary works in the osteosarcomas of extremities, and there were no considerable side effects and sequels in the long-term follow-up of these treatments.

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Complexity of chromosomal rearrangements in Down syndrome leukemia

Bani Bandana Ganguly, Nitin N Kadam, Prakash K Mandal

Journal of Cancer Research and Therapeutics 2017 13(2):381-383

Reports on imbalanced HSA21 gene expression and chromosomal rearrangements on leukemogenesis, drug sensitivity, and treatment outcome of leukemia in Down syndrome (DS) are limited. DS has been recognized as one of the most common leukemia-predisposing syndromes with unique clinical features, significant differences in treatment outcome and treatment-related toxicity profiles. Acute myeloid leukemia (AML), especially acute megakaryocytic leukemia, is reported with high cure rates presenting 80%–100% event-free survivals (EFSs); however, acute lymphoid leukemia indicates a worse prognosis in DS patients compared to non-DS children. Complex rearrangements are responsible for poor-to-very poor prognosis in all cases, irrespective of genetic predisposition or type of hematopoietic subunits affected. We report a 2-year-old female DS diagnosed with acute erythroleukemia (French–American–British: AML-M6) with highly complex chromosomal rearrangements in the bone marrow with 39 chromosomes. Parental consanguinity and genetic predisposition might be responsible for origin of multiple clones. Genetic instability and heterogeneity of complex clonal developments might cause poor prognosis. The case is a rare one with acute erythroleukemia in DS patient where too many rearrangements had masked identification of three 21s.

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Effects of EF-24, RAD001, and paclitaxel on the expression profiles of apoptotic and anti-apoptotic genes

Ebru Alp, Akin Yilmaz, Hacer Ilke Onen, Emine Sevda Menevse

Journal of Cancer Research and Therapeutics 2017 13(2):346-350

Context: Cancer cells exert differential responses to chemotherapeutics and inhibitors. To the best of our knowledge, a few or no research has been performed until now to determine the effect of EF-24 and RAD001 on MDA-MB-231 breast cancer cells with regard to mRNA expression of apoptotic and anti-apoptotic genes. Aims: In this study, we aimed to investigate the mRNA expression levels of apoptotic (caspase 2 [CASP2], CASP8, and CASP9) and anti-apoptotic (B-cell lymphoma 2 [BCL2] and BCL2-like protein 1 [BCL2L1]) genes after exposure to paclitaxel, EF-24, and RAD001 in MDA-MB-231 cells. Materials and Methods: After treatment, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to measure cell viability. mRNA expressions were analyzed using quantitative real-time polymerase chain reaction. Results: Decrease in cell viability ratios was seen in a dose-dependent manner for all chemicals. MDA-MB-231 cells responded slightly different to paclitaxel, EF-24, and RAD001 at the transcriptional level of apoptotic and anti-apoptotic genes. Conclusions: Our results showed that response of these cells to paclitaxel, EF-24, and RAD001 was found different at the transcriptional level of apoptotic and antiapoptotic genes. Therefore, understanding transcriptional changes after these drug exposure may give us a change to figure out more realistic results of the apoptotic pathway inhibition.

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Differential diagnoses of elevated lesions of the upper lip: An overview

Gowri Pandarinath Bhandarkar, Kushal Vasanth Shetty

Journal of Cancer Research and Therapeutics 2017 13(2):170-174

This paper comes with a purpose to help the clinician as how to arrive at a logical differential diagnosis when an upper lip mass is encountered in day-to-day practice. The labial mucosa is commonly traumatized. One must be aware of the type of structures contained in the mucosa of the area of a lesion as well as the patients habits since they may relate to a lesion presented for diagnosis. It also helps them to procure a sound knowledge of the lesions by describing the lesions according to their clinical appearance and to aid the clinician in arriving at a differential diagnosis by considering that certain lesions have a predilection for the upper lip. All clinically similar appearing lesions are discussed according to their relative frequency of occurrence. This paper covers only a minority of plethora of elevated lesions that may appear on the upper lip since almost any soft tissue lesion or neoplasm (benign and malignant) may occur here.

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An overview on small-field dosimetry in photon beam radiotherapy: Developments and challenges

Hamed Bagheri, Azadeh Soleimani, Nahideh Gharehaghaji, Asghar Mesbahi, Farhad Manouchehri, Babak Shekarchi, Banafsheh Dormanesh, Habib Alah Dadgar

Journal of Cancer Research and Therapeutics 2017 13(2):175-185

Small fields are more repeatedly used for radiation therapy as small segments in intensity-modulated radiotherapy or as in the form of independent fields in stereotactic radiosurgery and other novel equipment such as cyberknife and tomotherapy. Nevertheless, the application of small fields for radiotherapy of lung makes the dose calculation and planning inaccurate due to the existence of electronic disequilibrium and intrinsic deficiencies within most of the analytical dose calculation algorithms. The current review attempts to gather the information in this regard and focuses on the current progresses and retaining issues associated with this type of photon beams.

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Awareness of cervical cancer and willingness to participate in screening program: Public health policy implications

Somdatta Patra, Madhu Upadhyay, Pragti Chhabra

Journal of Cancer Research and Therapeutics 2017 13(2):318-323

Background: Cervical cancer is one of the most common malignancies among women in India. There is a high mortality as patients usually present at an advanced stage because of lack of awareness and nonexistent screening programs. Aim: This study was planned to find out awareness about cervical cancer among women and their willingness to utilize screening services in an urban resettlement colony of Delhi, India. Settings and Design: A community-based, cross-sectional study was carried out in a resettlement colony of North-West Delhi. Materials and Methods: Semi-structured interview schedule was used to collect information regarding different aspects of cervical cancer. Analysis was done using SPSS package (SPSS version 16 (UCMS and GTBH, Delhi, India)). Results: A total of 373 women were included in the study. Mean age of study participants was 39.14 years. Two-third of the study population were illiterate. Half of the study population was aware of cervical cancer, and only one-fourth of population were willing to participate in a screening test. Willingness was higher among educated, ever user of family planning method and having knowledge about at least one risk factor, signs or symptoms, or possibility of early diagnosis of cancer cervix. Conclusions: The country's national program advocates for opportunistic and targeted screening of women. An understanding of the factors that influences womens' willingness to participate in screening program is essential for the success of such programs. Hence, this study emphasizes the need for dissemination of knowledge about various aspects of cancer cervix which is critical for uptake of any screening program in a developing country.

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Cardiotoxic effects of radiotherapy and strategies to reduce them in patients with breast cancer: An overview

Katarzyna Rygiel

Journal of Cancer Research and Therapeutics 2017 13(2):186-192

Cardiotoxicity of various anticancer therapies, including radiotherapy (RT), can lead to cardiovascular (CV) complications, and their severity depends on many factors, including the site of action, the applied dose, the method of administration, the presence of pre-existing CV diseases, or CV risk factors, the individual patient characteristics, and the current or previous use of antineoplastic therapies. Cardiotoxicity can occur immediately upon administration of the anticancer therapy or it may have a delayed onset (months or years after the treatment). For an oncology treatment team, it is essential that the patients with cancer are in their best cardiac condition before they initiate anticancer therapy, during remission, and after its termination, and thus, a collaboration with cardiologists is of utmost importance. This article reviews cardiotoxicity associated with RT, focusing on patients with breast cancer. In addition, it outlines the main management strategies to assess, monitor, reduce, or possibly prevent RT-induced cardiotoxicity, based on the current research evidence. Medline literature review relating to this subject was performed, using the electronic search for the keywords "radiotherapy" and "cardiotoxicity" on PubMed for inclusion of the previous publications, and further search of reference articles on the detection and management of radiation-related heart disease in patients with breast cancer was conducted.

http://ift.tt/2rYP7Wc

Serum butyrylcholinesterase and zinc in breast cancer

Rupesh Kumar, Sairoz Razab, Krishnananda Prabhu, Satadru Ray, Bhanu Prakash

Journal of Cancer Research and Therapeutics 2017 13(2):367-370

Context: Even though, a large number of serological, molecular markers have been proposed for breast cancer screening, most of them lack specificity, sensitivity, prognostic value, and cost effectiveness. Butyrylcholinesterase (BChE) and its genes are aberrantly expressed in a variety of human cancers. It has-been linked to tumorigenesis, cell proliferation, and cell differentiation. Zinc (Zn) is a cofactor for superoxide dismutase, an enzyme that protects cellular components against free radical-induced damage and carcinogenesis. Therefore, the aim of present study was to estimate and compare serum BChE and serum Zn levels in healthy controls and biopsy proven breast cancer patients before definitive therapy. Aims: To estimate and compare serum BChE and serum Zn levels in healthy controls and biopsy proven breast cancer patients before definitive therapy. Settings and Design: Serum BChE and Zn were estimated in 46 newly diagnosed (preoperative) female patients with breast cancer and 50 healthy female volunteers. Subjects and Methods: Serum BChE and Zn were estimated by spectrophotometric method. Statistical Analysis Used: Data was expressed as median and inter quartile range. Comparisons between different stages of cancer were done using Kruskal–Wallis test. Results: There was a significant increase in serum BChE and Zn in breast cancer patients compared to controls (P < 0.001). Serum BChE showed a significant increase and Zn was significantly decreased in different stages of breast cancer. Conclusions: Both BChE and Zn are inexpensive and can easily be analyzed and may play a role in the management of breast cancer.

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The pitfalls in cytology diagnosis of poorly differentiated neuroendocrine carcinoma of lung and their treatment response

Debarshi Saha, Ankit Kumar, Sourjya Banerjee, M Nirupama, HB Sridevi, Priya Garg, Flora D Lobo

Journal of Cancer Research and Therapeutics 2017 13(2):213-217

Context: Lung is the most common site of small cell carcinoma (SCLC) – a poorly differentiated neuroendocrine carcinoma (PDNEC). SCLC comprises 15–20% of the invasive cancers of the lung. Aim: This study was conducted to appraise the accuracy and pitfalls of the diagnosis of PDNEC on cytology along with treatment responses if available. Settings and Design: Retrospective study for 2 years yielded 21 cases on cytology. Subjects and Methods: Slides of fine-needle aspiration of lymph nodes, the tumor, bronchial brush, and bronchoalveolar lavage specimens were used. The histological correlation was obtained as were treatment responses. Results: Eighteen SCLCs were confirmed on review. Of these, 13 initial reports were concordant and five, discordant. The rest three cases which initially reported as SCLC were found to be negative (2) and combined SCLC (1). One SCLC with concordant initial and reviewed diagnoses failed to confirm on histopathology. The patients, all heavy smokers, were predominantly males in the seventh to eighth decade age group. The sensitivity and specificity of reviewed diagnoses were better than that of the original. The difference between histopathology and cytology diagnoses (reviewed and original) was statistically insignificant. All patients were categorized as "extensive stage" by positron emission tomography-computerized tomography, and five were treated with etoposide and cisplatin with/without radiotherapy. Conclusion: Age group (61–70) and gender (males) distribution were statistically significant. Intermediate variants of SCLC may be misdiagnosed as adenocarcinoma. Similarly, combined SCLC may be missed on cytology if the observer does not sustain a high index of suspicion. Unequivocal cytology diagnosis opposed to negative histopathology report demands repeat biopsy.

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Changes in pharyngeal constrictor volumes during head and neck radiation therapy: Implications for dose delivery

Akila Kumarasiri, Chang Liu, Mona Kamal, Correen Fraser, Stephen Brown, Indrin J Chetty, Jinkoo Kim, Farzan Siddiqui

Journal of Cancer Research and Therapeutics 2017 13(2):218-223

Objective: The objective of this study was to evaluate the anatomical changes and associated dosimetric consequences to pharyngeal constrictor muscles (PCMs) that occur during head and neck (H and N) radiotherapy (RT). Materials and Methods: A cohort of 13 oropharyngeal cancer patients with daily cone beam computed tomography (CBCT) was retrospectively studied. On every 5th CBCT image, PCM was manually delineated by a radiation oncologist. The anterior-posterior PCM thickness was measured at the midline level of C3 vertebral body. Delivered dose to PCM was estimated by calculating dose on daily images and performing dose accumulation on corresponding planning CT images using a parameter-optimized B-spline-based deformable image registration algorithm. The mean and maximum delivered dose (Dmean, Dmax) to PCM were determined and compared with the corresponding planned quantities. Results: The average (±standard deviation) volume increase (ΔV) and thickness increase (Δt) over the course of 35 total fractions were 54 ± 33% (11.9 ± 7.6 cc) and 63 ± 39% (2.9 ± 1.9 mm), respectively. The resultant cumulative mean dose increase from planned dose to PCM (ΔDmean) was 1.4 ± 1.3% (0.9 ± 0.8 Gy), while the maximum dose increase (ΔDmax) was 0.0 ± 1.6% (0.0 ± 1.1 Gy). Patients who underwent adaptive replanning (n = 6) showed a smaller mean dose increase than those without (n = 7); 0.5 ± 0.2% (0.3 ± 0.1 Gy) versus 2.2 ± 1.4% (1.4 ± 0.9 Gy). There were statistically significant (P = 0.001) strong correlations between ΔDmean and Δt (Pearson coefficient r = 0.78), as well as between ΔDmean and ΔV (r = 0.52). Conclusion: The patients underwent considerable anatomical changes to PCM during H and N RT. However, the resultant increase in dose to PCM was minor to moderate. PCM thickness measured at C3 level is a good predictor for the mean dose increase to PCM.

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Adult rhabdomyosarcoma: Multimodality management and results

Abhijeet Ashok Salunke, Jaymin Shah, Nayan Gupta, Jyotindra Pandit

Journal of Cancer Research and Therapeutics 2017 13(2):384-386



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Thrombocytosis in gynecological cancers

Deepti Sharma, Garima Singh

Journal of Cancer Research and Therapeutics 2017 13(2):193-197

Thrombocytosis has been suggested to be a poor prognostic indicator in malignancies. Studies have shown that thrombocytosis is associated with a poor prognosis in various gynecological malignancies such as carcinoma ovary, cervical cancer, and endometrial cancer. The aim of this study is to analyze the impact of thrombocytosis on the prognosis of gynecological cancer. All the relevant data were retrieved by PubMed, MEDLINE, and Web of Science, and then studies were chosen in this analysis of association between thrombocytosis and gynecological malignancy. Thrombocytosis is common in advanced disease in patients with ovarian cancer, endometrial cancer, and cervical cancer. Therefore, it may be a marker of tumor burden or biologically more aggressive disease. Thrombocytosis is bad prognostic factor and associated with poorer outcomes.

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Regulation of various DNA repair pathways by E3 ubiquitin ligases

Chandramouli Natarajan, Kenichi Takeda

Journal of Cancer Research and Therapeutics 2017 13(2):157-169

DNA repair is the most important mechanism to maintain the normal cellular homeostasis. Owing to its complicated network, series of posttranslation modifications is required for proper function of the DNA repair proteins. One of such important posttranslation modifications is ubiquitination (attachment of ubiquitin). E3 ubiquitin ligases (UBLs) are a group of proteins that transfer ubiquitin from E2 conjugating enzymes to highly specific substrates such as DNA repair proteins. In this review, we have updated the role of different E3 UBL and how it regulates different DNA repair pathways.

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A prospective randomized controlled study of cisplatin versus carboplatin-based regimen in advanced squamous nonsmall cell lung cancer

Amr Shafik Saad, Ramy R Ghali, May Ahmed Shawki

Journal of Cancer Research and Therapeutics 2017 13(2):198-203

Background: The use of cisplatin (Cis) versus carboplatin (Carb) in the treatment of advanced nonsmall cell lung cancer (NSCLC) is controversial. The aim of the study was to compare the safety and efficacy of Cis versus Carb in squamous NSCLC. Patients and Methods: A prospective, randomized, controlled, open-label study was conducted on advanced squamous NSCLC patients who were randomly assigned to receive Cis (40 mg/m 2 [day 1 and day 8]) or Carb (area under the curve = 5 [day 1]) combined with gemcitabine [Gem] (1000 mg/m 2 [day 1 and day 8]) of a 3-week schedule for six cycles. Study objectives were a radiological response after three cycles and six cycles, 1-year progression-free survival (PFS), 1-year overall survival (OS), and quality of life (QOL) assessment using functional assessment of cancer therapy-lung at baseline, after three cycles, and after six cycles. Statistical Analysis: Statistical analysis was done using Statistical Package for Social Science version 15. A P < 0.05 was considered statistically significant. Results: Seventy-one patients were enrolled (Gem/Cis group [n = 36], Gem/Carb group [n = 35]). Response rates were comparable in both arms. Nonsignificant differences were found regarding 1-year PFS (P = 0.308) and 1-year OS (P = 0.929) between the two groups. Neutropenia was significantly higher in Gem/Carb group, while vomiting and ototoxicity were significantly higher in Gem/Cis group. The effect on QOL was similar in both groups. Conclusion: Cis and Carb have similar efficacy, tolerability, and effect on QOL and both can be used as a first-line treatment of squamous NSCLC.

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Dosimetric characterization of optically stimulated luminescence dosimeter with therapeutic photon beams for use in clinical radiotherapy measurements

Retna Ponmalar, Ravikumar Manickam, KM Ganesh, Sathiyan Saminathan, Arun Raman, Henry Finlay Godson

Journal of Cancer Research and Therapeutics 2017 13(2):304-312

Aim: The modern radiotherapy techniques impose new challenges for dosimetry systems with high precision and accuracy in in vivo and in phantom dosimetric measurements. The knowledge of the basic characterization of a dosimetric system before patient dose verification is crucial. This incites the investigation of the potential use of nanoDot optically stimulated luminescence dosimeter (OSLD) for application in radiotherapy with therapeutic photon beams. Materials and Methods: Measurements were carried out with nanoDot OSLDs to evaluate the dosimetric characteristics such as dose linearity, dependency on field size, dose rate, energy and source-to-surface distance (SSD), reproducibility, fading effect, reader stability, and signal depletion per read out with cobalt-60 (60 Co) beam, 6 and 18 MV therapeutic photon beams. The data acquired with OSLDs were validated with ionization chamber data where applicable. Results: Good dose linearity was observed for doses up to 300 cGy and above which supralinear behavior. The standard uncertainty with field size observed was 1.10% ± 0.4%, 1.09% ± 0.34%, and 1.2% ± 0.26% for 6 MV, 18 MV, and 60 Co beam, respectively. The maximum difference with dose rate was 1.3% ± 0.4% for 6 MV and 1.4% ± 0.4% for 18 MV photon beams. The largest variation in SSD was 1.5% ± 1.2% for 60 Co, 1.5% ± 0.9% for 6 MV, and 1.5% ± 1.3% for 18 MV photon beams. The energy dependence of OSL response at 18 MV and 60 Co with 6 MV beam was 1.5% ± 0.7% and 1.7% ± 0.6%, respectively. In addition, good reproducibility, stability after the decay of transient signal, and predictable fading were observed. Conclusion: The results obtained in this study indicate the efficacy and suitability of nanoDot OSLD for dosimetric measurements in clinical radiotherapy.

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The significance of serum leptin level in patients with early stage nonsmall cell lung cancer

Fatih Karatas, Bulent Yalcin, Suleyman Sahin, Hakan Akbulut, Gungor Utkan, Ahmet Demirkazik, Fikri Icli

Journal of Cancer Research and Therapeutics 2017 13(2):204-207

Backgrounds: The serum leptin level (SLL) has been shown to increase in patients with nonsmall cell lung cancer (NSCLC). However, available data regarding the relation between SLL and tumor subtypes, survival, cachexia, and tumor respectability in NSCLC are still under debate. The aim of this study is to evaluate SLL in NSCLC patients with and without cachexia. Materials and Methods: A total of 71 patients with early stage NSCLC were enrolled in this prospective study. SLL was measured by enzyme-linked immunosorbent assay. The relationship between SLL and clinicopathological factors including histopathological subtypes, weight loss, overall survival, and tumor resectability were evaluated. Results: Of the 71 patients, 57 (81%) were male with a mean age of 63.3 ± 8.2 years. The rates of histological subtypes of NSCLC were as follows: Squamous cell carcinoma 60.5%, adenocarcinoma 32%, and others 7.2%. Mean SLL was 12.9 ± 38.4 pmol/mL. There was no distinctive difference between SLL, weight loss, and survival. However, when stratifying the groups according to the lung cancer histological subtypes, mean SLL was significantly higher in patients with adenocarcinoma than those with squamous cell subtype (26.9 ± 6.2 pmol/mL vs. 5.1 ± 9.1 pmol/mL, P = 0.004). Conclusions: SLL might be beneficial as a useful biomarker in preclinical setting of NSCLC to guide detecting the lung cancer subtypes as well as monitoring the patients.

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Is neuroglial antigen 2 a potential contributor to cilengitide response in glioblastoma?

Hatice Sevim Nalkiran, Kerrie Leanne McDonald

Journal of Cancer Research and Therapeutics 2017 13(2):329-336

Background: Determining the expression levels of neuroglial antigen 2 (NG2) in glioma cell lines and to evaluate the potential contribution of NG2 to cilengitide response were aimed. Materials and Methods: Endogenous expression level of NG2 was determined using quantitative reverse transcription polymerase chain reaction and immunoblotting. Cilengitide responses of the cells were monitored to determine half maximal inhibitory concentration values. Whether the suppression of NG2 expression alters the response of A172 cells to cilengitide was examined. Results: The effect of cilengitide on inducing apoptosis of the cells was determined by TUNEL staining. High mRNA and protein expression of NG2 was detected in A172 and U-87MG cells, while T98G, M059K and M059J cells demonstrated low levels of NG2. A172, U-87MG and positive control MG-63 were relatively sensitive to cilengitide compared to T98G, M059K and M059J. MG-63, A172 and U-87MG were unexpectedly found to be more susceptible to cilengitide. In addition, NG2 knock-down showed no significant difference in cell death between small interfering RNA (siRNA)-transfected and cilengitide-treated groups. The results showed that cilengitide caused detachment and subsequently initiated apoptosis. Glioma cell lines express variable levels of NG2 and differ in their responses to cilengitide. Although increased numbers of apoptotic cells were found in untransfected cells compared to siRNA-transfected cells upon exposed to cilengitide, the difference was not documented to be significant between two groups. Conclusion: It may be proposed that the combination therapy of NG2 suppression and cilengitide treatment showed no considerable effect on glioblastoma compared to cilengitide therapy alone. Response to therapy may be further improved by targeting other factors act in concert in this signaling pathway.

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Modeling of lung cancer risk due to radon exhalation of granite stone in dwelling houses

Akbar Abbasi

Journal of Cancer Research and Therapeutics 2017 13(2):208-212

Aims: Due to increasing occurrences of lung cancer, radon exhalation rates, radon concentrations, and lung cancer risks in several types of commonly used granite stone, samples used for flooring in buildings, have been investigated. Subjects and Methods: We measured the radon exhalation rates due to granite stones by means of an AlphaGUARD Model PQ2000 in a cube container with changeable floor by various granite stones. The lung cancer risk and percentage of lung cancer deaths (LCRn) due to those conditions were calculated using Darby's model. Results: The radon exhalation rates ranged from 1.59 ± 0.41 to 9.43 ± 0.74 Bq/m 2/h. The radon concentrations in the standard room with poor and normal ventilation were calculated 20.10–71.09 Bq/m 3 and 16.12–47.01 Bq/m 3, respectively. Conclusions: The estimated numbers of lung cancer deaths attributable to indoor radon due to granite stones in 2013 were 145 (3.33%) and 103 (2.37%) for poor and normal ventilation systems, respectively. According to our estimations, the values of 3.33% and 2.37% of lung cancer deaths in 2013 are attributed to radon exhalation of granite stones with poor and normal ventilation systems, respectively.

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Validation of microsatellite instability histology scores with Bethesda guidelines in hereditary nonpolyposis colorectal cancer

Mustafa Kaya, Fatih Basak, Abdullah Sisik, Mustafa Hasbahceci, Gurhan Bas, Orhan Alimoglu, Cumhur Selçuk Topal, Gozde Kir

Journal of Cancer Research and Therapeutics 2017 13(2):356-361

Aims: Hereditary nonpolyposis colorectal cancer (HNPCC) is a subgroup of colorectal cancer (CRC) which should be differentiated because of the high risk for additional cancers and risk evaluation for other family members, especially for CRC. It is not practical to perform genetic testing for all CRC patients; therefore, various prediction modalities, for example, Bethesda guideline (BG) were studied in the literature. We aimed to assess the association of microsatellite instability (MSI), histology scores, and BG for predicting HNPCC risk. Subjects and Methods: Data were collected from CRC patients between 2009 and 2012. A total of 127 patients were retrospectively reviewed for BG status and the MSI scores, MsPath, and PathScore. Statistical Analysis Used: Definitive statistical methods (mean, standard deviation, median, frequency, and percentage) were used to evaluate the study data. Comparison used Student's t-test, Continuity (Yates) correction, Fisher-Freeman-Halton test, Pearson correlation, and receiver operating characteristics curve analysis. Results: Patients who were detected as Bethesda-positive had significantly higher MsPath and PathScore scores (P = 0.001 and P = 0.007, respectively). According to the cut-off value of 2.8 and 2.9 for MsPath and PathScore, respectively, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 90%, 43%, 22.8%, 95.8%, and 50.4% for MsPath, and 55%, 83.2%, 37.9%, 90.8%, and 78.7% for PathScore, respectively. Conclusions: The MSI scoring systems, MsPath, and PathScore, are reliable systems and effectively correlated with BG for predicting patients who need advanced analysis techniques because of the risk of HNPCC.

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Clear cell odontogenic carcinoma: A rare case report with emphasis on differential diagnosis

Uma Vasant Datar, Mamata Sharad Kamat, Sampada Shriram Kanitkar, Sanjay Satappa Byakodi

Journal of Cancer Research and Therapeutics 2017 13(2):374-377

Clear cell odontogenic carcinoma (CCOC) is a rare odontogenic malignancy with a female predilection, typically presenting as swelling in anterior region of mandible. CCOC was classified as a malignant neoplasm of odontogenic origin by the WHO in 2005 as it exhibits an aggressive growth pattern, local recurrence, and tendency of distant metastasis. Histologically, CCOC is characterized by sheets and islands of vacuolated/clear cells. Since clear cells are present in few odontogenic tumors, salivary gland neoplasms, and metastatic tumors to the jaws; presence of clear cells in a lesion of head and neck area poses a diagnostic challenge. Knowledge about the clinical course, histopathologic pattern, and immunoprofile of CCOC aids in differentiating it from other clear cell tumors. Herein, we present a case of CCOC in anterior mandibular region of 60-year-old female patient with an emphasis on its differential diagnosis from other clear cell lesions of the jaws.

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Di- n -butyl phthalate prompts interruption of spermatogenesis, steroidogenesis, and fertility associated with increased testicular oxidative stress in adult male rats

Abstract

Di-n-butyl phthalate (DBP) is extensively used as plasticizer, and it was ubiquitary released into the environment. The present study was aimed to investigate the effect of DBP on reproductive competence in adult male rats. Adult male rats were received corn oil or DBP injection intraperitoneally (ip) at 100 and 500 mg/kg body weight on 90, 97, 104, and 111 days. Following completion of the experimental period, adult male rats were cohabitated with untreated proestrus female rats for determination of fertilization capacity. Then, adult male rats were sacrificed, and other reproductive endpoints were determined by histopathology and biochemical analysis. The results revealed significant reduction of fertilization potential by decrease mating, fertility indices with increase pre-implantation and post-implantation losses, and resorptions in normal female rat cohabitation with DBP-treated adult male rats. The testes, seminal vesicle tissue somatic indices, epididymal sperm count, motility, viability, and hypoosmotic swelling (HOS) sperm were significantly decreased with increased sperm morphological abnormalities in DBP-treated adult male rats. The disorientation of spermatogenic cells decreased the diameter and epithelial thickness of seminiferous tubule in the testicular histopathology of DBP-exposed rats. Significant reduction of testicular 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase enzyme levels and serum testosterone with increased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were observed in DBP-treated groups. Higher testicular oxidative stress marker (lipid peroxidation product) with lower antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase levels in DBP-exposed groups was observed. From these results, it can be concluded that DBP increases oxidative stress; it leads to impairment of spermatogenesis, steroidogenesis, and fertility in adult male rats.



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How does vegetation structure influence woodpeckers and secondary cavity nesting birds in African cork oak forest?

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Publication date: August 2017
Source:Acta Oecologica, Volume 83
Author(s): Amalia Segura
The Great Spotted Woodpecker provides important information about the status of a forest in terms of structure and age. As a primary cavity creator, it provides small-medium size cavities for passerines. However, despite its interest as an ecosystem engineer, studies of this species in Africa are scarce. Here, spatially explicit predictive models were used to investigate how forest structural variables are related to both the Great Spotted Woodpecker and secondary cavity nesting birds in Maamora cork oak forest (northwest Morocco). A positive association between Great Spotted Woodpecker and both dead-tree density and large mature trees (>60 cm dbh) was found. This study area, Maamora, has an old-growth forest structure incorporating a broad range of size and condition of live and dead trees, favouring Great Spotted Woodpecker by providing high availability of foraging and excavating sites. Secondary cavity nesting birds, represented by Great Tit, African Blue Tit, and Hoopoe, were predicted by Great Spotted Woodpecker detections. The findings suggest that the conservation of the Maamora cork oak forest could be key to maintaining these hole-nesting birds. However, this forest is threatened by forestry practises and livestock overgrazing and the challenge is therefore to find sustainable management strategies that ensure conservation while allowing its exploitation.



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The effects of biome and spatial scale on the Co-occurrence patterns of a group of Namibian beetles

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Publication date: August 2017
Source:Acta Oecologica, Volume 83
Author(s): Monica Pitzalis, Francesca Montalto, Valentina Amore, Luca Luiselli, Marco A. Bologna
Co-occurrence patterns (studied by C-score, number of checkerboard units, number of species combinations, and V-ratio, and by an empirical Bayes approach developed by Gotelli and Ulrich, 2010) are crucial elements in order to understand assembly rules in ecological communities at both local and spatial scales. In order to explore general assembly rules and the effects of biome and spatial scale on such rules, here we studied a group of beetles (Coleoptera, Meloidae), using Namibia as a case of study. Data were gathered from 186 sampling sites, which allowed collection of 74 different species. We analyzed data at the level of (i) all sampled sites, (ii) all sites stratified by biome (Savannah, Succulent Karoo, Nama Karoo, Desert), and (iii) three randomly selected nested areas with three spatial scales each. Three competing algorithms were used for all analyses: (i) Fixed-Equiprobable, (ii) Fixed-Fixed, and (iii) Fixed-Proportional. In most of the null models we created, co-occurrence indicators revealed a non-random structure in meloid beetle assemblages at the global scale and at the scale of biomes, with species aggregation being much more important than species segregation in determining this non-randomness. At the level of biome, the same non-random organization was uncovered in assemblages from Savannah (where the aggregation pattern was particularly strong) and Succulent Karoo, but not in Desert and Nama Karoo. We conclude that species facilitation and similar niche in endemic species pairs may be particularly important as community drivers in our case of study. This pattern is also consistent with the evidence of a higher species diversity (normalized according to biome surface area) in the two former biomes. Historical patterns were perhaps also important for Succulent Karoo assemblages. Spatial scale had a reduced effect on patterning our data. This is consistent with the general homogeneity of environmental conditions over wide areas in Namibia.



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Pregabalin and uremic pruritus

Khichar Purnaram Shubhakaran

Journal of Pharmacy And Bioallied Sciences 2017 9(2):152-152



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Evaluation of therapeutic effectiveness of prescribed medications in patients with type 2 diabetes mellitus: Findings from a tertiary care hospital, Lahore, Pakistan

Bareera Rana, Allah Bukhsh, Tahir Mehmood Khan, Ammar Sarwar, Muhammad Ovais Omer, Shazia Qasim Jamshed

Journal of Pharmacy And Bioallied Sciences 2017 9(2):121-125

Aim: The present study was aimed to highlight the current prescribing pattern of oral hypoglycemia in type 2 diabetes mellitus and to evaluate the therapeutic effectiveness of these therapeutic categories in achieving target glycemic control. Methods: This is a prospective, cross-sectional, observational study of 6 months' duration conducted in a tertiary care hospital of Lahore, Pakistan. Results: The current research recruited 145 patients presented in diabetes management center of a tertiary care hospital in Lahore, Pakistan. Mean age of the participants was 50.2 (± 8.5) years. Out of the 145 patients, 63% were females and 37% were males. Most patients were diagnosed to have diabetes within the past 5 years. Diabetes-induced neuropathy was the most common complication (71.7%) among the patients. A large proportion of these patients (70.3%) were also suffering from other comorbidities among which the most common one is hypertension. The average number of prescribed medications was 1.31. Metformin was prescribed to a majority of patients (64%) as monotherapy while 28.96% received combination therapy. Mean glycated hemoglobin (HBA1c) before and after 3 months of treatment was 8.5 (± 2.3) and 8.04 (± 2.1), respectively. Inferential statistics show a strong association between HBA1c and life style modifications and adherence to medication therapy (P = 0.05). However, the correlation between HBA1c and Morisky score and duration of disease was inverse and weak (P = 0.6, 0.4). The t-test values show a small difference between HBA1c values before and after 3 months (t = 0.440 and 0.466, respectively). Conclusion: Optimization of medication regimen and continuous patient education regarding life style modification and adherence to medication therapy are necessitated to bring HBA1c values near to target.

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Statin therapy prescribing for patients with type 2 diabetes mellitus: A review of current evidence and challenges

Mohamed Hassan Elnaem, Mohamad Haniki Nik Mohamed, Hasniza Zaman Huri, Shah M Azarisman, Ramadan Mohamed Elkalmi

Journal of Pharmacy And Bioallied Sciences 2017 9(2):80-87

Use of statin therapy in patients with type 2 diabetes mellitus (T2DM) has been recommended by most clinical guidelines. Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among T2DM patients. It has been proved that statins are effective for primary or secondary CVD prophylaxis. Reports have highlighted the underutilization of statins in clinical practice and the suboptimal adherence to guideline recommendations. This review article points to summarize the current evidence confirming the role of statins in T2DM patients and to provide an overview of factors that may affect statins' prescribing patterns and compliance in clinical practice. Initiatives to enhance statin therapy prescribing should recognize the comprehensive nature of the prescribing process. Attempts to assure proper statin prescribing and utilization can help in achieving better clinical outcomes of statin therapy.

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