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

Αρχειοθήκη ιστολογίου

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Πέμπτη 21 Ιουλίου 2016

Erratum to: Prevalence and factors related to smoking and smoking cessation 6 months following a cancer diagnosis: a population-based study

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Association between CD14 SNP -159 C/T and gastric cancer: an independent case–control study and an updated meta-analysis

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Evaluation of MMP-9 and MMP-2 and their suppressor TIMP-1 and TIMP-2 in adenocarcinoma of esophagogastric junction

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Endocannabinoid system as a regulator of tumor cell malignancy – biological pathways and clinical significance

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Case 22-2016: A 65-Year-Old Man with Syncope, Dyspnea, and Leg Edema

Presentation of Case. Dr. David K. Rhee (Cardiology): A 65-year-old man was admitted to this hospital because of syncope, dyspnea, and leg edema. The patient had been in his usual health until approximately 1 month before admission, when cough occurred. One week later, his legs became swollen and…

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Randomized trial comparing efficacies of zoledronate and alendronate for improving bone mineral density and inhibiting bone remodelling in women with post-menopausal osteoporosis

Summary

What is known and objective

Bisphosphonates are the first-line medications for treating osteoporosis. The aim of our prospective study was to compare the efficacy of zoledronate with that of alendronate in women with post-menopausal osteoporosis based on the evaluations of bone mineral density (BMD) and serum levels of biochemical markers of bone remodelling.

Methods

Chinese women with post-menopausal osteoporosis were randomly assigned to the zoledronate (n = 52) or alendronate (n = 53) group, and were treated with 5 mg zoledronate intravenously once per year and 70 mg alendronate orally once per week, respectively. During a 3-year follow-up period, the lumbar spine, femoral neck and total hip were examined using dual-energy x-ray absorptiometry every 12 months to assess BMD, and the serum levels of amino-terminal propeptide of type I procollagen (P1NP) and carboxy-terminal cross-linked telopeptides of type 1 collagen (CTX) were measured to evaluate bone formation and resorption, respectively.

Results and discussion

Greater increases in BMD occurred in the zoledronate group over the 3-year follow-up period, with increases in BMD of 41·3%, 13·5% and 20·0% at the lumbar spine, femoral neck and total hip, respectively, compared with 16·9%, 5·88% and 8·93% in the alendronate group, respectively (P < 0·05 for all). At the 3-year follow-up, P1NP and β-CTX levels were reduced by 42·1% and 50·5% in the zoledronate group, respectively, whereas the levels of each were reduced by 19·5% and 19·4% in the alendronate group, respectively (P < 0·05 for all).

What is new and conclusions

Once yearly zoledronate administered intravenously was more efficacious for improving BMD and reducing the serum levels of P1NP and β-CTX in Chinese women with post-menopausal osteoporosis than alendronate administered orally once per week. The incidence of adverse events after the second and third zoledronate treatments was substantially lower than that in the alendronate group, suggesting a substantially lower risk of adverse events with long-term use of zoledronate in Chinese women, compared with that of alendronate use.

Thumbnail image of graphical abstract

Compared to alendronate, zoledronate medications of women with post-menopausal osteoporosis led to 1) better improvements of lumbar spine, femoral neck and total hip bone mineral densities and 2) was associated with superior reductions of the bone resorption marker P1NP and β-CTX expressions.



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Nerve growth factor: role in growth, differentiation and controlling cancer cell development

Abstract

Recent progress in the Nerve Growth Factor (NGF) research has shown that this factor acts not only outside its classical domain of the peripheral and central nervous system, but also on non-neuronal and cancer cells. This latter observation has led to divergent hypothesis about the role of NGF, its specific distribution pattern within the tissues and its implication in induction as well as progression of carcinogenesis. Moreover, other recent studies have shown that NGF has direct clinical relevance in certain human brain neuron degeneration and a number of human ocular disorders. These studies, by suggesting that NGF is involved in a plethora of physiological function in health and disease, warrant further investigation regarding the true role of NGF in carcinogenesis. Based on our long-lasting experience in the physiopathology of NGF, we aimed to review previous and recent in vivo and in vitro NGF studies on tumor cell induction, progression and arrest. Overall, these studies indicate that the only presence of NGF is unable to generate cell carcinogenesis, both in normal neuronal and non-neuronal cells/tissues. However, it cannot be excluded the possibility that the co-expression of NGF and pro-carcinogenic molecules might open to different consequence. Whether NGF plays a direct or an indirect role in cell proliferation during carcinogenesis remains to demonstrate.



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Safety of interferon-free therapies for chronic hepatitis C: a network meta-analysis

Summary

What is known and objective

Interferon-free (IFN-free) therapies for hepatitis C virus (HCV) have been developed to provide more effective, tolerable and safer therapeutic strategies. To date, no network meta-analysis (NMA) evaluating the safety profile of these regimens has been performed. This systematic review and NMA aimed to evaluate safety outcomes of IFN-free treatment options for chronic hepatitis C.

Methods

A systematic review was performed according to PRISMA and Cochrane recommendations. A literature search was conducted in PubMed/Medline, Scopus, Cochrane Library, International Pharmaceutical Abstracts and Web of Science electronic databases and included only randomized clinical trials that provided safety outcomes of interest of evaluated second-generation direct-acting antivirals: incidence of any adverse events (AEs) and serious AE. NMA allowed estimating probability for the relative safety of the interventions. A consistency model was used to draw conclusions about relative safety of treatments, presented as odds ratio (OR) and corresponding 95% credible interval (CrI).

Results

Fifty-one clinical trials were included (13 089 participants). Most participants had hepatitis C genotype 1 virus (76%) and were treated for 12 weeks. Two NMAs were built to investigate the incidence of AEs and serious AEs, comparing 13 and 10 IFN-free treatment options, respectively. For the outcome incidence of AEs, few significant differences were observed, which were explained by the presence of RBV. Elbasvir with grazoprevir and placebo were both safer than ombitasvir in combination with paritaprevir, ritonavir, daclatasvir plus RBV [ORs with 95% Crl of 4·09 (1·17–14·09) and 2·40 (1·19–4·77), respectively] and sofosbuvir with RBV [ORs with 95% Crl of 0·22 (0·07–0·72) and 2·69 (1·53–4·80), respectively]. Furthermore, elbasvir with grazoprevir was safer than sofosbuvir used with velpatasvir and RBV [OR 0·19 (95% CrI 0·03–0·98)]; ombitasvir in combination with paritaprevir, ritonavir, daclatasvir was safer than the same therapy but combined with RBV [OR 2·14 (95% CrI 1·09–4·44)]; and sofosbuvir used with velpatasvir was safer than sofosbuvir with RBV [OR 2·07 (95% CrI 1·13–3·79)]. Elbasvir with grazoprevir (50%) followed by placebo (28%) had the highest probabilities of less AEs. No significant differences were observed for serious AE outcomes.

What is new and conclusion

This meta-analysis included a large number of therapies. Small differences were observed in any AEs, but not in serious AEs.

Thumbnail image of graphical abstract

It was carried out network meta-analyses to assess safety of IFN-free therapies for hepatitis C. Two outcomes were evaluated: any adverse events and serious adverse events. Small differences were observed in any adverse events network meta-analysis, but not in serious adverse events network meta-analysis. Here it is presented the consistency analysis based on network meta-analysis results for any adverse events. Significant results are presented as odds ratio with 95% credible interval.



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Natural Convection Coupled with Thermal Radiation in a Square Porous Cavity Having a Heated Plate Inside

Abstract

This study reports a numerical simulation of the natural convection combined with thermal radiation in a square porous cavity with a thin isothermally heated plate placed horizontally or vertically at its center. The vertical walls of the cavity are cooled while the horizontal ones are adiabatic. The governing equations were solved using a finite volume method on a uniformly staggered grid system. The computational results are presented in the form of isotherm and streamline plots and Nusselt numbers. The effects of the Darcy number ( \(10^{-5} \le \mathrm{Da} \le ~10^{-2})\) , plate length ( \(0.25\le D \le 0.75\) ) and the radiation parameter ( \(0 \le R_{d} \le 2\) ) are investigated for the Rayleigh number Ra =  \(10^{7}\) . It is found that the Darcy number, the plate length and the radiation parameter enhance the overall heat transfer rate across the cavity.



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Effects of oral carbohydrate with amino acid solution on the metabolic status of patients in the preoperative period: a randomized, prospective clinical trial

Abstract

Objective

Enhanced recovery after surgery is increasingly desired nowadays, and preoperative nutrient intake may be beneficial for this purpose. In this study, we investigated whether the intake of preoperative carbohydrate with amino acid (ONS) solution can improve starvation status and lipid catabolism before the induction of anesthesia.

Methods

This randomized, prospective clinical trial included 24 patients who were divided into two groups before surgery under general anesthesia: a control group, comprising patients who fasted after their last meal the day before surgery (permitted to drink only water), and an ONS group, comprising patients who consumed ONS solution 2 h before surgery. Biochemical markers, the respiratory quotient, and psychosomatic scores were assessed at the initiation of anesthesia.

Results

Compared with the control group, the ONS group showed significantly lower serum free fatty acid levels [control group: 828 (729, 1004) µEq/L, ONS group: 479 (408, 610) µEq/L, P = 0.0002, median (25th, 75th percentile)] and total ketone bodies [control group: 119 (68, 440) µmol/L, ONS group: 40 [27, 64] µmol/L, P = 0.037]. In addition, analysis using the Visual Analog Scale showed higher preoperative scores for anxiety, hunger, and thirst for the control group, with no differences in any other measure of subjective well-being between groups.

Conclusions

The results of this study suggest that preoperative ONS intake improves lipid catabolism and starvation status before the induction of anesthesia. Furthermore, it can provide better preoperative mental health compared with complete fasting.



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Machine learning based methodology to identify cell shape phenotypes associated with microenvironmental cues

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Publication date: October 2016
Source:Biomaterials, Volume 104
Author(s): Desu Chen, Sumona Sarkar, Julián Candia, Stephen J. Florczyk, Subhadip Bodhak, Meghan K. Driscoll, Carl G. Simon, Joy P. Dunkers, Wolfgang Losert
Cell morphology has been identified as a potential indicator of stem cell response to biomaterials. However, determination of cell shape phenotype in biomaterials is complicated by heterogeneous cell populations, microenvironment heterogeneity, and multi-parametric definitions of cell morphology. To associate cell morphology with cell-material interactions, we developed a shape phenotyping framework based on support vector machines. A feature selection procedure was implemented to select the most significant combination of cell shape metrics to build classifiers with both accuracy and stability to identify and predict microenvironment-driven morphological differences in heterogeneous cell populations. The analysis was conducted at a multi-cell level, where a "supercell" method used average shape measurements of small groups of single cells to account for heterogeneous populations and microenvironment. A subsampling validation algorithm revealed the range of supercell sizes and sample sizes needed for classifier stability and generalization capability. As an example, the responses of human bone marrow stromal cells (hBMSCs) to fibrous vs flat microenvironments were compared on day 1. Our analysis showed that 57 cells (grouped into supercells of size 4) are the minimum needed for phenotyping. The analysis identified that a combination of minor axis length, solidity, and mean negative curvature were the strongest early shape-based indicator of hBMSCs response to fibrous microenvironment.



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Superhydrophobic materials for biomedical applications

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Publication date: October 2016
Source:Biomaterials, Volume 104
Author(s): Eric J. Falde, Stefan T. Yohe, Yolonda L. Colson, Mark W. Grinstaff
Superhydrophobic surfaces are actively studied across a wide range of applications and industries, and are now finding increased use in the biomedical arena as substrates to control protein adsorption, cellular interaction, and bacterial growth, as well as platforms for drug delivery devices and for diagnostic tools. The commonality in the design of these materials is to create a stable or metastable air layer at the material surface, which lends itself to a number of unique properties. These activities are catalyzing the development of new materials, applications, and fabrication techniques, as well as collaborations across material science, chemistry, engineering, and medicine given the interdisciplinary nature of this work. The review begins with a discussion of superhydrophobicity, and then explores biomedical applications that are utilizing superhydrophobicity in depth including material selection characteristics, in vitro performance, and in vivo performance. General trends are offered for each application in addition to discussion of conflicting data in the literature, and the review concludes with the authors' future perspectives on the utility of superhydrophobic biomaterials for medical applications.



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In-situ second harmonic generation by cancer cell targeting ZnO nanocrystals to effect photodynamic action in subcellular space

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Publication date: October 2016
Source:Biomaterials, Volume 104
Author(s): Bobo Gu, Artem Pliss, Andrey N. Kuzmin, Alexander Baev, Tymish Y. Ohulchanskyy, Jossana A. Damasco, Ken-Tye Yong, Shuangchun Wen, Paras N. Prasad
This paper introduces the concept of in-situ upconversion of deep penetrating near infrared light via second harmonic generation from ZnO nanocrystals delivered into cells to effect photo activated therapies, such as photodynamic therapy, which usually require activation by visible light with limited penetration through biological tissues. We demonstrated this concept by subcellular activation of a photodynamic therapy drug, Chlorin e6, excited within its strong absorption Soret band by the second harmonic (SH) light, generated at 409 nm by ZnO nanocrystals, which were targeted to cancer cells and internalized through the folate-receptor mediated endocytosis. By a combination of theoretical modeling and experimental measurements, we show that SH light, generated in-situ by ZnO nanocrystals significantly contributes to activation of photosensitizer, leading to cell death through both apoptotic and necrotic pathways initiated in the cytoplasm. This targeted photodynamic action was studied using label-free Coherent Anti-Stokes Raman Scattering imaging of the treated cells to monitor changes in the distribution of native cellular proteins and lipids. We found that initiation of photodynamic therapy with upconverted light led to global reduction in the intracellular concentration of macromolecules, likely due to suppression of proteins and lipids synthesis, which could be considered as a real-time indicator of cellular damage from photodynamic treatment. In prospective applications this in-situ photon upconversion could be further extended using ZnO nanocrystals surface functionalized with a specific organelle targeting group, provided a powerful approach to identify and consequently maximize a cellular response to phototherapy, selectively initiated in a specific cellular organelle.



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Hypoxia-directed and activated theranostic agent: Imaging and treatment of solid tumor

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Publication date: October 2016
Source:Biomaterials, Volume 104
Author(s): Rajesh Kumar, Eun-Joong Kim, Jiyou Han, Hyunseung Lee, Weon Sup Shin, Hyun Min Kim, Sankarprasad Bhuniya, Jong Seung Kim, Kwan Soo Hong
Hypoxia, a distinguished feature of various solid tumors, has been considered as a key marker for tumor progression. Inadequate vasculature and high interstitial pressures result in relatively poor drug delivery to these tumors. Herein, we developed an antitumor theranostic agent, 4, which is activated in hypoxic conditions and can be used for the diagnosis and treatment of solid tumors. Compound 4, bearing biotin, a tumor-targeting unit, and SN38, an anticancer drug, proved to be an effective theranostic agent for solid tumors. SN38 plays a dual role: as an anticancer drug for therapy and as a fluorophore for diagnosis, thus avoids an extra fluorophore and limits cytotoxicity. Compound 4, activated in the hypoxic environment, showed high therapeutic activity in A549 and HeLa cells and spheroids. In vivo imaging of solid tumors confirmed the tumor-specific localization, deep tissue penetration and activation of compound 4, as well as the production of a strong anticancer effect through the inhibition of tumor growth in a xenograft mouse model validating it as a promising strategy for the treatment of solid tumors.



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Machine learning based methodology to identify cell shape phenotypes associated with microenvironmental cues

S01429612.gif

Publication date: October 2016
Source:Biomaterials, Volume 104
Author(s): Desu Chen, Sumona Sarkar, Julián Candia, Stephen J. Florczyk, Subhadip Bodhak, Meghan K. Driscoll, Carl G. Simon, Joy P. Dunkers, Wolfgang Losert
Cell morphology has been identified as a potential indicator of stem cell response to biomaterials. However, determination of cell shape phenotype in biomaterials is complicated by heterogeneous cell populations, microenvironment heterogeneity, and multi-parametric definitions of cell morphology. To associate cell morphology with cell-material interactions, we developed a shape phenotyping framework based on support vector machines. A feature selection procedure was implemented to select the most significant combination of cell shape metrics to build classifiers with both accuracy and stability to identify and predict microenvironment-driven morphological differences in heterogeneous cell populations. The analysis was conducted at a multi-cell level, where a "supercell" method used average shape measurements of small groups of single cells to account for heterogeneous populations and microenvironment. A subsampling validation algorithm revealed the range of supercell sizes and sample sizes needed for classifier stability and generalization capability. As an example, the responses of human bone marrow stromal cells (hBMSCs) to fibrous vs flat microenvironments were compared on day 1. Our analysis showed that 57 cells (grouped into supercells of size 4) are the minimum needed for phenotyping. The analysis identified that a combination of minor axis length, solidity, and mean negative curvature were the strongest early shape-based indicator of hBMSCs response to fibrous microenvironment.



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Hypoxia-directed and activated theranostic agent: Imaging and treatment of solid tumor

S01429612.gif

Publication date: October 2016
Source:Biomaterials, Volume 104
Author(s): Rajesh Kumar, Eun-Joong Kim, Jiyou Han, Hyunseung Lee, Weon Sup Shin, Hyun Min Kim, Sankarprasad Bhuniya, Jong Seung Kim, Kwan Soo Hong
Hypoxia, a distinguished feature of various solid tumors, has been considered as a key marker for tumor progression. Inadequate vasculature and high interstitial pressures result in relatively poor drug delivery to these tumors. Herein, we developed an antitumor theranostic agent, 4, which is activated in hypoxic conditions and can be used for the diagnosis and treatment of solid tumors. Compound 4, bearing biotin, a tumor-targeting unit, and SN38, an anticancer drug, proved to be an effective theranostic agent for solid tumors. SN38 plays a dual role: as an anticancer drug for therapy and as a fluorophore for diagnosis, thus avoids an extra fluorophore and limits cytotoxicity. Compound 4, activated in the hypoxic environment, showed high therapeutic activity in A549 and HeLa cells and spheroids. In vivo imaging of solid tumors confirmed the tumor-specific localization, deep tissue penetration and activation of compound 4, as well as the production of a strong anticancer effect through the inhibition of tumor growth in a xenograft mouse model validating it as a promising strategy for the treatment of solid tumors.



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Graphene oxide reinforced polyvinyl alcohol/polyethylene glycol blend composites as high-performance dielectric material

Abstract

Novel flexible dielectric composites composed of polyvinyl alcohol (PVA), polyethylene glycol (PEG), and graphene oxide (GO) with high dielectric constant and low dielectric loss have been developed using facile and eco-friendly colloidal processing technique. The structure and morphology of the PVA/PEG/GO composites were evaluated using Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, UV-vis spectroscopy (UV-vis), X-ray diffraction (XRD), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The dielectric behavior of PVA/PEG/GO composites was investigated in the wide range of frequencies from 50 Hz to 20 MHz and temperature in the range 40 to 150 °C using impedance spectroscopy. The dielectric constant for PVA and PVA/PEG (50/50) blend film was found to be 10.71 (50 Hz, 150 °C) and 31.22 (50 Hz, 150 °C), respectively. The dielectric constant for PVA/PEG/GO composite with 3 wt% GO was found to be 644.39 (50 Hz, 150 °C) which is 60 times greater than the dielectric constant of PVA and 20 times greater than the dielectric constant of PVA/PEG (50/50) blend film. The PVA/PEG/GO composites not only show high dielectric constant but also show low dielectric loss which is highly attractive for practical applications. These findings underline the possibilities of using PVA/PEG/GO composites as a flexible dielectric material for high-performance energy storage applications such as embedded capacitors.



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Fugitive emissions from nanopowder manufacturing

Abstract

In response to health and safety questions and concerns regarding particulate matter emissions from equipment used for synthesizing NiFe and TiO2 nanopowders, a study was undertaken to assess their impact on the air quality inside and outside a laboratory where the manufacturing equipment is operated. Elemental concentrations determined by ion beam analysis (IBA) of air particulate matter (PM) samples collected hourly with a StreakerTM sampler were used to identify possible sources and estimate contributions from nanopowder production and other sources. The fugitive nanopowder emissions were the highest at the indoor sampling location when powders were being manufactured. Average fugitive emissions of 210 ng m−3 (1-h average) (maximum 2163 ng m−3 1-h average) represented 2 % (maximum 20 %) of the average PM collected (9359 ng m−3 1-h average). The measured NiFe alloy or TiO2 PM concentrations were much smaller than the 8-h time-weighted average (TWA) workplace exposure standards (WES) for these materials (≥1,000,000 ng m−3). Most PM was found to be from infiltrated outdoor ambient sources. This suggests that nanopowder production in the laboratory is not likely to have adverse health effects on individuals using the equipment, although further improvements can be made to further limit exposure.

Graphical abstract

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Tamoxifen metabolite endoxifen interferes with the polyamine pathway in breast cancer

Abstract

Tamoxifen is the most widely used drug to treat women with estrogen receptor α (ERα)-positive breast cancer. Endoxifen is recognized as the active metabolite of tamoxifen in humans. We studied endoxifen effects on ERα-positive MCF-7 breast cancer cells. Estradiol increased the proliferation of MCF-7 cells by two- to threefold and endoxifen suppressed its effects. Endoxifen suppressed c-myc, c-fos and Tff1 oncogene expression, as revealed by RT-PCR. Estradiol increased the activity of ornithine decarboxylase (ODC) and adenosyl methioninedecarboxylase (AdoMetDC), whereas endoxifen suppressed these enzyme activities. Endoxifen increased activities of spermine oxidase (SMO) and acetyl polyamine oxidase (APAO) significantly, and reduced the levels of putrescine and spermidine. These data suggest a possible mechanism for the antiestrogenic effects of tamoxifen/endoxifen, involving the stimulation of polyamine oxidase enzymes. Therefore, SMO and APAO stimulation might be useful biomarkers for the efficacy of endoxifen treatment of breast cancer.



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Gyroscopic behavior exhibited by the optical Kerr effect in bimetallic Au–Pt nanoparticles suspended in ethanol

Abstract

The modification in the third-order nonlinear optical response exhibited by rotating bimetallic Au–Pt nanoparticles in an ethanol solution was analyzed. The samples were prepared by a sol–gel processing route. The anisotropy associated to the elemental composition of the nanoparticles was confirmed by high-resolution transmission electron microscopy and energy-dispersive X-ray spectroscopy measurements. The size of the nanoparticles varies in the range from 9 to 13 nm, with an average size of 11 nm. Changes in the spatial orientation of the nanomaterials automatically generated a variation in their plasmonic response evaluated by UV–Vis spectroscopy. A two-wave mixing experiment was conducted to explore an induced birefringence at 532 nm wavelength with nanosecond pulses interacting with the samples. A strong optical Kerr effect was identified to be the main responsible effect for the third-order nonlinear optical phenomenon exhibited by the nanoparticles. It was estimated that the rotation of inhomogeneous nanostructures can provide a remarkable change in the participation of different surface plasmon resonances, if they correspond to multimetallic nanoparticles. Potential applications for developing low-dimensional gyroscopic systems can be contemplated.



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A photochemical approach to aromatic extension of the corannulene nucleus

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Chem. Commun., 2016, Advance Article
DOI: 10.1039/C6CC04910A, Communication
Venkatachalam Rajeshkumar, Mihaiela C. Stuparu
Conjugated aromatic units of choice can be fused to corannulene in an efficient manner through a photo-induced oxidative cyclization process.
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
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Pembrolizumab-Induced Demyelinating Polyradiculoneuropathy

To the Editor: Pembrolizumab and nivolumab, two humanized antibodies against programmed cell death 1 (PD-1) receptor, were recently approved for the treatment of unresectable or metastatic melanoma and for other cancers. We report two cases of severe demyelinating polyradiculoneuropathy that…

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Pembrolizumab-Induced Demyelinating Polyradiculoneuropathy

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To the Editor: Pembrolizumab and nivolumab, two humanized antibodies against programmed cell death 1 (PD-1) receptor, were recently approved for the treatment of unresectable or metastatic melanoma and for other cancers. We report two cases of severe demyelinating polyradiculoneuropathy that…

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What is the BMI threshold for open ventral hernia repair?

Abstract

Background

Overweight and obese patients are often asked to lose weight prior to ventral hernia repair (VHR). Improved outcomes are the reasons behind this strategy. Data regarding weight loss targets are scant, and it is not known at what body mass index (BMI) threshold postoperative complications increase. This study aimed to determine the threshold to allow proper patient counseling.

Methods

All patients who underwent open VHR at our institution between 2002 and 2015 captured in the NSQIP database were included. The primary outcome was defined as any (≥1) of 18 captured postoperative complications. Patients were divided into five groups based on BMI: group 1 (<25 kg/m2); 2 (25–29.99 kg/m2); 3 (30–34.99 kg/m2); 4 (35–39.99 kg/m2); and 5 (≥40 kg/m2). Multivariable, adjusted logistic regression was performed to evaluate the association between BMI categories and postoperative complications.

Results

Sixty seven of 922 patients (7.3 %) had at least one postoperative complication following VHR. The adjusted odds of complications in group 5 was 2.89 times greater compared to group 1 (OR 2.89; 95 % CI = 1.22–6.84), while there was no significant differences in odds of postoperative complications for groups 2, 3, or 4 compared to group 1. BMI category was also significantly associated with undergoing recurrent VHR, with 28.7 % of patients in group 5 having a recurrent repair compared to 14 % in patients in group 1 (p = 0.03).

Conclusions

After VHR, complications are most likely to occur in patients with BMI ≥ 40 kg/m2. This subset of patients also had a significantly higher risk of undergoing surgery for a recurrent hernia, suggesting that this group of patients is likely to experience adverse outcomes after VHR and should be counseled to consider bariatric surgery prior to attempts at VHR. VHR at lower BMIs appears appropriate, and delaying therapy to achieve preoperative weight loss will likely offer no advantage.



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Case 22-2016: A 65-Year-Old Man with Syncope, Dyspnea, and Leg Edema

Presentation of Case. Dr. David K. Rhee (Cardiology): A 65-year-old man was admitted to this hospital because of syncope, dyspnea, and leg edema. The patient had been in his usual health until approximately 1 month before admission, when cough occurred. One week later, his legs became swollen and…

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Simple risk factors to predict urgent endoscopy in nonvariceal upper gastrointestinal bleeding pre-endoscopically

Medicine

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Efficacy and safety of endoscopic balloon dilation for upper gastrointestinal strictures of Crohn's disease

Digestive Diseases and Sciences

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Association of visceral fat area with abdominal skeletal muscle distribution in overweight Japanese adults

Obesity Research & Clinical Practice

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Sleeve gastrectomy and anti-reflux procedures

Abstract

Background

Obesity is an epidemic in the USA that continues to grow, becoming a leading cause of premature avoidable death. Bariatric surgery has become an effective solution for obesity and its comorbidities, and one of the most commonly utilized procedures, the sleeve gastrectomy, can lead to an increase in gastroesophageal reflux following the operation. While these data are controversial, sometimes operative intervention can be necessary to provide durable relief for this problem.

Methods

We performed an extensive literature review examining the different methods of anti-reflux procedures that are available both before and after a sleeve gastrectomy.

Results

We reviewed several different types of anti-reflux procedures, including those that supplement the lower esophageal sphincter anatomy, such as magnetic sphincter augmentation and radiofrequency ablation procedures. Re-operation was also discussed as a possible treatment of reflux in sleeve gastrectomy, especially if the original sleeve becomes dilated or if a conversion to a Roux-en-Y gastric bypass or biliopancreatic diversion is deemed necessary. Sleeve gastrectomy with concomitant anti-reflux procedure was also reviewed, including the anti-reflux gastroplasty, hiatal hernia repair, and limited fundoplication.

Conclusion

A number of techniques can be used to mitigate the severity of reflux, either by maintaining the normal anatomic structures that limit reflux or by supplementing these structures with a plication or gastroplasty. Individuals with existing severe reflux should not be considered for a sleeve gastrectomy. New techniques that incorporate plication at the time of the index sleeve gastrectomy show some improvement, but these are in small series that will need to be further evaluated. The only proven method of treating intractable reflux after sleeve gastrectomy is conversion to a Roux-en-Y gastric bypass.



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HCV eradication does not impact gut dysbiosis or systemic inflammation in cirrhotic patients

Alimentary Pharmacology and Therapeutics

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Pembrolizumab-Induced Demyelinating Polyradiculoneuropathy

To the Editor: Pembrolizumab and nivolumab, two humanized antibodies against programmed cell death 1 (PD-1) receptor, were recently approved for the treatment of unresectable or metastatic melanoma and for other cancers. We report two cases of severe demyelinating polyradiculoneuropathy that…

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Pembrolizumab-Induced Demyelinating Polyradiculoneuropathy

nejmc1515584_f1.gif

To the Editor: Pembrolizumab and nivolumab, two humanized antibodies against programmed cell death 1 (PD-1) receptor, were recently approved for the treatment of unresectable or metastatic melanoma and for other cancers. We report two cases of severe demyelinating polyradiculoneuropathy that…

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What is the BMI threshold for open ventral hernia repair?

Abstract

Background

Overweight and obese patients are often asked to lose weight prior to ventral hernia repair (VHR). Improved outcomes are the reasons behind this strategy. Data regarding weight loss targets are scant, and it is not known at what body mass index (BMI) threshold postoperative complications increase. This study aimed to determine the threshold to allow proper patient counseling.

Methods

All patients who underwent open VHR at our institution between 2002 and 2015 captured in the NSQIP database were included. The primary outcome was defined as any (≥1) of 18 captured postoperative complications. Patients were divided into five groups based on BMI: group 1 (<25 kg/m2); 2 (25–29.99 kg/m2); 3 (30–34.99 kg/m2); 4 (35–39.99 kg/m2); and 5 (≥40 kg/m2). Multivariable, adjusted logistic regression was performed to evaluate the association between BMI categories and postoperative complications.

Results

Sixty seven of 922 patients (7.3 %) had at least one postoperative complication following VHR. The adjusted odds of complications in group 5 was 2.89 times greater compared to group 1 (OR 2.89; 95 % CI = 1.22–6.84), while there was no significant differences in odds of postoperative complications for groups 2, 3, or 4 compared to group 1. BMI category was also significantly associated with undergoing recurrent VHR, with 28.7 % of patients in group 5 having a recurrent repair compared to 14 % in patients in group 1 (p = 0.03).

Conclusions

After VHR, complications are most likely to occur in patients with BMI ≥ 40 kg/m2. This subset of patients also had a significantly higher risk of undergoing surgery for a recurrent hernia, suggesting that this group of patients is likely to experience adverse outcomes after VHR and should be counseled to consider bariatric surgery prior to attempts at VHR. VHR at lower BMIs appears appropriate, and delaying therapy to achieve preoperative weight loss will likely offer no advantage.



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Case 22-2016: A 65-Year-Old Man with Syncope, Dyspnea, and Leg Edema

Presentation of Case. Dr. David K. Rhee (Cardiology): A 65-year-old man was admitted to this hospital because of syncope, dyspnea, and leg edema. The patient had been in his usual health until approximately 1 month before admission, when cough occurred. One week later, his legs became swollen and…

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Sleeve gastrectomy and anti-reflux procedures

Abstract

Background

Obesity is an epidemic in the USA that continues to grow, becoming a leading cause of premature avoidable death. Bariatric surgery has become an effective solution for obesity and its comorbidities, and one of the most commonly utilized procedures, the sleeve gastrectomy, can lead to an increase in gastroesophageal reflux following the operation. While these data are controversial, sometimes operative intervention can be necessary to provide durable relief for this problem.

Methods

We performed an extensive literature review examining the different methods of anti-reflux procedures that are available both before and after a sleeve gastrectomy.

Results

We reviewed several different types of anti-reflux procedures, including those that supplement the lower esophageal sphincter anatomy, such as magnetic sphincter augmentation and radiofrequency ablation procedures. Re-operation was also discussed as a possible treatment of reflux in sleeve gastrectomy, especially if the original sleeve becomes dilated or if a conversion to a Roux-en-Y gastric bypass or biliopancreatic diversion is deemed necessary. Sleeve gastrectomy with concomitant anti-reflux procedure was also reviewed, including the anti-reflux gastroplasty, hiatal hernia repair, and limited fundoplication.

Conclusion

A number of techniques can be used to mitigate the severity of reflux, either by maintaining the normal anatomic structures that limit reflux or by supplementing these structures with a plication or gastroplasty. Individuals with existing severe reflux should not be considered for a sleeve gastrectomy. New techniques that incorporate plication at the time of the index sleeve gastrectomy show some improvement, but these are in small series that will need to be further evaluated. The only proven method of treating intractable reflux after sleeve gastrectomy is conversion to a Roux-en-Y gastric bypass.



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Note of the methodological flaws in the paper entitled “GSTT1 and GSTM1 polymorphisms predict treatment outcome for breast cancer: a systematic review and meta-analysis”

Abstract

With great interest, we read the paper "GSTT1 and GSTM1 polymorphisms predict treatment outcome for breast cancer: a systematic review and meta-analysis" (by Hu XY et al.), which has reached important conclusions that GSTM1 null and GSTT1/GSTM1 double null polymorphisms might be significantly associated with an increased tumor response in breast cancer. The result is encouraging. Nevertheless, several methodological flaws in this meta-analysis are worth noticing.



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Expression profiles of miR-29c, miR-200b and miR-375 in tumour and tumour-adjacent tissues of head and neck cancers

Abstract

Altered expression of microRNAs (miRNAs) has been shown in many types of malignancies including the head and neck squamous cell carcinoma (HNSCC). Although there are many new and innovative approaches in the treatment of HNSCC, a clear marker of this disease is still missing. Three candidate miRNAs (miR-29c-3p, miR-200b-5p and miR-375-3p) were studied in connection with HNSCC using quantitative real-time PCR expression levels in 42 tissue samples of HNSCC patients and histologically normal tumour-adjacent tissue samples of these patients. Primary HNSCC carcinoma tissues can be distinguished from histologically normal-matched noncancerous tumour-adjacent tissues based on hsa-miR-375-3p expression (sensitivity 87.5 %, specificity 65 %). Additionally, a significant decrease of hsa-miR-200b-5p expression was revealed in tumour-adjacent tissue samples of patients with node positivity. Lower expression of hsa-miR-200b-5p and hsa-miR-29c-3p in HNSCC tumour tissue was associated with higher tumour grade. Consequently, survival analysis was performed. Lower expression of hsa-miR-29c-3p in tumour-adjacent tissue was associated with worse overall and disease-specific survivals. Lower expression of miR-29c-3p in tumourous tissue was associated with worse relapse-free survival. hsa-miR-375-3p seems to be a relatively promising diagnostic marker in HNSCC but is not suitable for prognosis of patients. Furthermore, this study highlighted the importance of histologically normal tumour-adjacent tissue in HNSCC progress (significant decrease of hsa-miR-200b-5p expression in tumour-adjacent tissue of patients with node positivity and low expression of hsa-miR-29c-3p in HNSCC tumour-adjacent tissue associated with worse prognosis).



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A novel index for preoperative, non-invasive prediction of macro-radical primary surgery in patients with stage IIIC–IV ovarian cancer—a part of the Danish prospective pelvic mass study

Abstract

The purpose of this study was to develop a novel index for preoperative, non-invasive prediction of complete primary cytoreduction in patients with FIGO stage IIIC–IV epithelial ovarian cancer. Prospectively collected clinical data was registered in the Danish Gynecologic Cancer Database. Blood samples were collected within 14 days of surgery and stored by the Danish CancerBiobank. Serum human epididymis protein 4 (HE4), serum cancer antigen 125 (CA125), age, performance status, and presence/absence of ascites at ultrasonography were evaluated individually and combined to predict complete tumor removal. One hundred fifty patients with advanced epithelial ovarian cancer were treated with primary debulking surgery (PDS). Complete PDS was achieved in 41 cases (27 %). The receiver operating characteristic curves demonstrated an area under the curve of 0.785 for HE4, 0.678 for CA125, and 0.688 for age. The multivariate model (Cancer Ovarii Non-invasive Assessment of Treatment Strategy (CONATS) index), consisting of HE4, age, and performance status, demonstrated an AUC of 0.853. According to the Danish indicator level, macro-radical PDS should be achieved in 60 % of patients admitted to primary surgery (positive predictive value of 60 %), resulting in a negative predictive value of 87.5 %, sensitivity of 68.3 %, specificity of 83.5 %, and cutoff of 0.63 for the CONATS index. Non-invasive prediction of complete PDS is possible with the CONATS index. The CONATS index is meant as a supplement to the standard preoperative evaluation of each patient. Evaluation of the CONATS index combined with radiological and/or laparoscopic findings may improve the assessment of the optimal treatment strategy in patients with advanced epithelial ovarian cancer.



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Defining Metastatic Cell Latency

Metastatic disease accounts for more than 90% of cancer deaths. For example, the life expectancy of women who have breast cancer has dramatically improved over the past 10 years, but women with metastatic disease have a 5-year survival rate of only 20%. Approximately 30% of women without evidence…

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Occurrence of hepatotoxicity with pazopanib and other anti-VEGF treatments for renal cell carcinoma: an observational study utilizing a distributed database network

Abstract

Purpose

To quantify the hepatic safety of pazopanib and comparator anti-vascular endothelial growth factor (VEGF) therapies in clinical practice among renal cell carcinoma (RCC) patients.

Methods

A population-based cohort study of new anti-VEGF users was conducted in two US healthcare databases, Department of Veterans Affairs (VA) and an oncology practice network (Altos), and the PHARMO Database Network in The Netherlands. A common protocol was used to collect liver chemistry (LC) data from anti-VEGF initiation through 4 years of follow-up. In the VA population, suspected drug-induced liver injury (DILI) outcomes were investigated via chart review, with adjudication by hepatologists.

Results

In Altos and VA, respectively, the total RCC patients were: pazopanib (156, 243), bevacizumab (122, 99), sorafenib (82, 249) and sunitinib (285, 751). PHARMO contained too few patients to be included. Few cases of alanine aminotransferase (ALT) ≥8× the upper limit of normal were seen across the anti-VEGF cohorts; incidence rates (per 100 person-years) ranged from 0 (sunitinib) to 8.2 (pazopanib) in Altos and from 0 (bevacizumab and sorafenib) to 2.1 (pazopanib) among VA patients. No cases of Hy's law identified by combination LC elevations were seen in patients treated with pazopanib or bevacizumab; one case was observed in those treated with sorafenib, and two cases were found among sunitinib users. One case of adjudicated DILI was observed in a sunitinib-treated patient; none were found among patients treated with pazopanib, bevacizumab or sorafenib.

Conclusions

Severe liver injury occurred infrequently during exposure to pazopanib and other anti-VEGF therapies in a population-based setting.



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A multi-centred randomised trial of radical surgery versus adjuvant chemoradiotherapy after local excision for early rectal cancer

Abstract

Background

Rectal cancer surgery is accompanied with high morbidity and poor long term functional outcome. Screening programs have shown a shift towards more early staged cancers. Patients with early rectal cancer can potentially benefit significantly from rectal preserving therapy. For the earliest stage cancers, local excision is sufficient when the risk of lymph node disease and subsequent recurrence is below 5 %. However, the majority of early cancers are associated with an intermediate risk of lymph node involvement (5–20 %) suggesting that local excision alone is not sufficient, while completion radical surgery, which is currently standard of care, could be a substantial overtreatment for this group of patients.

Methods/Study design

In this multicentre randomised trial, patients with an intermediate risk T1-2 rectal cancer, that has been locally excised using an endoluminal technique, will be randomized between adjuvant chemo-radiotherapylimited to the mesorectum and standard completion total mesorectal excision (TME). To strictly monitor the risk of locoregional recurrence in the experimental arm and enable early salvage surgery, there will be additional follow up with frequent MRI and endoscopy. The primary outcome of the study is three-year local recurrence rate. Secondary outcomes are morbidity, disease free and overall survival, stoma rate, functional outcomes, health related quality of life and costs. The design is a non inferiority study with a total sample size of 302 patients.

Discussion

The results of the TESAR trial will potentially demonstrate that adjuvant chemoradiotherapy is an oncological safe treatment option in patients who are confronted with the difficult clinical dilemma of a radically removed intermediate risk early rectal cancer by polypectomy or transanal surgery that is conventionally treated with subsequent radical surgery. Preserving the rectum using adjuvant radiotherapy is expected to significantly improve morbidity, function and quality of life if compared to completion TME surgery.

Trial registration

NCT02371304, registration date: February 2015



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Prognostic value of quality of life score in disease-free survivors of surgically-treated lung cancer

Abstract

Background

We aimed to evaluate the prognostic value of quality of life (QOL) for predicting survival among disease-free survivors of surgically-treated lung cancer after the completion of cancer treatment.

Methods

We administered the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), the Quality of Life Questionnaire Lung Cancer Module (QLQ-LC13), Hospital Anxiety and Depression Scale (HADS), and Posttraumatic Growth Inventory (PTGI) to 809 survivors who were surgically-treated for lung cancer at two hospitals from 2001 through 2006. We gathered mortality data by linkage to the National Statistical Office through December 2011. We used Cox proportional hazard models to compute adjusted hazard ratios (aHRs) and 95 % confidence intervals (CIs) to estimate the relationship between QOL and survival.

Results

Analyses of QOL items adjusted for age, sex, stage, body mass index, and physical activity showed that scores for poor physical functioning, dyspnea, anorexia, diarrhea, cough, personal strength, anxiety, and depression were associated with poor survival. With adjustment for the independent indicators of survival, final multiple proportional hazard regression analyses of QOL show that physical functioning (aHR, 2.39; 95 % CI, 1.13–5.07), dyspnea (aHR, 1.56; 95 % CI, 1.01–2.40), personal strength (aHR, 2.36; 95 % CI, 1.31–4.27), and anxiety (aHR, 2.13; 95 % CI, 1.38–3.30) retained their independent prognostic power of survival.

Conclusion

This study suggests that patient-reported QOL outcomes in disease-free survivors of surgically-treated lung cancer after the completion of active treatment has independent prognostic value for long-term survival.



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CXCL12 expression promotes esophageal squamous cell carcinoma proliferation and worsens the prognosis

Abstract

Background

The chemokine CXCL12 and its corresponding receptor CXCR4 are key players in the development of several cancers. Therefore, we hypothesized that there is a functional causality between CXCL12 expression and tumor progression in patients with esophageal squamous cell carcinoma (ESCC).

Methods

We performed an immunohistochemical analysis in 79 consecutive patients with ESCC. We performed in vitro and in vivo cell proliferation assays using ESCC cell lines and a newly established transfectant stably overexpressing CXCL12.

Results

Immunohistochemistry revealed positive CXCR4 and CXCL12 expression in 48 (61 %) and 62 (78 %) patients, respectively. Additionally, the expression levels did not significantly correlate with any clinicopathological factors. The MIB-1 proliferation index was markedly higher in ESCC with a positive expression of CXCR4 or CXCL12. Positive CXCL12 expression was significantly correlated with lower recurrence-free survival (RFS, p = 0.02). Cox's hazard models revealed CXCL12 expression as an independent predictive factor for recurrence. In vitro, CXCL12 exposure or overexpression enhanced ESCC proliferation; and AMD3100, a specific inhibitor of CXCR4, equally decreased proliferation irrespective of CXCL12 exposure or overexpression. In the mouse model, AMD3100 significantly decreased ESCC tumor size (p = 0.03).

Conclusions

CXCL12 stimulates ESCC proliferation, and its expression levels are related to lower RFS in patients with ESCC. Our findings indicate that positive CXCL12 expression may be a useful marker for predicting the outcome in patients with ESCC and is a potentially new therapeutic target for ESCC.



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Erratum to: Prevalence and factors related to smoking and smoking cessation 6 months following a cancer diagnosis: a population-based study

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Note of the methodological flaws in the paper entitled “GSTT1 and GSTM1 polymorphisms predict treatment outcome for breast cancer: a systematic review and meta-analysis”

Abstract

With great interest, we read the paper "GSTT1 and GSTM1 polymorphisms predict treatment outcome for breast cancer: a systematic review and meta-analysis" (by Hu XY et al.), which has reached important conclusions that GSTM1 null and GSTT1/GSTM1 double null polymorphisms might be significantly associated with an increased tumor response in breast cancer. The result is encouraging. Nevertheless, several methodological flaws in this meta-analysis are worth noticing.



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Expression profiles of miR-29c, miR-200b and miR-375 in tumour and tumour-adjacent tissues of head and neck cancers

Abstract

Altered expression of microRNAs (miRNAs) has been shown in many types of malignancies including the head and neck squamous cell carcinoma (HNSCC). Although there are many new and innovative approaches in the treatment of HNSCC, a clear marker of this disease is still missing. Three candidate miRNAs (miR-29c-3p, miR-200b-5p and miR-375-3p) were studied in connection with HNSCC using quantitative real-time PCR expression levels in 42 tissue samples of HNSCC patients and histologically normal tumour-adjacent tissue samples of these patients. Primary HNSCC carcinoma tissues can be distinguished from histologically normal-matched noncancerous tumour-adjacent tissues based on hsa-miR-375-3p expression (sensitivity 87.5 %, specificity 65 %). Additionally, a significant decrease of hsa-miR-200b-5p expression was revealed in tumour-adjacent tissue samples of patients with node positivity. Lower expression of hsa-miR-200b-5p and hsa-miR-29c-3p in HNSCC tumour tissue was associated with higher tumour grade. Consequently, survival analysis was performed. Lower expression of hsa-miR-29c-3p in tumour-adjacent tissue was associated with worse overall and disease-specific survivals. Lower expression of miR-29c-3p in tumourous tissue was associated with worse relapse-free survival. hsa-miR-375-3p seems to be a relatively promising diagnostic marker in HNSCC but is not suitable for prognosis of patients. Furthermore, this study highlighted the importance of histologically normal tumour-adjacent tissue in HNSCC progress (significant decrease of hsa-miR-200b-5p expression in tumour-adjacent tissue of patients with node positivity and low expression of hsa-miR-29c-3p in HNSCC tumour-adjacent tissue associated with worse prognosis).



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A novel index for preoperative, non-invasive prediction of macro-radical primary surgery in patients with stage IIIC–IV ovarian cancer—a part of the Danish prospective pelvic mass study

Abstract

The purpose of this study was to develop a novel index for preoperative, non-invasive prediction of complete primary cytoreduction in patients with FIGO stage IIIC–IV epithelial ovarian cancer. Prospectively collected clinical data was registered in the Danish Gynecologic Cancer Database. Blood samples were collected within 14 days of surgery and stored by the Danish CancerBiobank. Serum human epididymis protein 4 (HE4), serum cancer antigen 125 (CA125), age, performance status, and presence/absence of ascites at ultrasonography were evaluated individually and combined to predict complete tumor removal. One hundred fifty patients with advanced epithelial ovarian cancer were treated with primary debulking surgery (PDS). Complete PDS was achieved in 41 cases (27 %). The receiver operating characteristic curves demonstrated an area under the curve of 0.785 for HE4, 0.678 for CA125, and 0.688 for age. The multivariate model (Cancer Ovarii Non-invasive Assessment of Treatment Strategy (CONATS) index), consisting of HE4, age, and performance status, demonstrated an AUC of 0.853. According to the Danish indicator level, macro-radical PDS should be achieved in 60 % of patients admitted to primary surgery (positive predictive value of 60 %), resulting in a negative predictive value of 87.5 %, sensitivity of 68.3 %, specificity of 83.5 %, and cutoff of 0.63 for the CONATS index. Non-invasive prediction of complete PDS is possible with the CONATS index. The CONATS index is meant as a supplement to the standard preoperative evaluation of each patient. Evaluation of the CONATS index combined with radiological and/or laparoscopic findings may improve the assessment of the optimal treatment strategy in patients with advanced epithelial ovarian cancer.



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Progressive impairment of cerebellar mGluR signalling and its therapeutic potential for cerebellar ataxia in spinocerebellar ataxia type 1 model mice

Abstract

Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disease that presents with cerebellar ataxia and motor learning defects. Previous studies have indicated that the pathology of SCA1, as well as other ataxic diseases, is related to signalling pathways mediated by the metabotropic glutamate receptor type 1 (mGluR1), which is indispensable for proper motor coordination and learning. However, the functional contribution of mGluR signalling to SCA1 pathology is unclear. In the present study, we show that SCA1 model mice develop a functional impairment of mGluR signalling which mediates slow synaptic responses, dendritic Ca2+ signals and short- and long-term synaptic plasticity at parallel fibre (PF)-Purkinje cell (PC) synapses in a progressive manner from the early disease stage (5 postnatal weeks) prior to PC death. Notably, impairment of mGluR-mediated dendritic Ca2+ signals linearly correlated with reduction of PC capacitance (cell surface area) in the disease progression. Enhancement of mGluR signalling by baclofen, a clinically available GABAB receptor agonist, led to an improvement of motor performance in SCA1 mice and the improvement lasted ∼1 week after a single application of baclofen. Moreover, the restoration of motor performance in baclofen-treated SCA1 mice matched the functional recovery of mGluR-mediated slow synaptic currents and mGluR-dependent short- and long-term synaptic plasticity. These results suggest that impairment of synaptic mGluR cascades is one of the important contributing factors to cerebellar ataxia in early and middle stages of SCA1 pathology, and that modulation of mGluR signalling by baclofen or other clinical interventions may be therapeutic targets to treat SCA1.

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Greener synthesis of indolizine analogues using water as a base and solvent: study for larvicidal activity against Anopheles arabiensis

Abstract

Greener synthesis of a series of novel indolizine analogues have been achieved by the cyclization of aromatic cycloimmoniumylides with electron deficient alkynes in presence of water as the base and solvent at 80 °C. Yield of the title compounds was good and reactions performed were eco-friendly. The structures of these newly synthesized compounds have been confirmed by spectroscopic techniques such as FTIR, NMR, LC-MS and elemental analysis. Characterized title compounds were evaluated for larvicidal activity against Anopheles arabiensis by standard WHO larvicidal assay using Temephos as standard at 4 μg/mL. Title compounds 2e, 2f and 2g emerged as promising larvicidal agents.

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The title compounds 2a-j have been synthesized by two step chemical reaction, purified by recrystallization method at 69-83% yield. Larvicidal results revealed that, title compounds 2e and 2g emerged as promising larvicidal agents compared to standard compound.



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The C-terminal sequences of porcine thrombin are active as antimicrobial peptides

Abstract

The C-terminal sequences of porcine thrombin encode a series of peptides with the characteristics of net positive charge and hydrophobicity, suggesting antimicrobial potential. In this study, we synthesized truncated C-terminal peptides to explore their antimicrobial potency and structure-activity relationship. The results showed that some peptides exerted antimicrobial activity against Gram-positive and Gram-negative bacteria, with selectivity for microbial membranes. The antimicrobial potency of the peptides increased with the extension of chain length. Considering toxicity to red blood cells, the 21-mer peptide T-6 displayed the highest therapeutic index of 43.4, suggesting its higher cell selectivity. Typical α-helical conformations were observed upon binding to a bacteria-mimicking environment. The derivatives tended to interact preferentially with negatively charged vesicles compared to zwitterionic vesicles. Flow cytometry and electron microscopy revealed that the peptides targeted bacterial cell membranes and disrupted cytoplasmic membrane integrity, thereby causing the release of cellular contents leading to cell death. Peptide-membrane interaction experiments provided evidence that the peptides killed bacteria via a membrane-mediating mechanism. In summary, the C-terminal sequence of porcine thrombin has antimicrobial functions.

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A series of short antimicrobial peptides were obtained from C-terminus of porcine thrombin to investigate their antimicrobial potency, structure-activity relationship and mechanism. The 21-residue peptide T-6 exhibited a considerably higher level of cell selectivity with TI of 43.4. T-6 demonstrated a typical α-helix structure in membrane-mimetic environment and rapidly disrupted the microbial membrane, leading to leakage of the intracellular content and eventual cell death at its MIC.



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