A Quadrangular Flap Technique for Vermilion Repair in Unilateral Cleft Lip

Summary: In unilateral cleft lip repair, the vermilion triangular flap technique reported by Noordhoff1 and its modification are widely accepted for the augmentation of the vermilion height on the medial side of the cleft; however, these techniques do not focus on the deformity of the labial tubercle. In this article, we herein report a modified technique for vermilion repair that is focused on the labial tubercle. The muco-vermilion quadrangular flap was elevated from the lateral lip to augment the labial tubercle. As a result, the amount of labial tubercle is appropriate. Fifty-three consecutive unilateral cleft lip repairs were performed. In most cases, the amount of the labial tubercle was appropriate, and the curvature of free margin was preferable. The technique could reduce the number of scars on the vermilion by placing some of the suture lines on the oral surface and enabled the augmentation of the labial tubercle. In conclusion, the quadrangular flap can be considered an ideal flap for the construction of the vermilion.

http://ift.tt/2tqZa60

ILF2 Is a Regulator of RNA Splicing and DNA Damage Response in 1q21-Amplified Multiple Myeloma

Publication date: Available online 29 June 2017
Source:Cancer Cell
Author(s): Matteo Marchesini, Yamini Ogoti, Elena Fiorini, Anil Aktas Samur, Luigi Nezi, Marianna D'Anca, Paola Storti, Mehmet Kemal Samur, Irene Ganan-Gomez, Maria Teresa Fulciniti, Nipun Mistry, Shan Jiang, Naran Bao, Valentina Marchica, Antonino Neri, Carlos Bueso-Ramos, Chang-Jiun Wu, Li Zhang, Han Liang, Xinxin Peng, Nicola Giuliani, Giulio Draetta, Karen Clise-Dwyer, Hagop Kantarjian, Nikhil Munshi, Robert Orlowski, Guillermo Garcia-Manero, Ronald A. DePinho, Simona Colla
Amplification of 1q21 occurs in approximately 30% of de novo and 70% of relapsed multiple myeloma (MM) and is correlated with disease progression and drug resistance. Here, we provide evidence that the 1q21 amplification-driven overexpression of ILF2 in MM promotes tolerance of genomic instability and drives resistance to DNA-damaging agents. Mechanistically, elevated ILF2 expression exerts resistance to genotoxic agents by modulating YB-1 nuclear localization and interaction with the splicing factor U2AF65, which promotes mRNA processing and the stabilization of transcripts involved in homologous recombination in response to DNA damage. The intimate link between 1q21-amplified ILF2 and the regulation of RNA splicing of DNA repair genes may be exploited to optimize the use of DNA-damaging agents in patients with high-risk MM.

Graphical abstract

Teaser

Marchesini et al. show that in multiple myeloma the overexpression of ILF2, resulting from chromosome 1q21 amplification, drives resistance to DNA-damaging agents partly by modulating the interaction between YB-1 and the splicing factor U2AF65 to promote the processing and stabilization of transcripts involved in homologous recombination.


http://ift.tt/2tw42aE

Reviewing the impact of lipid synthetic flux on Th17 function

Publication date: June 2017
Source:Current Opinion in Immunology, Volume 46
Author(s): Yoko Kidani, Steven J Bensinger
CD4+ T helper 17 cells (Th17) acquire specific effector functions in response to activation and instructional signals. Accumulating evidence indicates that specific cellular lipid metabolic pathways play essential roles in regulating the differentiation and function of Th17 cells. Mechanistic studies reveal that metabolic fluxes through both the cholesterol and long chain fatty acid biosynthetic pathways are important in controlling RORγ transcriptional activity through their ability to generate lipid ligands of RORγ. Genetic and pharmacologic studies demonstrate that altering the flux through these lipid biosynthetic pathways impacts the generation of IL-17 as well as the balance of Th17 and CD4+ regulatory T cells (Tregs). In this mini-review, we briefly introduce the mechanics of cholesterol and long chain fatty acid biosynthesis. We also discuss the evidence underlying the unique role that these lipid metabolic pathways play in intrinsically regulating the fate and function of Th17 cells under normal and pathogenic conditions.



http://ift.tt/2t7m7su

A prospective randomized cost billing comparison of local fasciocutaneous perforator vs free Gracilis flap for lower limb reconstruction

We read with extreme interest the article published by Dr Abdelrahman et al. [1]. The colleagues are to be commended for their aim of performing a prospective randomized cost billing charges comparison of local fasciocutaneous perforator vs free Gracilis flap reconstruction for lower limb reconstruction. We do agree with the authors that lower limb traumatic wounds are a complex surgical topic, which should be approached in a multidisciplinary way. Moreover, the financial impact of a surgical procedure is an essential element to take into consideration.

http://ift.tt/2smKWDT

Response to comments on: A prospective randomized cost billing comparison of local fasciocutaneous perforator versus free Gracilis flap reconstruction for lower limb in a developing economy

Thank you for your letter and for allowing us to respond. We acknowledge that dr. Mangano et al. agree with us on the importance and relevance of the study. Regarding the first comment we present here the method we used for sample size calculation based on the flap viability outcome for each flap using the following equation n = [ (Z α/2+ Zβ)/(P1-P2)] (P1q1 + P2q2) [1], where:

http://ift.tt/2t7p9wQ

Commentary on The New Opt-Out Dutch National Breast Implant Registry - Lessons learnt from the road to implementation

The Dutch can be considered fortunate in, unlike many other countries, an estimated 95% of implants are used by a single craft group and funding for a breast implant registry is forthcoming (1). The authors point out that the variance between the quality and uptake around the world of different registry projects has detracted from the ability to extract useful information from these data bases in the past, and believe that an opt out system will improve the situation. ICOBRA was established to increase the homogeneity of the data set, but without universality of uptake as in the Dutch system, assemblage of these various sources is questionable.

http://ift.tt/2sn2AY3

Recent trends for the removal of colored particles in industrial wastewaters

http://ift.tt/2t7mMtO

Body talk, weight status, and pathological eating behavior in romantic relationships

Publication date: 1 October 2017
Source:Appetite, Volume 117
Author(s): Ellen Hart, Chong Man Chow, Cin Cin Tan
This study examined whether engagement in body talk would interact with weight status (body mass index; BMI) to predict pathological eating behaviors among romantically involved adults. Adults (N = 137, females = 86.86%, average age = 23.50) involved in a romantic relationship were recruited to complete an online survey about their body image, dietary behaviors, and engagement in body talk. Results indicated that engagement in negative body talk was directly related to higher pathological eating (i.e., drive for thinness, dieting, and bulimia symptoms). Positive body talk, on the other hand, had a significant interaction effect with BMI to predict pathological eating. For individuals with a high BMI, high engagement in positive body talk was associated with increased drive for thinness, dieting, and bulimia symptoms. However, for those with a low BMI, high engagement in positive body talk was protective against pathological eating. These findings suggest that while negative body talk is harmful in general, positive body talk is uniquely problematic for individuals of a higher weight status.



http://ift.tt/2s80qY0

‘My lips are sealed’ - The impact of package resealability on the consumption of tempting foods

Publication date: 1 October 2017
Source:Appetite, Volume 117
Author(s): Caroline De Bondt, Anneleen Van Kerckhove, Maggie Geuens
Resealable packages are nowadays omnipresent on store shelves. While the main advantage of the resealability feature is its ability to reclose the package in order to extend the shelf life of the food product inside, the present research's aim is to assess whether this advantage also has implications for palatable, energy-dense food consumption. Two studies provide intentional as well as behavioral evidence for the claim that consumers are better able to self-regulate their consumption and thus eat less in one occasion when a palatable, energy-dense food product is offered in a resealable (vs. unresealable) package. A third study investigates the effect of package resealability across multiple consumption occasions and reveals that the resealability feature limits the volume consumed on each occasion (conditional on consumption incidence) while it does not accelerate consumption frequency, resulting in a lower total consumed volume of palatable, energy-dense snacks over a six-day period. This research offers actionable insights for consumer welfare and public health care and aids manufacturers in delineating optimal food packaging strategies.



http://ift.tt/2tqHgAk

Randomised controlled trial of a text messaging intervention for reducing processed meat consumption: The mediating roles of anticipated regret and intention

Publication date: 1 October 2017
Source:Appetite, Volume 117
Author(s): V. Carfora, D. Caso, M. Conner
The present study aimed to extend the literature on text messaging interventions involved in promoting healthy eating behaviours. The theoretical framework was the Theory of Planned Behaviour (TPB). A randomized controlled trial was used to test the impact of daily text messages compared to no message (groups) for reducing processed meat consumption (PMC) over a 2 week period, testing the sequential mediation role of anticipated regret and intention on the relationship between groups and PMC reduction. PMC and TPB variables were assessed both at Time 1 and Time 2. Participants were Italian undergraduates (at Time 1 N = 124) randomly allocated to control and message condition groups. Undergraduates in the message condition group received a daily SMS, which focused on anticipated regret and urged them to self-monitor PMC. Participants in the control group did not receive any message. Those who completed all measures at both time points were included in the analyses (N = 112). Findings showed that a daily messaging intervention, controlling for participants' past behaviour, reduced self-reported consumption of PMC. Mediation analyses indicated partial serial mediation via anticipated regret and intentions. The current study provided support for the efficacy of a daily messaging intervention targeting anticipated regret and encouraging self-monitoring in decreasing PMC. Outcomes showed the important mediating role of anticipated regret and intentions for reducing PMC.



http://ift.tt/2s83e7k

Consumption of key food groups during the postpartum period in low-income, non-Hispanic black mothers

Publication date: 1 October 2017
Source:Appetite, Volume 117
Author(s): Melissa C. Kay, Heather Wasser, Linda S. Adair, Amanda L. Thompson, Anna Maria Siega-Riz, Chirayath M. Suchindran, Margaret E. Bentley
The postpartum period can impact diet quality and subsequently place women at greater risk for overweight or obesity. This study examined consumption of key food groups during the first 2 years postpartum among low income, non-Hispanic black, first-time mothers. Data were from the Infant Care, Feeding and Risk of Obesity Study, a cohort of 217 mother–infant dyads, followed from 3 to 18 months postpartum, collected from 2003 to 2007. At each study visit (3, 6, 9, 12, and 18 months) 24-h dietary recalls were collected. Consumption levels were compared to those recommended from the 2010 Dietary Guidelines for Americans (DGAs) for each of the following food groups: fruits, vegetables, grains, whole grains, protein foods and dairy, as well as an estimated upper limit for sugar-sweetened beverage (SSB) consumption. At each time point, mothers met recommended intake levels for grains and protein foods only. In random-intercept logistic regression models, no demographic or household characteristics were associated with a likelihood of consuming recommended levels for any of the food groups according to the DGAs. Given the low intake of fruits, vegetables, whole grains and lean protein foods and high intake of SSBs and refined grains, interventions targeting women's diet during the postpartum period are warranted.



http://ift.tt/2tqGbZB

Modelling and Extraction of Pulsatile Radial Distension and Compression Motion for Automatic Vessel Segmentation from Video

Publication date: Available online 29 June 2017
Source:Medical Image Analysis
Author(s): Alborz Amir-Khalili, Ghassan Hamarneh, Rafeef Abugharbieh
Identification of vascular structures from medical images is integral to many clinical procedures. Most vessel segmentation techniques ignore the characteristic pulsatile motion of vessels in their formulation. In a recent effort to automatically segment vessels that are hidden under fat, we motivated the use of the magnitude of local pulsatile motion extracted from surgical endoscopic video. In this article we propose a new approach that leverages the local orientation, in addition to magnitude of motion, and demonstrate that the extended computation and utilization of motion vectors can improve the segmentation of vascular structures. We implement our approach using four alternatives to magnitude-only motion estimation by using traditional optical flow and by exploiting the monogenic signal for fast flow estimation. Our evaluations are conducted on both synthetic phantoms as well as two real ultrasound datasets showing improved segmentation results with negligible change in computational performance compared to the previous magnitude only approach.

Graphical abstract

http://ift.tt/2upzBPS

Estimation of individual axon bundle properties by a Multi-Resolution Discrete-Search method

Publication date: Available online 29 June 2017
Source:Medical Image Analysis
Author(s): Ricardo Coronado-Leija, Alonso Ramirez-Manzanares, Jose Luis Marroquin
A stable, accurate and robust-to-noise method for the estimation of the intra-voxel bundle-wise diffusion properties for diffusion-weighted magnetic resonance imaging is presented. The proposed method overcomes some of the limitations of most of the multi-fiber algorithms in the literature and extends them to estimate the diffusion profiles, improving the estimation of the intra-voxel geometry at challenging microstructure configurations, that is to say: relatively small crossing angles, different voxel-wise anisotropic diffusion profiles and low SNR. The proposed methodology is based on four key novel ideas: (i) A Multi-Resolution Discrete-Search determines the orientation of the fiber bundles accurately and naturally constrains the sparsity on the recovered solutions; (ii) the determination of the number of fiber bundles using the F-test combined with a Rician bias correction; (iii) a Simultaneous Denoising and Fitting procedure that exploits the spatial redundancy of the axon bundles to achieve robustness with respect to noise; and (iv) a general framework for the estimation of the axial and radial diffusivity parameters independently for each voxel. A new useful evaluation metric is also proposed, which combines the information of the success rate in the estimated number of bundles and the angular error, avoiding in this way, some of the limitations these metrics have individually. A novel methodology for the evaluation of the methods on in-vivo data is also proposed. This work presents an extensive evaluation: the proposed methodology has been tested on state-of-the-art biophysical synthetic data for a variety of conditions, on the challenging spatially coherent phantom used on the HARDI reconstruction Challenge 2012, and on the recently released in-vivo MASSIVE data-set. Our results present significant improvements on the estimation of the number and orientation of the fiber bundles over the Spherical Deconvolution algorithm for multi-shell data, which is one of the most widely used multi-fiber algorithm. The results also show that, by the voxel-wise estimation of the diffusion profiles, the axial and radial diffusivity parameters are robustly estimated, being this essential for a better understanding of the individual bundle diffusion properties at challenging structural configurations.

Graphical abstract

http://ift.tt/2upyJdR

Guest editors of MICCAI 2016 Special Issues of Medical Imaging Analysis: The 19th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 2016)

Publication date: Available online 29 June 2017
Source:Medical Image Analysis
Author(s): Sebastien Ourselin, Mert R. Sabuncu, William Wells, Leo Joskowicz, Gozde Unal, Andreas Maier




http://ift.tt/2upXg2x

Cross-sectional association of coffee and caffeine consumption with sex hormone-binding globulin in healthy non-diabetic women

Abstract

Objective

Low sex hormone-binding globulin (SHBG) is a consistent risk factor for type 2 diabetes, particularly in women. Coffee consumption has been associated with a lower risk of type 2 diabetes but its effects on SHBG are less known.

Design and methods

This was a cross-sectional study of 2,377 non-diabetic pre- and post-menopausal women from the E3N cohort study whose baseline SHBG was measured. Information on diet (including coffee and caffeine consumption), lifestyle, and medical conditions was collected through questionnaires. The relationship between coffee and caffeine consumption and SHBG was modeled, with adjustment for covariates and stratification by body mass index (BMI) categories (< or ≥25 kg/m²) and menopausal status.

Results

The mean age was 57.3 ± 6.4 years and 61% of the 2,453 women were postmenopausal. High coffee (≥3 cups/day) and caffeine (≥265 mg/day) intakes were associated with a reduced risk of being in the 1^st quartile of the SHBG level distribution (<46.3 nmol∙L⁻¹) in a multivariate adjusted model (OR: 0.69 [95% CI 0.52-0.92] and OR: 0.68 [95% CI 0.50-0.94] respectively). No association was found between tea consumption and SHBG levels. In multivariate models stratified on BMI categories and menopausal status, associations were restricted to women with a BMI ≥25 kg/m² or being postmenopausal. The association with SHBG was consistently noted with both consumption of caffeinated coffee and caffeine, but not for decaffeinated coffee.

Conclusions

High coffee and caffeine consumptions are associated with a reduced risk of low SHBG, an established risk marker for T2DM, which might contribute to the protective effects of coffee for type 2 diabetes.

This article is protected by copyright. All rights reserved.

http://ift.tt/2tw3H7I

Relaxation induced by the nitric oxide donor and cyclooxygenase inhibitor NCX2121 in renal hypertensive rat aortas

Publication date: 30 September 2017
Source:European Journal of Pharmaceutical Sciences, Volume 107
Author(s): Tiago Dal-Cin de Paula, Bruno R. Silva, Marcella D. Grando, Laena Pernomian, Alejandro Ferraz do Prado, Lusiane Maria Bendhack

Graphical abstract

http://ift.tt/2upNpts

Freeze dried solid dispersion of exemestane: A way to negate an aqueous solubility and oral bioavailability problems

Publication date: 30 September 2017
Source:European Journal of Pharmaceutical Sciences, Volume 107
Author(s): Shamandeep Kaur, Sunil K. Jena, Sanjaya K. Samal, Vaishali Saini, Abhay T. Sangamwar
This study was envisaged to demonstrate the potential of exemestane loaded phospholipid/sodium deoxycholate solid dispersions (EXE-PL/SDC-SDs) on the solubility and oral bioavailability of EXE. Initial studies were performed to screen the best suitable phospholipid among lysophosphatidylcholine, Phospholipon® P80H and Lipoid® E80S for solid dispersion preparation. Further studies were carried out to optimize the molar concentration of phospholipid and sodium deoxycholate (SDC) for EXE-PL/SDC-SDs preparation. Optimized EXE-PL/SDC-SDs was prepared using Lipoid® E80S and SDC in 1:4M concentration, respectively and lyophilized using 10% w/w 2-hydroxypropyl-β-cyclodextrin (2-HPCD). The physical state of EXE in lyophilized formulation was confirmed by DSC and PXRD. Lyophilized formulation exhibits a significant increase in solubility and dissolution rate as compared to free drug EXE. Apparent permeability study was performed on Caco-2 cell line for 2h. The lyophilized EXE-PL/SDC-SDs exhibits 4.6-fold increase in absorptive transport as compared to EXE. Pharmacokinetic study in fasted female Sprague-Dawley rats revealed a 2.3-fold increase in AUC0-72h. Thus, the results suggest that PL/SDC-SDs is a promising carrier for EXE delivery.

Graphical abstract

http://ift.tt/2upUxGi

Investigating therapeutic usage of combined Ticagrelor and Aspirin through solid-state and analytical studies

Publication date: 30 September 2017
Source:European Journal of Pharmaceutical Sciences, Volume 107
Author(s): Hassane Sadou Yayé, Ivo B. Rietveld, Maria Barrio, Philippe-Henri Secrétan, Antoine Faucheron, Maher Karoui, Patrick Tilleul, Najet Yagoubi, Bernard Do
The mainstay treatment for patients with acute coronary syndrome is an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA). To improve patient adherence to such treatments, combination therapies (polypill) are envisioned. Physicochemical solid-state studies have been carried out to develop a preformulation strategy of ASA with the P2Y12-receptor antagonist Ticagrelor (TIC). The investigations were carried out using differential scanning calorimetry, liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSⁿ) and as complementary techniques Fourier transform infrared measurements and thermogravimetric analysis. A simple eutectic transition at 98°C with a mole fraction for the eutectic liquid of 0.457 has been observed and the mixing of ASA and TIC molecules in each other's crystal structures appears to be limited. No cocrystals of TIC and ASA have been found. The appearance of the eutectic liquid was linked with a clear onset of chemical instability of the two pharmaceuticals. The decomposition mechanism in the liquid phase involves prior decomposition of ASA, whose residues react with well-identified TIC interaction sites. Seven interaction products were observed by LC-HR-MSⁿ linked to corresponding degradation products. The most important degradation pathway is N-dealkylation. In conclusion, polypills of ASA and TIC are a viable approach, but the decomposition of ASA should be avoided by eliminating high temperatures and high humidity.

Graphical abstract

http://ift.tt/2upAJTF

Transcriptional Consequences of XPA Disruption in Human Cell Lines

Publication date: Available online 29 June 2017
Source:DNA Repair
Author(s): Mandira Manandhar, Megan G. Lowery, Karen S. Boulware, Kevin H. Lin, Yue Lu, Richard D. Wood
Nucleotide excision repair (NER) in mammalian cells requires the xeroderma pigmentosum group A protein (XPA) as a core factor. Remarkably, XPA and other NER proteins have been detected by chromatin immunoprecipitation at some active promoters, and NER deficiency is reported to influence the activated transcription of selected genes. However, the global influence of XPA on transcription in human cells has not been determined. We analyzed the human transcriptome by RNA sequencing (RNA-Seq). We first confirmed that XPA is confined to the cell nucleus even in the absence of external DNA damage, in contrast to previous reports that XPA is normally resident in the cytoplasm and is imported following DNA damage. We then analyzed four genetically matched human cell line pairs deficient or proficient in XPA. Of the ∼14,000 genes transcribed in each cell line, 325 genes (2%) had a significant XPA-dependent directional change in gene expression that was common to all four pairs (with a false discovery rate of 0.05). These genes were enriched in pathways for the maintenance of mitochondria. Only 27 genes were different by more than 1.5-fold. The most significant hits were AKR1C1 and AKR1C2, involved in steroid hormone metabolism. AKR1C2 protein was lower in all of the immortalized XPA-deficient cells. Retinoic acid treatment led to modest XPA-dependent activation of some genes with transcription-related functions. We conclude that XPA status does not globally influence human gene transcription. However, XPA significantly influences expression of a small subset of genes important for mitochondrial functions and steroid hormone metabolism. The results may help explain defects in neurological function and sterility in individuals with xeroderma pigmentosum.



http://ift.tt/2upsXsD

Appendiceal Mucinous Neoplasms: Diagnosis and Management

AbstractObjective.Appendiceal mucinous neoplasms (AMNs) are a rare and heterogeneous disease for which clinical management is challenging. We aim to review the literature regarding modalities of treatment to guide the management of AMNs.Methods and Review Criteria.We conducted a PubMed search in February 2016 for English‐language publications, using the terms "appendiceal," "appendix," "carcinoma," "cancer," "mucinous," "treatment," "genes," "target," "genomic," and terms listed in the articles' subheadings. Published reports and abstracts from the American Society of Clinical Oncology meetings were also searched.Results.In this review, we summarize current data and controversies in AMN classification, clinical presentation, molecular alterations, treatment outcomes with regard to cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), and the role of systemic chemotherapy.Conclusion.Appendiceal mucinous neoplasms are a heterogeneous group of tumors with a rising incidence. Treatment is based on stage and histology. Low‐grade tumors are treated surgically with resection of the primary site in early stage disease, or peritoneal debulking and HIPEC in patients with advanced stage disease. Treatment of high‐grade tumors requires further prospective trials, and options include debulking surgery and HIPEC with or without preoperative chemotherapy. Trials evaluating novel therapies based on the molecular profiling of AMN tumors are needed to evaluate therapeutic options in patients who are not surgical candidates.Implications for Practice.This review provides a reference to guide gastroenterologists, pathologists, surgeons, and oncologists in the management of appendiceal mucinous neoplasms (AMNs), a rare and heterogeneous disease with no consensus on histologic classification or guidelines for treatment algorithms. This review summarizes all AMN classifications and proposes a treatment algorithm based on stage and histology of disease.

http://ift.tt/2sXbBFK

Label-free electrochemiluminescence assay for aqueous Hg2+ through oligonucleotide mediated assembly of gold nanoparticles

Publication date: 15 December 2017
Source:Biosensors and Bioelectronics, Volume 98
Author(s): Dong-Mei Wang, Qi-Qi Gai, Rong-Fu Huang, Xingwang Zheng
Development of ultrasensitive method for Hg²⁺ analysis is important for human health protection and environment monitoring. In this work, we present a highly sensitive and selective electrochemiluminescence (ECL) assay in a "turn-on" mode for the detection of Hg²⁺ through selective assembly of gold nanoparticles (AuNPs) on the surface of indium tin oxide (ITO) electrode. In the absence of Hg²⁺, the nonthiolated ssDNA could protected AuNPs against its assembly on ITO surface, producing rather low ECL emission for Ru(bpy)3²⁺/TPA system. Conversely, binding of Hg²⁺ with the Hg²⁺-specific oligonucleotide through thymine-Hg²⁺-thymine coordination formed the double-stranded structure, which could not effectively adsorb to AuNPs in solution. The assembly of free-state AuNPs is achieved, which well preserves electronical conductivity. The presence of AuNPs can catalyze the electro-oxidation of TPA, producing significantly enhanced ECL signal. Through detecting the ECL signal mediated by assembly of AuNPs, the proposed method was able to ensure substantial signal amplification and a low background. It was demonstrated that the ECL intensity was correlated with the ssDNA-based recognition reaction, enabling quantitative analysis of Hg²⁺ over the range of 8pM to 2nM, with a detection limit of 2pM. ECL intensity of the system were extremely specific for Hg²⁺ even in the presence of 1000-fold higher concentrations of other metal ions. Analytical results of Hg²⁺ spiked into water samples by the proposed ECL method were in good agreement with that obtained by atomic fluorescent spectrometry or mass spectrometry data.



http://ift.tt/2upNiOF

Field-effect transition sensor for KI detection based on self-assembled calixtube monolayers

Publication date: 15 December 2017
Source:Biosensors and Bioelectronics, Volume 98
Author(s): Kirill Puchnin, Mariia Andrianova, Alexander Kuznetsov, Vladimir Kovalev
A series of novel calixarene-based tubes comprising different numbers of silatrane anchoring groups was synthesized. For the first time, a self-assembled monolayer (SAM) derived from calixtubes was formed on a SiO2 surface. The formation of the SAM was confirmed by X-ray photoelectron spectroscopy, scanning electron microscopy-energy dispersive X-ray analysis, and contact angle measurements. Modification of the sensitive surface of a conventional ion-selective field effect transistor (ISFET) with the afforded SAM resulted in the production of a KI-sensitive sensor. This sensor selectively determined KI compare to different alkali metal iodides: NaI, RbI, CsI; also investigation of different potassium salts (acetate, iodide, nitrate, chloride, dihydrophosphate, perchlorate) showed the highest response to KI. This sensor was successfully employed to determine the presence of KI in artificial saliva with a limit of detection of ~3 × 10⁻⁸ М. In addition, it was found that the detection limit of the sensor could be increased by combining the sensor with a microfluidic system. Due to the obtained sensor sensitivity and its ability to detect KI in artificial saliva, we could conclude that this sensor shows great potential for application in the determination of KI in different media, such as the human body and in biological liquids, such as saliva or urine.



http://ift.tt/2ts4g1O

Fluorescent carbon nanoparticle-based lateral flow biosensor for ultrasensitive detection of DNA

Publication date: 15 December 2017
Source:Biosensors and Bioelectronics, Volume 98
Author(s): Sunitha Takalkar, Kwaku Baryeh, Guodong Liu
We report a fluorescent carbon nanoparticle (FCN)-based lateral flow biosensor for ultrasensitive detection of DNA. Fluorescent carbon nanoparticle with a diameter of around 15nm was used as a tag to label a detection DNA probe, which was complementary with the part of target DNA. A capture DNA probe was immobilized on the test zone of the lateral flow biosensor. Sandwich-type hybridization reactions among the FCN-labeled DNA probe, target DNA and capture DNA probe were performed on the lateral flow biosensor. In the presence of target DNA, FCNs were captured on the test zone of the biosensor and the fluorescent intensity of the captured FCNs was measured with a portable fluorescent reader. After systematic optimizations of experimental parameters (the components of running buffers, the concentration of detection DNA probe used in the preparation of FCN-DNA conjugates, the amount of FCN-DNA dispensed on the conjugate pad and the dispensing cycles of the capture DNA probes on the test-zone), the biosensor could detect a minimum concentration of 0.4 fM DNA. This study provides a rapid and low-cost approach for DNA detection with high sensitivity, showing great promise for clinical application and biomedical diagnosis.



http://ift.tt/2upVyym

Mice exposure to tannery effluents changes their olfactory capacity, and their response to predators and to the inhibitory avoidance test

Abstract

The current study has assessed whether the oral and/or dermal exposure of C57Bl/6 J mice to tannery effluent (a complex pollutant consisting of xenobiotic mixtures) could damage their olfactory functions, as well as whether it changes their aversive behavior in the inhibitory avoidance test. Accordingly, the animals were distributed in groups which were exposed or not to this xenobiotic through two different routes (oral and dermal), for 15 days. The effluent group subjected to oral exposure received drinking water containing 5% tannery effluent, whereas the animals in the dermal group were exposed to raw tannery effluent for 1 h/day. The animals dermally exposed to the tannery effluent (males and females) have shown the highest latency to find palatable food in the buried food test. The shortest time spent by the animals (orally or dermally) exposed to tannery effluent in the safety zone of the apparatus used in the predator exposure test, as well as the longest time spent by them in the aversive zone, have shown failures in their perception to the risk represented by the presence of the predator (cat). The passive avoidance test results have shown that the dermal exposure to tannery effluent led to partial memory deficit in male and female mice; therefore, the present study has confirmed the tannery effluent toxicity to mammals. Moreover, the present study was pioneer in demonstrating that the dermal exposure to this xenobiotic, even for a short period-of-time, can change the olfactory and cognitive functions of animals, as well as lead to harmful consequences to their health.

http://ift.tt/2ssfI9w

Bacterial periphytic communities related to mercury methylation within aquatic plant roots from a temperate freshwater lake (South-Western France)

Abstract

Macrophyte floating roots are considered as hotspots for methylmercury (MeHg) production in aquatic ecosystems through microbial activity. Nevertheless, very little is known about periphyton bacterial communities and mercury (Hg) methylators in such ecological niches. The ability to methylate inorganic Hg is broadly distributed among prokaryotes; however, sulfate-reducers have been reported to be the most important MeHg producers in macrophyte floating roots. In the present work, the periphyton bacterial communities colonizing Ludwigia sp. floating roots were investigated through molecular methods. Among the 244 clones investigated, anaerobic microorganisms associated with the sulfur biogeochemical cycle were identified. Notably, members of the sulfur-oxidizing prokaryotes and the anoxygenic, purple non-sulfur bacteria (Rhodobacteraceae, Comamonadaceae, Rhodocyclaceae, Hyphomicrobiaceae) and the sulfate reducers (Desulfobacteraceae, Syntrophobacteraceae, and Desulfobulbaceae) were detected. In addition, 15 sulfate-reducing strains related to the Desulfovibrionaceae family were isolated and their Hg-methylation capacity was tested using a biosensor. The overall results confirmed that Hg methylation is a strain-specific process since the four strains identified as new Hg-methylators were closely related to non-methylating isolates. This study highlights the potential involvement of periphytic bacteria in Hg methylation when favorable environmental conditions are present in such ecological micro-niches.

http://ift.tt/2t6SozU

Efficient model calibration method based on phase experiments for anaerobic–anoxic/nitrifying (A2N) two-sludge process

Abstract

A systematic calibration and validation procedure for the complex mechanistic modeling of anaerobic–anoxic/nitrifying (A2N) two-sludge system is needed. An efficient method based on phase experiments, sensitivity analysis, and genetic algorithm is proposed here for model calibration. Phase experiments (anaerobic phosphorus release, aerobic nitrification, and anoxic denitrifying phosphate accumulation) in an A2N sequencing batch reactor (SBR) were performed to reflect the process conditions accurately and improve the model calibration efficiency. The calibrated model was further validated using 30 batch experiments and 3-month dynamic continuous flow (CF) experiments for A2N-SBR and CF-A2N process, respectively. Several statistical criteria were conducted to evaluate the accuracy of model predications, including the average relative deviation (ARD), mean absolute error (MAE), root mean square error (RMSE), and Janus coefficient. Visual comparisons and statistical analyses indicated that the calibrated model could provide accurate predictions for the effluent chemical oxygen demand (COD), ammonia nitrogen (NH₄⁺-N), total nitrogen (TN), and total phosphorus (TP), with only one iteration.

http://ift.tt/2sn238h

Biogeochemical and engineered barriers for preventing spread of contaminants

Abstract

The intensive industrial development and urbanization, as well as the negligible return of hazardous components to the deeper layers of the Earth, increases the contamination load on the noosphere (i.e., the new status of the biosphere, the development of which is mainly controlled by the conscious activity of a human being). The need for reducing the spread and mobility of contaminants is growing. The insights into the role of the tree in the reduction of contaminant mobility through its life cycle are presented to show an important function performed by the living matter and its products in reducing contamination. For maintaining the sustainable development, natural materials are often used as the media in the environmental protection technologies. However, due to increasing contamination intensity, the capacity of natural materials is not sufficiently high. Therefore, the popularity of engineered materials, such as biochar which is the thermochemically modified lignocellulosic product, is growing. The new approaches, based on using the contaminant footprint, as well as natural (biogeochemical) and engineered barriers for reducing contaminant migration and their application, are described in the paper.

http://ift.tt/2t6Cp4R

Overview of Cancer Stem Cells and Stemness for Community Oncologists

Abstract

Advances in cancer research in the past have led to an evolving understanding of cancer pathogenesis and the development of novel drugs that significantly improve patient outcomes. However, many patients still encounter treatment resistance, recurrence, or metastasis and eventually die from progressing disease. Experimental evidence indicates that a subpopulation of cancer cells, called cancer stem cells (CSCs), possess "stemness" properties similar to normal stem cells, including self-renewal, differentiation, and proliferative potential. These stemness properties are lost during differentiation and are governed by pathways such as STAT3, NANOG, NOTCH, WNT, and HEDGEHOG, which are highly dysregulated in CSCs due to genetic and epigenetic changes. Promising results have been observed in preclinical models targeting these CSCs through the disruption of stemness pathways in combination with current treatment modalities. This has led to anti-CSC–based clinical trials in multiple stages of development. In this review, we discuss the role of CSCs and stemness pathways in cancer treatment and how they relate to clinical observations. Because CSCs and the stemness pathways governing them may explain the negative clinical outcomes observed during treatment, it is important for oncologists to understand how they contribute to cancer progression and how they may be targeted to improve patient outcomes.

http://ift.tt/2srXyES

Viral Replication Complexes Are Targeted by LC3-Guided Interferon-Inducible GTPases

Publication date: Available online 29 June 2017
Source:Cell Host & Microbe
Author(s): Scott B. Biering, Jayoung Choi, Rachel A. Halstrom, Hailey M. Brown, Wandy L. Beatty, Sanghyun Lee, Broc T. McCune, Erin Dominici, Lelia E. Williams, Robert C. Orchard, Craig B. Wilen, Masahiro Yamamoto, Jörn Coers, Gregory A. Taylor, Seungmin Hwang
All viruses with positive-sense RNA genomes replicate on membranous structures in the cytoplasm called replication complexes (RCs). RCs provide an advantageous microenvironment for viral replication, but it is unknown how the host immune system counteracts these structures. Here we show that interferon-gamma (IFNG) disrupts the RC of murine norovirus (MNV) via evolutionarily conserved autophagy proteins and the induction of IFN-inducible GTPases, which are known to destroy the membrane of vacuoles containing bacteria, protists, or fungi. The MNV RC was marked by the microtubule-associated-protein-1-light-chain-3 (LC3) conjugation system of autophagy and then targeted by immunity-related GTPases (IRGs) and guanylate-binding proteins (GBPs) upon their induction by IFNG. Further, the LC3 conjugation system and the IFN-inducible GTPases were necessary to inhibit MNV replication in mice and human cells. These data suggest that viral RCs can be marked and antagonized by a universal immune defense mechanism targeting diverse pathogens replicating in cytosolic membrane structures.

Graphical abstract

Teaser

The replication complexes (RCs) of positive-sense RNA viruses have been considered impenetrable to antiviral responses. Biering et al. discovered that viral RCs can be marked by the LC3 conjugation system of autophagy and targeted by IFN-inducible GTPases, demonstrating a universal effector mechanism against cytosolic vacuoles containing viruses, bacteria, protists, or fungi.


http://ift.tt/2tqaaAZ

Cutaneous Leishmaniasis Induces a Transmissible Dysbiotic Skin Microbiota that Promotes Skin Inflammation

Publication date: Available online 29 June 2017
Source:Cell Host & Microbe
Author(s): Ciara Gimblet, Jacquelyn S. Meisel, Michael A. Loesche, Stephen D. Cole, Joseph Horwinski, Fernanda O. Novais, Ana M. Misic, Charles W. Bradley, Daniel P. Beiting, Shelley C. Rankin, Lucas P. Carvalho, Edgar M. Carvalho, Phillip Scott, Elizabeth A. Grice
Skin microbiota can impact allergic and autoimmune responses, wound healing, and anti-microbial defense. We investigated the role of skin microbiota in cutaneous leishmaniasis and found that human patients infected with Leishmania braziliensis develop dysbiotic skin microbiota, characterized by increases in the abundance of Staphylococcus and/or Streptococcus. Mice infected with L. major exhibit similar changes depending upon disease severity. Importantly, this dysbiosis is not limited to the lesion site, but is transmissible to normal skin distant from the infection site and to skin from co-housed naive mice. This observation allowed us to test whether a pre-existing dysbiotic skin microbiota influences disease, and we found that challenging dysbiotic naive mice with L. major or testing for contact hypersensitivity results in exacerbated skin inflammatory responses. These findings demonstrate that a dysbiotic skin microbiota is not only a consequence of tissue stress, but also enhances inflammation, which has implications for many inflammatory cutaneous diseases.

Graphical abstract

Teaser

The role of skin commensal microbes in dermal cellular responses is largely unknown. Gimblet et al. investigate the role of the skin microbiota during cutaneous leishmaniasis. Leishmania infection creates a dysbiotic skin microbiota that is transmissible to naive skin. Additionally, dysbiosis prior to infection or injury exacerbates skin inflammation.


http://ift.tt/2tqa8ZT

Ludwigia octovalvis extract improves glycemic control and memory performance in diabetic mice

Publication date: 31 July 2017
Source:Journal of Ethnopharmacology, Volume 207
Author(s): Wei-Sheng Lin, Jung-Hsin Lo, Jo-Hsuan Yang, Hao-Wei Wang, Shou-Zen Fan, Jui-Hung Yen, Pei-Yu Wang
Ethnopharmacological relevanceLudwigia octovalvis (Jacq.) P.H. Raven (Onagraceae) extracts have historically been consumed as a healthful drink for treating various conditions, including edema, nephritis, hypotension and diabetes.Aim of the studyWe have previously shown that Ludwigia octovalvis extract (LOE) can significantly extend lifespan and improve age-related memory deficits in Drosophila melanogaster through activating AMP-activated protein kinase (AMPK). Since AMPK has become a critical target for treating diabetes, we herein investigate the anti-hyperglycemic potential of LOE.Materials and methodsDifferentiated C2C12 muscle cells, HepG2 hepatocellular cells, streptozotocin (STZ)-induced diabetic mice and high fat diet (HFD)-induced diabetic mice were used to investigate the anti-hyperglycemic potential of LOE. The open field test and novel object recognition test were used to evaluate spontaneous motor activity and memory performance of HFD-induced diabetic mice.ResultsIn differentiated C2C12 muscle cells and HepG2 hepatocellular cells, treatments with LOE and its active component (β-sitosterol) induced significant AMPK phosphorylation. LOE also enhanced uptake of a fluorescent glucose derivative (2-NBDG) and inhibited glucose production in these cells. The beneficial effects of LOE were completely abolished when an AMPK inhibitor, dorsomorphin, was added to the culture system, suggesting that LOE requires AMPK activation for its action in vitro. In streptozotocin (STZ)-induced diabetic mice, we found that both LOE and β-sitosterol induced an anti-hyperglycemic effect comparable to that of metformin, a drug that is commonly prescribed to treat diabetes. Moreover, LOE also improved glycemic control and memory performance of mice fed a HFD.ConclusionsThese results indicate that LOE is a potent anti-diabetic intervention that may have potential for future clinical applications.

Graphical abstract

http://ift.tt/2smMm0S

IFC (Journal of Ethnopharmacology)

Publication date: 12 July 2017
Source:Journal of Ethnopharmacology, Volume 206





http://ift.tt/2smMXj5

Commentary on The Clinical and Histological Effect of a Low-Fluence Q-Switched 1,064-nm Neodymium: Yttrium-Aluminum-Garnet Laser for the Treatment of Melasma and Solar Lentigo in Asians.

No abstract available

http://ift.tt/2s7dGfo

Commentary on The Facial Platysma and Its Underappreciated Role in Lower Face Dynamics and Contour.

No abstract available

http://ift.tt/2tpQD3A

A Multicenter Pivotal Study to Evaluate Tissue Stabilized-Guided Subcision Using the Cellfina Device for the Treatment of Cellulite With 3-Year Follow-up.

BACKGROUND: Cellulite is a common female cosmetic concern for which no single treatment option had been proven effective over the long term. A novel tissue stabilized-guided subsicion system (TS-GS system) has demonstrated significant reduction in the appearance of cellulite after treatment. OBJECTIVE: The objective of this extended follow-up period was to assess the effectiveness of TS-GS out to 3 years after initial treatment. PATIENTS AND METHODS: After completing an open-label, multicenter, pivotal study, 45 subjects were followed for an extended period of up to 3 years after receiving a single treatment using the TS-GS system. Treatment areas were photographed prior to the procedure and at multiple time points post-treatment throughout the 3 years. In this open-label study, subjects served as their own controls. Effectiveness was assessed based on blinded independent physician panel assessments of improvement from baseline using a cellulite severity scale. Subject aesthetic improvement and patient-reported satisfaction were also collected. RESULTS: The results of this trial supported Food and Drug Administration clearance of the device for the long-term reduction in the appearance of cellulite following TS-GS. CONCLUSION: These data further demonstrate the safety and efficacy of this treatment with no reduction in treatment benefits out to 3 years. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2s6EDjD

Pulsed Dye Laser Treatment of a Nonhealing Chronic Wound that Developed After Incision and Drainage of a Hidradenitis Suppurativa Abscess.

No abstract available

http://ift.tt/2tprZjy

Treatment Patterns, Outcomes, and Patient Satisfaction of Primary Epidermally Limited Nonmelanoma Skin Cancer.

BACKGROUND: Epidermally limited nonmelanoma skin cancer (ELNMSC) (superficial basal cell carcinoma [SBCC] and squamous cell carcinoma in situ [SCCIS]) is common. Data on outcomes and patient satisfaction are lacking. OBJECTIVE: To examine treatment efficacy and satisfaction in ELNMSC patients. PATIENTS AND METHODS: Retrospective cohort study of adults with primary SBCC or SCCIS. A 25% random subset completed a satisfaction questionnaire. RESULTS: Five hundred and fifty patients with 227 SBCC and 451 SCCIS were included; 329 tumors (49%) were treated with Mohs micrographic surgery (MMS) and 349 (51%) with non-MMS (imiquimod [n = 26], 5% 5-fluorouracil [n = 234], ingenol mebutate [n = 32], or cryotherapy [n = 57]). Five-year recurrence-free survival was high in both groups, with MMS having a small but statistically significant advantage (99% vs 95%, p = .004). More MMS patients were willing to undergo treatment again (97% vs 86%, p = .024). Dissatisfaction was mostly due to prolonged treatment course and pain associated with non-MMS treatments. CONCLUSION: Surgical and nonsurgical treatments for primary ELNMSC have low recurrence rates, though cure rate and patient satisfaction are higher with MMS. Treatment choice for epidermal NMSC may be guided through patient preferences regarding ability to comply with topical treatment, out-of-pocket costs, desire to treat surrounding field disease, and desire to avoid a surgical scar. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2s6U8bg

In a Pinch? Rocker-Slide Punch Biopsy Technique.

No abstract available

http://ift.tt/2tpIeNj

Resectable Invasive IPMN versus Sporadic Pancreatic Adenocarcinoma of the head of the pancreas: should these two different diseases receive the same treatment? A matched comparison study of the French Surgical Association (AFC)

Publication date: Available online 29 June 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Pauline Duconseil, Julie Périnel, Aurélie Autret, Mustapha Adham, Alain Sauvanet, Laurence Chiche, Jean-Yves Mabrut, Jean-Jacques Tuech, Christophe Mariette, Nicolas Régenet, Jean-Michel Fabre, Philippe Bachellier, Jean-Robert Delpéro, François Paye, Olivier Turrini
PurposeTo compare survival and impact of adjuvant chemotherapy in patients who underwent pancreaticoduodenectomy (PD) for invasive intraductal papillary mucinous neoplasm (IIPMN) and sporadic pancreatic ductal adenocarcinoma (PDAC).MethodsFrom 2005 to 2012, 240 patients underwent pancreatectomy for IIPMN and 1327 for PDAC. Exclusion criteria included neoadjuvant treatment, pancreatic resection other than PD, vascular resection, carcinoma in situ, or <11 examined lymph nodes. Thus, 82 IIPMN and 506 PDAC were eligible for the present study. Finally, The IIPMN group was matched 1:2 to compose the PDAC group according to TNM disease stage, perineural invasion, lymph node ratio, and margin status.ResultsThere was no difference in patient's characteristics, intraoperative parameters, postoperative outcomes, and histologic parameters. Overall survival and disease-free survival times were comparable between the 2 groups. In each group, overall survival time was significantly poorer in patients who did not achieve adjuvant chemotherapy (p=0.03 for the IIPMN group; p=0.03 for the PDAC group). In lymph-node negative patients of the IIPMN group, adjuvant chemotherapy did not have any significant impact on overall survival time (OR=0.57; 95% CI [0.24-1.33]). Considering the whole population (i.e. patients with IIPMN and PDAC; n=246), patients who did not achieve adjuvant chemotherapy had poorer survival (p<0.01).ConclusionsThe courses of IIPMN and PDAC were similar after an optimized stage-to-stage comparison. Adjuvant chemotherapy was efficient in both groups. However, in lymph node negative patients, adjuvant chemotherapy seemed not to have a significant impact.



http://ift.tt/2t5YQqO

Long non-coding RNA NEAT1 overexpression is associated with unfavorable prognosis in patients with hepatocellular cacinoma after hepatectomy: A Chinese Population-based Study

Publication date: Available online 28 June 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Liu Zhao, Chang Qing, Yang Fan, Liu Bing, Yao Hong-Wei, Bai Zhi-Gang, Pu Chang-Sheng, Ma Xue-Mei, Yang Yao, Wang Ting-Ting, Guo Wei, Zhou Xiao-Na, Zhang Zhong-Tao
AimTo identify the association between the expression of lncRNA NEAT1 and clinicopathological characteristics of patients with HCC, and to explore the prognostic significance of lncRNA NEAT1 in predicting prognosis of HCC.MethodsWe retrospectively reviewed 86 patients with HCC(35 female, 51 male) managed in our institution between 2009 and 2014. The expression level of lncRNA NEAT1 were detected by real-time PCR. Prognostic factors were evaluated using Kaplan-Meier curves and Cox proportional hazards models.ResultsFor the entire cohort of 86 patients, we showed that the expression level of NEAT1 was significantly higher in HCC tissues compared with non-tumorous tissues and NEAT1 was increased obviously in the HCC cell lines including SMMC-7721, Huh-7 and Hep3B(P<0.001). MTT assay showed that si-NEAT1 remarkably inhibited the cell proliferation in three HCC cell lines. Moreover, over-expression of lncRNA NEAT1 was closely related to liver cirrhosis (P=0.026), microvascular invasion(MVI) (P=0.023), and TNM stage (P=0.017). After adjusting for competing risk factors, we identified that expression level of lncRNA NEAT1 was an independently risk factor associated with the prognosis of patients with HCC(P=0.031).Conclusionsin this study, we found NEAT1 expressed significantly higher in HCC tissues compared with non-tumorous tissues. Overexpression of lncRNA NEAT1 was an independently risk factor associated with the prognosis of patients with HCC.



http://ift.tt/2smnw18

Retrospective cohort analysis of neoadjuvant treatment and survival in resectable and borderline resectable pancreatic ductal adenocarcinoma in a high volume referral centre

Publication date: Available online 28 June 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Malinda Itchins, Jennifer Arena, Christopher B. Nahm, Joel Rabindran, Sia Kim, Emma Gibbs, Sarah Bergamin, Terence C. Chua, Anthony J. Gill, Richard Maher, Connie Diakos, Matthew Wong, Anubhav Mittal, George Hruby, Andrew Kneebone, Nick Pavlakis, Jaswinder Samra, Stephen Clarke
BackgroundPancreatic ductal adenocarcinoma (PDAC) is a deadly disease. Neoadjuvant therapy (NA) with chemotherapy (NAC) and radiotherapy (RT) prior to surgery provides promise. In the absence of prospective data, well annotated clinical data from high-volume units may provide pilot data for randomised trials.MethodsMedical records from a tertiary hospital in Sydney, Australia, were analysed to identify all patients with resectable or borderline resectable PDAC. Data regarding treatment, toxicity and survival were collected.ResultsBetween January 1 2010 and April 1 2016, 220 sequential patients were treated: 87 with NA and 133 with upfront operation (UO). Forty-three NA patients (52%) and 5 UO patients (4%) were borderline resectable at diagnosis. Twenty-four borderline patients received NA RT, 22 sequential to NAC. The median overall survival (OS) in the NA group was 25.9 months (mo); 95% CI (21.1-43.0mo) compared to 26.9mo (19.7, 32.7) in the UO; HR 0.89; log-ranked p-value=0.58.Sixty-nine NA patients (79%) were resected, mOS was 29.2mo (22.27, not reached (NR)). Twenty-two NA (31%) versus 22 UO (17%) were node negative at operation (N0).In those managed with NAC/RT the mOS was 29.0mo (17.3, NR).There were no post-operative deaths with NA within 90-days and three in the UO arm.DiscussionThis is an hypothesis generating retrospective review of a selected real-world population in a high-throughput unit. Treatment with NA was well tolerated. The long observed survival in this group may be explained by lymph node sterilisation by NA, and the achievement of R0 resection in a greater proportion of patients.



http://ift.tt/2t6kE5F

Prevalence of Hidradenitis Suppurativa Among Patients with Down Syndrome: a population based cross sectional analysis

Summary

Background

Hidradenitis Suppurativa (HS) has been linked to Down syndrome (DS).

Objective

To determine whether Down syndrome patients have a higher prevalence of HS, and whether diagnosis of HS occurs at an earlier age.

Methods

Cross-sectional analysis in a population sample of 11,936 DS patients and 16,813,290 non-DS patients. The primary outcome was diagnosis of HS. SNOMED-CT terms were used to identify patients with DS and HS. We used logistic regression models and significant interaction terms to evaluate the relationship between DS and HS. We also compared proportion of incident HS cases within five-year age groups to determine whether DS patients had earlier diagnosis of HS.

Results

Prevalence of HS among DS patients was 2.1%, compared to 0.3% for patients without DS (p<0.001). HS prevalence was greatest among DS patients who were aged 18-29 years. HS prevalence was not different between female and male DS patients or between white and non-white DS patients, after controlling for age, gender and obesity. Compared to those without DS, patients with the condition had increased odds of HS in unadjusted [OR 7.84, 95% CI 6.93-8.88] and adjusted [OR 5.24, 95% CI 4.62-5.94] analyses. Diagnosis of HS was made by the age of 29 years in 81.8% of patients with DS, compared to 34.0% of patients without the condition (p<0.001).

Conclusion

HS is strongly associated with DS across demographic subgroups, and the disease may present earlier life in these patients. These findings have implications for surveillance and care of patients with DS.

This article is protected by copyright. All rights reserved.

http://ift.tt/2tr1VEf

Finite Element Analysis to Investigate Variability of MR Elastography in the Human Thigh

Publication date: Available online 29 June 2017
Source:Magnetic Resonance Imaging
Author(s): L. Hollis, E. Barnhill, M. Perrins, P. Kennedy, N. Conlisk, C. Brown, P.R. Hoskins, P. Pankaj, N. Roberts
Purpose: To develop finite element analysis (FEA) of magnetic resonance elastography (MRE) in the human thigh and investigate inter-individual variability of measurement of muscle mechanical properties.Methods: Segmentation was performed on MRI datasets of the human thigh from 5 individuals and FEA models consisting of 12 muscles and surrounding tissue created. The same material properties were applied to each tissue type and a previously developed transient FEA method of simulating MRE using Abaqus was performed at 4 frequencies. Synthetic noise was applied to the simulated data at various levels before inversion was performed using the Elastography Software Pipeline. Maps of material properties were created and visually assessed to determine key features. The coefficient of variation (CoV) was used to assess the variability of measurements in each individual muscle and in the groups of muscles across the subjects. Mean measurements for the set of muscles were ranked in size order and compared with the expected ranking.Results: At noise levels of 2% the CoV in measurements of |G^*| ranged from 5.3 to 21.9% and from 7.1 to 36.1% for measurements of ϕ in the individual muscles. A positive correlation (R² value 0.80) was attained when the expected and measured |G^*| ranking were compared, whilst a negative correlation (R² value 0.43) was found for ϕ.Conclusions: Created elastograms demonstrated good definition of muscle structure and were robust to noise. Variability of measurements across the 5 subjects was dramatically lower for |G^*| than it was for ϕ. This large variability in ϕ measurements was attributed to artefacts.



http://ift.tt/2tp8G9Y

Histone modifications: a review about the presence of this epigenetic phenomenon in carcinogenesis

Publication date: Available online 28 June 2017
Source:Pathology - Research and Practice
Author(s): Emanuely Silva Chrun, Filipe Modolo, Filipe Ivan Daniel
Among the epigenetic changes, histone acetylation has been recognized as a fundamental process that strongly affects gene expression regulation. Disrupt of this phenomenon has been linked to carcinogenesis. In this review, we analysed studies reporting the process of histone modification, the enzymes associated and affected genes concerning human malignancies and histone enzyme inhibitor drugs used in cancer treatment. Variable degrees of expression of HDACs (histone deacetylases) and HATs (histone acetyltransferases) are found in many human malignant tissues and the histones acetylation seems to influence different processes including the progression of cell cycle, the dynamics of chromosomes, DNA recombination, DNA repair and apoptosis. Thus, the control of aberrant activity and/or expression of these proteins have been favorable in treatment of diseases as cancer. HDACi have shown efficacy in clinical trials in solid and hematological malignancies. Therefore, the development and use of HDACs inhibitors are increasing, leading to continue studying these enzyme expressions and behavior, aiming to determine tumors that will respond better to this type of treatment.



http://ift.tt/2t5YQY0

Decreased expression of microRNA-122 is associated with an unfavorable prognosis in childhood acute myeloid leukemia and function analysis indicates a therapeutic potential

Publication date: Available online 28 June 2017
Source:Pathology - Research and Practice
Author(s): Juan Yang, Yufang Yuan, Xiaochun Yang, Ze Hong, Lijuan Yang
MicroRNA (miR)-122 functions as a tumor suppressor in various human cancers. However, its involvement in childhood acute myeloid leukemia (AML) remains unknown. In this study, quantitative real-time PCR assay demonstrated that miR-122 expression in bone marrow specimens from AML children were significantly lower than that in non-malignant controls (P<0.001). Statistically, AML children with low miR-122 expression more frequently had large white blood cell count (P=0.022), French-American-British classification subtype M7 (P<0.001), unfavorable cytogenetics (P=0.002) and day 7 response to the treatment (P=0.036), short relapse-free (P=0.001) and overall (P=0.008) survivals than those with high expression. Multivariate analysis also determined that miR-122 expression was an independent prognostic factor for both relapse-free and overall survivals. Functionally, the enforced expression of miR-122 in AML cell lines efficiently suppressed cell proliferation and reduced the ratio of S-phase cells in vitro (all P<0.05). In conclusion, the abnormal expression of miR-122 may be a marker of the aggressive progression in childhood AML. Importantly, its downregulation may serve as a prognostic factor to predict poor outcome. Our study also reveal that miR-122 may function as a tumor suppressor in childhood AML, highlighting a new therapeutic strategy for this malignancy.



http://ift.tt/2smrgzH

Prognostic Significance of Extensive Necrosis in Renal Cell Carcinoma

Publication date: Available online 29 June 2017
Source:Human Pathology
Author(s): Jennifer Collins, Jonathan I. Epstein
Few studies using the current classification of renal cell carcinoma (RCC) have looked at a large number of cases with near total necrosis. We identified 21 cases of resections of RCC with >90% necrosis from the archives of Johns Hopkins Hospital between 2000–2015. Patients' mean age was 59yrs. (43–77) with 16 (76%) males. 12 (57%) cases were papillary RCC, 4 (19%) clear cell papillary RCC, 4 (19%) clear cell RCC, 1 (5%) unclassified with sarcomatoid differentiation. International Society of Urological Pathology (ISUP) nucleolar grade was grade 1 (9 cases) or grade 2 (9 cases). Two cases were ISUP nucleolar grade 3 and 1 case was grade 4. Pathological stage was low (pT1–2) in 20 (95%) with the unclassified RCC with sarcomatoid differentiation RCC stage pT3a. Mean tumor size was 6.3cm. (1.2–17). In 52% (11) of cases, it was difficult to identify viable tumor requiring multiple sections; 4 cases of papillary RCC were diagnosed in part due to necrotic tumor "ghost" architecture. Follow-up was available in 17 (81%) cases with a mean follow-up of 59months. Thirteen (62%) patients are alive without disease. The patient with unclassified carcinoma with sarcomatoid differentiation died of cancer and 2 died due to causes unrelated to cancer. 1 patient (5%) with low grade clear cell RCC developed metastases, yet had a contralateral RCC. In the setting of a low grade RCC, extensive necrosis does not have an adverse prognosis.



http://ift.tt/2s6Rp1f

Differential expression pattern of key regulatory developmental genes in pre-implant zona free cloned vs in vitro fertilized goat embryos

Publication date: Available online 29 June 2017
Source:Gene Expression Patterns
Author(s): Dharmendra Kumar, Bikash Chandra Sarkhel
The success of Somatic cell nuclear transfer (SCNT) primarily depends on the extent of reprogramming of donor cells genome. The error of reprogramming may lead to inappropriate expression of embryonic genes at any stage of development. Under the present study the relative expression of different genes related to pluripotency (Oct-4 and Nanog), growth factors (IGF-2 and IGF-2R) and DNA methyltransferase gene (Dnmt-1) was evaluated in SCNT embryos at 8–16 cells, morula and blastocyst stages as compared to IVF group. In SCNT, significantly higher degree of relative expression was observed for Oct-4 in morula (1.41) and blastocysts (1.14) as compared to 8–16 cells (referral stage) whereas in IVF, a lower expression was observed at morula (0.82) stage. The expression of Nanog in SCNT embryos was increased significantly in morula (2.23) and decreased subsequently in blastocyst (0.56), whereas it was increased significantly from 8 to 16 cells to morula (1.62) and blastocyst (4.5) of IVF group. The IGF-2 and IGF-2R showed significantly higher expression rates in morula and blastocysts of SCNT (6.56, 5.90 and 1.11, 1.4) and IVF (8.69, 8.25 and 2.96, 3.91) embryos, respectively as compared to referral stage. The expression of Dnmt-1 was significantly higher in SCNT morula (1.29) and blastocyst (1.15) however in IVF, it was similar in 8–16 cells stage and morula but, higher in blastocyst (1.58). The dissimilar pattern of gene expression of SCNT might be a consequence of incomplete reprogramming of donor nucleus which resulted into lower blastocyst rate of SCNT as compared to IVF embryos.



http://ift.tt/2tuvLsc

Effects of interferon tau on endometrial epithelial cells in caprine in vitro

Publication date: Available online 29 June 2017
Source:Gene Expression Patterns
Author(s): Yue Zhang, Lei Zhang, Chao-Feng Yu, Xiao-Yan Du, Xiao-Rui Liu, Jun-Ze Liu, Xiao-Peng An, Jian-Gang Wang, Yu-Xuan Song, Guang Li, Bin-Yun Cao
Embryo attachment, a precondition of ruminant pregnancy, has been recognized to be related to apoptosis in endometrial epithelial cells (EECs). In ruminants, interferon tau (IFNT) is secreted by trophoblast of conceptus and works in a concentration-dependent style. To verify the function of IFNT in caprine embryo attachment, caprine EECs were dealt with IFNT at 0, 1, 10 and 100 ng/ml. In this study, IFNT arrested caprine EEC cell cycle in G2 phase and induced cell apoptosis at 1 ng/ml and 10 ng/ml of IFNT. Interestingly, pro-apoptotic protein FAS and PRβ together with anti-apoptotic proteins SP1 and IGF1R were all up-regulated at 1 ng/ml of IFNT. It demonstrated that IFNT at 1 ng/ml might induce caprine EEC apoptosis and keep a balance between apoptosis and proliferation. Furthermore, regulation of HOXA10, COX-2, PRL, PTEN and STAT3 pathway in caprine EECs was likely to be contributed by IFNT at 1 ng/ml to improve the chances for embryo attachment.



http://ift.tt/2u3QnV4

The Effect of Gender on Resident Autonomy in the Operating room

Publication date: Available online 29 June 2017
Source:Journal of Surgical Education
Author(s): Shari L. Meyerson, Joel M. Sternbach, Joseph B. Zwischenberger, Edward M. Bender
ObjectiveDiscrimination against women training in medicine and surgery has been subjectively described for decades. This study objectively documents gender differences in the degree of autonomy given to thoracic surgery trainees in the operating room.DesignThoracic surgery residents and faculty underwent frame of reference training on the use of the 4-point Zwisch scale to measure operative autonomy. Residents and faculty then submitted evaluations of their perception of autonomy granted for individual operations as well as operative difficulty on a real-time basis using the "Zwisch Me!!" mobile application. Differences in autonomy given to male and female residents were elucidated using chi-square analysis and ordered logistic regression.SettingSeven academic medical centers with thoracic surgery training programs.ParticipantsVolunteer thoracic surgery residents in both integrated and traditional training pathways and their affiliated cardiothoracic faculty.ResultsResidents (n = 33, female 18%) submitted a total of 596 evaluations to faculty (n = 48, female 12%). Faculty gave less autonomy to female residents with only 56 of 184 evaluations (30.3%) showing meaningful autonomy (passive help or supervision only) compared to 107 of 292 evaluations (36.7%) at those levels for male residents (p = 0.02). Resident perceptions of autonomy showed even more pronounced differences with female residents receiving only 38 of 197 evaluations (19.3%) with meaningful autonomy compared to 133 of 399 evaluations (33.3%) for male residents (p < 0.001). Potential influencing factors explored included attending gender and specialty, case type and difficulty, and resident level of training. In multivariate analysis, only case difficultly, resident gender, and level of training were significantly related to autonomy granted to residents.ConclusionsEvaluations of operative autonomy reveal a significant bias against female residents. Faculty education is needed to encourage allowing female residents more operative autonomy.



http://ift.tt/2t5WkAW

Self-Directed Interactive Video-Based Instruction Versus Instructor-Led Teaching for Myanmar House Surgeons: A Randomized, Noninferiority Trial

Publication date: Available online 29 June 2017
Source:Journal of Surgical Education
Author(s): Albert Thein Lwin, Thein Lwin, Phyu Naing, Yee Oo, David Kidd, Marcelo Cerullo, Joshua Posen, Kyaw Hlaing, Gayane Yenokyan, Kyi Kyi Thinn, Zaw Wai Soe, Kent A. Stevens
ObjectiveTo compare self-directed interactive video-based instruction (IVBI) with instructor-led teaching in the acquisition of basic surgical skills by House Surgeons at University of Medicine 1, Yangon.DesignA prospective, 1:1 randomized controlled trial was conducted. Participants were randomized into 2 teaching arms: (1) self-directed IVBI or (2) instructor-led teaching. Self-directed IVBI participants were provided with a portable DVD player that could play, fast forward, rewind, and skip through skills modules. Participants in the instructor-led teaching group were taught in small groups by standardized instructors. Pretesting and posttesting of 1-handed knot tie, 2-handed knot tie, vertical mattress suture, and instrument tie was performed using the Objective Structured Assessment of Technical Skills (OSATS). Students randomized to self-directed IVBI completed an exit survey to assess satisfaction. Demographic data were collected of all participants.SettingUniversity of Medicine 1, Yangon, Myanmar.ParticipantsFifty participants were randomly selected from 78 eligible House Surgeons who were enrolled in their basic surgery rotation.ResultsDemographic characteristics and baseline skills were comparable in participants randomized to IVBI and instructor-led teaching. Mean OSATS score increased from pretest to posttest in both groups (p < 0.001). The mean posttest OSATS score of the IVBI group was 0.72 points below that of the instructor-led teaching group (90% CI: −3.8 to 5.2), with the 90% CI falling below the a priori noninferiority margin, satisfying criteria for noninferiority. More than 90% of students marked either "agree" or "strongly agree" to the following statements on the exit survey: further expansion of IVBI into other skills modules and integration of IVBI into training curriculum.ConclusionIVBI is noninferior to instructor-led teaching of surgical skills based on OSATS scores. House Surgeons highly rated self-directed IVBI. Self-directed IVBI has the potential to significantly reduce the personnel required for skills teaching and may serve as a long-term learning adjunct in low-resource settings.



http://ift.tt/2sm9M6v

Heterologous prime-boost immunization of Newcastle disease virus vectored vaccines protected broiler chickens against highly pathogenic avian influenza and Newcastle disease viruses

Publication date: Available online 28 June 2017
Source:Vaccine
Author(s): Shin-Hee Kim, Siba K. Samal
Avian Influenza virus (AIV) is an important pathogen for both human and animal health. There is a great need to develop a safe and effective vaccine for AI infections in the field. Live-attenuated Newcastle disease virus (NDV) vectored AI vaccines have shown to be effective, but preexisting antibodies to the vaccine vector can affect the protective efficacy of the vaccine in the field. To improve the efficacy of AI vaccine, we generated a novel vectored vaccine by using a chimeric NDV vector that is serologically distant from NDV. In this study, the protective efficacy of our vaccines was evaluated by using H5N1 highly pathogenic avian influenza virus (HPAIV) strain A/Vietnam/1203/2004, a prototype strain for vaccine development. The vaccine viruses were three chimeric NDVs expressing the hemagglutinin (HA) protein in combination with the neuraminidase (NA) protein, matrix 1 protein, or nonstructural 1 protein. Comparison of their protective efficacy between a single and prime-boost immunizations indicated that prime immunization of 1-day-old SPF chicks with our vaccine viruses followed by boosting with the conventional NDV vector strain LaSota expressing the HA protein provided complete protection of chickens against mortality, clinical signs and virus shedding. Further verification of our heterologous prime-boost immunization using commercial broiler chickens suggested that a sequential immunization of chickens with chimeric NDV vector expressing the HA and NA proteins following the boost with NDV vector expressing the HA protein can be a promising strategy for the field vaccination against HPAIVs and against highly virulent NDVs.



http://ift.tt/2uoB4pv

An increasing, potentially measles-susceptible population over time after vaccination in Korea

Publication date: Available online 29 June 2017
Source:Vaccine
Author(s): Hae Ji Kang, Young Woo Han, Su Jin Kim, You-Jin Kim, A-Reum Kim, Joo Ae Kim, Hee-Dong Jung, Hye Eun Eom, Ok Park, Sung Soon Kim
BackgroundIn Korea, measles occurs mainly in infants <12months of age, who are unvaccinated. In addition, vaccine populations, including adolescents and young adults, can become infected though importation. Thus, the question arises whether the current level of herd immunity in Korea is now insufficient for protecting against measles infection.MethodsAge-specific measles seroprevalence was evaluated by performing enzyme immunoassays and plaque reduction-neutralization tests on 3050 subjects aged 0–50years (birth cohort 1964–2014) and 480 subjects aged 2–30years (birth cohort 1984–2012).ResultsThe overall seropositivity and measles antibody concentrations were 71.5% and 1366mIU/mL, respectively. Progressive decline in antibody levels and seropositivity were observed over time after vaccination in infants, adolescents, and young adults. The accumulation of potentially susceptible individuals in the population was confirmed by comparing data from 2010 and 2014 seroprevalence surveys. The statistical correlation between measles incidence and measles seronegativity was determined.ConclusionsWaning levels of measles antibodies with increasing time post-vaccination suggests that measles susceptibility is potentially increasing in Korea. This trend may be related to limitations of vaccine-induced immunity in the absence of natural boosting by the wild virus, compared to naturally acquired immunity triggered by measles infection. This study provides an important view into the current measles herd immunity in Korea.



http://ift.tt/2tqEBXb

Influenza vaccines effectiveness 2013–14 through 2015–16, a test-negative study in children

Publication date: Available online 29 June 2017
Source:Vaccine
Author(s): Heather L. Valdin, Rodolfo E. Bégué
BackgroundTrivalent inactivated and live attenuated influenza vaccines (IIV3 and LAIV3) have been reformulated with an extra B strain (IIV4 and LAIV4). They were licensed based on immunogenicity and their effectiveness (VE) still must be empirically tested.MethodsChildren 1–17years tested for influenza during 2013–16 were included and their immunization status verified. They were considered vaccinated if received ≥1 dose of an influenza vaccine ≥10days before evaluated for a respiratory episode. Age-groups were classified as 1–4years or 5–17years. VE was estimated by comparing vaccination status of influenza-positive versus influenza-negative cases.Results6779 children were enrolled in the three seasons. Overall, 27.2% received an influenza vaccine (87.1% IIV3 or IIV4 and 12.9% LAIV4), and 15.6% tested positive for influenza (77.9% A). IIV3 was predominantly used in 2013–14 and IIV4 in 2014–15 and 2015–16. IIV3 and IIV4 had comparable VE over the three seasons (60%, 57% and 53%) and performed similarly against influenza A and B and both age-groups. LAIV4 performed poorly for influenza A (15%, 37% and 48%) but better for influenza B (100%, 56% and 100%), especially among children 5–17years of age with VE=100% (95%CI: 55, 100).ConclusionsInfluenza vaccination showed modest but consistent effectiveness over the years. The switch from IIV3 to IIV4 did not affect VE. LAIV4 did not perform as well as IIVs, yet it improved over the years and was particularly good protecting older children against influenza B. These results emphasize the regional nature of influenza and the need for local surveillance.



http://ift.tt/2uohjhO

Meningococcal serogroup C immunogenicity, antibody persistence and memory B-cells induced by the monovalent meningococcal serogroup C versus quadrivalent meningococcal serogroup ACWY conjugate booster vaccine: A randomized controlled trial

Publication date: Available online 28 June 2017
Source:Vaccine
Author(s): Mariëtte B. van Ravenhorst, Fiona R.M. van der Klis, Debbie M. van Rooijen, Mirjam J. Knol, Susanne P. Stoof, Elisabeth A.M. Sanders, Guy A.M. Berbers
BackgroundAdolescents are considered the key transmitters of meningococci in the population. Meningococcal serogroup C (MenC) antibody levels wane rapidly after MenC conjugate vaccination in young children, leaving adolescents with low antibody levels. In this study, we compared MenC immune responses after booster vaccination in adolescence with either tetanus toxoid conjugated MenC (MenC-TT) or MenACWY (MenACWY-TT) vaccine, and aimed to establish an optimal age for this booster.MethodsHealthy 10-, 12-, and 15-year-olds, who received a single dose of MenC-TT vaccine in early childhood, were randomized to receive MenC-TT or MenACWY-TT vaccine. MenC serum bactericidal antibody (rSBA) titers, MenC polysaccharide (PS) specific IgG, IgG1 and IgG2 and MenC-specific IgG and IgA memory B-cells were determined before, one month and one year after the booster. Non-inferiority was tested by comparing geometric mean titers (GMTs) between vaccinees at one year.ResultsOf 501 participants, 464 (92.6%) were included in the 'according to protocol' cohort analysis. At one month, all participants developed high MenC rSBA titers (>24,000 in all groups) and MenC-PS-specific IgG levels. Non-inferiority was not demonstrated one year after the booster with higher MenC GMTs after the monovalent vaccine, but 462/464 (99.6%) participants maintained protective MenC rSBA titers. IgG levels mainly consisted of IgG1, but similar levels of increase were observed for IgG1 and IgG2. Both vaccines induced a clear increase in the number of circulating MenC-PS specific IgG and IgA memory B-cells. Between one month and one year, the highest antibody decay rate was observed in the 10-year-olds.ConclusionBoth MenC-TT and MenACWY-TT vaccines induced robust protective MenC immune responses after the booster vaccination, although non-inferiority could not be demonstrated for the MenACWY-TT vaccine after one year. Our results underline the importance of optimal timing of a meningococcal booster vaccination to protect against MenC disease in the long-term.



http://ift.tt/2tqjLaj

Safety and effectiveness of Human Papillomavirus (HPV) vaccination: NCI of Milan position statement

Publication date: Available online 29 June 2017
Source:Vaccine
Author(s): Giorgio Bogani, Domenica Lorusso, Francesco Raspagliesi




http://ift.tt/2uoqGxW

Long-term protection after hepatitis B vaccination in people living with HIV

Publication date: Available online 29 June 2017
Source:Vaccine
Author(s): Amanda Nazareth Lara, Ana Marli Sartori, Marise Oliveira Fonseca, Marta Heloísa Lopes
BackgroundHepatitis B vaccine is important in people living with HIV (PLHIV) since both viruses have the same transmission routes and co-infection has greater morbidity.PLHIV usually have poor response to hepatitis B vaccine. The duration of immunity in PLHIV is unknown.The objective of this study is to evaluate the duration of serological response and clinical protection provided by hepatitis B vaccination in PLHIV.MethodsRetrospective study of a PLHIV cohort primarily vaccinated for hepatitis B virus (HBV) from 2001 to 2002. Markers of infection and protection from HBV were investigated in those individuals who were still attending the outpatient clinic, in São Paulo, Brazil from 2012 to 2014. Three groups were analyzed. Group 1: adults who responded to primary vaccine series. Group 2: non-responders to primary vaccine series. Group 3: subjects from both Groups 1 and 2 who did not receive any booster doses after seroconversion.ResultsA cohort of 121 PLHIV was analyzed for seroconversion and persistence of anti-HBs. The majority were female (54.5%) and mean age was 50.1years.After 11years, none of the patients had serologic evidence of HBV infection.Overall, 41/58 (70.7%) of the initial responders (Group 1) had maintained anti-HBs≥10mIU/mL. Greater CD4+ values and anti-HBs>100mIU/mL at the time of first vaccine series were associated with persistence of anti-HBs.During the time of evaluation, 35/63 (55.6%) of the initial non-responders (Group 2) successfully seroconverted (anti-HBs≥10mIU/mL) in response to one or more booster doses.From the time of their seroconversion, 70 of the patients did not receive any further booster doses (Group 3). After 10years, 54/70 (77.1%) of these individuals has maintained anti-HBs≥10mIU/mL.ConclusionsEvaluation of long-term immunity for hepatitis B in PLHIV following vaccination showed a strong persistence of anti-HBs and no serologic evidence of HBV infection. Boosters may be effective in PLHIV non-responders to primary vaccination.



http://ift.tt/2uodMjN

Characteristics of pediatric invasive pneumococcal diseases and the pneumococcal isolates in Suzhou, China before introduction of PCV13

Publication date: Available online 28 June 2017
Source:Vaccine
Author(s): Xiyan Zhang, Jianmei Tian, Wei Shan, Jian Xue, Yunzhen Tao, Qian Geng, Yunfang Ding, Genming Zhao, Tao Zhang
BackgroundData on characteristics of invasive pneumococcal diseases (IPD) is limited in China. We aimed to understand the clinical features and explore the molecular characteristics of the pneumococcal isolates in China.MethodsSince 2010, we prospectively collected the pneumococcal isolates and the IPD patients' demographic and clinical information in Suzhou University Affiliated Children's Hospital (SCH). The antibiotic susceptibility, serotypes, genotypes of Streptococcus pneumoniae strains were identified by E-test, quellung reaction and/or multiplex PCR, and multi-locus sequence typing, respectively.ResultsDuring the period from January 2010 to December 2015, a total of 80 IPD patients were identified. They were diagnosed as meningitis (31.3%), septicemia (27.5%), pneumonia (21.3%) and others (20.0%). About half of them required vancomycin treatment, 42.5% were admitted to ICUs, 36.2% had complications and 6.2% were hospitalized for over 1year. The most common serotypes of the pneumococcal isolates were serotypes 6B and 14, the coverage of PCV13 was 92.5%, and CC236s and CC199s were the most common clone complexes.ConclusionsPediatric IPD patients had severe clinical symptoms, demanded intensive treatment, suffered poor prognosis and substantial burden. The pneumococcal isolates' serotype coverage of PCV13 vaccine was high, which leads to implication of PCV vaccine usage among children in China.



http://ift.tt/2tqwx8G

M2SR, a novel live influenza vaccine, protects mice and ferrets against highly pathogenic avian influenza

Publication date: Available online 28 June 2017
Source:Vaccine
Author(s): Yasuko Hatta, David Boltz, Sally Sarawar, Yoshihiro Kawaoka, Gabriele Neumann, Pamuk Bilsel
The emergence of highly pathogenic avian influenza H5N1 viruses has heightened global concern about the threat posed by pandemic influenza. To address the need for a highly effective universal influenza vaccine, we developed a novel M2-deficient single replication (M2SR) influenza vaccine virus and previously reported that it provided strong heterosubtypic protection against seasonal influenza viruses in mice. In the current study, we assessed M2SR induced protection against H5N1 influenza in mice and ferrets.Mice were intranasally inoculated with M2SR viruses containing the HA and NA from A/Vietnam/1203/2004 (M2SR H5N1) or A/California/07/2009 (M2SR H1N1). All M2SR vaccinated mice survived lethal challenge with influenza A/Vietnam/1203/2004 (H5N1), whereas 40% of mice vaccinated with recombinant H5 HA and none of the naïve controls survived. M2SR H5N1 provided sterile immunity, whereas low levels of virus were detected in the lungs of some M2SR H1N1 vaccinated mice. In contrast, recombinant H5 HA vaccinated mice and naïve controls showed systemic infection.M2SR H5N1 induced strong serum and mucosal antibody responses (IgG and IgA classes) against H5 HA, with high hemagglutination inhibition (HAI) titers. In contrast, while M2SR H1N1 elicited cross-reactive antibodies recognizing the H5 HA2 stalk region or the neuraminidase, no HAI activity against H5N1 virus was detected after M2SR H1N1 immunization.Both M2SR H5N1 and H1N1 also protected ferrets against lethal challenge with A/Vietnam/1203/2004. A prime–boost regimen provided optimal protection with no virus detected in the respiratory tract or brain after challenge. As in the mouse model, only the M2SR H5N1 vaccine induced HAI antibodies against the challenge virus in ferrets, while the M2SR H1N1 was able to provide protection without the induction of HAI antibodies.In summary, effective protection against highly pathogenic H5N1 influenza virus was provided by both homologous H5N1 M2SR and heterologous H1N1 M2SR demonstrating the cross-protective attributes of the M2SR platform.



http://ift.tt/2uodBow

Safety and immunogenicity of an inactivated cell culture-derived H7N9 influenza vaccine in healthy adults: A phase I/II, prospective, randomized, open-label trial

Publication date: Available online 28 June 2017
Source:Vaccine
Author(s): Un-In Wu, Szu-Min Hsieh, Wen-Sen Lee, Ning-Chi Wang, Hsiang-Chi Kung, Tsong-Yih Ou, Fu-Lun Chen, Te-Yu Lin, Yee-Chun Chen, Shan-Chwen Chang
BackgroundWe conducted a phase I/II clinical trial to evaluate the safety and immunogenicity of a Madin-Darby canine kidney (MDCK) cell-grown inactivated H7N9 influenza vaccine for pandemic preparedness purposes.MethodsBetween April 7, 2015 and May 27, 2016, healthy adults aged 20–60years were enrolled sequentially in phase I (n=40) and phase II (n=160) from three hospitals in Taiwan and randomized to receive 2 doses of whole-virus H7N9 vaccine (15 or 30μg hemagglutinin antigen (HA) with or without an aluminum hydroxide adjuvant) at 21-day intervals. Safety up to 180days and changes in hemagglutinin inhibition (HI) titers at 21days after each vaccination were determined.ResultsOf the 200 randomized subjects, 193 (96.5%) received 2 doses of the study vaccine and were included in the intention-to-treat analysis for safety, and 190 (95%) were included in the per-protocol analysis for immunogenicity. Most adverse events were mild and transient; no death or vaccine-related serious adverse events were reported. Overall, higher immune responses were observed in the groups administered with 30μgHA formulation than in the other two groups administered with 15μgHA formulation. The highest immune response was observed in subjects who received 2 doses of the adjuvanted vaccine containing 30μgHA with HI titer, seroprotection rate, seroconversion rate, and seroconversion factor of 36.2, 64.6%, 64.6% and 5.7, respectively.ConclusionsOur study demonstrated that the H7N9 influenza vaccine containing 30µgHA with aluminum hydroxide adjuvant was immunogenic and safe in adults aged 20–60years.CLINICALTRIALS.GOV identifier: NCT02436928.



http://ift.tt/2tqIMlN

Innovative Approach to Triage Oral Precancer

Conditions:   Oral Cancer;   Oral Premalignant Lesion
Intervention:  
Sponsors:   British Columbia Cancer Agency;   BC Cancer Foundation;   University of British Columbia
Recruiting - verified June 2017

http://ift.tt/2sVEqCx

Assessment of Pb and pyrene accumulation in Scirpus triqueter assisted by combined alkyl polyglucoside and nitrilotriacetic acid application

Abstract

To understand the accumulation and uptake of polycyclic aromatic hydrocarbons (PAHs) and heavy metals by plants is an important part of the assessment of phytoremediation for PAHs and heavy metals co-contaminated soil. This study was an investigation of the accumulation and uptake of pyrene and lead (Pb) by Scirpus triqueter under the condition of alkyl polyglucoside (APG) and nitrilotriacetic acid (NTA) combined application. The results indicated that the accumulation of Pb by S. triqueter was significantly improved by NTA and APG addition into the soil. The pyrene accumulation in plant was also increased after application of APG when compared to the control treatment. However, the pyrene accumulation was decreased when APG was applied together with NTA. SEM and TEM images of root surface suggested that more Pb in the soil transferred to the plant by combined application of APG and NTA. More importantly, TEM images of xylem cells of S.triqueter root showed that permeability of cell membrane was improved by application of APG.

http://ift.tt/2tqAc6I

Can liming change root anatomy, biomass allocation and trace element distribution among plant parts of Salix × smithiana in trace element-polluted soils?

Abstract

Willows (Salix spp.) are considered to be effective for the phytoremediation of trace elements from contaminated soils, but their efficiency is limited in heavily polluted soils because of poor growth. Liming can be a desirable measure to decrease the plant availability of elements, resulting in improved plant development. Notably, large root area and maximum soil penetration are basic parameters that improve the efficiency of phytoremediation. The impact of soil chemical properties on willow root anatomy and the distribution of trace elements below-ground have rarely been studied. The effect of liming on root parameters, biomass allocation and trace element distribution in non-harvestable (coarse roots, fine roots, stumps) and harvestable plant parts (twigs and leaves) of Salix × smithiana was assessed at the end of a 4-year pot experiment with two trace element-polluted soils that differed in terms of soil pH. Stump biomass predominated in weakly acidic soil. In neutral soil, the majority of biomass was located in fine roots and stumps; the difference from other plant parts was minor. Trace elements were the most concentrated in fine roots. Translocation to above-ground biomass increased as follows: Pb < As < Zn~Cd. In contrast to Cd and Zn, great differences in As and Pb mobility in plants were recorded after measurements of individual below-ground biomass (stumps < coarse roots < fine roots). Lime application decreased the concentrations of mobile Cd and Zn and related levels in plants, improved biomass production and root parameters and increased the removal of all trace elements in weakly acidic soil. None or minimum differences in the monitored parameters were recorded for dolomite treatments in both soils. The dose and source of liming had crucial effects on root anatomy. Growing willows in limed trace element-polluted soils is a suitable measure for combination of two remediation strategies, i.e. phytoextraction of Cd and Zn and assisted phytostabilization of As and Pb.

http://ift.tt/2uonoef

IFC (Ed. Board)

Publication date: June 2017
Source:Brain Research Bulletin, Volume 132





http://ift.tt/2s6pxdG

A potential contribution of tenascin-X to blood vessel formation in peripheral nerves

Publication date: Available online 28 June 2017
Source:Neuroscience Research
Author(s): Hiromichi Sakai, Shigefumi Yokota, Naoyo Kajitani, Tsunao Yoneyama, Kohei Kawakami, Yukihiko Yasui, Ken-ichi Matsumoto
Tenascin-X (TNX), an extracellular matrix protein, is abundantly expressed in peripheral nerves. However, the physiological role of TNX in peripheral nerves remains unknown. In this study, we found that actin levels in sciatic nerves of TNX-deficient mice were markedly decreased. Since actin was highly expressed in endothelial cells in wild-type sciatic nerves, we assessed morphological alterations of blood vessels in TNX-null sciatic nerves. The density of blood vessels was significantly decreased and the size of blood vessels was larger than those in wild-type sciatic nerves. Immunofluorescence showed that TNX was expressed by Schwann cells and fibroblasts in sciatic nerves. The results suggest that TNX secreted from Schwann cells and/or fibroblasts is involved in blood vessel formation in peripheral nerves.



http://ift.tt/2slxEao

Toll-Like Receptor-4/p38 MAPK Signaling in the Dorsal Horn Contributes to P2X4 Receptor Activation and BDNF Over-secretion In Cancer Induced Bone Pain

Publication date: Available online 28 June 2017
Source:Neuroscience Research
Author(s): Xiao-wen Meng, Jian-ling Gao, Jian-Ling Zuo, Li-Na Wang, Si-lan Liu, Xiao-Hong Jin, Ming Yao, Michael Namaka
Our previous research suggested that the P2X4 receptor (P2X4R) expression in microglia was involved in the activation of toll-like receptor-4 (TLR4) in the dorsal horn in the rat model of cancer induced bone pain (CIBP). In this study, we focused on whether TLR4- mitogen-activated protein kinases, p38 (p38 MAPK) contributes to P2X4R activation and brain-derived neurotrophic factor (BDNF) over-secretion in CIBP. In in vitro experiment, the results showed that BDNF expression evoked by ATP stimulation was dependent on TLR4-p38. In in vivo experiment, the results demonstrated that an intrathecal injection of TLR4 siRNA alleviated nociception induced by lipopolysaccharide (LPS) plus ATP or CIBP with decreased expression of P2X4R, TLR4, BDNF, interleukin-6 (IL-6) and phosphorylated-p38 MAPK (p-p38 MAPK). Moreover, injection with p38MAPK inhibitor SB203580 resulted in an identical pattern compared with treatment with TLR4 siRNA. Our results demonstrate that the activation of TLR4-p38MAPK-P2X4R signaling in microglial possibility plays an important role in the process of nociceptive transmission in CIBP, suggesting new mechanism and potential therapeutic targets for CIBP.



http://ift.tt/2t5tzVc

Measurement of phase resetting curves using optogenetic barrage stimuli

Publication date: Available online 28 June 2017
Source:Journal of Neuroscience Methods
Author(s): Matthew H. Higgs, Charles J. Wilson
BackgroundThe phase resetting curve (PRC) is a primary measure of a rhythmically firing neuron's responses to synaptic input, quantifying the change in phase of the firing oscillation as a function of the input phase. PRCs provide information about whether neurons will synchronize due to synaptic coupling or shared input. However, PRC estimation has been limited to in vitro preparations where stable intracellular recordings can be obtained and background activity is minimal, and new methods are required for in vivo applications.New methodWe estimated PRCs using dense optogenetic stimuli and extracellular spike recording. Autonomously firing neurons in substantia nigra pars reticulata (SNr) of Thy1-channelrhodopsin 2 (ChR2) transgenic mice were stimulated with random barrages of light pulses, and PRCs were determined using multiple linear regression.ResultsThe PRCs obtained were type-I, showing only phase advances in response to depolarizing input, and generally sloped upward from early to late phases. Secondary PRCs, indicating the effect on the subsequent ISI, showed phase delays primarily for stimuli arriving at late phases. Phase models constructed from the optogenetic PRCs accounted for a large fraction of the variance in ISI length and provided a good approximation of the spike-triggered average stimulus.Comparison with existing methodsCompared to methods based on intracellular current injection, the new method sacrifices some temporal resolution. However, it should be much more widely applicable in vivo, because only extracellular recording and optogenetic stimulation are required.ConclusionsThese results demonstrate PRC estimation using methods suitable for in vivo applications.



http://ift.tt/2t5G1UU

Fix the problem − a practical guide to whole-mount immunohistochemistry of teased nerve fibres

Publication date: Available online 28 June 2017
Source:Journal of Neuroscience Methods
Author(s): Simone Gross, Ninja Kolb, Marco Rosati, Kaspar Matiasek
BackgroundImmunohistochemical staining of entire nerve fibres allows for studying the molecular composition of functional fibre subunits and may add to the diagnostic value of nerve fibre teasing.New methodIn this study, we established a sealed-slide method for reproducible immunostaining of deep axoplasmic proteins in permanently straightened nerve fibres.ResultsImmunostaining of teased nerve fibres very much is facilitated by tip-fixation with biocompatible glass adhesives. Antibody penetration in fresh nerves can be achieved by thermic and chemical permeabilisation while enzymatic digestion allows for sufficient permeability after aldehyde fixation.Comparison with existing methodsThe methods recommended herein are easy to perform and represent a reliable and reproducible way to whole mount immunostaining.ConclusionsSealed-slide immunostaining of tip-fixed and permeabilised nerve biopsies will help to validate neurophysiological abnormalities and to screen for target molecules and predictive markers of peripheral nerve disorders such as in inherited neuropathies and Guillain-Barré syndrome.



http://ift.tt/2slJpOf

Rare splicing defects of FAS underly severe recessive autoimmune lymphoproliferative syndrome

Publication date: Available online 29 June 2017
Source:Clinical Immunology
Author(s): N. Agrebi, I. Ben-Mustapha, N. Matoussi, N. Dhouib, M. Ben-Ali, N. Mekki, M. Ben-Ahmed, B. Larguèche, S. Ben Becher, M. Béjaoui, M.R. Barbouche
Autoimmune lymphoproliferative syndrome (ALPS) is a prototypic disorder of impaired apoptosis characterized by autoimmune features and lymphoproliferation. Heterozygous germline or somatic FAS mutations associated with preserved protein expression have been described. Very rare cases of homozygous germline FAS mutations causing severe autosomal recessive form of ALPS with a complete defect of Fas expression have been reported.We report two unrelated patients from highly inbred North African population showing a severe ALPS phenotype and an undetectable Fas surface expression. Two novel homozygous mutations have been identified underlying rare splicing defects mechanisms. The first mutation breaks a branch point sequence and the second alters a regulatory exonic splicing site. These splicing defects induce the skipping of exon 6 encoding the transmembrane domain of CD95. Our findings highlight the requirement of tight regulation of FAS exon 6 splicing for balanced alternative splicing and illustrate the importance of such studies in highly consanguineous populations.



http://ift.tt/2t4ToEJ