The Burden of Common Skin Diseases Assessed with the EQ5D: a European Multi-centre Study in 13 Countries

Abstract

Background

Generic instruments measuring health related quality of life (HRQoL), like EQ5D, enable comparison of skin diseases with healthy populations and non-dermatological medical conditions, as well as calculation of utility data.

Objectives

The aims were to measure HRQoL in patients with common skin diseases and healthy controls across Europe using the EQ5D.

Methods

This multi-center observational cross-sectional study was conducted in 13 European countries. Each dermatology clinic recruited at least 250 consecutive adult outpatients to complete questionnaires, including the EQ5D.

Results

There were 5369 participants, 4010 patients and 1359 controls. Mean self-rated health state reported by patients was 69.9 (SD 19.7), controls 82.2 (SD 15.5). When adjusted for confounding factors, including comorbidity, mean patient EQ-VAS scores were 10.5 points lower than for controls (standardized β = −0.23). Odds ratio with 95% confidence interval for impairment in all 5 dimensions of EQ5D adjusted for confounders was doubled for patients compared with controls. Patients with hidradenitis suppurativa (HS), blistering conditions, leg ulcers, psoriasis and eczemas had the highest risk for reduction in HRQoL in most dimensions (two-tenfold). Data on differences of impairment by dimensions offer new insights.

Conclusions

This study confirms the large impact skin conditions have on patients' wellbeing, differentiating between aspects of HRQoL. Patients with HS, blistering diseases, leg ulcers, infections and most chronic skin diseases reported reduced HRQoL comparable to patients with chronic obstructive lung disease, diabetes mellitus, cardio-vascular disease and cancers. These findings are important in the prioritization of resource allocation between medical fields and within dermatological sub-specialities.

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Percutaneous CT-fluoroscopic–guided radioisotope seed placement for the management of adenoid cystic carcinoma of the trachea

Publication date: Available online 28 December 2016
Source:Brachytherapy
Author(s): Stephen Doggett, Shigeru Chino, Todd Lempert, Jay Federhart
PurposeTracheal and paratracheal malignancies present challenges in radiotherapeutic management due to their proximity to sensitive structures, central location, and because of the potential for catastrophic radiation induced fistula. The use of external beam radiation therapy and intraluminal brachytherapy has a limited number of reports in the literature. We have searched for a technique for treating tracheal and paratracheal malignancies allowing application of a high dose of radiation while minimizing dose to normal tissues. Our group has considerable experience in the use of percutaneous CT-guided radioisotope seed implants for intrathoracic malignancies. We have previously reported our technique for percutaneous CT-fluoroscopic–guided radioisotope seed implants in the management of thoracic malignancies. We have now treated several tracheal and paratracheal malignancies with our technique and report our results here. This is to our knowledge the first report of treatment of tracheal malignancy with CT-guided permanent seed implant.Methods and MaterialsThree patients with tracheal adenoid cystic carcinoma were implanted with ¹⁰³Pd under CT-fluoroscopic guidance utilizing percutaneous approach.ResultsAll patients tolerated the procedure well, and at 9-month average followup, all show disease regression, symptom improvement, and no sign of toxicity.ConclusionsWe believe this to be the first published series on CT-directed permanent seed brachytherapy for tracheal malignancies. Review of PubMed literature to 1990 discloses no prior writings on the use of permanent seed implantation for tracheal cancers. Tracheal malignancies provide a vexing radiation therapy challenge to stay within the therapeutic window. CT-directed permanent seed brachytherapy allows a high dose to be delivered to the tumor with a rapid falloff to the surrounding tissues. Short-term results from seed implant are excellent. Our 3 patients responded well in the short term to permanent seed brachytherapy with no chronic side effects and with reduction or relief of cough and pain. CT-fluoro–guided permanent seed implantation is an effective and low morbidity treatment for tracheal malignancies. Long-term followup is needed to further elucidate durability of response and toxicity.



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A directional 103Pd brachytherapy device: Dosimetric characterization and practical aspects for clinical use

Publication date: Available online 28 December 2016
Source:Brachytherapy
Author(s): Mark J. Rivard
PurposeA brachytherapy (BT) device has been developed with shielding to provide directional BT for preferentially irradiating malignancies while sparing healthy tissues. The CivaSheet is a flexible low-dose-rate BT device containing CivaDots with ¹⁰³Pd shielded by a thin Au disk. This is the first report of a clinical dosimetric characterization of the CivaSheet device.Methods and MaterialsRadiation dose distributions near a CivaDot were estimated using the MCNP6 radiation transport code. CivaSheet arrays were also modeled to evaluate the dose superposition principle for treatment planning. The resultant data were commissioned in a treatment planning system (TPS) (VariSeed 9.0), and the accuracy of the dose superposition principle was evaluated for summing individual elements comprising a planar CivaSheet.ResultsThe dose-rate constant (0.579 cGy/h/U) was lower than for ¹⁰³Pd seeds due to Au L-shell x-rays increasing the air-kerma strength. Radial dose function values at 0.1, 0.5, 2, 5, and 10 cm were 1.884, 1.344, 0.558, 0.088, and 0.0046, respectively. The two-dimensional anisotropy function exhibited dramatic reduction between the forward (0°) and rearward (180°) directions by a factor of 276 at r = 0.1 cm, 24 at r = 1 cm, and 5.3 at r = 10 cm. This effect diminished due to increasingly scattered radiation. The largest gradient in the two-dimensional anisotropy function was in contact with the device at 92° due to the Au disk shielding. TPS commissioning and dose superposition accuracies were typically within 2%.ConclusionsSimulations of the CivaDot yielded comprehensive dosimetry parameters that were entered into a TPS and deemed acceptable for clinical use. Dosimetry measurements of the CivaSheet are also of interest to the BT community.



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Comparing organ-at-risk doses for high–dose rate vaginal brachytherapy between three different planning workflows

Publication date: Available online 28 December 2016
Source:Brachytherapy
Author(s): J.D. Gruhl, D. Zheng, J.L. Longo, C. Enke, A.O. Wahl
PurposeThe aim of this study was to compare the organ-at-risk doses to the rectum and the bladder in postoperative endometrial cancer patients who receive high–dose rate vaginal brachytherapy (HDR-VB), when using three different methods of treatment planning: (Workflow A) individualized treatment planning before every fraction, (Workflow B) individualized treatment planning for first fraction only), and (Workflow C) using a template plan based on applicator choice and prescription specifics without patient-specific imaging or planning (standardized template approach).Methods and MaterialsAlternative plans were retrospectively created using workflows B and C for 22 patients who previously received postoperative HDR-VB using a vaginal cylinder and planned using Workflow A for endometrial cancer. The rectum and bladder were contoured on the CTs used for each fraction for dose comparison between the three methods. D50, D2cc, D1cc, D0.1cc, and V100 of the bladder and the rectum were compared using the two-sided Wilcoxon signed-rank test.ResultsA total of 123 fractions were available for comparison. For Workflow A vs. Workflow B, there was no significant difference for any rectal or bladder dosimetric parameter. For Workflow A vs. Workflow C, Workflow A delivered a significantly higher median dose to the rectum than Workflow C for D50, D2cc, D1cc, and V100. Workflow C delivered a significantly higher dose to the bladder than Workflow A: D2cc, D1cc, D0.1cc, and V100. However, the magnitudes of the differences were small; the dose index difference was >75 cGy for only two fractions.ConclusionPlan standardization in HDR-VB may result in considerable time and cost savings with minimal organ-at-risk dose differences.



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A Genome Wide Association Study of Fast Beta EEG in Families of European Ancestry

Publication date: Available online 28 December 2016
Source:International Journal of Psychophysiology
Author(s): Jacquelyn L. Meyers, Jian Zhang, Niklas Manz, Madhavi Rangaswamy, Chella Kamarajan, Leah Wetherill, David B. Chorlian, Sun J. Kang, Lance Bauer, Victor Hesselbrock, John Kramer, Samuel Kuperman, John I. Nurnberger, Jay Tischfield, Jen Chyong Wang, Howard J. Edenberg, Alison Goate, Tatiana Foroud, Bernice Porjesz
BackgroundDifferences in fast beta (20-28 Hz) electroencephalogram (EEG) oscillatory activity distinguish some individuals with psychiatric and substance use disorders, suggesting that it may be a useful endophenotype for studying the genetics of disorders characterized by neural hyper-excitability. Despite the high heritability estimates provided by twin and family studies, there have been relatively few genetic studies of beta EEG, and to date only one genetic association finding has replicated (i.e., GABRA2).MethodIn a sample of 1,564 individuals from 117 families of European Ancestry (EA) drawn from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a Genome-Wide Association Study (GWAS) on resting-state fronto-central fast beta EEG power, adjusting regression models for family relatedness, age, sex, and ancestry. To further characterize genetic findings, we examined the functional and behavioral significance of GWAS findings.ResultsThree intronic variants located within DSE (dermatan sulfate epimerase) on 6q22 were associated with fast beta EEG at a genome wide significant level (p<5x10^-8). The most significant SNP was rs2252790 (p<2.6x10^-8; MAF= 0.36; β= 0.135). rs2252790 is an eQTL for ROS1 expressed most robustly in the temporal cortex (p= 1.2x10^-6) and for DSE/TSPYL4 expressed most robustly in the hippocampus (p=7.3x10^-4; β= 0.29). Previous studies have indicated that DSE is involved in a network of genes integral to membrane organization; gene-based tests indicated that several variants within this network (i.e., DSE, ZEB2, RND3, MCTP1, and CTBP2) were also associated with beta EEG (empirical p<0.05), and of these genes, ZEB2 and CTBP2 were associated with DSM-V Alcohol Use Disorder (AUD; empirical p<0.05).DiscussionIn this sample of EA families enriched for AUDs, fast beta EEG is associated with variants within DSE on 6q22; the most significant SNP influences the mRNA expression of DSE and ROS1 in hippocampus and temporal cortex, brain regions important for beta EEG activity. Gene-based tests suggest evidence of association with related genes, ZEB2, RND3, MCTP1, CTBP2, and beta EEG. Converging data from GWAS, gene expression, and gene-networks presented in this study provide support for the role of genetic variants within DSE and related genes in neural hyperexcitability, and has highlighted two potential candidate genes for AUD and/or related neurological conditions: ZEB2 and CTBP2. However, results must be replicated in large, independent samples.



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Ovarian teratoma development after anti-NMDA receptor encephalitis treatment

Publication date: Available online 28 December 2016
Source:Brain and Development
Author(s): Taku Omata, Kazuo Kodama, Yoshimi Watanabe, Yukiko Iida, Yoshiaki Furusawa, Akiko Takashima, Yukitoshi Takahashi, Hiroshi Sakuma, Keiko Tanaka, Katsunori Fujii, Naoki Shimojo
BackgroundAnti-NMDA-R receptor encephalitis occurs predominantly in younger women and is often comorbid with ovarian teratoma, a feature that is often absent in children. Here, we report our experience with two pediatric patients, in whom no tumors were present during treatment for encephalitis, but in whom ovarian teratomas developed without encephalitis relapse after treatment was completed.CasesPatient 1 was a 14-year-old girl who was diagnosed due to characteristic symptoms and anti-NMDA-R antibody. MRI scanning during treatment revealed no ovarian tumors, but a tumor developed in the right ovary 10months after onset. Another tumor developed in the left ovary 3years after onset, and a mature ovarian teratoma was confirmed after bilateral partial ovariectomy. Patient 2 was an 11-year old girl who was also diagnosed due to characteristic symptoms and anti-NMDA-R antibody. Imaging during treatment revealed no ovarian tumors, but a 2.5-cm tumor mass was found in the left ovary 10months after onset, and a mature ovarian teratoma was confirmed after partial ovariectomy.DiscussionThis case report suggests the need for regular tumor screening after treatment for anti-NMDA receptor encephalitis because of potential subsequent tumor development, even in pediatric patients who initially present with no comorbid tumors. No analysis of relapse risk has yet been reported in cases of tumor development after treatment, and at this point, whether or not resection is needed to prevent relapse remains unclear. However, because teratomas usually grow, have an associated risk of torsion, and can be malignant, tumor removal should be considered.



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A comparison between effect of photodynamic therapy by LED and calcium hydroxide therapy for root canal disinfection against Enterococcus faecalis: A randomized controlled trial

Publication date: Available online 28 December 2016
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Mohammad Asnaashari, Hengameh Ashraf, Afsaneh Rahmati, Neda Amini
BackgroundInsufficient root canal disinfection is one of the main reasons for persistent periapical pathology. Photodynamic therapy (PDT) has been proven effective in disinfecting infected root canals. The aim of this study was to evaluate the antimicrobial effect of photo activated disinfection (PAD) when using toluidine blue as photosensitizer and a LED lamp after the conventional treatment, and comparing it with calcium hydroxide therapy in vivo.MethodsThis clinical trial includes 20 patients with molars requiring endodontic retreatment. After the conventional treatment, first microbiological samples were obtained using sterile rotary ProTaper F2 file and 3 paper points and transferred to a microbiology laboratory. Group 1 (n=10) specimens underwent PAD with photosensitizer (PS) solution (0.1mg/ml TB) and irradiation with Fotosan light emitting diode (LED) lamp (635nm, 200mW/cm2) for 60s. Creamy Ca(OH)2 paste was used in group 2 (n=10) for two weeks. A second sample was then obtained. The samples were cultured and then bacterial colonies were counted. Data included number of colony forming units (CFUs) before and after treatments, analyzed by t-test and analysis of covariance (ANCOVA) using SPSS vs.18.ResultsA significant difference between results of before and after treatment of both groups (calcium hydroxide therapy p=0.02<0.05, PAD p<0.0001) indicated the efficacy of both treatments. The mean numbers for log 10 CFUs/mL before calcium hydroxide therapy and PAD with LED irradiation was 10.1968 and 11.3773. After treatment, the mean numbers were 9.4202 and 8.3772, respectively. The difference in results after treatment between groups was significant (p=0.01<0.05) and indicate that PAD was more effective.ConclusionPAD and calcium hydroxide therapy, as auxiliary methods adjunct to conventional root canal therapy, are both effective in root canal disinfection. In comparison with calcium hydroxide therapy, PAD leads to a greater reduction in enterococcus faecalis number in the infected root canals.



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Applications of Higenamine in pharmacology and medicine

Publication date: 20 January 2017
Source:Journal of Ethnopharmacology, Volume 196
Author(s): Nana Zhang, Zeqin Lian, Xueying Peng, Zijian Li, Haibo Zhu
Ethnopharmacological relevanceAconitum has been used as local and traditional medicines in many asian regions for the treatment of various diseases such as collapse, syncope, painful joints, oedema, bronchial asthma et al. Higenamine, a plant-based alkaloid, was initially isolated from Aconitum and identified as the active cardiotonic component of Aconitum. It has been tested as a candidate of pharmacologic stress agent in the detection of coronary artery diseases (CADs) and now researchers have just accomplished the phase III clinical studies successfully in China. Besides, a large number of studies have revealed the various pharmacological properties and potentially multi-spectral medical applications of higenamine. However, to date, no comprehensive review on higenamine has been published.Aim of the reviewThis present paper aims to compile a comprehensive update regarding the biochemistry, pharmacokinetic features, pharmacological activities, clinical and potential clinical uses and toxicities on higenamine with the ultimate objective of providing a guide for future research on this drug.Materials and methodsThe selection of relevant data was made through a search using the keyword "higenamine" in "Web of science", "Pubmed", and "China Knowledge Resource Integrated (CNKI)". Information was also acquired from local classic herbal literature, government reports and conference papers.ResultsIn addition to Aconitum, higenamine also exists in many other plants including Tinospora crispa, Nandina domestica THUNBERG, Gnetum Parvifolium C.Y. Cheng, sarum Heterotropoides,Nelumbo nucifera,N.nucifera. The pharmacokinetic studies conducted in animals and humans showed that higenamine conformed to a two-compartment pharmacokinetic model. Studies over the last four decades on higenamine have revealed its various pharmacological properties such as positive inotropic and chronotropic effect, activating slow channel effect, vascular and tracheal relaxation effect, anti-thrombotic, anti-apoptotic and anti-oxidative effect, anti-inflammatory and immunomodulatory effect. This phytochemical constituent has shown its potential therapeutic effects for diseases like heart failure, disseminated intravascular coagulation (DIC), shock, arthritis, asthma, ischemia/reperfusion (I/R) injuries and erectile dysfunction.ConclusionsExtensive basic and clinical studies on higenamine showed valuable therapeutic effects on different disorders. However, the underlying mechanisms of higenamine have not been established. Therefore, the safety, tolerability and efficacy of higenamine are as yet, not fully understood. Additionally, some of the studies were small sample-sized and unreliable. To sum up, there is a need for deeper investigation in the mechanisms of higenamine action, as well as well-designed preclinical and clinical trials studies to test the safety and clinical value of the drug.

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Total coumarins of Hedyotis diffusa induces apoptosis of myelodysplastic syndrome SKM-1 cells by activation of caspases and inhibition of PI3K/Akt pathway proteins

Publication date: 20 January 2017
Source:Journal of Ethnopharmacology, Volume 196
Author(s): Jianping Jiang, Bo Wang, Jing Li, Baodong Ye, Shengyun Lin, Wenbin Qian, Letian Shan, Thomas Efferth
Ethnopharmacological relevanceHedyotis diffusa is an ethno-medicine used for anti-cancer treatment in the clinic of traditional Chinese medicine (TCM). The total coumarins of Hedyotis diffusa (TCHD) was a selected extract with observed antiproliferative activity, which has not been tested in treatment of myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML).Aim of the studyThis study aimed to evaluate the apoptosis-inducing effect of TCHD on human MDS cell line (SKM-1) and explore its action mechanism in association with caspase family and PI3K/Akt signaling pathway.Materials and methodsThe chemical constituents and total coumarins content of TCHD were determined by High Performance Liquid Chromatography-tandem mass spectrometry (HPLC-MS/MS) and UV–vis spectrophotometry, respectively. MTT assay, Hoechst 33258 staining, and Annexin V-FITC/PI double labeling were applied to evaluate TCHD's efficacy on SKM-1 cells. Western blot analysis was also used to clarify the action mechanism of TCHD on protein expression level.ResultsTwo compounds, p-coumaric acid and E-6-O-p-coumaroyl scandoside methyl ester, were identified in TCHD, and its total coumarins content reached 87.4%. By MTT assay, apoptosis-inducing effect of TCHD on SKM-1 cells was found in a dose-dependent manner after 24–48h treatment, with IC50 values of 104.48μg/ml and 100.66μg/ml, respectively. Morphological and flow cytometry observation also confirmed such effect of TCHD. Western blot analysis clarified its action mechanism associating with the activation of caspases and inhibition of PI3K/Akt pathway proteins.ConclusionsThis is the first report regarding the apoptosis-inducing efficacy and mechanism of TCHD on SKM-1 cells, providing a promising candidate of TCM for MDS and AML therapy with fewer side effects.

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Antiplasmodial activity of Heinsia crinita (Rubiaceae) and identification of new iridoids

Publication date: 20 January 2017
Source:Journal of Ethnopharmacology, Volume 196
Author(s): P. Tshisekedi Tshibangu, P. Mutwale Kapepula, M.J. Kabongo Kapinga, A. Tujibikila Mukuta, Dibungi T. Kalenda, Alembert T. Tchinda, Ange A. Mouithys-Mickalad, O. Jansen, E. Cieckiewicz, M. Tits, L. Angenot, M. Frédérich
Ethnopharmacological relevanceHeinsia crinita is used in traditional medicine for the treatment of febrile illness and erectile dysfunction. Its stem bark powder is found in some peripheral markets in the Democratic Republic of the Congo (DRC) as a remedy against malaria. Investigations were conducted on crude extracts of leaves, fruits and stem barks in view to validate their use and to determine which plant part possesses the best antiplasmodial properties.Materials and methodsDifferent plant parts were extracted with methanol, ethanol and dichloromethane. Based on the preliminary assays, the dichloromethane extract of the stem bark was subjected to fractionation using preparative HPLC system and column chromatography. This step led to the isolation of two new iridoids which had their structures elucidated by NMR, UV, MS and FT-IR spectroscopic techniques. Extracts and pure compounds were tested in vitro against the 3D7 strain of Plasmodium falciparum. The inhibition of the parasite growth was evaluated in vitro by colorimetric method (p-LDH assay) and their cytotoxicity evaluated in vitro against the human non-cancer fibroblast cell line (WI38) through WST1 assay.The in vivo antiplasmodial activity was assessed by the inhibition of Plasmodium berghei growth in infected mice treated with the ethanol extract of H. crinita stem bark at the concentrations of 200 and 300mg/Kg/day per os, using a protocol based on the 4-d suppressive test of Peters and compared to a non-treated negative control group of mice (growth =100%). Finally the antioxidant activity of the same extract was evaluated using ABTS, DPPH and cell-based assays.ResultsA moderate in vitro antiplasmodial activity was observed for the dichloromethane extract of the stem bark of H. crinita (IC50 =29.2±1.39µg/mL) and for the two new iridoids, lamalbide 6, 7, 8- triacetate (IC50 =16.39±0.43µg/mL) as well as for its aglycone lamiridosin 6, 7, 8-triacetate (IC50 =0.44.56±1.12µg/mL).The ethanolic stem bark extract (200 and 300mg/kg/day, oral route) showed a moderate in vivo antimalarial activity in Plasmodium berghei-infected mice with 27.84±2.75% and 48.54±3.76% of inhibition of the parasite growth, respectively (p<0.01).). This extract displayed high cellular antioxidant activity using dichlorofluorescein-diacetate (DCFDA) on HL-60 monocytes.These crude extracts and pure compounds tested at the higher concentration of 100µg/mL did not show any cytotoxicity against WI38 cells.ConclusionsThe results showed that H. crinita extracts possess antimalarial activity and contain some unusual iridoids with moderate antiplasmodial activity, therefore justifying to some extent its traditional use by the local population in DRC for this purpose. This is the first report of the isolation and antiplasmodial activity of these two new iridoids.

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Molecular and cellular physiology of sodium-dependent glutamate transporters

Publication date: Available online 28 December 2016
Source:Brain Research Bulletin
Author(s): Christine R. Rose, Daniel Ziemens, Verena Untiet, Christoph Fahlke
Glutamate is the major excitatory transmitter in the vertebrate brain. After its release from presynaptic nerve terminals, it is rapidly taken up by high-affinity sodium-dependent plasma membrane transporters. While both neurons and glial cells express these excitatory amino acid transporters (EAATs), the majority of glutamate uptake is accomplished by astrocytes, which convert synaptically-released glutamate to glutamine or feed it into their own metabolism. Glutamate uptake by astrocytes not only shapes synaptic transmission by regulating the availability of glutamate to postsynaptic neuronal receptors, but also protects neurons from hyper-excitability and subsequent excitotoxic damage. In the present review, we provide an overview of the molecular and cellular characteristics of sodium-dependent glutamate transporters and their associated anion permeation pathways, with a focus on astrocytic glutamate transport. We summarize their functional properties and roles within tripartite synapses under physiological and pathophysiological conditions, exemplifying the intricate interactions and interrelationships between neurons and glial cells in the brain.

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Wake-sleep and cardiovascular regulatory changes in rats made obese by a high-fat diet

Publication date: 1 March 2017
Source:Behavioural Brain Research, Volume 320
Author(s): Marco Luppi, Abed A. Al-Jahmany, Flavia Del Vecchio, Matteo Cerri, Alessia Di Cristoforo, Timna Hitrec, Davide Martelli, Emanuele Perez, Giovanni Zamboni, Roberto Amici
Obesity is known to be associated with alterations in wake-sleep (WS) architecture and cardiovascular parameters. This study was aimed at assessing the possible influence of diet-induced obesity (DIO) on sleep homeostasis and on the WS state‐dependent levels of arterial pressure (AP) and heart rate in the rat. Two groups of age-matched Sprague-Dawley rats were fed either a high-fat hypercaloric diet, leading to DIO, or a normocaloric standard diet (lean controls) for 8 weeks. While under general anesthesia, animals were implanted with instrumentation for the recording of electroencephalogram, electromyogram, arterial pressure, and deep brain temperature. The experimental protocol consisted of 48h of baseline, 12h of gentle handling, enhancing wake and depressing sleep, and 36-h post-handling recovery. Compared to lean controls, DIO rats showed: i) the same amount of rapid-eye movement (REM) and non-REM (NREM) sleep in the rest period, although the latter was characterized by more fragmented episodes; ii) an increase in both REM sleep and NREM sleep in the activity period; iii) a comparable post-handling sleep homeostatic response, in terms of either the degree of Delta power increase during NREM sleep or the quantitative compensation of the REM sleep loss at the end of the 36-h recovery period; iv) significantly higher levels of AP, irrespectively of the different WS states and of the changes in their intensity throughout the experimental protocol. Overall, these changes may be the reflection of a modification in the activity of the hypothalamic areas where WS, autonomic, and metabolic regulations are known to interact.



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Myosin phosphorylation on stress fibers predicts contact guidance behavior across diverse breast cancer cells

Publication date: March 2017
Source:Biomaterials, Volume 120
Author(s): Juan Wang, Ian C. Schneider
During cancer progression the extracellular matrix is remodeled, forming aligned collagen fibers that proceed radially from the tumor, resulting in invasion. We have recently shown that different invasive breast cancer cells respond to epitaxially grown, aligned collagen fibrils differently. This article develops insight into why these cells differ in their contact guidance fidelity. Small changes in contractility or adhesion dramatically alter directional persistence on aligned collagen fibrils, while migration speed remains constant. The directionality of highly contractile and adhesive MDA-MB-231 cells can be diminished by inhibiting Rho kinase or β1 integrin binding. Inversely, the directionality of less contractile and adhesive MTLn3 cells can be enhanced by activating contractility or integrins. Subtle, but quantifiable alterations in myosin II regulatory light chain phosphorylation on stress fibers explain the tuning of contact guidance fidelity, separate from migration per se indicating that the contractile and adhesive state of the cell in combination with collagen organization in the tumor microenvironment determine the efficiency of migration. Understanding how distinct cells respond to contact guidance cues will not only illuminate mechanisms for cancer invasion, but will also allow for the design of environments to separate specific subpopulations of cells from patient-derived tissues by leveraging differences in responses to directional migration cues.



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Ovarian Adrenal Rest Tumors Undetected by Imaging Studies and Identified at Surgery in Three Females with Congenital Adrenal Hyperplasia Unresponsive to Increased Hormone Therapy Dosage

Abstract

Patients with congenital adrenal hyperplasia have a predisposition for developing adrenal rest tumors. In contrast to testicular adrenal rest tumors, ovarian adrenal rest tumors are less common, and only a few cases have been reported in the literature. This report presents three Chinese female congenital adrenal hyperplasia patients (9 to 15 years of age) with small ectopic adrenal cortical nodules that were not detected by imaging but were diagnosed at surgery. All three patients developed virilization with elevation of 17- hydroxyprogesterone, androstenedione, and androgen levels despite receiving maximum adrenal hormone replacement therapy. Ultrasound and magnetic resonance imaging of the abdomen and pelvis suggested bilateral expansion of the adrenal glands, but no lesions of the ovaries were observed. Laparoscopy and/or laparotomy revealed small nodular lesions surrounding the pelvic gonad in all three cases. Histopathological examination of the resected tissue in all cases revealed hyperplasic nodules of cells surrounded by fibrous tissue. The cells were arranged as nests with abundant cytoplasm, which were partially lightly stained with a small centered nucleus. Immunohistochemistry staining revealed the cells to be synaptophysin positive, melan-A positive, and chromogranin A negative, indicating the cells were adrenocortical tissue and not adrenal medullary cells. Thus, the findings of the histopathological examination were consistent with ovarian adrenal rest tumors. Female congenital adrenal hyperplasia patients with virilization who showed an inadequate response to hormone therapy and had negative imaging results may benefit from laparoscopic examination or laparotomy in order to confirm the diagnosis of ovarian adrenal rest tumors while receiving unilateral subtotal adrenalectomy or subtotal bilateral adrenalectomy.

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Early-phase trial demonstrates shrinkage in pediatric neural tumors

In an early-phase clinical trial of a new oral drug, selumetinib, children with the common genetic disorder neurofibromatosis type 1 (NF1) and plexiform neurofibromas, tumors of the peripheral nerves, tolerated selumetinib and, in most cases, responded to it with tumor shrinkage.

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Halofuginone enhances the chemo-sensitivity of cancer cells by suppressing NRF2 accumulation

Publication date: Available online 28 December 2016
Source:Free Radical Biology and Medicine
Author(s): Kouhei Tsuchida, Tadayuki Tsujita, Makiko Hayashi, Asaka Ojima, Nadine Keleku-Lukwete, Fumiki Katsuoka, Akihito Otsuki, Haruhisa Kikuchi, Yoshiteru Oshima, Mikiko Suzuki, Masayuki Yamamoto
The KEAP1-NRF2 system regulates the cellular defence against oxidative and xenobiotic stresses. NRF2 is a transcription factor that activates the expression of cytoprotective genes encoding antioxidative, detoxifying and metabolic enzymes as well as transporters. Under normal conditions, KEAP1 represses NRF2 activity by degrading the NRF2 protein. When cells are exposed to stresses, KEAP1 stops promoting NRF2 degradation, and NRF2 rapidly accumulates and activates the transcription of target genes. Constitutive accumulation of NRF2 via a variety of mechanisms that disrupt KEAP1-mediated NRF2 degradation has been observed in various cancer types. Constitutive NRF2 accumulation confers cancer cells with a proliferative advantage as well as resistance to anti-cancer drugs and radiotherapies. To suppress the chemo- and radio-resistance of cancer cells caused by NRF2 accumulation, we conducted high-throughput chemical library screening for NRF2 inhibitors and identified febrifugine derivatives. We found that application of the less-toxic derivative halofuginone in a low dose range rapidly reduced NRF2 protein levels. Halofuginone induced a cellular amino acid starvation response that repressed global protein synthesis and rapidly depleted NRF2. Halofuginone treatment ameliorated the resistance of NRF2-addicted cancer cells to anti-cancer drugs both in vitro and in vivo. These results provide preclinical proof-of-concept evidence for halofuginone as an NRF2 inhibitor applicable to treatment of chemo- and radio-resistant forms of cancer.

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2,3-Dehydrosilybin A/B as a pro-longevity and anti-aggregation compound

Publication date: Available online 28 December 2016
Source:Free Radical Biology and Medicine
Author(s): Konstantina Filippopoulou, Nikoletta Papaevgeniou, Maria Lefaki, Anna Paraskevopoulou, David Biedermann, Vladimír Křen, Niki Chondrogianni
Aging is an unavoidable process characterized by gradual failure of homeostasis that constitutes a critical risk factor for several age-related disorders. It has been unveiled that manipulation of various key pathways may decelerate the aging progression and the triggering of age-related diseases. As a consequence, the identification of compounds, preferably natural-occurring, administered through diet, with lifespan-extending, anti-aggregation and anti-oxidation properties that in parallel exhibit negligible side-effects is the main goal in the battle against aging. Here we analyze the role of 2,3-dehydrosilybin A/B (DHS A/B), a minor component of silymarin used in a plethora of dietary supplements. This flavonolignan is well-known for its anti-oxidative and neuroprotective properties, among others. We demonstrate that DHS A/B confers oxidative stress resistance not only in human primary cells but also in the context of a multi-cellular aging model, namely Caenorhabditis elegans (C. elegans) where it also promotes lifespan extension. We reveal that these DHS A/B outcomes are FGT-1 and DAF-16 dependent. We additionally demonstrate the anti-aggregation properties of DHS A/B in human cells of nervous origin but also in nematode models of Alzheimer's disease (AD), eventually leading to decelerated progression of AD phenotype. Our results identify DHS A/B as the active component of silymarin extract and propose DHS A/B as a candidate anti-aging and anti-aggregation compound.

Graphical abstract

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First-dose and steady-state pharmacokinetics of orally administered crizotinib in children with solid tumors: a report on ADVL0912 from the Children’s Oncology Group Phase 1/Pilot Consortium

Abstract

Purpose

Characterize the pharmacokinetics of oral crizotinib in children with cancer.

Methods

Sixty-four children with solid tumors or anaplastic large-cell lymphoma (ALCL) enrolled on a phase 1/2 trial of the ALK, MET and ROS1 inhibitor, crizotinib, had pharmacokinetic sampling after the first dose (n = 15) or at steady state (n = 49). Dose levels studied were 100, 130, 165, 215, 280 and 365 mg/m²/dose administered twice daily. Two capsule and two oral liquid formulations were used over the course of the trial. Crizotinib was quantified with a validated HPLC/tandem mass spectrometry method with a lower limit of detection of 0.2 ng/mL. Pharmacokinetic parameters were derived using non-compartmental analysis.

Results

Time to peak plasma concentration was 4 h. At 280 mg/m² (MTD), mean (±SD) steady-state peak plasma concentration was 717 ± 201 ng/mL, and steady-state trough plasma concentration was 480 ± 176 ng/mL. At steady state, AUC_0–τ was proportional to dose over the dose range of 215–365 mg/m²/dose. Apparent clearance of crizotinib was 731 ± 241 mL/min/m². Steady-state AUC_0–τ at 280 mg/m²/dose was 2.5-fold higher than the AUC_0–∞ in adults receiving 250 mg (~140 mg/m²). Age, sex and drug formulation do not account for the inter-subject variability in AUC_0–τ at steady state. The accumulation index was 4.9, and the half-life estimated from the accumulation index was 36 h.

Conclusions

The pharmacokinetics of oral crizotinib in children is similar to that in adults. Steady-state trough-free crizotinib concentrations in plasma at the MTD exceed inhibitory concentrations of crizotinib in ALCL cell lines.

ClinicalTrials.gov identifier

NCT00939770.

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Organic-inorganic polybenzoxazine copolymers with double decker silsesquioxanes in the main chains: Synthesis and thermally activated ring-opening polymerization behavior

Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): Ning Liu, Lei Li, Lei Wang, Sixun Zheng
A series of organic-inorganic polybenzoxazine (PBZ) copolymers with double deck silsesquioxane (DDSQ) in the main chains were synthesized via Mannich polycondensation. First, 3,13-dianilino DDSQ, a well-defined polyhedral oligomeric silsesquioxane (POSS) diamine was synthesized. Thereafter, this POSS diamine together with 4,4-diaminodiphenylmethane was utilized to react with 4,4'-dihydroxyldiphenylisopropane and formaldehyde to obtain the PBZ hybrids with DDSQ in the main chains. The high-molecular-weight products were obtained and they displayed excellent film-forming properties. Transmission electron microscopy showed that the PBZ-DDSQ copolymers were microphase-separated in bulks; the spherical POSS microdomains with the diameter of 10–20 nm were dispersed in the continuous PBZ matrix. Compared to plain PBZ, the PBZ-DDSQ copolymers displayed enhanced surface hydrophobicity as evidenced with the static contact angle measurements. These PBZ-DDSQ copolymers can easily undergo the thermally-activated ring-opening polymerization and the organic-inorganic thermosetting nanocomposites were obtained. The curing kinetics showed that the inclusion of DDSQ in the main chains of PBZ enhanced the activation energy of curing reaction. All the organic-inorganic thermosets possessed the enhanced thermal stability as evidenced with thermogravimetric analysis.

Graphical abstract

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Tailoring the crystalline morphology and mechanical property of olefin block copolymer via blending with a small amount of UHMWPE

Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): Yongsheng Zhao, Yanling Zhu, Guopeng Sui, Feng Chen, Qiang Fu
In this study, the crystalline morphology and mechanical property of Olefin Block Copolymer (OBC) were tailored by adding a small amount (up to 10 wt%) of ultrahigh molecular weight polyethylene (UHMWPE). To do this, OBC and UHMWPE was solution blended first and then subjected to compression molding or injection molding, respectively. It was found that a small quantity of UHMWPE (0.5 wt%, 1 wt%) can be fully mixed with OBC, while phase separation occurs when UHMWPE content is higher than 2.5 wt%, as suggested by SEM and DSC results. For compression molded samples, an obvious increase of Young's modulus from 12 MPa to 22 MPa while maintaining the good elasticity of OBC was observed as the content of UHMWPE is less than 2.5 wt% (in the phase miscible range). With further increasing of UHMWPE content to 10 wt%, only slightly increased Young's modulus is seen. Thus the miscibility between OBC and UHMWPE plays an important role in determining the mechanical property for compression molded samples. However, a continuous increase of Young's modulus was observed with the increase of UHMWPE content for samples obtained via injection molding, with a slight increase (from 23 MPa to 40 MPa) as the content of UHMWPE is less than 2.5 wt%, while with a large increase (from 40 MPa to 156 MPa) as the content of UHMWPE increases from 2.5 wt% to 10 wt%, accompanied with a greatly decrease of elongation (from 1100% to 50%). Even elastomer-to-plastic transition takes place when the content of UHMWPE is large (5 wt%, 10 wt%). Structural analysis of injection-molded samples shows that shish-kebab-like structures can be successfully induced as addition of UHMWPE along with gradually increased crystal orientation. It was interesting to find that small-addition of UHMWPE favors increased tie-effect due to the miscibility between OBC and UHMWPE, which is helpful to the elasticity retaining as well as strength enhancement, while large-addition of UHMWPE gives rise to phase separation and mixed shish-kebabs (OBC/UHMWPE hybrid shish-kebabs and UHMWPE homo-shish-kebabs), leading to elastomer-to-plastic transition.

Graphical abstract

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In situ polymerization of styrene into a PMMA matrix by using an extensional flow mixing device: A new experimental approach to elaborate polymer blends

Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): François Xavier Pierrot, Rigoberto Ibarra-Gómez, Michel Bouquey, René Muller, Christophe A. Serra
The present work consisted in the in situ polymerization of a liquid monomer (styrene) into a melt polymer matrix (PMMA) as an innovative method to prepare polymer blends at fine dispersions. That was possible by using an original mixing/reactor device called RMX^®, which significantly develops extensional flow, greatly enhancing the mixing efficiency. Resultant morphology was characterized by TEM and average particle sizes were obtained by means of image analysis. A high distributive efficiency was observed at very fine dispersed phase morphology, tens of nanometers in diameter, in fact, in the absence of compatibilizing agents. It was found, by comparing self (thermal) and peroxide-initiated systems, that morphology strongly depends on the balance between polymerization rate and monomer diffusion into the polymer matrix (as enhanced by PMMA solubility into styrene) during mixing. Finally, a comparison of morphology between compounds prepared by reactive blending and those elaborated by conventional melt mixing was done.

Graphical abstract

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Covalent three-dimensional networks of graphene and carbon nanotubes: synthesis and environmental applications

Publication date: Available online 28 December 2016
Source:Nano Today
Author(s): Archi Dasgupta, Lakshmy Pulickal Rajukumar, Christopher Rotella, Yu Lei, Mauricio Terrones
In recent years tremendous efforts have been made to exploit the exceptional properties of 1-Dimensional carbon nanotubes and 2-Dimensional graphene in order to interconnect those forming 3-Dimensional hybrid systems. Such macroscopic 3-D networks possess several advantages such as highly accessible surface area, minimized agglomeration or re-stacking, enhanced thermal and electrical transport, and robust mechanical properties as compared to their nanoscale 1-D or 2-D building blocks. This review aims to provide a fundamental understanding of state-of-the-art synthesis methodologies for interconnecting these carbon nanostructures, structure-property relationships as well as potential environmental applications related to adsorption, catalysis, sensing, and energy conversion. The technical challenges and future research opportunities are also discussed.

Graphical abstract

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Photoluminescence mechanism in graphene quantum dots: Quantum confinement effect and surface/edge state

Publication date: Available online 28 December 2016
Source:Nano Today
Author(s): Shoujun Zhu, Yubin Song, Joy Wang, Hao Wan, Yuan Zhang, Yang Ning, Bai Yang
As a new class of fluorescent carbon materials, graphene quantum dots (GQDs) have drawn increasing attention due to their outstanding properties and potential applications. Herein, GQDs prepared by chemical synthetic strategies, which mainly contain cutting different carbon resources and carbonization from small molecules or polymers, are discussed. Although the photoluminescence (PL) mechanism of GQDs can be explained by the size of the GQDs, surface chemical groups, and doping atoms, there is no universal agreement on the specific PL mechanism. The dominant PL mechanism of GQDs consists of the quantum confinement effect of conjugated π-domains, the surface/edge state in GQDs, as well as the synergistic effect of these two factors.

Graphical abstract

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Application of Au based nanomaterials in analytical science

Publication date: Available online 28 December 2016
Source:Nano Today
Author(s): Peilong Wang, Zhenyu Lin, Xiaoou Su, Zhiyong Tang
Au based nanomaterials (AuNMs) are known to poessess many attractive features such as unique electrical, optical and catalytic properties as well as excellent biocompatibility. These outstanding characteristics make them promising candidates as the signal reporters, enhancement materials or others involved with bioassay, food safety and environmental monitoring. In this review, we summarize the current advancement on application of AuNMs in analytical sciences based on their local surface plasmon resonance, fluorescence and electrochemistry properties. Finally future development in this research area is also prospected.

Graphical abstract

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Effects of decreased dopamine transporter levels on nigrostriatal neurons and paraquat/maneb toxicity in mice

Publication date: March 2017
Source:Neurobiology of Aging, Volume 51
Author(s): Franziska Richter, Lauryn Gabby, Kimberly A. McDowell, Caitlyn K. Mulligan, Krystal De La Rosa, Pedrom C. Sioshansi, Farzad Mortazavi, Ingrid Cely, Larry C. Ackerson, Linda Tsan, Niall P. Murphy, Nigel T. Maidment, Marie-Françoise Chesselet
How genetic variations in the dopamine transporter (DAT) combined with exposure to environmental toxins modulate the risk of Parkinson's disease remains unclear. Using unbiased stereology in DAT knock-down mice (DAT-KD) and wild-type (WT) littermates, we found that decreased DAT caused a loss of tyrosine hydroxylase–positive (dopaminergic) neurons in subregions of the substantia nigra pars compacta at 3–4 days, 5 weeks, and 18 months of age. Both genotypes lost dopaminergic neurons with age and remaining neurons at 11 months were resilient to paraquat/maneb. In 5-week-old mice, the toxins decreased substantia nigra pars compacta dopaminergic neurons in both genotypes but less in DAT-KD. Regional analysis revealed striking differences in the subsets of neurons affected by low DAT, paraquat/maneb, and aging. In particular, we show that a potentially protective effect of low DAT against toxin exposure is not sufficient to reduce death of all nigrostriatal dopaminergic neurons. Thus, different regional vulnerability of nigrostriatal dopaminergic neurons may contribute to an increased risk of developing Parkinson's disease when multiple factors are combined.



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Proangiogenic characteristics of activated macrophages from patients with age-related macular degeneration

Publication date: March 2017
Source:Neurobiology of Aging, Volume 51
Author(s): Shira Hagbi-Levi, Michelle Grunin, Tareq Jaouni, Liran Tiosano, Batya Rinsky, Sarah Elbaz-Hayoun, Amnon Peled, Itay Chowers
Macrophages were previously implicated in the pathogenesis of neovascular age-related macular degeneration (nvAMD). It is unclear if a specific macrophage phenotype is associated with nvAMD, and if macrophages from nvAMD patients are more pathogenic as compared with controls. To address these issues, we evaluated macrophages derived from peripheral blood monocytes of nvAMD patients and age-matched controls. Macrophages were assessed in terms of their expression profile and of their angiogenic potential in the choroid sprouting assay and the rat model of laser-induced choroidal neovascularization. Results showed a proangiogenic and inflammatory gene and protein expression profiles in classic (M[IFNγ and LPS]) and alternative (M[IL-4 and IL-13]) polarized macrophages. Furthermore, activated macrophages, particularly of the M(IFNγ and LPS) phenotype from nvAMD patients, were proangiogenic ex vivo and in vivo. These findings implicate activated human macrophages, particularly M(IFNγ and LPS) macrophages from nvAMD patients, in nvAMD. Further research is required to determine whether activated macrophages can serve as therapeutic targets in nvAMD.

Graphical abstract

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Exploring the contribution of spatial navigation to cognitive functioning in older adults

Publication date: March 2017
Source:Neurobiology of Aging, Volume 51
Author(s): Jan Laczó, Ross Andel, Zuzana Nedelska, Martin Vyhnalek, Kamil Vlcek, Sebastian Crutch, John Harrison, Jakub Hort
Spatial navigation (SN) impairment is present early in Alzheimer's disease (AD). We tested whether SN performance, self-centered (egocentric) and world-centered (allocentric), was distinguishable from performance on established cognitive functions—verbal and nonverbal memory, executive and visuospatial function, attention/working memory, and language function. 108 older adults (53 cognitively normal [CN] and 55 with amnestic mild cognitive impairment [aMCI]) underwent neuropsychological examination and real-space navigation testing. Subset (n = 63) had automated hippocampal volumetry. In a factor analysis, allocentric and egocentric navigation tasks loaded highly onto the same factor with low loadings on other factors comprising other cognitive functions. In linear regression, performance on other cognitive functions was not, or was only marginally, associated with spatial navigation performance in CN or aMCI groups. After adjustment for age, gender, and education, right hippocampal volume explained 26% of the variance in allocentric navigation in aMCI group. In conclusion, spatial navigation, a known cognitive marker of early AD, may be distinguished from other cognitive functions. Therefore, its assessment along with other major cognitive functions may be highly beneficial in terms of obtaining a comprehensive neuropsychological profile.



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Periodontitis is associated with diabetic retinopathy in non-obese adults

Abstract

Purpose

Patients with diabetes retinopathy appear to show increased susceptibility to periodontal disease. This study was performed to assess the relationship between periodontitis and the prevalence of diabetic retinopathy in a large probability sample of the Korean population. A subgroup analysis was performed using body mass index <25 kg/m² as the criterion to evaluate the effect of obesity on this relationship.

Methods

This study is based on data from the Korean National Health and Nutrition Examination Survey of the Korean population, conducted between 2008 and 2010. The presence of diabetic retinopathy in relation to demographic variables and anthropometric characteristics of the participants is presented as means with their standard errors. The presence of periodontitis and presence of retinopathy categorized by body mass index (<25 and ≥25 kg/m²) were evaluated. Multiple logistic regression analyses were used to assess the associations between periodontitis and diabetic retinopathy after adjustment with variables, including age, sex, smoking, drinking, exercise, hypertension, metabolic syndrome, HbA1c, and duration of diabetes mellitus.

Results

There was a statistically significant increase in the prevalence of periodontitis in individuals who had proliferative diabetic retinopathy. The odds ratios [95% confidence intervals] of prevalence of diabetic retinopathy were 1.193 [0.757–1.881] for the whole population after adjustments with confounding factors. Subgroup analysis after adjustments with confounding factors showed that the odds ratios [95% confidence intervals] of prevalence were 2.206 [1.114–4.366] and 0.588 [0.326–1.061] among participants with body mass index <25 kg/m² and body mass index 37 ≥25 kg/m², respectively.

Conclusions

The diabetic retinopathy was positively associated with the presence of periodontitis in non-obese diabetic Korean adults after adjustment with confounding variables. Our findings suggest that when a periodontist finds the presence of periodontitis in non-obese diabetic patients, timely evaluation of the patient's ophthalmic evaluation should be 44 recommended.

http://ift.tt/2ir7o5R

Hormone replacement therapy in Turner syndrome is important—a new meta-analysis points at many shortcomings in the available literature

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Erratum to “Predictors and consequences of intraoperative microvascular problems in autologous breast reconstruction” [J Plast Reconstr Aesthet Surg 69 (2016), 1349–1355]

The publisher regrets that the name of the author Stefan Hofer was not represented in its full form in the original version of this article. This author should be referred to as Stefan O.P. Hofer.

http://ift.tt/2iG4spB

Assessment of the link between quantitative biexponential diffusion-weighted imaging and contrast-enhanced MRI in the liver

Publication date: May 2017
Source:Magnetic Resonance Imaging, Volume 38
Author(s): Hildebrand Dijkstra, Matthijs Oudkerk, Peter Kappert, Paul E. Sijens
PurposeTo investigate if intravoxel incoherent motion (IVIM) modeled diffusion-weighted imaging (DWI) can be linked to contrast-enhanced (CE-)MRI in liver parenchyma and liver lesions.MethodsTwenty-five patients underwent IVIM-DWI followed by multiphase CE-MRI using Gd-EOB-DTPA (n=20) or Gd-DOTA (n=5) concluded with IVIM-DWI. Diffusion (Dslow), microperfusion (Dfast), its fraction (ffast), wash-in-rate (Rearly) and late-enhancement-rate (Rlate) of Gd-EOB-DTPA were calculated voxel-wise for the liver. Parenchyma and lesions were segmented. Pre-contrast IVIM was compared 1) between low, medium and high Rearly for parenchyma 2) to post-contrast IVIM substantiated with simulations 3) between low and high Rlate per lesion type.ResultsDfast and ffast increased (P<0.001) with 25.6% and 33.8% between low and high Rearly of Gd-EOB-DTPA. Dslow decreased (−15.0%; P<0.001) with increasing Rearly. Gd-DOTA demonstrated similar observations. ffast (+10%; P<0.001) and Dfast (+6.6%; P<0.001) increased after Gd-EOB-DTPA, while decreasing after Gd-DOTA (−4.2% and −5.7%, P<0.001) and were confirmed by simulations. For focal nodular hyperplasia lesions (n=5) Dfast and ffast increased (P<0.001) with increasing Rlate, whereas for hepatocellular carcinoma (n=4) and adenoma (n=7) no differences were found.ConclusionMicroperfusion measured by IVIM reflects perfusion in a way resembling CE-MRI. Also IVIM separated intra- and extracellular MR contrast media. This underlines the potential of IVIM in quantitative liver imaging.



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Free-radical scavenging properties of mannitol and its role as a constituent of hyaluronic acid fillers: a literature review

Abstract

Mannitol has both hydrating and anti-oxidant properties that make it an ideal excipient for use with hyaluronic acid (HA) fillers. This review examines the role of reactive oxygen species in the aging process and their effects on both endogenous HA and HA products developed for aesthetic use. Evidence is presented to show that the free-radical scavenging properties of mannitol provide it with a two-fold mechanism of action when combined with HA fillers: reducing the inflammation and swelling associated with the injection procedure itself, and preventing the degradation of the injected HA by free radicals. Mannitol also has a long and well-established safety profile in both the food and pharmaceutical industry. Having established the rationale for using mannitol in combination with an HA filler, the products using this strategy are then reviewed. The addition of mannitol to HA fillers is a viable and safe option for improving both short- and long-term HA aesthetic effects.

This article is protected by copyright. All rights reserved.

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A novel tandem mass spectrometry method for first-line screening of mainly beta-thalassemia from dried blood spots

Publication date: 10 February 2017
Source:Journal of Proteomics, Volume 154
Author(s): Chaowen Yu, Shuodan Huang, Ming Wang, Juan Zhang, Hao Liu, Zhaojian Yuan, Xingbin Wang, Xiaoyan He, Jie Wang, Lin Zou
Traditional methods for thalassemia screening are time-consuming and easily affected by cell hemolysis or hemoglobin degradation in stored blood samples. Tandem mass spectrometry (MS/MS) proved to be an effective technology for sickle cell disorders (SCD) screening. Here, we developed a novel MS/MS method for β-thalassemia screening from dried blood spots (DBS). Stable isotopic-labeled peptides were used as internal standards for quantification and calculation of the α:β-globin ratios. We used the α:β-globin ratio cutoffs to differentiate between normal individuals and patients with thalassemia. About 781 patients and 300 normal individuals were analyzed. The α:β-globin ratios showed significant difference between normal and β-thalassemia patients (P<0.01), particularly when the disease was homozygous or double heterozygous with another α- or β-thalassemia mutation. In the parallel study, all cases screened for suspected thalassemia from six hundred DBS samples by using this MS/MS method were successfully confirmed by genotyping. The intra-assay and inter-assay CVs of the ratios ranged from 2.4% to 3.9% and 4.7% to 7.1%, and there was no significant sample carryover or matrix effect for this MS/MS method. Combined with SCD screening, this MS/MS method could be used as a first-line screening assay for both structural and expression abnormalities of human hemoglobin.Biological significanceTraditional methods for thalassemia screening were depending on the structural integrity of tetramers and could be affected by hemolysis and degradation of whole blood samples, especially when stored. We used proteospecific peptides produced by the tryptic digestion of each globin to evaluate the production ratio between α- and β-globin chains, which turned out to be quite stable even when stored for more than two months. Though most of the peptides were specific to α-globin or β-globin, we only chose four most informative peptides and its stable isotopic-labeled peptides as internal standards for analysis, which could obtain a high accuracy. Currently, we are the first to address the application of MS/MS for thalassemia screening, when combined with SCD screening, this MS/MS method could be used as a first-line screening assay for both structural and expression abnormalities of human hemoglobin.

Graphical abstract

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Review of 3-dimensional Facial Anatomy: Injecting Fillers and Neuromodulators

Summary: To achieve consistent results utilizing facial injectables, practitioners must understand the pertinent anatomy of the forehead, temple, cheek, nose, and perioral areas. A detailed understanding of facial blood vessels, nerves, and musculature is essential for safe and effective placement of fillers and neuromodulators. Copyright (C) 2016 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

http://ift.tt/2hOxMG8

Does dental trauma in the primary dentition increases the likelihood of trauma in the permanent dentition? A longitudinal study

Abstract

Objectives

The aim of this longitudinal study was to assess the likelihood of children suffering traumatic dental injuries in the permanent dentition subsequent to traumatic dental injuries in their primary dentition.

Materials and methods

A longitudinal study was conducted in Pelotas, Brazil. Children were assessed in 2007, when they were aged 2–5 years, and in 2013, at which time, they were aged 8–11 years. Data collection included interviews with parents and clinical oral examination for dental trauma and occlusion. The classification proposed by Andreasen and Andreasen was used, and crown discoloration and fistula were added to this criterion in order to assess pulp involvement. Child/parent report was used to aid in the diagnosis of both treated and untreated injuries. As a limitation, no radiographs were taken. Descriptive, univariate, and multivariate logistic regression analyses were performed.

Results

A total of 110 children were included. Dental trauma frequency in the primary dentition was 38.2% and that in the permanent dentition was 30.9%. In the multivariate analyses, children with dental trauma in the primary dentition showed a higher likelihood of suffering dental trauma in the permanent dentition [odds ratio (OR) 2.97, 95% confidence interval (CI) 1.01–8.91, P = 0.05].

Conclusions

Individuals with previous trauma in the primary dentition are prone to further trauma in the permanent dentition. The history of dental trauma may be used to predict dental trauma in the permanent dentition and to establish preventive measures.

Clinical relevance

Behavioral characteristics may be related to the risk of a child suffering injuries. The results suggested that some children are accident-prone.

http://ift.tt/2hprk7F

Evaluation of ultrasonic and conventional surgical techniques for genioplasty combined with two different osteosynthesis plates: a cadaveric study

Abstract

Objectives

The aim of this study was to compare genioplasties performed using traditional saw or piezosurgery combined with different osteosynthesis plates.

Materials and methods

Thirty-two genioplasties were first performed on fresh human cadavers using a saw or piezosurgery, followed by chin osteosynthesis with bending or pre-shaped plates. The time required for osteotomy and plate fixation was measured, and the suprahyoid pedicle was inspected.

Results

The mean time required was 204 s (SD 43) with the saw and 52 s (SD 67) with piezosurgery. Osteosynthesis fixation time was 100 s (SD 31) for pre-shaped plates and 124 s (SD 24) for individual plates. Statistical differences were found between both osteotomy techniques (p < 0.001) and osteosynthesis plates (p = 0.025). Injuries of the suprahyoid muscle pedicle were found in 10/16 saw cases and 3/16 piezosurgery cases (p = 0.012).

Conclusions

Although piezosurgery is more time consuming compared with saw osteotomy, it is still adequate in time and allows a reduction of the suprahyoid pedicle injuries. Therefore, piezosurgery seems to be a viable alternative technique for genioplasty. From a clinical point of view, the time difference for osteosynthesis fixation has no significance.

Clinical relevance

The time taken for ultrasonic surgery is suitable for clinical use and leads additional to less damage to the suprahyoid pedicle.

http://ift.tt/2iFpF2Z

IL-22 promotes Fas expression in oligodendrocytes and inhibits FOXP3 expression in T cells by activating the NF-κB pathway in multiple sclerosis

Publication date: February 2017
Source:Molecular Immunology, Volume 82
Author(s): Jin Zhen, Jun Yuan, Yongwang Fu, Runxiu Zhu, Meiling Wang, Hong Chang, Yan Zhao, Dong Wang, Zuneng Lu
Multiple sclerosis (MS) is characterized by an increase in interleukin-22 and Fas, and a decrease in FOXP3, among other factors. In this study, we examined patients with MS and healthy control subjects and used the experimental autoimmune encephalomyelitis (EAE) animal model to identify the effects of IL-22 on oligodendrocytes and T cells in MS development. In MS, the expression of Fas in oligodendrocytes and IL-22 in CD4⁺CCR4⁺CCR6⁺CCR10⁺ T cells was enhanced. Ikaros and FOXP3 were both decreased in T cells. Depending on exogenous IL-22, Fas increased the phosphorylation of mitogen- and stress-activated protein kinase 1 and activated the nuclear factor-κB pathway in oligodendrocytes, leading to an increase in Fas and oligodendrocyte apoptosis. IL-22 decreased FOXP3 expression by activating NF-κB, and it further inhibited PTEN and Ikaros expression. Tregs reversed the functions of IL-22. Taken together, these findings help to elucidate the mechanisms of IL-22 in MS development.



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Analysis of the energy consumption of private households in Germany using multi-level cross-impact balance approach - Data

Publication date: February 2017
Source:Data in Brief, Volume 10
Author(s): Stefan Vögele, Patrick Hansen, Witold-Roger Poganietz, Sigrid Prehofer, Wolfgang Weimer-Jehle
Many studies stress the needs of interdependence analysis under the special conditions of multidisciplinary systems that include social systems. This applies, in particular, to scenarios on future energy demand and supply. Using the example of the residential sector in Germany we provide information on factors and their possible outcomes taking multidisciplinary aspects into account. In addition, futures are presented reflecting consistent combinations of the outcomes of the selected factors. These futures can be used as storylines for further analyses (see (S. Vögele, P. Hansen, W-R. Poganietz, S. Prehofer, W. Weimer-Jehle) [1]).



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18F-Choline PET/CT and multiparametric MRI for the detection of early local recurrence of prostate cancer initially treated by radiotherapy: comparison with systematic 3D-transperineal mapping biopsy

Publication date: Available online 28 December 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Salim Kanoun, Paul Walker, Jean-Marc Vrigneaud, Edouard Depardon, Vincent Barbier, Olivier Humbert, Morgan Moulin, Gilles Créhange, Luc Cormier, Romaric Loffroy, François Brunotte, Alexandre Cochet
PurposeTo compare the diagnostic performance of ¹⁸F-Fluorocholine PET/CT (FCH-PET/CT), multiparametric prostate MRI (mpMRI) and a combination of both techniques for the detection of local recurrence of prostate cancer initially treated by radiotherapy.MethodsThis was a retrospective single-institution study of 32 patients with suspected prostate cancer recurrence, who underwent both FCH-PET/CT and 3T mpMRI within 3 months of one another for the detection of recurrence. All included patients had to be cleared for metastatic recurrence. The reference procedure was systematic 3D-transperineal prostate biopsy for the final assessment of local recurrence. Both imaging modalities were analyzed by two experienced readers blinded to clinical data. The analysis was made per-patient and per-segment using a 4-segment model.ResultsThe median PSA at the time of imaging was 2.92ng/mL. The mean PSA doubling time was 14 months. Of the 32 patients, 31 had a positive 3D-transperineal mapping biopsy for a local relapse. On a patient-based analysis, the detection rate was 71% (22/31) for mpMRI and 74% (23/31) for FCH-PET/CT. On a segment-based analysis, the sensitivity and specificity were 32% and 87% for mpMRI, 34% and 87% for FCH-PET/CT, and 43% and 83% for the combined analysis of both techniques. Accuracy was 64, 65 and 66% respectively. The inter-observer agreement was kappa=0.92 for FCH-PET/CT and kappa=0.74 for mpMRI.ConclusionsBoth mpMRI and FCH-PET/CT show limited sensitivity but good specificity for the detection of local cancer recurrence after radiotherapy, when compared with 3D-transperineal mapping biopsy. Prostate biopsy still appears mandatory to diagnose local relapse and select patients who could benefit from local salvage therapy.

Teaser

The aim of the study is to compare the diagnosis performances of 18FCH-PET/CT and mpMRI in the diagnosis of early local relapse of prostate cancer. We designed a retrospective study with a systematic gold standard 3D-mapping biopsy. The results highlight the low sensitivity of both imaging modalities and the importance of prostate biopsies to assess intra-prostatic relapse before local salvage treatment.


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Application of noninvasive brain stimulation for post-stroke dysphagia rehabilitation

Publication date: Available online 27 December 2016
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Zhuo Wang, Wei-Qun Song, Liang Wang
Noninvasive brain stimulation (NIBS), commonly consisting of transcranial magnetic stimulation (TMS), transcranial direct-current stimulation (tDCS), as well as paired associative stimulation (PAS), has attracted increased interest and been applied experimentally in the treatment of post-stroke dysphagia (PSD). This review presented a synopsis of the current research for the application of NIBS on PSD. The intention here was to understand the current research progress and limitations in this field and to stimulate potential research questions not yet investigated for the application of NIBS on patients with PSD. Here we successively reviewed advances of repetitive TMS (rTMS), tDCS, and PAS techniques on both healthy participants and PSD patients in three aspects, including scientific researches about dysphagia mechanism, applied studies about stimulation parameters, and clinical trials about their therapeutic effects. The techniques of NIBS, especially rTMS, have been used by the researchers to explore the different mechanisms between swallowing recovery and extremity rehabilitation. The key findings included the important role of intact hemisphere reorganization for PSD recovery, and the use of NIBS on the contra-lesional side as a therapeutic potential for dysphagia rehabilitation. Though significant results were achieved in most studies by using NIBS on swallowing rehabilitation, it is still difficult to draw conclusions for the efficacy of these neurostimulation techniques, considering the great disparities between studies.



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Effects of the biochar aromaticity and molecular structures of the chlorinated organic compounds on the adsorption characteristics

Abstract

Adsorption behaviors of the chlorinated organic compounds (COCs) (i.e., trichloroethylene (TCE), 1,2,4-trichlorobenzene (1,2,4-TCB); 1,2-dichlorobenzene (1,2-DCB); and monochlorobenzene (MCB)) by the commercial rice husk-based biochar (RH500) and the laboratory-prepared biochars from corn stalks under different pyrolytic temperatures (i.e., CS300, CS500, CS700) were examined and interpreted by the pseudo-first-order kinetic model, the double layer model with two energies, and the Freundlich model. It is identified that the first-order adsorption rate constants (k ₁ = 0.06∼0.51 h⁻¹) were proportional to the high aromaticity and/or low polarity of biochars and the strong hydrophobicity of the COCs. The saturated adsorption capacity for the COCs was followed by the order of RH500 > CS500 > CS700 > CS300. RH500 showed the highest adsorption capacity for the COCs due to its high surface area (SA) and total pore volume (TPV). However, CS500 with low SA and TPV development highlighted the important roles of the aromaticity and/or low polarity on the COCs adsorption. In addition, 1,2,4-TCB showed the highest saturated adsorption capacity on all biochars, followed by TCE, 1,2-DCB, and MCB. The results further revealed the positive effects of the physical properties (α, N _M, ε ₁, and ε ₂), the hydrophobicity and electrostatic forces (i.e., π-π interaction and electron donor-acceptor interaction) between the adsorbates and the aromatic moieties of biochar surfaces on the adsorption of COCs.

http://ift.tt/2i7PFTj

Trace elements in starter infant formula: dietary intake and safety assessment

Abstract

The aim of this study was to investigate the concentrations of five essential (Fe, Mn, Zn, Cu and Se) and four non-essential/toxic elements (Cr, Cd, Ni and Pb) in 35 different starter infant formulas (0–6 months) sold in Italy. In addition, a safety assessment of these trace elements was carried out, by comparing the estimated daily intake (EDI) with the adequate intake (AI) and the provisional tolerable daily intake (PTDI), with a view to provide information on the metal distribution patterns and health risk to infants arising from the consumption of these products. The concentrations were determined by using inductively coupled plasma mass spectrometry after microwave digestion. The concentrations expressed in geometric mean ± geometric standard deviation of Fe (6.17 ± 1.61 mg/L), Zn (6.21 ± 1.31 mg/L), Cu (416.4 ± 1.21 μg/L), Mn (121.5 ± 1.85 μg/L) and Se (13.27 ± 1.67 μg/L) were within legal limits. In spite of this, the mean EDIs of Fe (4.81 mg/day) and Mn (94.75 μg/day) were many times higher than the recommended AI, especially for Mn. Chromium, Ni, Cd and Pb concentrations were not detectable in 11, 37, 57 and 66% of the samples, respectively. Considering the overall sample, the GM ± GSD of these elements were 4.80 ± 5.35 μg/L for Cr, 1.02 ± 11.65 μg/L for Ni, 0.21 ± 14.83 μg/L for Cd and 0.14 ± 17.13 μg/L for Pb. The mean EDIs were far below the respective PTDI. When the safety assessment was based on the 75° percentile level of each elements, all EDIs remained well below the PTDI, with the exception of Cd, whose EDI approached (74.7%), albeit remaining below the PTDI. In conclusion, our results and the increased awareness on the potential risks of excessive Mn and Fe for infants support that an urgent scientific-based definition of the appropriated levels of fortification in formulas is required. Moreover, regular monitoring of all the stages of production of infant formulas is essential in order to limit toxic metal contamination.

http://ift.tt/2iEwWvU

Individual and mixture acute toxicity of model pesticides chlordecone and pyriproxyfen in the estuarine copepod Eurytemora affinis

Abstract

Due to the increase in the use of phytosanitary products during the last few decades, the importance to study the effect of pesticide mixtures has been established. In this study, we investigated the acute toxicity of two model insecticides, chlordecone (CLD) and pyriproxyfen (PXF), alone and in mixtures, in the estuarine copepod Eurytemora affinis. After 48 h of exposure, the relative LC50 were 73.24 and 131.61 μg/L for PXF and CLD, respectively. The lower concentration tested (10 μg/L) did not affect the mortality of E. affinis whatever the considered chemical compound. To understand the interaction between compounds in mixture, the results were fitted to the concentration addition, Vølund, and Hewlett models. The best fit was obtained with the Hewlett model, suggesting a synergistic effect of the mixture.

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Periodontitis is associated with diabetic retinopathy in non-obese adults

Abstract

Purpose

Patients with diabetes retinopathy appear to show increased susceptibility to periodontal disease. This study was performed to assess the relationship between periodontitis and the prevalence of diabetic retinopathy in a large probability sample of the Korean population. A subgroup analysis was performed using body mass index <25 kg/m² as the criterion to evaluate the effect of obesity on this relationship.

Methods

This study is based on data from the Korean National Health and Nutrition Examination Survey of the Korean population, conducted between 2008 and 2010. The presence of diabetic retinopathy in relation to demographic variables and anthropometric characteristics of the participants is presented as means with their standard errors. The presence of periodontitis and presence of retinopathy categorized by body mass index (<25 and ≥25 kg/m²) were evaluated. Multiple logistic regression analyses were used to assess the associations between periodontitis and diabetic retinopathy after adjustment with variables, including age, sex, smoking, drinking, exercise, hypertension, metabolic syndrome, HbA1c, and duration of diabetes mellitus.

Results

There was a statistically significant increase in the prevalence of periodontitis in individuals who had proliferative diabetic retinopathy. The odds ratios [95% confidence intervals] of prevalence of diabetic retinopathy were 1.193 [0.757–1.881] for the whole population after adjustments with confounding factors. Subgroup analysis after adjustments with confounding factors showed that the odds ratios [95% confidence intervals] of prevalence were 2.206 [1.114–4.366] and 0.588 [0.326–1.061] among participants with body mass index <25 kg/m² and body mass index 37 ≥25 kg/m², respectively.

Conclusions

The diabetic retinopathy was positively associated with the presence of periodontitis in non-obese diabetic Korean adults after adjustment with confounding variables. Our findings suggest that when a periodontist finds the presence of periodontitis in non-obese diabetic patients, timely evaluation of the patient's ophthalmic evaluation should be 44 recommended.

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Hormone replacement therapy in Turner syndrome is important—a new meta-analysis points at many shortcomings in the available literature

http://ift.tt/2htlyVP

Medication-Assisted Treatment Models of Care for Opioid Use Disorder in Primary Care Settings [Internet].

The majority of medication treatment for opioid use disorder (OUD) is provided in primary care settings. Effective and innovative models of care for medication-assisted treatment (MAT) in primary care settings (including rural or other underserved settings) could facilitate implementation and enhance provision and uptake of agonist and antagonist pharmacotherapy in conjunction with psychosocial services for more effective treatment of OUDs.

http://ift.tt/2htfqN7

The use of fibrin sealant during non-emergency surgery: a systematic review of evidence of benefits and harms.

This study found that the effectiveness of fibrin sealants do not appear to vary according to surgical procedures with regard to reducing the risk of seroma or haematoma.

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Alopecia areata incognita in Cronkhite-Canada Syndrome

Summary

Cronkhite-Canada syndrome is an acquired inflammatory polyposis syndrome in which alopecia, onychomadesis and hyperpigmentation occur concurrently with gastrointestinal symptoms. The pathophysiology of alopecia in Cronkhite-Canada Syndrome has not been definitively elucidated and we present evidence for alopecia incognita as a possible mechanism of hair loss.

This article is protected by copyright. All rights reserved.

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The effect of unilateral subthalamic nucleus deep brain stimulation on depression in Parkinson's disease

Publication date: Available online 27 December 2016
Source:Brain Stimulation
Author(s): Elizabeth L. Birchall, Harrison C. Walker, Gary Cutter, Stephanie Guthrie, Allen Joop, Raima A. Memon, Ray L. Watts, David G. Standaert, Amy W. Amara
BackgroundDepression is common in Parkinson's disease (PD) and adversely affects quality of life. Both unilateral and bilateral subthalamic (STN) deep brain stimulation (DBS) effectively treat the motor symptoms of PD, but questions remain regarding the impact of unilateral STN DBS on non-motor symptoms, such as depression.MethodsWe report changes in depression, as measured by the Hamilton Depression Rating Scale (HAMD-17), in 50 consecutive PD patients who underwent unilateral STN DBS. Participants were also evaluated with UPDRS part III, Parkinson's Disease Questionnaire-39, and Pittsburgh Sleep Quality Index. The primary outcome was change in HAMD-17 at 6 months versus pre-operative baseline, using repeated measures analysis of variance (ANOVA). Secondary outcomes included the change in HAMD-17 at 3, 12, 18, and 24 months post-operatively and correlations amongst outcome variables using Pearson correlation coefficients. As a control, we also evaluated changes in HAMD-17 in 25 advanced PD patients who did not undergo DBS.ResultsParticipants with unilateral STN DBS experienced significant improvement in depression 6 months post-operatively (4.94 ± 4.02) compared to preoperative baseline (7.90 ± 4.44) (mean ± SD) (p = <0.0001). HAMD-17 scores did not correlate with UPDRS part III at any time-point. Interestingly, the HAMD-17 was significantly correlated with sleep quality and quality of life at baseline, 3 months, and 6 months post-operatively. Participants without DBS experienced no significant change in HAMD-17 over the same interval.ConclusionUnilateral STN DBS improves depression 6 months post-operatively in patients with PD. Improvement in depression is maintained over time and correlates with improvement in sleep quality and quality of life.



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Stimulating cognition in schizophrenia: A controlled pilot study of prefrontal transcranial direct current stimulation during memory and learning

Publication date: Available online 28 December 2016
Source:Brain Stimulation
Author(s): Natasza D. Orlov, Derek K. Tracy, Daniel Joyce, Shinal Patel, Joanna Rodzinka-Pasko, Hayley Dolan, John Hodsoll, Tracy Collier, John Rothwell, Sukhwinder S. Shergill
BackgroundSchizophrenia is characterized by prominent cognitive deficits, impacting largely on memory and learning; strongly associated with the prefrontal cortex.Objective/hypothesisWe combined two interventions, transcranial direct current stimulation (tDCS) over the prefrontal cortex and cognitive training, to examine change in cognitive performance in patients with schizophrenia.MethodsA double blind, sham-controlled pilot study of 49 patients with schizophrenia, randomized into real or sham tDCS stimulation groups. Subjects participated in 4 days of cognitive training (days 1, 2, 14, 56) with tDCS applied at day-1 and day-14. The primary outcome measure was change in accuracy on working memory and implicit learning tasks from baseline. The secondary outcome measure was the generalization of learning to non-trained task indexed by the CogState neuropsychological battery. Data analysis was conducted using multilevel modelling and multiple regressions.Results24 participants were randomized to real tDCS and 25 to sham. The working memory task demonstrated a significant mean difference in performance in the tDCS treatment group: at day-2 (b = 0.68, CI 0.14–1.21; p = 0.044) and at day-56 (b = 0.71, 0.16–1.26; p = 0.044). There were no significant effects of tDCS on implicit learning. Trend evidence of generalization onto untrained tasks of attention and vigilance task (b = 0.40, 0.43–0.77; p = 0.058) was found.ConclusionsThis is the first study to show a significant longer-term effect of tDCS on working memory in schizophrenia. Given the current lack of effective therapies for cognitive deficits, tDCS may offer an important novel approach to modulating brain networks to ameliorate cognitive deficits in schizophrenia.



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Temporal and spatial expression pattern of Nnat during mouse eye development

Publication date: Available online 27 December 2016
Source:Gene Expression Patterns
Author(s): Saadettin Sel, Eva Patzel, Lucia Poggi, Delia Kaiser, Thomas Kalinski, Martin Schicht, Friedrich Paulsen, Norbert Nass
BackgroundNeuronatin (Nnat) was initially identified as a highly expressed gene in neonatal mammalian brain. In this study, we analyze the spatial and temporal expression pattern of Nnat during mouse eye development as well as in the adult.MethodsThe expression of Nnat was analyzed on mRNA as well as protein level. The presence of Nnat transcripts in the adult retina was examined using reverse transcription-polymerase chain reaction (RT-PCR). Nnat protein expression was evaluated by Western blot and immunohistochemistry during eye development at embryonic day (E) 12, 15, 16 and postnatal day (P) 7, 14, 30 and 175 (adult).ResultsImmunohistochemical studies of the developing mouse eye revealed Nnat expression in embryonic and adult neuroretina as well as in corneal epithelial, stromal, endothelial cells and in lens epithelium. Expression of Nnat was detected from E12 onwards and was also present in adult eyes.ConclusionsThe expression pattern suggests that Nnat may play an important role during eye development and in the maintenance of mature eye.



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A novel semi-robotized device for high-precision 18F-FDG-guided breast cancer biopsy

Publication date: Available online 28 December 2016
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): D. Hellingman, S.C. Teixeira, M.L. Donswijk, E.J. Rijkhorst, L. Moliner, J. Alamo, C.E. Loo, R.A. Valdés Olmos, M.P.M. Stokkel
PurposeTo assess the 3D geometric sampling accuracy of a new PET-guided system for breast cancer biopsy (BCB) from areas within the tumour with high ¹⁸F-FDG uptake.Materials and methodsIn the context of the European Union project MammoCare, a prototype semi-robotic stereotactic prototype BCB-device was incorporated into a dedicated high resolution PET-detector for breast imaging. The system consists of 2 stacked rings, each containing 12 plane detectors, forming a dodecagon with a 186mm aperture for 3D reconstruction (1mm³ voxel). A vacuum-assisted biopsy needle attached to a robot-controlled arm was used. To test the accuracy of needle placement, the needle tip was labelled with ¹⁸F-FDG and positioned at 78 target coordinates distributed over a 35mm×24mm×28mm volume within the PET-detector field-of-view. At each position images were acquired from which the needle positioning accuracy was calculated. Additionally, phantom-based biopsy proofs, as well as MammoCare images of 5 breast cancer patients, were evaluated for the 3D automated locating of ¹⁸F-FDG uptake areas within the tumour.ResultsNeedle positioning tests revealed an average accuracy of 0.5mm (range 0–1mm), 0.6mm (range 0–2mm), and 0.4mm (range 0–2mm) for the x/y/z-axes, respectively. Furthermore, the MammoCare system was able to visualize and locate small (<10mm) regions with high ¹⁸F-FDG uptake within the tumour suitable for PET-guided biopsy after being located by the 3D automated application.ConclusionsAccuracy testing demonstrated high-precision of this semi-automatic 3D PET-guided system for breast cancer core needle biopsy. Its clinical feasibility evaluation in breast cancer patients scheduled for neo-adjuvant chemotherapy will follow.



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Editorial Board

Publication date: February 2017
Source:Annals of Diagnostic Pathology, Volume 26





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Masthead

Publication date: February 2017
Source:Annals of Diagnostic Pathology, Volume 26





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Table of Contents

Publication date: February 2017
Source:Annals of Diagnostic Pathology, Volume 26





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Instructions to Authors

Publication date: February 2017
Source:Annals of Diagnostic Pathology, Volume 26





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ImmunoModulation by the Combination of Ipilimumab and Nivolumab Neoadjuvant to Surgery In Advanced or Recurrent Head and Neck Carcinoma

Conditions:   Immunotherapy;   Head and Neck Neoplasms
Intervention:   Drug: Nivolumab with or without Ipilimumab
Sponsor:   The Netherlands Cancer Institute
Not yet recruiting - verified December 2016

http://ift.tt/2hNuAKU

Feasibility Testing of a Novel Endoscope for Reflectance Confocal Microscopy of Normal Oral Tissue In Vivo

Condition:   Oral Tissue
Intervention:   Device: Reflectance Confocal Microscopy (RCM) endoscope device
Sponsor:   Memorial Sloan Kettering Cancer Center
Recruiting - verified December 2016

http://ift.tt/2hwk6DE

Body mass index, height and early-onset basal cell carcinoma in a case-control study

Publication date: February 2017
Source:Cancer Epidemiology, Volume 46
Author(s): Yanchang Zhang, Brenda Cartmel, Courtney C. Choy, Annette M. Molinaro, David J. Leffell, Allen E. Bale, Susan T. Mayne, Leah M. Ferrucci
IntroductionBasal cell carcinoma (BCC) is the most common malignancy in the US. Body mass index (BMI) and height have been associated with a variety of cancer types, yet the evidence regarding BCC is limited. Therefore, we evaluated BMI and height in relation to early-onset BCC (under age 40) and explored the potential role of ultraviolet (UV) radiation exposure and estrogen-related exposures in the BMI-BCC relationship.MethodsBCC cases (n=377) were identified through a central dermatopathology facility in Connecticut. Control subjects (n=389) with benign skin conditions were randomly sampled from the same database and frequency matched to cases on age (median=36, interquartile range 33–39), gender, and biopsy site. Participants reported weight (usual adult and at age 18), adult height, sociodemographic, phenotypic, and medical characteristics, and prior UV exposures. We calculated multivariate odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression models.ResultsAdult BMI was inversely associated with early-onset BCC (obese vs. normal OR=0.43, 95% CI=0.26–0.71). A similar inverse association was present for BMI at age 18 (OR=0.54, 95% CI=0.34–0.85). Excluding UV exposures from the BMI models and including estrogen-related exposures among women only did not alter the association between BMI and BCC, indicating limited mediation or confounding. We did not observe an association between adult height and BCC (OR per cm=1.00, 95% CI=0.98–1.02).ConclusionsWe found a significant inverse association between BMI and early-onset BCC, but no association between height and BCC. This association was not explained by UV exposures or estrogen-related exposures in women.



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Patients with Acromegaly Presenting with Colon Cancer: A Case Series.

Related Articles

Patients with Acromegaly Presenting with Colon Cancer: A Case Series.

Case Rep Endocrinol. 2016;2016:5156295

Authors: Gordon MB, Nakhle S, Ludlam WH

Abstract
Introduction. Frequent colonoscopy screenings are critical for early diagnosis of colon cancer in patients with acromegaly. Case Presentations. We performed a retrospective analysis of the incidental diagnoses of colon cancer from the ACCESS trial (ClinicalTrials.gov identifier: NCT01995734). Colon cancer was identified in 2 patients (4.5%). Case  1 patient was a 36-year-old male with acromegaly who underwent transsphenoidal surgery to remove the pituitary adenoma. After surgery, the patient underwent routine colonoscopy screening, which revealed a 40 mm tubular adenoma in the descending colon. A T1N1a carcinoma was surgically removed, and 1 of 22 lymph nodes was positive for metastatic disease, leading to a diagnosis of stage 3 colon cancer. Case  2 patient was a 50-year-old male with acromegaly who underwent transsphenoidal surgery to remove a 2 cm pituitary adenoma. The patient reported severe cramping and lower abdominal pain, and an invasive 8.1 cm(3) grade 2 adenocarcinoma with signet rings was identified in the ascending colon and removed. Of the 37 lymph nodes, 34 were positive for the presence of tumor cells, and stage 3c colon cancer was confirmed. Conclusion. Current guidelines for colonoscopy screening at the time of diagnosis of acromegaly and at appropriate follow-up intervals should be followed.

PMID: 28025627 [PubMed]

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Co-expression of TIM-3 and CEACAM1 promotes T cell exhaustion in colorectal cancer patients

Publication date: February 2017
Source:International Immunopharmacology, Volume 43
Author(s): Yang Zhang, Pengcheng Cai, Lei Li, Liang Shi, Panpan Chang, Tao Liang, Qianqian Yang, Yang Liu, Lin Wang, Lihua Hu
T-cell immunoglobulin domain and mucin domain-3(TIM-3) is an activation induced inhibitory molecule involved in immune tolerance and is recently reported to induce T cell exhaustion which is mediated by carcinoembryonic antigen cell adhesion molecule 1(CEACAM1), another well-known molecule expressed on activated T cells and involved in T cell inhibition. To investigate the expression of TIM-3 and CEACAM1 on circulating CD8⁺ T cells and tumor infiltrating lymphocytes (TILs), 65 diagnosed colorectal cancer (CRC) patients and 38 healthy controls were enrolled in this study and the results showed that TIM-3 and CEACAM1 were both highly expressed on circulating CD8⁺ T cells in CRC patients and elevated on TILs compared with paraneoplastic T cells. Furthermore, TIM-3⁺CEACAM1⁺ CD8⁺ T cells represented the most dysfunctional population with the least IFN-γ production. In addition, the expressions of TIM-3 and CEACAM1 were correlated with advanced stage and could be independent risk factors for CRC. We for the first time to our knowledge suggested that co-expression of TIM-3 and CEACAM1 can mediate T cell exhaustion and may be potential biomarkers for CRC prediction, highlighting the possibility of being immunotherapy targets.



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A novel isolation protocol and probe-based RT-PCR for diagnosis of gastric infections with the zoonotic pathogen Helicobacter suis

Abstract

Background

Helicobacter suis is a very fastidious microorganism associated with gastritis, gastric ulcers, and mucosa-associated lymphoid tissue lymphoma in humans. In vitro isolation of this agent from human patients has so far been unsuccessful.

Materials and methods

A probe-based real-time PCR (RT-PCR) for the rapid detection of H. suis in gastric biopsies was developed. Secondly, a mouse-passage-based protocol was optimized for isolation of low numbers of viable H. suis bacteria. Mice were inoculated with different numbers of viable H. suis (10²-10⁸) and kept for 4 weeks to allow multiplication of this pathogen.

Results

The probe-based real-time PCR (RT-PCR) exhibited a high degree of diagnostic specificity and analytical sensitivity, high linear correlations (r² between 0.995 and 0.999), and high amplification efficiencies (>90%) for H. suis. No cross-reactivity was detected with human, porcine, non-human primate, and murine DNA nor with DNA from other bacteria including Helicobacter spp. and Campylobacter spp. H. suis was successfully re-isolated from the stomach of mice inoculated with at least 10⁴ viable H. suis, using a biphasic medium (pH 5), consisting of Brucella agar with Brucella broth on top, both supplemented with vitox supplement, Campylobacter-selective supplement, amphotericin (5 μg/mL), HCl (0.05%), fetal bovine serum (20%), and linezolid (5 μg/mL). Linezolid was necessary to inhibit proliferation of contaminants, including lactobacilli.

Conclusion

The methods described above can be implemented for detection or isolation of H. suis from human gastric biopsies.

http://ift.tt/2iE5MVP

The influence of Helicobacter pylori on the ethnic distribution of esophageal eosinophilia

Abstract

Background

Environmental factors associated with ethnicity may contribute to the occurrence of eosinophilic esophagitis. Our study aimed to investigate the influence of Helicobacter pylori on the ethnic variation of esophageal eosinophilia in a large national sample of patients undergoing esophago-gastro-duodenoscopy.

Methods

The Miraca Life Sciences Database is an electronic repository of histopathologic patient records. A case-control study evaluated the influence of ethnicity on the occurrence of esophageal eosinophilia and how age, gender, and histologic diagnosis of H. pylori modify this relationship.

Results

The total study population comprised 596 479 subjects, of whom 25 969 harbored a diagnosis of esophageal eosinophilia. Young age, male sex, and H. pylori infection in declining order exerted the strongest influence on the occurrence of esophageal eosinophilia. In comparison with the population comprising of Caucasians and African-Americans, esophageal eosinophilia was less common among patients of African (OR=0.10, 95% CI=0.01-0.46), Middle Eastern (0.22, 0.15-0.31), East Asian (0.32, 0.26-0.38), Indian (0.28, 0.21-0.37), Hispanic (0.40, 0.37-0.43), or Jewish descent (0.58, 0.51-0.66), but more common among patients of Northern European descent (1.25, 1.07-1.45). With the exception of Northern Europeans, all ethnic subgroups were characterized by a higher prevalence of H. pylori than the comparison group. A low prevalence of H. pylori was significantly associated with a high prevalence of esophageal eosinophilia (R²=0.90, P<.001).

Conclusion

Esophageal eosinophilia prevalence markedly varies by patient ethnicity. As there is a strong inverse correlation between H. pylori and esophageal eosinophilia, H. pylori infection may be in part responsible for the observed ethnic distribution of esophageal eosinophilia.

http://ift.tt/2i7j53V

RNA: The code in the cap

Nature Reviews Genetics. doi:10.1038/nrg.2016.165

Author: Linda Koch

http://ift.tt/2igrVNu

Development: Modifying sex in flies

Nature Reviews Genetics. doi:10.1038/nrg.2016.164

Author: Denise Waldron

http://ift.tt/2ignMZG

Genetic engineering: A genome-editing off switch

Nature Reviews Genetics. doi:10.1038/nrg.2016.166

Author: Ross Cloney

http://ift.tt/2igAh7T

Down syndrome and the complexity of genome dosage imbalance

Nature Reviews Genetics. doi:10.1038/nrg.2016.154

Author: Stylianos E. Antonarakis

http://ift.tt/2iguZcw

COF-1-modified magnetic nanoparticles for highly selective and efficient solid-phase microextraction of paclitaxel

Publication date: 1 April 2017
Source:Talanta, Volume 165
Author(s): Yuling Chen, Zilin Chen
Novel covalent organic framework-1 modified magnetic nanoparticles (M-COF-1) were prepared for extraction of paclitaxel from rat plasma samples. Paclitaxel is an important anti-cancer drug in clinical chemotherapy. COF-1 was immobilized on the surface of magnetic nanoparticles by bio-inspired polydopamine functionalization method because polydopamine can supply catechol groups for supporting the immobilization of COF-1. The formation of M-COF-1 has been confirmed by Fourier transform infrared spectroscopy and transmission electron microscopy. A M-COF-1-based extraction method was developed for selective extraction of paclitaxel in aqueous solutions. Extraction conditions were investigated, including sample pH value, acetonitrile content, extraction time and sample volume. By combining with HPLC, this method showed a good linear range of 0.1–200ng/mL with a low limit of detection of 0.02ng/mL. The method was also applied for the pretreatment of paclitaxel in rat plasma samples, which showed effective enrichment efficiency and good clean-up capacity. Recoveries were calculated to be 99.4–103.7% with relative standard deviations less than 2.3%.

Graphical abstract

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