Publication date: Available online 3 January 2018
Source:Pathology - Research and Practice
Author(s): Masanobu Sato, Hidetaka Yamamoto, Yui Hatanaka, Toshimitsu Nishijima, Rina Jiromaru, Ryuji Yasumatsu, Kenichi Taguchi, Muneyuki Masuda, Takashi Nakagawa, Yoshinao Oda
Differential diagnosis among basal cell adenoma (BCA), basal cell adenocarcinoma (BCAC), adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA) of the salivary gland can be challenging due to their similar histological appearance. Although frequent nuclear β-catenin expression and CTNNB1 mutations have been reported in BCA, further details of the Wnt/β-catenin signal alterations are unclear. The aim of this study was to assess the diagnostic utility of Wnt/β-catenin signal alteration in BCA and morphological mimics. We performed immunohistochemical staining for β-catenin and mutation analysis for Wnt/β-catenin-related genes (CTNNB1, APC, AXIN1 and AXIN2) in BCA (n = 34), BCAC (n = 3), ACC (n = 67) and PA (n = 31). We also analyzed ACC-specific MYB and MYBL1 gene rearrangements by fluorescence in situ hybridization (FISH). Nuclear β-catenin expression (≥3%) was present in 32/34 cases (94.1%) of BCA, and the nuclear β-catenin labeling index was significantly higher than in other tumor types (p = < 0.0001). In BCA, we found mutations in CTNNB1, APC and AXIN1 genes (41.1%, 2.9% and 8.8%, respectively). In BCAC, nuclear β-catenin expression with CTNNB1 mutation was present in 1/3 cases (33.3%). As for ACC, nuclear β-catenin expression was observed in 3/67 cases (4.4%), but all 3 cases harbored either MYB or MYBL1 gene rearrangement. The results suggest that nuclear β-catenin immunoreactivity with appropriate criteria may be helpful to distinguish BCA from histologically similar tumors. However, a minor subset of ACCs with nuclear β-catenin expression require careful diagnosis. In addition, Wnt/β-catenin signal alteration may play a role in the pathogenesis of BCA and BCAC.
http://ift.tt/2DUU2ZI
Τρίτη 2 Ιανουαρίου 2018
Wnt/β-catenin signal alteration and its diagnostic utility in basal cell adenoma and histologically similar tumors of the salivary gland
Genomic Analysis Reveals Distinct Subtypes in Two Rare Cases of Primary Ovarian Lymphoma
Publication date: Available online 3 January 2018
Source:Pathology - Research and Practice
Author(s): Pallavi Khattar, Puneet Bedi, Marion Gonzalez, Minghao Zhong, Changhong Yin, Weihua Huang, Humayun K. Islam, John T. Fallon
Primary (localized) non-Hodgkin lymphoma (NHL) of the ovary is extremely rare; only few cases have been reported in the literature. We report two cases of primary ovarian lymphoma (POL), one involving bilateral ovaries in a 15-year-old girl and other involving one ovary in a 5-year-old girl. This report describes detailed clinical, histopathological, and imaging findings, along with the review of literature of primary diffuse large B-cell lymphoma (DLBCL) arising from an ovary. In addition we describe findings of targeted capture panel sequencing on both tumors and identify the major genetic mutations that are recurrently mutated in pan-cancers. Compared to the genomic mutation features of major subtypes of DLBCL, we distinguish that each POL belongs to distinctive subtypes, GCB (germinal center B-cell type) DLBCL and ABC (activated B-cell type) DLBCL, respectively. The findings from the genomic analysis may help to understand the pathogenesis of POL and to guide potential targeted therapy in the future.
http://ift.tt/2EGQOKF
Hyalinizing Clear Cell Carcinoma of Salivary Glands: A Retrospective Study Focused on Uncommon Morphology, Immunohistochemistry, and Detection of Gene Fusion Using Fluorescence In Situ Hybridization
Publication date: Available online 3 January 2018
Source:Pathology - Research and Practice
Author(s): Yi-nuo Zhao, Xiao Wang, Fen-hua Liang, Wen-jie Zhang, Xiang-tao Song
http://ift.tt/2DUTUJI
Clinical value of survivin and its underlying mechanism in ovarian cancer: A bioinformatics study based on GEO and TCGA data mining
Publication date: Available online 2 January 2018
Source:Pathology - Research and Practice
Author(s): Xiao-jiao Li, Jin-shu Pang, Yao-mei Li, Farah Abdirahman Ahmed, Rong-quan He, Jie Ma, Fu-chao Ma, Gang Chen
ObjectiveAn increasing number of studies have confirmed that survivin (BIRC5) plays essential roles in ovarian cancer. Nevertheless, inconsistent or controversial results exist in some studies. In the present study, we sought to determine the clinical significance of survivin and its potential molecular pathways.MethodsThe correlation between survivin (BIRC5) expression and diagnostic value, prognostic value and clinicopathological features was assessed by meta-analysis with more than 4000 patients from literature, GEO and TCGA. In addition, the potential molecular mechanism of survivin in ovarian cancer was also determined.ResultsThe pooled sensitivity and specificity were 0.71 (95%CI: 0.68–0.74) and 0.97 (95%CI: 0.94–0.98), respectively. The AUC of sROC was 0.8765. The results showed that there was also a significant relationship between survivin expression and poor overall survival (HR: 1.24, 95%CI: 1.14–1.35, p < 0.001), disease-free survival (HR: 1.53, 95%CI: 0.57–4.09, p < 0.001), as well as higher recurrence rate (HR: 1.11, 95%CI: 0.97–1.27). Moreover, survivin expression was also associated with tumor progression (cancerous vs. benign, OR: 11.29, 95%CI: 8.96–14.24, p < 0.001), TNM stage (III + IV vs. I + II, OR: 5.38, 95%CI: 4.16–6.97, p < 0.001), histological grades (G3 vs. G1 ∼ G2, OR: 4.36, 95%CI: 3.29–5.77, p < 0.001), and lymphatic metastasis (metastasis vs. non-metastasis, 3.35, 95%CI 2.36–4.75, p < 0.001). Bioinformatics analysis revealed the 50 most frequently altered neighboring genes of survivin in OC, and then Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted. GO analysis showed that these genes were related to signal conduction, cell cycle, apoptosis, and metabolism. KEGG pathways analysis indicated that these genes were primarily enriched in mitotic prometaphase, PLK1 signaling events and the regulation of glucokinase by the glucokinase regulatory protein.ConclusionSurvivin (BIRC5) expression might become a specific but low-sensitivity biomarker in ovarian cancer patients, and its presence indicated poor prognosis and worse TNM stages. This protein might function as an oncoprotein by influencing specific pathways involving the 50 genes identified herein. Additional studies are needed to confirm these results.
http://ift.tt/2EIMz14
Analysis of the Proliferative Activity in Lung Adenocarcinomas with Specific Driver Mutations
Publication date: Available online 2 January 2018
Source:Pathology - Research and Practice
Author(s): Mark Kriegsmann, Alexander Harms, Daniel Kazdal, Sebastian Fischer, Albrecht Stenzinger, Jonas Leichsenring, Roland Penzel, Rémi Longuespée, Katharina Kriegsmann, Thomas Muley, Seyer Safi, Arne Warth
In the last decade it became evident that many lung adenocarcinomas (ADC) harbor key genetic alterations such as KRAS, EGFR or BRAF mutations as well as rearrangements of ROS1 or ALK that drive these tumors. In the present study we investigated whether different driver mutations of ADC result in different proliferation rates, which might have clinical impact, including resistance to therapy, recurrence and prognosis.
http://ift.tt/2DVakSf
Up-regulated Expression of SNHG6 Predicts Poor Prognosis in Colorectal Cancer
Publication date: Available online 3 January 2018
Source:Pathology - Research and Practice
Author(s): Min Li, Zehua Bian, Surui Yao, Jia Zhang, Guoying Jin, Xue Wang, Yuan Yin, Zhaohui Huang
Long non-coding RNAs (lncRNAs) have been shown to play important roles in tumor formation and development. Small nucleolar RNA host gene 6 (SNHG6) is a recently identified cancer-related lncRNA, and its role in colorectal cancer (CRC) remains to be explored. The aim of this study was to evaluate the expression and function of SNHG6 in CRC. The expression of SNHG6 was detected by real time quantitative RT-PCR (qRT-PCR) in 74 CRC tissues and matched noncancerous tissues (NCTs). Relationships between the expression levels of SNHG6 and various clinicopathological features were analyzed by Chi-square test. The Kaplan-Meier method and log-rank test were applied to compare the survival distribution between different groups. CCK8 assay and colony formation assay were used to measure the effect of SNGH6 on cell proliferation. Flow cytometric analysis was performed to measure the effect of SNHG6 on cell cycle and apoptosis. Our results showed that SNHG6 was up-regulated more than 1.5-fold in 50.0% (37/74) of CRC tissues compared with paired NCTs (P < 0.0001). High level of SNHG6 expression was strongly associated with advanced tumor stage (P = 0.026) and predicted poor prognosis of CRC (P = 0.0215). The Cox proportional hazards model demonstrated that SNHG6 expression was an independent prognostic factor for CRC (HR, 2.568; 95% CI, 1.055–6.252; P = 0.038). Furthermore, SNHG6 knockdown by siRNA could inhibit cell proliferation, cell cycle progression, and induce apoptosis. Taken together, SNHG6 functions as an oncogene in CRC and appears as a novel prognositic factor for CRC patients.
http://ift.tt/2EGQQSN
Tumor Budding and Poorly-differentiated Cluster in Prognostication in Stage II Colon Cancer
Publication date: Available online 2 January 2018
Source:Pathology - Research and Practice
Author(s): Victor Wai Kwan Lee, Kui Fat Chan
Comparison between tumor budding (TB) and poorly-differentiated clusters (PDC) for prognostication in Stage II colon cancer was not extensively studied in literature. In this retrospective study, we assessed TB (according to the consensus statement in 2016) and PDC in 135 Stage II colon adenocarcinoma resection specimens. Counting of TB and PDC was performed on H&E slides. High-grade TB (Bd3 (>=10 tumor buds in 0.785 mm2)) and high-grade PDC (Grade 3 (>=10)) were found in 20% and 17% of cases respectively. High-grade TB was associated with pT4 (p = 0.008) and presence of lymphovascular invasion (p = 0.001). There was correlation between TB and PDC grades (p < 0.001), in which both grades were the same or one grade apart in majority of the cases (97%). Both TB and PDC correlated with 5-year disease-specific survival (DSS) and overall survival (OS) (DSS for TB: 89% (Bd1); 73% (Bd2); 52% (Bd3), p = 0.001) (DSS for PDC: 88% (Grade 1); 72% (Grade 2); 61% (Grade 3), p = 0.021). Survival curves of Stage II colon cancer could be further stratified by TB and PDC (log-rank tests: TB p < 0.001; PDC p = 0.009). Combining TB and PDC grades into single grading system (high-grade: Bd3 + G2, Bd2 + G3, Bd3 + G3; low-grade: other combinations) was found to have strong correlation with both 5-year DSS (p < 0.001) and OS (p = 0.006). Our study has confirmed TB and PDC as independent prognostic factors in Stage II colon cancer, and might help selecting high-risk patients for adjuvant chemotherapy.
http://ift.tt/2DVakBJ
Whole-exome sequencing of chondroid hamartoma of lung identified no driver mutations
Publication date: Available online 2 January 2018
Source:Pathology - Research and Practice
Author(s): Su Hye Choi, Hyeon-Chun Park, Min Sung Kim, Yeun-Jun Chung, Sug Hyung Lee
http://ift.tt/2EFwidb
Features and outcomes of drugs for combination therapy as multi-targets strategy to combat Alzheimer's disease
Publication date: 6 April 2018
Source:Journal of Ethnopharmacology, Volume 215
Author(s): Atish Kumar Sahoo, Jagnehswar Dandapat, Umesh Chandra Dash, Satish Kanhar
Ethnopharmacological relevanceAlzheimer's disease (AD), a deleterious neurodegenerative disorder that impairs memory, cognitive functions and may lead to dementia in late stage of life. The pathogenic cause of AD remains incompletely understood and FDA approved drugs are partial inhibitors rather than curative. Most of drugs are synthetic or natural products as galanthamine is an alkaloid obtained from Galanthus spp. Huperzine A, an alkaloid found in Huperzia spp., gingkolides a diterpenoids from Gingko biloba and many ethnobotanicals like Withania somnifera (L.) Dunal., Physostigma venenosum Balf., Bacopa monnieri (L.) Wettst., Centella asiatica (L.) Urb. have been used by traditional Indian, Chinese, and European system of medicines in AD. Clinical significance opioid alkaloid in Papaver somniferum has shown another dimension to this study. Over exploitation of medicinal plants with limited bioactive principles has provided templates to design synthetic drugs in AD e.g. rivastigmine, phenserine, eptastigmine based on chemical structure of physostigmine of Physostigma venenosum Balf. Even ZT-1 a prodrug of Hup A and memogain a prodrug of galantamine has achieved new direction in drug development in AD. All these first-line cholinesterase-inhibitors are used as symptomatic treatments in AD. Single modality of "One-molecule-one-target" strategy for treating AD has failed and so future therapies on "Combination-drugs-multi-targets" strategy (CDMT) will need to address multiple aspects to block the progression of pathogenesis of AD. Besides, cholinergic and amyloid drugs, in this article we summarize proteinopathy-based drugs as AD therapeutics from a variety of biological sources. In this review, an attempt has been made to elucidate the molecular mode of action of various plant products, and synthetic drugs investigated in various preclinical and clinical tests in AD. It also discusses current attempts to formulate a comprehensive CDMT strategy to counter complex pathogenesis in AD.Materials and methodsInformation were collected from classical books on medicinal plants, pharmacopoeias and scientific databases like PubMed, Scopus, GoogleScholar, Web of Science and electronic searches were performed using Cochrane Library, Medline and EMBASE. Also published scientific literatures from Elsevier, Taylor and Francis, Springer, ACS, Wiley publishers and reports by government bodies and documentations were assessed.Results60 no. of natural and synthetic drugs have been studied with their significant bioactivities. A decision matrix designed for evaluation of drugs for considering to the hypothetic "CDMT" strategy in AD. We have introduced the scoring pattern of individual drugs and based on scoring pattern, drugs that fall within the scoring range of 18–25 are considered in the proposed CDMT. It also highlights the importance of available natural products and in future those drugs may be considered in CDMT along with the qualified synthetic drugs.ConclusionA successful validation of the CDMT strategy may open up a debate on health care reform to explore other possibilities of combination therapy. In doing so, it should focus on clinical and molecular relationships between AD and CDMT. A better understanding of these relationships could inform and impact future development of AD-directed treatment strategies. This strategy also involves in reducing costs in treatment phases which will be affordable to a common man suffering from AD.
Graphical abstract
http://ift.tt/2CFfAKh
Inhaled Lavandula angustifolia essential oil inhibits consolidation of contextual- but not tone-fear conditioning in rats
Publication date: 6 April 2018
Source:Journal of Ethnopharmacology, Volume 215
Author(s): Laura Segismundo Coelho, Nelson Francisco Correa-Netto, Marcia Yuriko Masukawa, Ariadiny Caetano Lima, Samia Maluf, Alessandra Linardi, Jair Guilherme Santos-Junior
Although the current treatment for anxiety is effective, it promotes a number of adverse reactions and medical interactions. Inhaled essential oils have a prominent action on the central nervous system, with minimal systemic effects, primarily because of reduced systemic bioavailability. The effects of drugs on the consolidation of fear conditioning reflects its clinical efficacy in preventing a vicious cycle of anticipatory anxiety leading to fearful cognition and anxiety symptoms. In this study, we investigated the effects of inhaled Lavandula angustifolia essential oil on the consolidation of aversive memories and its influence on c-Fos expression. Adult male Wistar rats were subjected to a fear conditioning protocol. Immediately after the training session, the rats were exposed to vaporized water or essential oil (1%, 2.5% and 5% solutions) for 4h. The next day, the rats underwent contextual- or tone-fear tests and 90min after the test they were euthanized and their brains processed for c-Fos immunohistochemistry. In the contextual-fear test, essential oil at 2.5% and 5% (but not 1%) reduced the freezing response and its respective c-Fos expression in the ventral hippocampus and amygdala. In the tone-fear test, essential oil did not reduce the freezing response during tone presentation. However, rats that inhaled essential oil at 2.5% and 5% (but not 1%) showed decreased freezing in the three minutes after tone presentation, as well as reduced c-Fos expression in the prefrontal cortex and amygdala. These results show that the inhalation of L. angustifolia essential oil inhibited the consolidation of contextual- but not tone-fear conditioning and had an anxiolytic effect in a conditioned animal model of anxiety.
Graphical abstract
http://ift.tt/2CKc2q4
Combination of Sonoelastography and TIRADS for the Diagnostic Assessment of Thyroid Nodules
Source:Ultrasound in Medicine & Biology
Author(s): Simone Schenke, Michael Zimny
To evaluate the diagnostic performance of elastography alone and combined with Thyroid Imaging Reporting And Data System (TIRADS) for the assessment of non-autonomous thyroid nodules. We included 244 thyroid nodules and analyzed the visual elasticity scores, strain value (SV) and TIRADS classification. Histologic examination revealed 38 malignant (16%) and 206 benign nodules. The SV was lower in malignant nodules than in benign with an optimal cutoff ≤0.225. The visual elasticity scores showed a better diagnostic performance than the SV measurement. The risk for malignancy increased with higher TIRADS category. The sensitivity, specificity, positive predictive value and negative predictive value of TIRADS were superior to sonoelastography. The combination of TIRADS ≥4C and SV ≤0.225 showed the highest odds ratio to predict malignancy. Kwak-TIRADS classification is superior to elastography for the differentiation of benign and malignant thyroid nodules. Our data demonstrate that a high TIRADS class alone is predictive for thyroid carcinoma and the clinical relevance of sonoelastography is negligible.
http://ift.tt/2Cu37M5
Automated Visualization and Quantification of Spiral Artery Blood Flow Entering the First-Trimester Placenta, Using 3-D Power Doppler Ultrasound
Source:Ultrasound in Medicine & Biology
Author(s): Gordon N. Stevenson, J. Alison Noble, Alec W. Welsh, Lawrence Impey, Sally L. Collins
The goal of our research was to quantify the placental vascularity in 3-D at 11–13 + 6 wk of pregnancy at precise distances from the utero-placental interface (UPI) using 3-D power Doppler ultrasound. With this automated image analysis technique, differences in vascularity between normal and pathologic pregnancies may be observed. The algorithm was validated using a computer-generated image phantom and applied retrospectively in 143 patients. The following features from the PD data were recorded: The number of spiral artery jets into the inter-villous space, total geometric and PD area. These were automatically measured at discrete millimeter distances from the UPI. Differences in features were compared with pregnancy outcomes: Pre-eclamptic versus normal, all small-for-gestational age (SGA) to appropriate-for-gestational age (AGA) patients and AGA versus SGA in normotensives (Mann-Whitney). The Benjamini-Hochberg procedure was used (false discovery rate 10%) for multiple comparison testing. Features decreased with increasing distance from the UPI (Kruskal-Wallis test; p < 0.001). At 2– 3 mm from the UPI, all features were smaller in pre-eclamptic compared with normal patients and for some in SGA compared with AGA patients (p < 0.05). For AGA versus SGA in normotensive patients, no significant differences were found. Number of jets measured at 2–5 mm from the UPI did not vary because of the position of the placenta in the uterus (ANOVA; p > 0.05). This method provides a new in-vivo imaging tool for examining spiral artery development through pregnancy. Size and number of entrances of blood flow into the UPI could potentially be used to identify high-risk pregnancies and may provide a new imaging biomarker for placental insufficiency.
http://ift.tt/2lJmbLV
Solid polymer electrolyte based on crosslinked polyrotaxane
Publication date: 31 January 2018
Source:Polymer, Volume 136
Author(s): Ying-Cheng Lin, Kohzo Ito, Hideaki Yokoyama
In this work, we introduce a new "mobile crosslink" concept for the fabrication of solid polymer electrolytes (SPEs) through the crosslinking of α-cyclodextrins (α-CDs) in a poly(ethylene glycol)-based (PEG-based) polyrotaxane. The PEG axis facilitates the conduction of lithium ions, while the crosslinked CDs that are not chemically bound to the PEG form mobile crosslinks that suppress the crystallization of PEG, maintaining its segmental mobility even after crosslinking. To weaken the strong hydrogen bonds between the abundant hydroxyl groups on the CDs, which restrict the segmental motion of PEG resulting in lower ionic conductivity, an appropriate amount of propyl isocyanate is added to effectively enhance the ionic conductivity and robustness of the SPE.
Graphical abstract
http://ift.tt/2CvBfXF
Stable gadolinium based nanoscale lyophilized injection for enhanced MR angiography with efficient renal clearance
Source:Biomaterials, Volume 158
Author(s): Kun Liu, Liang Dong, Yunjun Xu, Xu Yan, Fei Li, Yang Lu, Wei Tao, Huangyong Peng, Yadong Wu, Yang Su, Daishun Ling, Tao He, Haisheng Qian, Shu-Hong Yu
There is a great demand to develop high-relaxivity nanoscale contrast agents for magnetic resonance (MR) angiography with high resolution. However, there should be more focus on stability, ion leakage and excretion pathway of the intravenously injected nanoparticles, which are closely related to their clinic potentials. Herein, uniform ultrasmall-sized NaGdF4 nanocrystal (sub-10 nm) was synthesized using a facile high temperature organic solution method, and the nanocrystals were modified by a ligand-exchange approach using PEG-PAA di-block copolymer. The PEG-PAA modified NaGdF4 nanocrystal (denoted as ppNaGdF4 nanocrystal) exhibited a high r1 relaxivity which was twice of commercially used gadopentetate dimeglumine (Gd-DTPA) injection. MR angiography on rabbit using ppNaGdF4 nanocrystal at a low dose showed enhanced vascular details and long circulation time. Lyophilized powder of ppNaGdF4 nanocrystals have been successfully prepared without aggregation or reduction of MR performance, indicating the stability and an effective way to store this nanoscale contrast agent. No haemolysis was induced by ppNaGdF4 nanocrystal, and an extremely low leakage of gadolinium ions was confirmed. Furthermore, efficient renal excretion was one of the clearance pathways of ppNaGdF4 nanocrystal according to both the time dependent distribution data in blood and tissues and MR images. The in vivo toxicity evaluation further validated the great potential as a clinical agent for blood pool imaging.
http://ift.tt/2AbPiMV
Targeting death receptors for drug-resistant cancer therapy: Codelivery of pTRAIL and monensin using dual-targeting and stimuli-responsive self-assembling nanocomposites
Publication date: March 2018
Source:Biomaterials, Volume 158
Author(s): Fan Xu, Huihai Zhong, Ya Chang, Dongdong Li, Hongyue Jin, Meng Zhang, Huiyuan Wang, Chen Jiang, Youqing Shen, Yongzhuo Huang
Chemoresistance remains a formidable hurdle against cancer therapy. Seeking for novel therapy strategies is an urgent need for those who no longer benefit from chemotherapy. Chemoresistance is usually associated with the dysfunction of intrinsic apoptosis. Targeting extrinsic apoptosis via TRAIL signaling and the death receptors could be a potential solution to treat chemoresistant cancer. A highly biocompatible nano system for codelivery of the TRAIL DNA and the death receptor sensitizer monensin was developed, in which low-molecular-weight PEI (LMW-PEI) was crosslinked by the sulfhydryl cyclodextrin via disulfide bonds, and then bound with DNA, thus forming the bioreducible polyplex cores. In addition, the cyclodextrin also functioned as a carrier for the hydrophobic monensin via host-guest inclusion. Poly-γ-glutamic acid (γ-PGA) was used to modify the polyplex core via charge interaction. The γ-PGA corona can specifically bind with the tumor-associated gamma-glutamyl transpeptidase (GGT) overexpressed on the tumor cells, and achieve tumor-targeting delivery. Moreover, the tumor-homing peptide RGD-modified γ-PGA was also prepared as the surface coating materials for further improving gene delivery efficiency. This gene delivery system was characterized by the dual ligand-targeting, dual stimuli-responsive features. The ligands of RGD and γ-PGA can target the tumor-associated receptors (i.e., integrin and GGT). The conformation of γ-PGA is pH-sensitive, and the tumor acidic micro environments could trigger the detachment of surface-coating γ-PGA. The disulfide crosslinking LMW-PEI is redox-sensitive, and its fast disassembling in the tumor cells could favor the efficient gene delivery. The anti-tumor efficacy was demonstrated both in vitro and in vivo. Moreover, MYC-mediated synthetic lethality could be an important mechanism for overcoming the drug resistance. An important finding of our studies is the demonstration of the in vivo treatment efficacy of TRAIL/monensin, thus providing a potential novel therapeutic strategy for overcoming drug-resistant cancer.
Graphical abstract
http://ift.tt/2AaTWLb
Targeting polysialic acid-abundant cancers using oncolytic adenoviruses with fibers fused to active bacteriophage borne endosialidase
Publication date: March 2018
Source:Biomaterials, Volume 158
Author(s): Nikolas T. Martin, Christoph Wrede, Julia Niemann, Jennifer Brooks, David Schwarzer, Florian Kühnel, Rita Gerardy-Schahn
Genetic replacement of adenoviral fiber knobs by ligands that enable tumor specific targeting of oncolytic adenoviruses is challenging because the fiber knob contributes to virus assembly. Here, we present a novel concept by describing stable recombinant adenoviruses with tumor specific infection mode. The fiber knob was replaced by endosialidaseNF (endoNF), the tailspike protein of bacteriophage K1F. EndoNF recognizes polysialic acid, an oncofetal antigen characteristic for high malignant tumors of neuroendocrine origin. An intramolecular chaperone contained in endoNF warrants folding and compensates for the knob function in virus assembly. Obtained recombinant viruses demonstrated polysialic acid dependent infection modes, strong oncolytic capacity with polysialic acid positive cells in culture and a high potential to inhibit tumor growth in a therapeutic mouse model of subcutaneous neuroblastoma. With a single genetic manipulation we achieved ablation of the fiber knob, introduction of a tumor specific ligand, and folding control over the chimeric fiber construct.
http://ift.tt/2A8Z6Hr
Nrf2 mediates the expression of BAG3 and autophagy cargo adaptor proteins and tau clearance in an age-dependent manner
Source:Neurobiology of Aging, Volume 63
Author(s): Maoping Tang, Changyi Ji, Susanne Pallo, Irfan Rahman, Gail V.W. Johnson
During aging, decreased efficiency of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation and autophagic processes in the brain may be a contributing factor in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. Therefore, we analyzed the expression of Bcl-2–associated athanogene 3, a cochaperone that mediates autophagy, and the autophagy adaptors NBR1, NDP52, and sequestosome 1/p62 in the brains of 4-, 8-, and 12-month-old wild-type and Nrf2 knockout (−/−) mice. We also analyzed the levels of total tau and phospho-tau species. There were minimal differences in the expression of autophagy-related genes or tau species in 4-month-old animals; however, by 12 months, all of these autophagy-associated genes were expressed at significantly lower levels in the Nrf2 (−/−) mice. The decreases in the autophagy-associated genes were accompanied by significantly elevated levels of phospho-tau species in the 12-month-old Nrf2 (−/−) brains. These findings indicate that Nrf2 regulation of autophagy-related genes likely plays a greater role in mediating the clearance of tau as an organism ages.
http://ift.tt/2Cf5kHB
An APOE-independent cis-eSNP on chromosome 19q13.32 influences tau levels and late-onset Alzheimer’s disease risk
Source:Neurobiology of Aging
Author(s): Shuquan Rao, Mahdi Ghani, Zhiyun Guo, Yuetiva Deming, Kesheng Wang, Rebecca Sims, Canquan Mao, Yao Yao, Carlos Cruchaga, Dietrich A. Stephan, Ekaterina Rogaeva
Although multiple susceptibility loci for late-onset Alzheimer's disease (LOAD) have been identified; a large portion of the genetic risk for this disease remains unexplained. LOAD risk may be associated with single nucleotide polymorphisms responsible for changes in gene expression (eSNPs). To detect eSNPs associated with LOAD, we integrated data from LOAD genome-wide association studies and expression quantitative trait loci using Sherlock (a Bayesian statistical method). We identified a cis-regulatory eSNP (rs2927438) located on chromosome 19q13.32, for which subsequent analyses confirmed the association with both LOAD risk and the expression level of several nearby genes. Importantly, rs2927438 may represent an APOE-independent LOAD eSNP according to the weak linkage disequilibrium of rs2927438 with the two polymorphisms (rs7412 and rs429358) defining the APOE-ε2, -ε3 and -ε4 alleles. Furthermore, rs2927438 does not influence chromatin interaction events at the APOE locus or cis-regulation of APOE expression. Further exploratory analysis revealed that rs2927438 is significantly associated with tau levels in cerebrospinal fluid. Our findings suggest that rs2927438 may confer APOE-independent risk for LOAD.
http://ift.tt/2CHFA7L
Local changes in computational non-rapid eye movement sleep depth in infants
Publication date: February 2018
Source:Clinical Neurophysiology, Volume 129, Issue 2
Author(s): Anna-Liisa Satomaa, Outi Saarenpää-Heikkilä, Eero Huupponen, Turkka Kirjavainen, Juhani Heinonen, Sari-Leena Himanen
ObjectiveDeep NREM sleep and its hallmark EEG phenomenon slow wave activity (SWA) are under homeostatic control in adults. SWA is also locally regulated as it increases in the brain areas that have been used intensively. Moreover, in children, SWA is a marker of cortical maturation. In the present study the local properties of NREM sleep depth were evaluated using the quantitative mean frequency method. We aimed to study if age is related to NREM sleep depth in young infants. In addition, we studied if young infants have local differences in their NREM sleep.MethodsAmbulatory over-night polysomnographies were recorded in 59 healthy and full-term infants at the age of one month. The infants were divided into two age groups (<44 weeks and ≥44 weeks) to allow maturational evaluations.ResultsThe quantitative sleep depth analysis showed differences between the age groups. In addition, there were local sleep depth differences within the age groups.ConclusionsThe sleep depth change with age is most likely related to cortical maturation, whereas the local sleep depth gradients might also reflect the use-dependent properties of SWA.SignificanceThe results support the idea that young infants have frontal cortical processing.
http://ift.tt/2lJxHqv
Predictors of deep brain stimulation outcome in tremor patients
Source:Brain Stimulation
Author(s): Claire Sandoe, Vibhor Krishna, Diellor Basha, Francesco Sammartino, Joao Tatsch, Marina Picillo, Lazzaro di Biase, Yu-Yan Poon, Clement Hamani, Duemani Reddy, Renato P. Munhoz, Andres M. Lozano, William D. Hutchison, Alfonso Fasano
BackgroundDeep brain stimulation of the ventro-intermedius nucleus of the thalamus is an established treatment for tremor of differing etiologies but factors that may predict the short- and especially long-term outcome of surgery are still largely unknown.MethodsWe retrospectively investigated the clinical, pharmacological, electrophysiological and anatomical features that might predict the initial response and preservation of benefit in all patients who underwent deep brain stimulation for tremor. Data were collected at the following time points: baseline (preoperative), one-year post-surgery, and most recent visit. Tremor severity was recorded using the Fahn-Tolosa-Marin Tremor Rating Scale and/or the Unified Parkinson's Disease Rating Scale.ResultsA total of 52 patients were included in the final analysis: 31 with essential tremor, 15 with cerebellar tremor of different etiologies, and 6 with Parkinson's disease. Long-term success (mean follow-up duration 34.7 months, range 1.7–121.1 months) was reported in 63.5%. Predictors of long-term benefit were: underlying tremor etiology (best outcome in Parkinson's disease, worst outcome in cerebellar tremor); age at surgery (the older the better); baseline tremor severity (the greater the better); lack of response to benzodiazepines; a more anterior electrode placement and single-unit beta power (the greater the better).ConclusionsSpecific patients' features (including single unit beta activity) and electrode locations may predict the short- and long-term benefit of thalamic stimulation for tremor. Future prospective studies enrolling a much larger sample of patients are needed to substantiate the associations detected by this retrospective study.
http://ift.tt/2CbkdL5
Genetic manipulation of Fonsecaea pedrosoi using particles bombardment and Agrobacterium mediated transformation
Source:Microbiological Research
Author(s): Camille Silva Florencio, Fabiana Alves Silva Brandão, Marcus de Mello Teixeira, Anamélia Lorenzetti Bocca, Maria Sueli S. Felipe, Vânia Aparecida Vicente, Larissa Fernandes
Fonsecaea pedrosoi, a melanized fungal pathogen that causes Chromoblastomycosis, a human disease with a worldwide distribution. Biolistic is a widely used technique for direct delivery of genetic material into intact cells by particles bombardment. Another well-established transformation method is Agrobacterium-mediated transformation (ATMT), which involves the transfer of a T-DNA from the bacterium to the target cells. In F. pedrosoi there are no reports of established protocols for genetic transformation, which require optimization of physical and biological parameters. In this work, intact conidia of F. pedrosoi were particle bombarded and subjected to ATMT. In addition, we proposed Hygromycin B, Nourseothricin and Neomycin as dominant selective markers for F. pedrosoi and vectors were constructed. We tested two parameters for biolistic: the distance of the particles to the target cells and time of cells recovery in nonselective medium. The biolistic efficiency was 37 transformants/μg of pFpHYG, and 45 transformants/μg of pAN7.1. Transformants expressing GFP were successfully obtained by biolistic. A co-culture ratio of 10: 1 (bacterium: conidia) and co-incubation time of 72 hours yielded the largest number of transformants after ATMT. Southern blot analysis showed the number of foreign DNA insertion into the genome is dependent upon the plasmid used to generate the mutants. This work describes for the first time two efficient methods for genetic modification of Fonsecaea and these results open new avenues to better understand the biology and pathogenicity of the main causal agent of this neglected disease.
http://ift.tt/2DTYRT8
Efficacy and the toxicity of the interstitial high-dose-rate brachytherapy in the management of recurrent keloids: 5-year outcomes
Source:Brachytherapy
Author(s): Ping Jiang, Matthias Geenen, Frank-André Siebert, Julia Bertolini, Bjoern Poppe, Ulf Luetzen, Juergen Dunst, Daniel Druecke
PurposeRecurring keloids are a clinical challenge. Interdisciplinary treatments are required in most cases. Owing to the wide variety of concepts, the optimal treatment regime remains unclear. Our clinic established a protocol of perioperative interstitial high-dose-rate brachytherapy with three fractions of 6 Gy and achieved an excellent 2-year local control rate of 94% (In search of the optimal treatment of keloids: Report of a series and a review of the literature). This report is an update on our long-term results of prospective study. Twenty-nine patients were included with a median followup of 5 years.Methods and MaterialsFrom 2009 to 2015, 29 patients with 37 recurrent keloids were treated with perioperative interstitial high-dose-rate brachytherapy; 3 patients had been previously treated with adjuvant external beam radiotherapy and presented with recurrences in the pretreated area. Brachytherapy was given in three fractions with a single dose of 6 Gy in 5-mm tissue depth and covered the scar in total length. Followup visits were scheduled at 6 weeks, 3 months, 6 months, 1 year, and annually thereafter. Therapeutic outcome was assessed in terms of recurrence, acute and late complications, and cosmetic results.ResultsNo procedure-related complications occurred. Improvement of keloid-related symptoms was noticed in all patients after treatment. After a median followup of 49.7 months (range: 7.9–91.9 months), three keloid recurrences and two hypertrophied scars were observed.ConclusionsOur results suggest that brachytherapy may be advantageous in the management of high-risk keloids, even after failure of external beam radiotherapy and other treatment procedures. Our three-fraction treatment schedule reduces the treatment period to 2 days and is therefore convenient for the patients.
http://ift.tt/2lH1Uat
Psychological interventions for anxiety in adult primary care patients: A review and recommendations for future research
Source:Journal of Anxiety Disorders
Author(s): Robyn L. Shepardson, Laura J. Buchholz, Risa B. Weisberg, Jennifer S. Funderburk
Anxiety symptoms are prevalent in primary care, yet treatment rates are low. The integration of behavioral health providers into primary care via the Primary Care Behavioral Health (PCBH) model offers a promising way to improve treatment options by adding a team member with the necessary skillset to deliver evidence-based psychological interventions for anxiety. We conducted a narrative review of psychological interventions for anxiety applied within adult primary care settings (k = 44) to update the literature and evaluate the fit of existing interventions with the PCBH model. The majority of studies were randomized controlled trials (RCTs; 70.5%). Most interventions utilized cognitive-behavioral therapy (68.2%) and were delivered individually, face-to-face (52.3%). Overall, 65.9% of interventions (58.6% of RCTs, 91.7% of pre-post) were effective in reducing anxiety symptoms, and 77.8% maintained the gains at follow-up. Although it is encouraging that most interventions significantly reduced anxiety, their longer formats (i.e., number and duration of sessions) and narrow symptom targets make translation into practice difficult. Methodological limitations of the research included homogenous samples, failure to report key procedural details, pre-post designs, and restrictive eligibility criteria. We offer recommendations to guide future research to improve the likelihood of successful translation of anxiety interventions into clinical practice.
http://ift.tt/2lHxhBB
Identifying mechanisms of stance control: A single stimulus multiple output model-fit approach
Source:Journal of Neuroscience Methods, Volume 296
Author(s): Adam D. Goodworth, Robert J. Peterka
BackgroundPosture control models are instrumental to interpret experimental data and test hypotheses. However, as models have increased in complexity to include multi-segmental dynamics, discrepancy has arisen amongst researchers regarding the accuracy and limitations of identifying neural control parameters using a single stimulus.New methodThe current study examines this topic using simulations with a parameterized model-fit approach. We first determine if the model-fit approach can identify parameters in the theoretical situation with no noise. Then, we measure variability and bias of parameter estimates when realistic noise is included. We also address how the accuracy is influenced by the frequency bandwidth of the stimulus, signal-to-noise of the data, and fitting procedures.ResultsWe found perfect identification of parameters in the theoretical model without noise. With realistic noise, bias errors were 4.4% and 7.6% for fits that included frequencies 0.02–1.2 Hz and 0.02–0.4 Hz, respectively. Fits between 0.02–1.2 Hz also had the lowest variability in parameter estimates compared to other bandwidths. Parameters with the lowest variability tended to have the largest influence on body sways. Results also demonstrated the importance of closely examining model fits because of limitations in fitting algorithms.Comparison with existing methodThe single-input model-fit approach may be a simpler and more practical method for identifying neural control mechanisms compared to a multi-stimulus alternative.ConclusionsThis study provides timely theoretical and practical considerations applicable to the design and analysis of experiments contributing to the identification of mechanisms underlying stance control of a multi-segment body.
http://ift.tt/2EDH0km
Evaluation of an artifact reduction strategy for electrically evoked auditory steady-state responses: Simulations and measurements
Source:Journal of Neuroscience Methods, Volume 296
Author(s): Andreas Bahmer, Sabrina Pieper, Uwe Baumann
BackgroundElectrically evoked steady-state response (EASSR) recording is a measure of neuronal response strength after continuous electrical stimulation of the auditory system. In order to suppress the large electrical artifact generated by intracochlear electrical stimulation, a sophisticated artifact reduction processing strategy ("Hofmann procedure") has been proposed (Hofmann and Wouters, 2010). So far, EASSR recordings with artifact reduction procedures were reported only in cochlear implant (CI) users implanted with Cochlear devices (Macquarie, Australia).New methodHere, we demonstrate the application of the Hofmann procedure in CI users implanted with MED-EL (Innsbruck, Austria) devices. To demonstrate potential limitations of the procedure, we calculated discrete time Fourier transformations (DTFT) of various pulse patterns which may be used for EASSR.ResultsEASSR recordings were obtained in three subjects and processed with the Hofmann procedure. Neural response amplitude growth functions and phase for modulated and unmodulated pulse trains at various stimulation rates could be assessed. Simulations of three different interpolation methods aimed to suppress the electrical artifact show that the interpolation of a sinusoidal signal in a temporal window between 0 and 1 ms has demonstrated negligible impact on the spectral amplitude of the signal with a superior performance of a spline interpolation.Comparison with existing methodThe Hofmann procedure, initially developed for recording EASSRs with CIs from the manufacturer Cochlear, was validated for MED-EL devices.ConclusionIt is feasible to record EASSRs with the described measurement setup and CIs from the manufacturer MED-EL.
http://ift.tt/2DRoxzJ
Isolation of Satellite Glial Cells for High-Quality RNA purification
Source:Journal of Neuroscience Methods
Author(s): Sara Buskbjerg Jager, Lone Tjener Pallesen, Christian Bjerggaard Vaegter
BackgroundSatellite glial cells (SGCs) envelope the neuronal somas in the dorsal root ganglia (DRG) and are believed to provide important neuronal support. Animal models of peripheral nerve injury, diabetes or chemotherapy all demonstrate activation of SGCs, suggesting important physiological roles for SGCs in various states of peripheral neuropathy. However, the biology of these glial cells is only poorly characterized under normal as well as pathological conditions due to suboptimal isolation methods.New MethodThe method presented here allows complete dissociation and isolation of highly pure SGCs from rat DRGs by fluorescence-activated cell sorting (FACS) using SGC-specific antibodies. The method further allows purification of high-quality RNA from the fixed and permeabilized cells.ResultsThe purified RNA shows very little degradation, demonstrated by RNA integrity number (RIN) analysis with an average value of 8. The purified RNA, therefore, lends itself very well to downstream applications such as qPCR and transcriptome analysis.Comparison with existing methodsPrimary SGC cultures have previously been established for in vitro studies. Unfortunately, SGCs quickly change morphology and gene expression in vitro, complicating biologically meaningful interpretation of the obtained results. In contrast, this method allows the investigation of SGC gene regulation in vivo by isolation of high-quality RNA.ConclusionsThis method enables investigation of SGC transcriptional response in vivo by isolation and analysis of mRNA expression, allowing a more detailed investigation of SGC biology under normal as well as pathological conditions.
http://ift.tt/2CtYSAQ
Machine-Learning neuroimaging challenge for automated diagnosis of mild cognitive impairment: Lessons learnt
Source:Journal of Neuroscience Methods
Author(s): Isabella Castiglioni, Christian Salvatore, Javier Ramirez, Juan Manuel Górriz Sáez
http://ift.tt/2A95AX0
Antimicrobial photodynamic activity of Rose Bengal, alone or in combination with Gentamicin, against planktonic and biofilm Staphylococcus aureus
Source:Photodiagnosis and Photodynamic Therapy, Volume 21
Author(s): Vanesa Pérez-Laguna, Isabel García-Luque, Sofía Ballesta, Luna Pérez-Artiaga, Verónica Lampaya-Pérez, Sofía Samper, Pilar Soria-Lozano, Antonio Rezusta, Yolanda Gilaberte
Antimicrobial photodynamic therapy (aPDT) could constitute an alternative therapy to antibiotics especially against superficial infections caused by bacteria involved in multidrug resistance processes.The aim of this study is to compare the efficacy of aPDT using the photosensitizer rose bengal (RB), combined or uncombined with gentamicin (GN), against Staphylococcus aureus.Different concentrations of RB (ranging from 0.03 to 64 μg/ml) were added to S. aureus in water suspensions or forming biofilms in the absence or presence of GN (1–40 μg/ml) and the samples were irradiated (18 or 37 J/cm2). The number of viable bacteria was quantified by counting colony-forming units.RB-aPDT shows significant photoactivity. The combination of GN and RB-aPDT exerts a synergistic bactericidal effect against planktonic S. aureus. On the other hand, a synergistic effect is observed only when the maximum concentration tested of RB and GN was used in biofilm.According to these result the use of RB-aPDT alone or in combination with GN could be implemented against S. aureus.
http://ift.tt/2A7kT2x
Would glucagon peptide-1 receptor agonists have efficacy in binge eating disorder and bulimia nervosa? A review of the current literature
Source:Medical Hypotheses
Author(s): Susan L. McElroy, Nicole Mori, Anna I. Guerdjikova, Paul E. Keck
Binge eating, eating an abnormally large amount of food in a discrete period of time with a sense of loss of control over eating, is a defining feature of the eating disorders binge eating disorder (BED) and bulimia nervosa (BN). Both BED and BN are important public health problems for which there are few medical treatments. However, almost all drugs with central nervous system-mediated weight loss properties studied thus far in randomized, placebo-controlled trials in persons with BED or BN have been efficacious for reducing binge eating behavior. Glucagon-like peptide-1 (GLP-1) receptor agonists, marketed for type 2 diabetes and chronic weight management, produce weight loss in a dose dependent manner and have favorable psychiatric adverse event profiles. We hypothesize that GLP-1 receptor agonists will safely reduce binge eating behavior in individuals with BED or BN, including those with co-occurring psychiatric disorders, and propose that randomized, placebo-controlled clinical trials of GLP-1 receptor agonists be conducted in persons with BED and those with BN. To support this hypothesis, we review studies of GLP-1 and GLP-1 receptor agonists in preclinical models of binge eating, studies of GLP-1 levels in individuals with BED or BN, and preliminary data of GLP-1 receptor agonists in humans with abnormal eating behavior.
http://ift.tt/2lH7x8y
Table of Contents
Source:Pediatric Neurology, Volume 78
http://ift.tt/2CwzEkE
Editorial Board and Masthead
Source:Pediatric Neurology, Volume 78
http://ift.tt/2lIC9FT
Phenotypic and Molecular Spectrum of Aicardi-Goutières Syndrome: A Study of 24 Patients
Publication date: January 2018
Source:Pediatric Neurology, Volume 78
Author(s): Fuad Al Mutairi, Majid Alfadhel, Marwan Nashabat, Ayman W. El-Hattab, Tawfeg Ben-Omran, Jozef Hertecant, Wafaa Eyaid, Rehab Ali, Ali Alasmari, Majdi Kara, Waleed Al-Twaijri, Rana Filimban, Abduljabbar Alshenqiti, Mohammed Al-Owain, Eissa Faqeih, Fowzan S. Alkuraya
BackgroundAicardi-Goutières syndrome is a rare genetic neurological disorder with variable clinical manifestations. Molecular detection of specific mutations is required to confirm the diagnosis. The aim of this study was to review the clinical and molecular diagnostic findings in 24 individuals with Aicardi-Goutières syndrome who presented during childhood in an Arab population.Materials and MethodsWe reviewed the records of 24 patients from six tertiary hospitals in different Arab countries. All included patients had a molecular diagnosis of Aicardi-Goutières syndrome.ResultsSix individuals with Aicardi-Goutières syndrome (25%) had a neonatal presentation, whereas the remaining patients presented during the first year of life. Patients presented with developmental delay (24 cases, 100%); spasticity (24 cases, 100%); speech delay (23 cases, 95.8%); profound intellectual disability (21 cases, 87.5%); truncal hypotonia (21 cases, 87.5%); seizures (eighteen cases, 75%); and epileptic encephalopathy (15 cases, 62.5%). Neuroimaging showed white matter abnormalities (22 cases, 91.7%), cerebral atrophy (75%), and small, multifocal calcifications in the lentiform nuclei and deep cerebral white matter (54.2%). Homozygous mutations were identified in RNASEH2B (54.2%), RNASEH2A (20.8%), RNASEH2C (8.3%), SAMHD1 (8.3%), TREX1 (4.2%), and heterozygous mutations in IFIH1 (4.2%), with c.356A>G (p.Asp119Gly) in RNASEH2B being the most frequent mutation. Three novel mutations c.987delT and c.625 + 1G>A in SAMHD1 gene and c.961G>T in the IFIHI1 gene were identified.ConclusionsThis is the largest molecularly confirmed Aicardi-Goutières syndrome cohort from Arabia. By presenting these clinical and molecular findings, we hope to raise awareness of Aicardi-Goutières syndrome and to demonstrate the importance of specialist referral and molecular diagnosis.
http://ift.tt/2CxavGe
Meetings of Interest
Source:Pediatric Neurology, Volume 78
http://ift.tt/2Cujjg3
Editorial Board
Source:Practical Radiation Oncology, Volume 8, Issue 1
http://ift.tt/2qh36WU
Table of Contents
Source:Practical Radiation Oncology, Volume 8, Issue 1
http://ift.tt/2lF2d5M
Masthead
Source:Practical Radiation Oncology, Volume 8, Issue 1
http://ift.tt/2q9bS9c
Average crop yield (2001–2017) in Ethiopia: Trends at national, regional and zonal levels
Source:Data in Brief, Volume 16
Author(s): Logan Cochrane, Yeshtila W. Bekele
This article presents average agricultural yield data per hectare for key cereal, legume and root crops from 2001 until 2017. Data was obtained from the annual Agricultural Sample Surveys of the Central Statistics Agency (CSA) of Ethiopia. We present data at national, regional (SNNPRS) and zonal (Wolaita) levels. The data shows that average yields for all crops, at all levels, show increasing trends during the time period. Data for the main cereal crops is consistent and aligns with literature relatively well, however we raise questions about the root crop data in an effort to encourage greater critical reflection of components of data from the CSA.
http://ift.tt/2lI2Z0R
Quality of life comparing carboplatin with cisplatin in the treatment of non–small cell lung cancer
Source:European Journal of Cancer
Author(s): Michael Snee
http://ift.tt/2Ct2GlZ
Long-term estradiol-17β exposure decreases the cholinergic innervation pattern of the pig ovary
Publication date: Available online 2 January 2018
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): B. Jana, K.A. Meller, M. Czajkowska, J. Całka
Elevated levels of endogenous estrogens in the course of pathological states of ovaries, as well as xenoestrogens, may lead to hyperestrogenism. It has previously been demonstrated that long-term estradiol-17β (E2) administration in adult gilts affected the population of sympathetic intraovarian nerve fibers. The aim of this study has been to determine the effect of long-term E2 exposure on the cholinergic innervation pattern of porcine ovaries. Intraovarian distribution and the density of nerve fibers immunoreactive (IR) to vesicular acetylocholine transporter (VAChT) and/or neuronal isoform of nitric oxide synthase (nNOS), vasoactive intestinal polypeptide (VIP), somatostatin (SOM) were determined. From day 4 of the first estrous cycle to day 20 of the second studied cycle, experimental gilts were intramuscularly injected with E2, while control gilts received corn oil. The ovaries were then collected and processed for double-labelling immunofluorescence. After E2 administration, the total number of fibers IR to VAChT, nNOS and VIP decreased significantly. The numbers of VAChT-, nNOS- and VIP-IR fibers within the ground plexus were significantly lower, while they were significantly higher around small or medium tertiary follicles. In the E2-affected ovaries, the numbers of nNOS- and VIP-IR fibers were significantly higher near secondary follicles and VAChT-IR in the vicinity of medullar blood vessels. In turn, around the latter structures there were significantly lowered populations of nNOS- and VIP-IR nerve fibers. These results suggest that the elevated E2 levels that occur during pathological states may affect the cholinergic innervation pattern of ovaries and their function(s).
http://ift.tt/2lG72L8
INDUCED POST-TRAUMATIC APEXIFICATION: 20 YEAR FOLLOW-UP AND MORPHOLOGICAL STUDY AFTER NEW FRACTURE
Publication date: Available online 1 January 2018
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Federica Fonzar, Leopoldo Forner, Riccardo Fabian-Fonzar, Carmen Llena
Apexification is an endodontic technique used in immature necrotic teeth, the primary goal of which is to induce a calcified barrier in roots with open apices and to promote the continuation of apical root development. A 7-year-old patient with a coronal fracture in a maxillary central incisor was treated with an apexification technique using calcium hydroxide. The apical closure was obtained after one year, then a permanent root canal filling was performed. The tooth was monitored for a period of 20 years, up to when a trauma caused its extraction. The newly formed root was analyzed macroscopically, histologically and through scanning electron microscopy. A morphologically normal root was observed, with a large apex and accessory foramina, showing a combination of tissue structures similar to secondary and tertiary dentine, close to amorphous mineralized areas. Despite the final evolution of the case, calcium hydroxide apexification is a good therapy in order to treat pulp necrosis in an immature tooth, leading to complete development of the root and allowing the tooth to be kept in the mouth.
http://ift.tt/2lHwX57
Biomolecules in the treatment of lichen planus refractory to corticosteroid therapy: clinical and histopathological assessment
Publication date: Available online 1 January 2018
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Laura Piñas, Mohammad Hamdan Alkhraisat, Ricardo Suárez Fernández, Eduardo Anitua
BackgroundLocal deficit of several biomolecules have been described in oral lichen planus (OLP). Such a deficit impairs cellular functions and cell-matrix communication.PurposeAssess the efficacy of the local application of autologous biomolecules in the treatment of erosive OLP.Materials and methodsIn this study, the use of plasma rich in growth factors (PRGF) as a source of blood-derived and autologous growth factors and proteins were tested in erosive oral lichen planus refractory to corticosteroids. Histopathological features of the disease were also analysed at the time of diagnosis. Clinical data were the number of recurrences and achievement of pain reduction and complete healing of the lesions. A total of 10 patients with erosive OLP refractory to treatment by corticosteroids were included in the study. All patients were females with a mean age of 48±12years.ResultsA complete remission of the disease was achieved after one infiltration of PRGF in 8 patients. Only 2 patients required a total of 2 infiltrations to heal. Hydropic degeneration of the epithelium basal layer, band-like subepithelial lymphocytic infiltration and fibrin deposits in the epithelium were observed in all patients. Interestingly plasma cells were present in 2 patients. All patients presenting plasma cells healed after only one PRGF infiltration. However, 2 patients out of 6 (no plasma cells) required 2 infiltrations.ConclusionsThe local administration of autologous local factors could overcome the deficit of biomolecular clues and thus improve cell functions and restore cell-matrix communication.
http://ift.tt/2Cud3VL
Scholar : These new articles for Advances in Mental Health are available online
|
Scholar : These new articles for International Journal of Rail Transportation are available online
|
Evaluation of the p53 and Thioredoxin reductase in sperm from asthenozoospermic males in comparison to normozoospermic males
Publication date: Available online 2 January 2018
Source:Free Radical Biology and Medicine
Author(s): Mohmmad-nabi Moradi, Jamshid Karimi, Iraj Khodadadi, Iraj Amiri, Manoochehr Karami, Massoud Saidijam, Akram Vatannejad, Heidar Tavilani
Thioredoxin (Trx) system has a defensive role against the harmful effect of oxidative stress in sperm. p53 is an important regulator of apoptosis and normal process of spermatogenesis. Regulation of p53 by redox state of the cell and Thioredoxin system has been reported. The aim of this study was to evaluate the ROS level, Thioredoxin reductase (TrxR) activity and p53 protein levels in sperm of asthenozoospermic and normozoospermic males.Semen samples from 80 donors were divided into asthenozoospermic (n=40) and normozoospermic (n=40) groups using the WHO criteria. DNA fragmentation (TUNEL assay) of spermatozoa was identified. H2O2 and O2•− were determined by flow cytometry. p53 protein levels and TrxR activity were measured in sperm cell lysate by appropriate kit. Total antioxidant capacity (TAC) and thiol groups in seminal plasma were measured spectrophotometery. MDA content in seminal plasma was determined fluorometrically.ResultsThe percentage of cells with H2O2, O2•− and DNA fragmentation was higher in asthenozoospermic compared to normozoospermic groups (p<0.05). The p53 protein level was significantly higher in asthenozoospermic group (P<0.001). TrxR activity in normozoospermic was significantly higher than asthenozoospermic group (P<0.001). Total thiol groups and TAC levels were significantly higher in normozoospermic samples (P < 0.05). A significantly high negative correlation was seen between p53 protein levels with TrxR activity (r = −0.49, P < 0.001), total motility (r = −0.65, P< 0.001).p53 and ROS levels were increased in asthenozoospermic males while the TrxR activity was decreased. These changes lead to an increase in apoptotic, immotile and immature spermatozoa in the ejaculatory semen.
Graphical abstract
http://ift.tt/2CbueYI
Manganese porphyrin decorated on DNA networks as quencher and mimicking enzyme for construction of ultrasensitive photoelectrochemistry aptasensor
Source:Biosensors and Bioelectronics, Volume 104
Author(s): Liaojing Huang, Li Zhang, Liu Yang, Ruo Yuan, Yali Yuan
In this work, the manganese porphyrin (MnPP) decorated on DNA networks could serve as quencher and mimicking enzyme to efficiently reduce the photocurrent of photoactive material 3,4,9,10-perylene tetracarboxylic acid (PTCA), which was elaborately used to construct a novel label-free aptasensor for ultrasensitive detection of thrombin (TB) in a signal-off manner. The Au-doped PTCA (PTCA-PEI-Au) with outstanding membrane-forming and photoelectric property was modified on electrode to acquire a strong initial photoelectrochemistry (PEC) signal. Afterward, target binding aptamer Ι (TBAΙ) was modified on electrode to specially recognize target TB, which could further combine with TBAII and single-stranded DNA P1-modified platinum nanoparticles (TBAII-PtNPs-P1) for immobilizing DNA networks with abundant MnPP. Ingeniously, the MnPP could not only directly quench the photocurrent of PTCA, but also acted as hydrogen peroxide (HRP) mimicking enzyme to remarkably stimulate the deposition of benzo-4-chlorhexidine (4-CD) on electrode for further decreasing the photocurrent of PTCA, thereby obtaining a definitely low photocurrent for detection of TB. As a result, the proposed PEC aptasensor illustrated excellent sensitivity with a low detection limit down to 3 fM, exploiting a new avenue about intergrating two functions in one substance for ultrasensitive biological monitoring.
http://ift.tt/2A6EQ9v
Ultrasensitive detection of lysozyme in droplet-based microfluidic devices
Source:Biosensors and Bioelectronics, Volume 104
Author(s): Maria Chiara Giuffrida, Giovanni Cigliana, Giuseppe Spoto
Lysozyme (LYS) is a bacteriolytic enzyme, available in secretions such as saliva, tears and human milk. LYS is an important defence molecule of the innate immune system, and its overexpression can be a consequence of diseases such as leukemia, kidney disease and sarcoidosis. This paper reports on a digital microfluidic-based approach that combines the gold nanoparticle-enhanced chemiluminescence with aptamer interaction to detect human lysozyme into droplets 20 nanoliters in volume. The described method allows identifying LYS with a 44.6 femtomolar limit of detection, using sample volume as low as 1μL and detection time in the range of 10min. We used luminol to generate the chemiluminescence and demonstrated that the compartmentalization of LYS in droplets also comprising gold nanoparticles provided enhanced luminescence. We functionalized the gold nanoparticles with a thiolated aptamer to achieve the required selectivity that allowed us to detect LYS in human serum.
http://ift.tt/2CqlFgM
QCM-D surpassing clinical standard for the dose administration of new oral anticoagulant in the patient of coagulation disorders
Source:Biosensors and Bioelectronics, Volume 104
Author(s): Munawar Hussain, Hans Peter Wendel, Katrin Schmidt, Elisabeth Langer, Mareike Kristina Körber, Oksana Faul, Hinnak Northoff, Christian von Heymann, Frank K. Gehring
The study focuses the dose administration of dabigatran to avoid the deaths due to hemorrhagic complications and thromboembolic stroke in clinics worldwide. To target the issue, a novel emerging acoustic technology, namely ''Quartz Crystal Microbalance with Dissipation'' (QCM-D) has been applied, while the acoustic assays namely ''activated Partial Thromboplastin Time'' (aPTT) and ''Prothrombinase complex-induced Clotting Test'' (PiCT) have been compared with the standard methods in parallel. Both techniques have been applied to 300 samples, including 220 plasma samples of patients suffering coagulation disorders and 80 plasma samples of non-patients. In comparison, the coagulation times of the acoustic aPTT and PiCT yielded an excellent correlation with the standard methods with in analytical standard deviation limits. Finally, the acoustic aPTT assay is the ''gold standard'' for a dose administration of the new oral anticoagulant, where the Δf/ΔΓ ratio of the acoustic assay demonstrates that dabigatran with FEIBA 50 combination could be a safe remedy to avoid the deaths in clinics.
http://ift.tt/2A6EOyp
Scholar : Journal of Natural History, Volume 52, Issue 1-2, January - January 2018 is now available online on Taylor & Francis Online
@media screen and (max-width:400px) { .two .column, .two .left, .two .right{ max-width: 100% !important; } } @media screen and (min-width: 401px) and (max-width:620px){ .two .column, .two .left, .two .right { max-width: 100% !important; } }
|
Release of ICTP and CTX telopeptides from demineralized dentin matrices: Effect of time, mass and surface area
Source:Dental Materials
Author(s): Gianluca Turco, Milena Cadenaro, Tatjana Maravić, Andrea Frassetto, Eleonora Marsich, Annalisa Mazzoni, Roberto Di Lenarda, Franklin R. Tay, David H. Pashley, Lorenzo Breschi
ObjectiveThe present study evaluated the influence of time, mass and surface area of demineralized dentin collagen matrices on telopeptides release. The hypotheses tested were that the rates of ICTP and CTX release by matrix bound endogenous proteases are 1) not time-dependent, 2) unrelated to specimen mass, 3) unrelated to specimen surface area.MethodsNon-carious human molars (N=24) were collected and randomly assigned to three groups. Dentin slabs with three different thicknesses: 0.37mm, 0.75mm, and 1.50mm were completely demineralized and stored in artificial saliva for one week. Collagen degradation was evaluated by sampling storage media for ICTP and CTX telopeptidases. Activity of MMPs in the aging medium was evaluated using fluorometric activity assay kit.ResultsA statistically significant (p<0.05) decrease in the release of both ICTP and CTX fragments over time was observed irrespective of the specimen thickness. When data were normalized by the specimen mass, no significant differences were observed. Releases of ICTP and CTX were significantly related to the aging time as a function of surface area for the first 12h. Total MMP activity, mainly related to MMP-2 and -9, decreased with time (p<0.05).SignificanceBecause the release of collagen fragments was influenced by specimen storage time and surface area, it is likely that cleaved collagen fragments closer to the specimen surface diffuse into the incubation medium; those further away from the exposed surface are still entrapped within the demineralized dentin matrix. Bound MMPs can only degrade the substrate within the limited zone of their molecular mobility.
http://ift.tt/2lB24Af
Influence of a surface conditioner to pre-sintered zirconia on the biaxial flexural strength and phase transformation
Source:Dental Materials
Author(s): Tomofumi Sawada, Christine Schille, Judit Zöldföldi, Ernst Schweizer, Jürgen Geis-Gerstorfer, Sebastian Spintzyk
ObjectivesTo assess the influence of a surface conditioner applied to pre-sintered yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) on the biaxial flexural strength and phase transformation.MethodsConditioner-coated specimens (12mm diameter×0.8mm thickness) were prepared by application of a slurry conditioner using a brush on pre-sintered Y-TZP discs, followed by sandblasting with 50-μm Al2O3 after sintering (C-SB) or no further treatment (C-NT). The remaining conditioner-free specimens were subjected to sandblasting before sintering (NC-SB) or were maintained without treatment (NC-NT). Surface roughness measurements and scanning electron microscopy (SEM) in conjunction with energy dispersive X-ray spectroscopy (SEM-EDX) were performed for surface characterizations. The phase transformation of Y-TZP was identified by X-ray diffraction (XRD), and the biaxial flexural strength was measured using the piston-on-three-ball test according to ISO 6872:2015. The data were analyzed using nonparametric Kruskal–Wallis tests and Weibull distributions with the maximum likelihood estimation.ResultsSandblasting resulted in significantly rougher surfaces, irrespective of conditioner application. Conditioner layers were observed on surfaces in the C-NT and C-SB specimens. Monoclinic contents were present in a very small amount in the C-SB specimens. Both median biaxial flexural and characteristic strengths of all specimens exceeded ISO 6872:2015 requirements (Class 5: >800MPa), except the NC-SB specimens which showed significantly the lowest strength (p<0.001). Although no statistical difference was observed in Weibull modulus among the specimens (p=0.598), the NC-SB specimens showed the highest.SignificanceSurface conditioner application does not affect the biaxial flexural strength and phase stability of Y-TZP and can be considered practical for clinical use.
http://ift.tt/2qbsUUm
-
Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
-
The online platform for Taylor & Francis Online content New for Canadian Journal of Remote Sen...
