Introduction. The neurobiological mechanisms underlying the chemotherapy-induced neuropathic pain are only partially understood. Among them, microglia activation was identified as the key component of neuropathic pain. The aim of this study was to identify differentially expressed genes (DEGs) and pathways associated with vincristine-induced neuropathic pain by using bioinformatics analysis and observe the effects of oxycodone on these DEG expressions in a vincristine-induced microglia activation model. Methods. Based on microarray profile GSE53897, we identified DEGs between vincristine-induced neuropathic pain rats and the control group. Using the ToppGene database, the prioritization DEGs were screened and performed by gene ontology (GO) and signaling pathway enrichment. A protein-protein interaction (PPI) network was used to explore the relationship among DEGs. Then, we built the vincristine-induced microglia activation model and detected several DEG expressions by real-time polymerase chain reaction (PCR) and western blotting. Meanwhile, the effects of different concentrations of oxycodone on inflammatory response in primary microglia induced by vincristine were observed. Results. A total of 38 genes were differentially expressed between normal and vincristine-treated rats. GO and pathway enrichment analysis showed that prioritization DEGs are involved in cAMP metabolic process, inflammatory response, regulation of cell proliferation, and chemokine pathway. The in vitro studies showed that vincristine had dose-dependent cytotoxic effects in microglia. Compared to the control group, vincristine (0.001 μg/ml) could lead to inflammation in primary microglia induced by vincristine and upregulated the CXCL10, CXCL9, SFRP2, and PF4 mRNA and made an obvious reduction in IRF7 mRNA. At protein levels, oxycodone (50, 100 ng/ml) decreased the expression of CXCL10 and CXCL9 in activated microglia. Conclusion. Our study obtained several DEG expressions and signaling pathways in the vincristine-induced neuropathic pain rat model by bioinformatics analysis. Oxycodone could alleviate the vincristine-induced inflammatory signaling in primary microglia and downregulate some DEGs. Further molecular mechanisms need to be explored in the future.
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Σάββατο 9 Φεβρουαρίου 2019
Investigation of Key Genes and Pathways in Inhibition of Oxycodone on Vincristine-Induced Microglia Activation by Using Bioinformatics Analysis
The effect of high UV radiation exposure environment on the novel PVC polymers
Abstract
Although plastic induces environmental damages, almost the consumption of poly(vinyl chloride) never stops increasing. Therefore, this work abstracted by two parts, first, synthesis of Schiff bases 1–4 compounds through the reaction of amino group with appropriate aromatic aldehyde, reaction of PVC with Schiff bases compounds 1–4 in THF to form a new modified PVC-1, PVC-2, PVC-3, and PVC-4. The structures of Schiff bases 1–4 and the modified PVC-1, PVC-2, PVC-3, and PVC-4 have been characterized by different spectroscopic analyses. Second, the influence of introducing 4-amino-1,2,4-triazole as a pendent groups into PVC chain investigated on photostability rules of tests. The modified polymers photostability investigated by observing indices (ICO, Ipo, and IOH), weight loss, UV and morphological studies, and all results obtained indicated that PVC-1, PVC-2, PVC-3 and PVC-4 gave lower growth rate of ICO, IPO, and IOH through UV exposure time. The photostability are given as PVC-4 < PVC-3 < PVC-2 < PVC-1 from different mechanisms which suggested building on existence of 4-amino-1,2,4-triazole moieties in the polymer chain.
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Responses of Contents and Structure of DOM to Spartina alterniflora Invasion in Yanghe Estuary Wetland of Jiaozhou Bay, China
Abstract
This paper aimed to explore the effects of Spartina alterniflora invasion on the contents and structure of soil dissolved organic matter (DOM, including dissolved organic carbon (DOC), dissolved organic nitrogen (DON), dissolved organic phosphorus (DOP), and dissolved organic sulphur (DOS)) in the Yanghe estuary, by the aid of ultraviolet-visible spectrum, three-dimensional fluorescence spectrum, and Fourier transform infrared spectroscopy. Soil samples were collected at 0–60 cm depths in different invasion years (0, 1, 5, and 8). The results showed that the DOC increased gradually with the increase of invasion time of S.alterniflora; whereas the contents of DON and DOP decreased. In the vertical section, all the DOM showed a decreasing trend with the increase of the soil profile except the DOC content in SAF-5 and SAF-8 plots (The SAF-5 and SAF-8 represent for the invasion time of 5 years and 8 years). The spectral analysis showed that the macromolecules of DOM increased after the invasion. The molecular weight and number of molecules of DOM changed after invasion. The changes were mainly concentrated in refractory macromolecules. S.alterniflora had a significant effect on the number of structural units and functional groups of soil DOM. The intensity of functional group peaks became stronger, and aromatic, aliphatic, and carbohydrate substances increased. In addition, the quantity and quality of soil DOM input by S.alternifolia strongly affect the complexity of DOM chemical structure. With the increase of invasion time, the degree of humification increases and the structure of DOM tends to be more complex. The findings of this study indicate that the invasion of S.alternifolia would enhance DOM owing to greater amount of biomass.
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The influence of particle size and mineralogy on both phosphorus retention and release by streambed sediments
Abstract
Purpose
In many streams worldwide including those on the south coast of Western Australia (WA), sediments of the > 2-mm fraction often contribute up to 50% of the streambed. However, most analysis and interpretation of sediment chemistry, including phosphorus (P), is conducted on the < 2-mm fraction as this fraction is considered the most chemically reactive. This paper aims to identify the contribution of the > 2-mm fraction to P retention and release in sandy-gravely streams.
Material and methods
Sediment samples were collected from streams in agricultural catchments, and P retention and release by the < 2-mm and > 2-mm (typically lateritic; iron rich) sediment fractions were examined using fluvarium and batch experiments. Phosphorus sorbed by sediment was estimated on a mass (mg P kg−1) and area basis (mg P m−2).
Results and discussion
Phosphorus sorption measurements suggested that mineralogy as well as particle size were important factors influencing P retention by stream sediments. Stream sediments retained approximately 30% of added P. In a desorption phase, approximately 8% of the retained P was released into stream water.
Conclusions
Stream sediments in south western WA appear to be net immobilisers of P, retaining more P than they release, dependent on the stream P concentration. Exclusion of the > 2-mm fraction when determining stream sediment P dynamics may therefore underestimate whole stream sediment P retention and release.
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Influence of phytase enzyme on ruminal biogas production and fermentative digestion towards reducing environmental contamination
Abstract
Environmental impact of livestock production has received a considerable public scrutiny because of the adverse effects of nutrient run-offs, primarily N and P, from agricultural land harboring intensive energy livestock operations. Hence, this study was designed to determine the efficacy of dietary phytase supplementation on fermentation of a sorghum grain–based total mixed ration (TMR) using a ruminal in vitro digestion approach. Phytase was supplemented at three doses: 0 (control), 540 (P540), and 720 (P720) g/t dry matter, equivalent to 0, 2.7 × 106, and 3.6 × 106 CFU/t DM, respectively. Compared to P720 and the control, gas production was higher for P540 after 12 h (P = 0.02) and 24 h (P = 0.03) of fermentation suggesting a higher microbial activity in response to phytase supplementation at lower phytase levels. Correspondingly, dry matter degradability was found to have improved in P540 and P720 compared to the control by 13 and 11% after 24 h of incubation (P = 0.05). For ammonia nitrogen (NH3-N), a tendency towards lower values was only observed for P540 at 24 h of fermentation (P = 0.07), while minimal treatment effects were observed at other fermentation times. The concentrations of total volatile fatty acids (VFA) were higher (P < 0.05) after 48 h of fermentation for P540 and P720 compared to the control (P = 0.03) by 10% and 14%, respectively. Ruminal acetate tended towards higher values in the presence of phytase after 12 h of fermentation (P = 0.10), but towards lower values after 24 h of fermentation (P = 0.02), irrespective of the phytase dose applied. A trend towards lower ruminal propionate levels was observed in the presence of phytase after 6 h (P = 0.10) and 12 h (P = 0.06) of fermentation, while no effects were found at other fermentation times. In conclusion, phytase supplementation has the potential to improve metabolic energy activity of rumen microorganisms and the use of feed constituents. Thus, phytase supplementation could help to reduce environmental contamination in areas of ruminant production.
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Ameliorative effect of zinc oxide nanoparticles against potassium bromate-mediated toxicity in Swiss albino rats
Abstract
Potassium bromate (PB) is a commonly used food additive, a prominent water disinfection by-product, and a class IIB carcinogen. It exerts a various degree of toxicity depending on its dose and exposure duration consumed with food and water in the living organisms. The present investigation aims to demonstrate the protective efficacy of zinc oxide nanoparticles (ZnO NPs) derived from Ochradenus arabicus (OA) leaf extract by green technology in PB-challenged Swiss albino rats. The rodents were randomly distributed, under the lab-standardized treatment strategy, into the following six treatment groups: control (group I), PB alone (group II), ZnO alone (group III), ZnO NP alone (group IV), PB + ZnO (group V), and PB + ZnO NPs (group VI). The rats were sacrificed after completion of the treatment, and their blood and liver samples were collected for further analysis. Group II showed extensive toxic effects with altered liver function markers (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transferase, glutathione-S-transferase, and thioredoxin reductase) and compromised redox status (SOD, CAT, GR, GPx, GSH, MDA, and total carbonyl content). The histopathological analysis and comet assay further supported the biochemical results of the same group. Besides, group III also showed moderate toxicity evidenced by an alteration in most of the studied parameters while group IV demonstrated mild toxicity after biochemical analysis indicating the excellent biocompatibility of the NPs. However, group VI exhibited attenuation of the PB-induced toxic insults to a significant level as compared to group II, whereas group V failed to show similar improvement in the studied parameters. All these findings entail that the ZnO NPs prepared by green synthesis have significant ameliorative property against PB-induced toxicity in vivo. Moreover, administration of the NPs improved the overall health of the treated animals profoundly. Hence, these NPs have significant therapeutic potential against the toxic effects of PB and similar compounds in vivo, and they are suitable to be used at the clinical and industrial levels.
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Uptake and distribution of phenanthrene and pyrene in roots and shoots of maize ( Zea mays L.)
Abstract
Polycyclic aromatic hydrocarbons as byproducts of carbon-based fuel combustion are an important group of pollutants with wide distribution in the environment. Polycyclic aromatic hydrocarbons are known as toxic compounds for almost all organisms. Different plant species can uptake polycyclic aromatic hydrocarbons by roots and translocate them to various aerial parts. The aim of this study is to investigate the uptake, translocation, and accumulation of pyrene and phenanthrene in maize under controlled conditions. Seeds were cultivated in perlite containing 25, 50, 75, and 100 ppm of phenanthrene and pyrene, and their concentrations in the roots and shoots of the plants were measured using high-performance liquid chromatography technique after 7, 14, and 21 days. The results revealed that phenanthrene naturally existed in maize and its concentration showed a time-dependent decrease in shoots and roots. In contrast, the concentration of pyrene was increased in the roots and reduced in the shoots. Although pyrene had higher uptake than phenanthrene in roots of maize, the translocation factor value for pyrene was lower than for phenanthrene. According to these findings, phenanthrene could be metabolized in maize in the shoot and root tissues, but pyrene had more tendency to be accumulated in roots.
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Composition, diversity and abundance of Candidatus M. oxyfera -like bacteria in response to the estuary salinity gradient
Abstract
"Candidatus Methylomirabilis oxyfera" (M. oxyfera) bacteria has attracted much attention recently since it plays an important role in performing methane oxidation. Most studies on M. oxyfera-like bacteria have been carried out in freshwater ecosystems, however it remains unclear about its distribution along the salinity gradient of estuarine and coastal environments. In this study, we used molecular analyses to reveal the community, diversity and abundance of M. oxyfera-like bacteria in the Yangtze estuarine and coastal sediments. Clone library analyses confirmed the wide distributions of M. oxyfera-like bacterial 16S rRNA and pmoA genes in the study area. The M. oxyfera-like bacterial 16S rRNA gene sequences were grouped into eleven separate OTUs, which were assigned to groups A and B of M. oxyfera-like bacteria. Most sequences (89.4–97.6% of total sequences) of M. oxyfera-like bacterial 16S rRNA gene were affiliated with group B, while only few clone sequences (2.4–10.6% of total sequences) were affiliated with group A. The retrieved M. oxyfera-like bacterial pmoA gene sequences were grouped into five distinct clusters. Bray–Curtis dissimilarity of M. oxyfera-like bacterial 16S rRNA and pmoA genes differed greatly among the low, middle and high salinity sites. M. oxyfera-like bacterial 16S rRNA and pmoA abundances were mainly recovered from the oligohaline sites rather than from the saline sites. In addition, the large differences in 16S rRNA and pmoA gene sequences between estuarine and land freshwater environments suggested that salinity could be able to affect the community distribution of M. oxyfera-like bacteria. Also, sediment nitrate/ammonium played an important role in affecting the M. oxyfera-like bacteria. Overall, these results indicate that salinity has a great influence on M. oxyfera-like bacteria community in estuarine environments.
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Future Oncology; +24 new citations
24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2019/02/09
PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
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Self-Related Processing and Future Thinking: Distinct Contributions of Ventromedial Prefrontal Cortex and the Medial Temporal Lobes
Publication date: Available online 8 February 2019
Source: Cortex
Author(s): Mieke Verfaellie, Aubrey A. Wank, Allison G. Reid, Elizabeth Race, Margaret M. Keane
Abstract
Episodic future thinking depends on a core network of regions that involves, in addition to the medial temporal lobes (MTL), the ventromedial prefrontal cortex (vmPFC). Neuroimaging studies suggest that vmPFC is particularly involved when future thinking requires consideration of self-relevant information, but lesion evidence for a special role of vmPFC in constructing self-relevant scenarios is limited. To clarify the involvement of vmPFC in future thinking, eight patients with vmPFC lesions were asked to imagine future events pertaining to the self or to another person, and their performance was contrasted with that of eight patients with MTL lesions. Patients with vmPFC lesions were no more detailed in their description of future events pertaining to the self than of events pertaining to another person. In contrast, like controls, patients with MTL lesions showed a self-benefit, despite impoverished performance overall. These findings accord with evidence from neuroimaging studies and elucidate the distinct contributions of vmPFC and MTL to future thinking.
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Automated Generation of Radiologic Descriptions on Brain Volume Changes From T1-Weighted MR Images: Initial Assessment of Feasibility.
| Related Articles |
Automated Generation of Radiologic Descriptions on Brain Volume Changes From T1-Weighted MR Images: Initial Assessment of Feasibility.
Front Neurol. 2019;10:7
Authors: Akazawa K, Sakamoto R, Nakajima S, Wu D, Li Y, Oishi K, Faria AV, Yamada K, Togashi K, Lyketsos CG, Miller MI, Mori S
Abstract
Purpose: To examine the feasibility and potential difficulties of automatically generating radiologic reports (RRs) to articulate the clinically important features of brain magnetic resonance (MR) images. Materials and Methods: We focused on examining brain atrophy by using magnetization-prepared rapid gradient-echo (MPRAGE) images. The technology was based on multi-atlas whole-brain segmentation that identified 283 structures, from which larger superstructures were created to represent the anatomic units most frequently used in RRs. Through two layers of data-reduction filters, based on anatomic and clinical knowledge, raw images (~10 MB) were converted to a few kilobytes of human-readable sentences. The tool was applied to images from 92 patients with memory problems, and the results were compared to RRs independently produced by three experienced radiologists. The mechanisms of disagreement were investigated to understand where machine-human interface succeeded or failed. Results: The automatically generated sentences had low sensitivity (mean: 24.5%) and precision (mean: 24.9%) values; these were significantly lower than the inter-rater sensitivity (mean: 32.7%) and precision (mean: 32.2%) of the radiologists. The causes of disagreement were divided into six error categories: mismatch of anatomic definitions (7.2 ± 9.3%), data-reduction errors (11.4 ± 3.9%), translator errors (3.1 ± 3.1%), difference in the spatial extent of used anatomic terms (8.3 ± 6.7%), segmentation quality (9.8 ± 2.0%), and threshold for sentence-triggering (60.2 ± 16.3%). Conclusion: These error mechanisms raise interesting questions about the potential of automated report generation and the quality of image reading by humans. The most significant discrepancy between the human and automatically generated RRs was caused by the sentence-triggering threshold (the degree of abnormality), which was fixed to z-score >2.0 for the automated generation, while the thresholds by radiologists varied among different anatomical structures.
PMID: 30733701 [PubMed]
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A Case of Hemoperitoneum Due to Spontaneous Bleeding from a Uterine Leiomyoma.
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A Case of Hemoperitoneum Due to Spontaneous Bleeding from a Uterine Leiomyoma.
Am J Case Rep. 2019 Feb 08;20:167-170
Authors: Althobaiti FA, Alsaadi KK, Althobaiti AA
Abstract
BACKGROUND Uterine leiomyoma, or uterine fibroid, is the most common gynecologic neoplasm and its management usually results in a good clinical outcome. This report is of a rare case of hemoperitoneum associated with spontaneous hemorrhage from a benign uterine leiomyoma. CASE REPORT A 27-year-old single woman presented with generalized acute abdominal pain and vomiting. Clinical examination showed a distended abdomen and unstable vital signs. Following active resuscitation, ultrasound and computed tomography (CT) imaging showed an intraperitoneal fluid collection and heterogenous uterine mass. The patient underwent emergency laparotomy with the identification of bleeding blood vessels, which were clipped, resulting in hemostasis. The uterine lesion was completely excised and histopathology confirmed the diagnosis of benign leiomyoma. The patient's postoperative course was unremarkable. Five days following admission, the patient was discharged from hospital without further complications. CONCLUSIONS Hemoperitoneum secondary to spontaneous hemorrhage from a benign uterine leiomyoma is rare. This case demonstrates that clinical history, imaging, and surgical exploration are required to identify and control the source of bleeding to prevent a potentially fatal outcome.
PMID: 30733430 [PubMed - in process]
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Sustained somatostatin gene expression reverses kindling-induced increases in the number of dividing Type-1 neural stem cells in the hippocampi of behaviorally responsive rats.
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Sustained somatostatin gene expression reverses kindling-induced increases in the number of dividing Type-1 neural stem cells in the hippocampi of behaviorally responsive rats.
Epilepsy Res. 2019 Jan 11;150:78-94
Authors: Leibowitz JA, Natarajan G, Zhou J, Carney PR, Ormerod BK
Abstract
Neurogenesis persists throughout life in the hippocampi of all mammals, including humans. In the healthy hippocampus, relatively quiescent Type-1 neural stem cells (NSCs) can give rise to more proliferative Type-2a neural progenitor cells (NPCs), which generate neuronal-committed Type-2b NPCs that mature into Type-3 neuroblasts. Many Type-3 neuroblasts survive and mature into functionally integrated granule neurons over several weeks. In kindling models of epilepsy, neurogenesis is drastically upregulated and many new neurons form aberrant connections that could support epileptogenesis and/or seizures. We have shown that sustained vector-mediated hippocampal somatostatin (SST) expression can both block epileptogenesis and reverse seizure susceptibility in fully kindled rats. Here we test whether adeno-associated virus (AAV) vector-mediated sustained SST expression modulates hippocampal neurogenesis and microglial activation in fully kindled rats. We found significantly more dividing Type-1 NSCs and a corresponding increased number of surviving new neurons in the hippocampi of kindled versus sham-kindled rats. Increased numbers of activated microglia were found in the granule cell layer and hilus of kindled rats at both time points. After intrahippocampal injection with either eGFP or SST-eGFP vector, we found similar numbers of dividing Type-1 NSCs and -2 NPCs and surviving BrdU+ neurons and glia in the hippocampi of kindled rats. Upon observed variability in responses to SST-eGFP (2/4 rats exhibited Grade 0 seizures in the test session), we conducted an additional experiment. We found significantly fewer dividing Type-1 NSCs in the hippocampi of SST-eGFP vector-treated responder rats (5/13 rats) relative to SST-eGFP vector-treated non-responders and eGFP vector-treated controls that exhibited high-grade seizures on the test session. The number of activated microglia was upregulated in the GCL and hilus of kindled rats, regardless of vector treatment. These data support the hypothesis that sustained SST expression exerts antiepileptic effects potentially through normalization of neurogenesis and suggests that abnormally high proliferating Type-1 NSC numbers may be a cellular mechanism of epilepsy.
PMID: 30735971 [PubMed - as supplied by publisher]
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Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents.
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Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents.
Cochrane Database Syst Rev. 2019 Feb 08;2:CD003032
Authors: Brigo F, Igwe SC, Lattanzi S
Abstract
BACKGROUND: This is an updated version of the Cochrane Review previously published in 2017.Absence seizures (AS) are brief epileptic seizures which present in childhood and adolescence. Depending on clinical features and electroencephalogram (EEG) findings they are divided into typical, atypical absences, and absences with special features. Typical absences are characterised by sudden loss of awareness and an EEG typically shows generalised spike wave discharges at three cycles per second. Ethosuximide, valproate and lamotrigine are currently used to treat absence seizures. This review aims to determine the best choice of antiepileptic drug for children and adolescents with AS.
OBJECTIVES: To review the evidence for the effects of ethosuximide, valproate and lamotrigine as treatments for children and adolescents with absence seizures (AS), when compared with placebo or each other.
SEARCH METHODS: For the latest update we searched the Cochrane Register of Studies (CRS Web, 29 May 2018), which includes the Cochrane Epilepsy Group's Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946 to 29 May 2018), ClinicalTrials.gov (29 May 2018) and the WHO International Clinical Trials Registry Platform (ICTRP, 29 May 2018). Previously we searched Embase (1988 to March 2005) and SCOPUS (1823 to 31 March 2014), but this is no longer necessary because randomised controlled trials (RCTs) and quasi-RCTs in Embase and SCOPUS are now included in CENTRAL. No language restrictions were imposed. In addition, we contacted Sanofi Winthrop, Glaxo Wellcome (now GlaxoSmithKline) and Parke Davis (now Pfizer), manufacturers of sodium valproate, lamotrigine and ethosuximide respectively.
SELECTION CRITERIA: Randomised parallel group monotherapy or add-on trials which include a comparison of any of the following in children or adolescents with AS: ethosuximide, sodium valproate, lamotrigine, or placebo.
DATA COLLECTION AND ANALYSIS: Outcome measures were: (1) proportion of individuals seizure free at one, three, six, 12 and 18 months post randomisation; (2) people with a 50% or greater reduction in seizure frequency; (3) normalisation of EEG and/or negative hyperventilation test; and (4) adverse effects. Data were independently extracted by two review authors. Results are presented as risk ratios (RR) with 95% confidence intervals (95% CIs). We used GRADE quality assessment criteria to evaluate the certainty of evidence derived from all included studies.
MAIN RESULTS: On the basis of our selection criteria, we included no new studies in the present review. Eight small trials (total number of participants: 691) were included from the earlier review. Six of them were of poor methodological quality (unclear or high risk of bias) and seven recruited less than 50 participants. There are no placebo-controlled trials for ethosuximide or valproate, and hence, no evidence from RCTs to support a specific effect on AS for either of these two drugs. Due to the differing methodologies used in the trials comparing ethosuximide, lamotrigine and valproate, we thought it inappropriate to undertake a meta-analysis. One large randomised, parallel double-blind controlled trial comparing ethosuximide, lamotrigine and sodium valproate in 453 children with newly diagnosed childhood absence epilepsy found that at 12 months, the freedom-from-failure rates for ethosuximide and valproic acid were similar and were higher than the rate for lamotrigine. The frequency of treatment failures due to lack of seizure control (P < 0.001) and intolerable adverse events (P < 0.037) was significantly different among the treatment groups, with the largest proportion of lack of seizure control in the lamotrigine cohort, and the largest proportion of adverse events in the valproic acid group. Overall, this large study demonstrates the superior effectiveness of ethosuximide and valproic acid compared to lamotrigine as initial monotherapy aimed to control seizures without intolerable adverse effects in children with childhood absence epilepsy. The risk of bias for this study was low. We rated the overall certainty of the evidence available from the included studies to be moderate or high.
AUTHORS' CONCLUSIONS: Since the last version of this review was published, we have found no new studies. Hence, the conclusions remain the same as the previous update. With regards to both efficacy and tolerability, ethosuximide represents the optimal initial empirical monotherapy for children and adolescents with AS. However, if absence and generalised tonic-clonic seizures coexist, valproate should be preferred, as ethosuximide is probably inefficacious on tonic-clonic seizures.
PMID: 30734919 [PubMed - as supplied by publisher]
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A Practical Guide to Treatment of Childhood Absence Epilepsy.
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A Practical Guide to Treatment of Childhood Absence Epilepsy.
Paediatr Drugs. 2019 Feb 08;:
Authors: Kessler SK, McGinnis E
Abstract
Childhood absence epilepsy (CAE) is a common pediatric epilepsy syndrome with distinct seizure semiology, electroencephalography (EEG) features, and treatment. A diagnosis of CAE can be obtained during an office visit with a careful history, physical exam including prolonged hyperventilation, and a routine EEG. The treatment of choice for CAE with absence seizures only is ethosuximide. Valproic acid and lamotrigine are also effective treatments for many patients, but when compared to ethosuximide, valproic acid has more adverse effects and lamotrigine is less effective. Attention to predictors of response to treatment, including clinical, electrographic, and genetic factors, is increasing. Refractory CAE occurs in fewer than half of patients, and treatment strategies are available, though efficacy data are lacking. Careful assessment and treatment of psychosocial comorbidities is essential in caring for patients with CAE.
PMID: 30734897 [PubMed - as supplied by publisher]
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Psychiatric Assessment in Patients with Mild Temporal Lobe Epilepsy.
| Related Articles |
Psychiatric Assessment in Patients with Mild Temporal Lobe Epilepsy.
Behav Neurol. 2019;2019:4139404
Authors: Bruni A, Martino I, Caligiuri ME, Vaccaro MG, Trimboli M, Segura Garcia C, De Fazio P, Gambardella A, Labate A
Abstract
Objectives: The findings of previous studies focused on personality disorders in epileptic patients are difficult to interpret due to nonhomogeneous samples and noncomparable methods. Here, we aimed at studying the personality profile in patients with mild temporal lobe epilepsy (mTLE) with psychiatric comorbidity.
Materials and Methods: Thirty-five patients with mTLE (22 males, mean age 40.7 ± 12.1) underwent awake and sleep EEG, 3T brain MRI, and an extensive standardized diagnostic neuropsychiatric battery: Temperament and Character Inventory-Revised (TCI-R), Beck Depression Inventory-2, and State-Trait Anxiety Inventory. Drug history was collected in detail. Hierarchical Cluster Analysis was performed on TCI-R data, while all other clinical and psychological variables were compared across the resulting clusters.
Results: Scores of Harm Avoidance (HA), Reward Dependence (RD), Persistence (P), Cooperativeness (C), and Self-Transcendence (ST) allowed the identification of two clusters, describing different personality subtypes. Cluster 1 was characterized by an early onset, more severe anxiety traits, and combined drug therapy (antiepileptic drug and Benzodiazepine/Selective Serotonin Reuptake Inhibitors) compared to Cluster 2.
Conclusions: Our findings suggest that different personality traits may play a role in determining the clinical outcome in patients with mTLE. Specifically, lower scores of HA, RD, P, C, and ST were associated with worse clinical outcome. Thus, personality assessment could serve as an early indicator of greater disease severity, improving the management of mTLE.
PMID: 30733834 [PubMed - in process]
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Characterizing the Interplay Between Autism Spectrum Disorder and Comorbid Medical Conditions: An Integrative Review.
| Related Articles |
Characterizing the Interplay Between Autism Spectrum Disorder and Comorbid Medical Conditions: An Integrative Review.
Front Psychiatry. 2018;9:751
Authors: Tye C, Runicles AK, Whitehouse AJO, Alvares GA
Abstract
Co-occurring medical disorders and associated physiological abnormalities in individuals with autism spectrum disorder (ASD) may provide insight into causal pathways or underlying biological mechanisms. Here, we review medical conditions that have been repeatedly highlighted as sharing the strongest associations with ASD-epilepsy, sleep, as well as gastrointestinal and immune functioning. We describe within each condition their prevalence, associations with behavior, and evidence for successful treatment. We additionally discuss research aiming to uncover potential aetiological mechanisms. We then consider the potential interaction between each group of conditions and ASD and, based on the available evidence, propose a model that integrates these medical comorbidities in relation to potential shared aetiological mechanisms. Future research should aim to systematically examine the interactions between these physiological systems, rather than considering these in isolation, using robust and sensitive biomarkers across an individual's development. A consideration of the overlap between medical conditions and ASD may aid in defining biological subtypes within ASD and in the development of specific targeted interventions.
PMID: 30733689 [PubMed]
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Neuromodulation of autism spectrum disorders using vagal nerve stimulation.
| Related Articles |
Neuromodulation of autism spectrum disorders using vagal nerve stimulation.
J Clin Neurosci. 2019 Feb 04;:
Authors: van Hoorn A, Carpenter T, Oak K, Laugharne R, Ring H, Shankar R
Abstract
Influential theories propose an important role for the autonomic nervous system in social behaviour and emotion regulation. Difficulties with these capabilities occur in autism spectrum disorders (ASD). Vagus nerve stimulation (VNS) is a neuromodulation technique that stimulates autonomic pathways by means of an electrode implanted around the left vagus nerve in the neck. It is a licenced treatment for epilepsy and depression. This study searches the literature for evidence of VNS effects on behaviour in ASD. A literature search was conducted by two independent reviewers using Embase, Medline, PsycInfo and Cochrane using relevant search terms following the principals of the PRISMA guidance. The search strategy utilised a combination of text words and thesaurus terms to retrieve records relating to autism/pervasive developmental disorder and vagus nerve stimulation. No limits were applied. Supplementary searches were carried out on trials registers, and using backwards and forwards citation searching. A predesigned inclusion and exclusion criteria was administered to the identified results. From the 242 results identified search strategy 11 were found to satisfy the full search criteria and used to discuss the hypothesis. Eight studies were case series and three case reports. There is some evidence that VNS, when performed for epilepsy, may improve behaviour in people with ASD. There are indications that this occurs independently of its effects on seizure frequency and mood, although more rigorous studies are required.
PMID: 30732986 [PubMed - as supplied by publisher]
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Management of Pediatric Febrile Seizures.
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Management of Pediatric Febrile Seizures.
Int J Environ Res Public Health. 2018 10 12;15(10):
Authors: Laino D, Mencaroni E, Esposito S
Abstract
Febrile seizures (FS), events associated with a fever in the absence of an intracranial infection, hypoglycaemia, or an acute electrolyte imbalance, occur in children between six months and six years of age. FS are the most common type of convulsions in children. FS can be extremely frightening for parents, even if they are generally harmless for children, making it important to address parental anxiety in the most sensitive manner. The aim of this review was to focus on the management of FS in the pediatric age. An analysis of the literature showed that most children with FS have an excellent prognosis, and few develop long-term health problems. The diagnosis of FS is clinical, and it is important to exclude intracranial infections, in particular after a complex FS. Management consists of symptom control and treating the cause of the fever. Parents and caregivers are often distressed and frightened after a FS occurs and need to be appropriately informed and guided on the management of their child's fever by healthcare professionals. Due to the inappropriate use of diagnostic tests and treatments, it is extremely important to improve the knowledge of pediatricians and neurologists on FS management and to standardize the diagnostic and therapeutic work-up.
PMID: 30321985 [PubMed - indexed for MEDLINE]
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Introduction to the 9th Young Scientists School on Systems Biology and Bioinformatics (SBB'2017).
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Introduction to the 9th Young Scientists School on Systems Biology and Bioinformatics (SBB'2017).
J Bioinform Comput Biol. 2018 02;16(1):1802001
Authors: Orlov YL, Tatarinova TV, Zakhartsev MV, Kolchanov NA
PMID: 29439645 [PubMed - indexed for MEDLINE]
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Traumatic brain injury is a longitudinal disease process.
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Traumatic brain injury is a longitudinal disease process.
Curr Opin Neurol. 2017 12;30(6):563-564
Authors: Vespa P
PMID: 29095717 [PubMed - indexed for MEDLINE]
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Utility of Skin Biopsy in a Case of Progressive Myoclonic Epilepsy: Challenge.
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Utility of Skin Biopsy in a Case of Progressive Myoclonic Epilepsy: Challenge.
Am J Dermatopathol. 2018 Sep;40(9):e123
Authors: Frantz T, Fortson E, Strowd LC
PMID: 28692462 [PubMed - indexed for MEDLINE]
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Development of In Vivo Imaging Tools for Investigating Astrocyte Activation in Epileptogenesis.
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Development of In Vivo Imaging Tools for Investigating Astrocyte Activation in Epileptogenesis.
Mol Neurobiol. 2018 May;55(5):4463-4472
Authors: Kostoula C, Pascente R, Ravizza T, McCown T, Schoch S, Vezzani A, Becker AJ, van Loo KMJ
Abstract
Insights into the dynamic changes in molecular processes occurring in the brain during epileptogenesis can substantially improve our understanding of their pathogenetic relevance. In this context, neuroinflammation is a potential mechanism of epileptogenesis which has recently been investigated in animal models by MRI or PET molecular imaging. Here, we developed an alternative and complementary molecular imaging strategy by designing a serotype 8 recombinant adeno-associated virus (AAV8) harboring promoter fragments of the GFAP or IL-1β promoter and a luciferase reporter gene. Mice were injected intrahippocampally with rAAV8 and treated with intracortical kainic acid to induce status epilepticus (SE) and hence epileptogenesis. In vivo bioluminescence imaging combined with immunohistochemistry revealed a significant activation of the GFAP promoter 24 h and 3 days after kainate-induced SE. For IL-1β, we identified the promoter region required for studying cell-specific induction of the promoter in longitudinal studies. We conclude that the GFAP promoter fragment represents a useful tool for monitoring the in vivo activation of astrocytes with an inflammatory phenotype during epileptogenesis, or under other pathophysiological conditions.
PMID: 28669125 [PubMed - indexed for MEDLINE]
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Editorial.
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Editorial.
Curr Opin Neurol. 2017 04;30(2):165-166
Authors: Walker MC
PMID: 28212176 [PubMed - indexed for MEDLINE]
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Assessment of Ki-67 as a potential biomarker in patients with breast cancer.
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Assessment of Ki-67 as a potential biomarker in patients with breast cancer.
J Genet Eng Biotechnol. 2018 Dec;16(2):479-484
Authors: Ragab HM, Samy N, Afify M, El Maksoud NA, Shaaban HM
Abstract
Breast cancer is the most common cancer in females, it accounts for one third of all malignancies affecting women. Appropriate biomarkers play significant role in predicting the prognosis and decide the specific therapy to each patient. In this study we aimed at evaluating the value of Ki-67 as a prognostic marker in breast cancer patients and to analyze the associations between Ki-67 and their clinicopathological parameters. This study included 92 patients with developed non metastatic breast cancer and 10 women had benign breast tumor served as controls. We measured the serum level by ELISA technique and tissue expression of Ki-67 by immunohistochemical technique. Our results showed that there were no statistically significant differences in serum Ki-67 levels between the two studied groups. As for Ki-67expression in breast cancer cells, the score increases with increase of tumor size, grade, premenopausal, Ki-67 expression in estrogen and progesterone receptor positive tumors showed lower values than estrogen and progesterone negative tumors, while higher Ki-67 expression was more frequently associated with HER2-positive. In conclusion; our study supports the finding that tissue Ki-67 expression may add prognostic information to that obtained from classical prognostic factors and can provide data of significant value to other important prognostic indicators such as pathological grading, and axillary lymph node involvement.
PMID: 30733763 [PubMed]
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Prognostic utility of tumor-infiltrating lymphocytes in residual tumor after neoadjuvant chemotherapy with trastuzumab for HER2-positive breast cancer.
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Prognostic utility of tumor-infiltrating lymphocytes in residual tumor after neoadjuvant chemotherapy with trastuzumab for HER2-positive breast cancer.
Sci Rep. 2019 Feb 07;9(1):1583
Authors: Kurozumi S, Inoue K, Matsumoto H, Fujii T, Horiguchi J, Oyama T, Kurosumi M, Shirabe K
Abstract
Predictive utility of tumor-infiltrating lymphocytes (TILs) in HER2-positive breast cancer patients receiving neoadjuvant chemotherapy (NAC) with concurrent trastuzumab remains unclear. We examined TILs grades of pretreatment cancer tissue specimens and residual tumors after NAC with trastuzumab and determined the predictive utility of the TILs grade in pathological complete response (pCR) and the prognostic power of TILs in HER2-positive breast cancer. This cohort study included 128 HER2-positive breast cancer who received NAC with trastuzumab. TILs grading of the tumor stroma in pretreatment biopsy specimens and residual tumors after NAC with trastuzumab was categorized as low, intermediate, and high based on the criteria of the International Working Group. In current study, the pCR rate was 64.8%, and the Relapse-free survival (RFS) was significantly worse in the non-pCR group than in the pCR group. The pCR rate correlated with the TILs grade in pretreatment tumors. In 45 non-pCR patients, TILs grade was higher in the residual tumors than in the pretreatment tumors. The RFS was significantly better in residual tumors with high TILs grade than those with low TILs grade (p = 0.033). In conclusion, assessment of the TILs grade in residual tumors after NAC with trastuzumab might be necessary to determine patients with good prognosis among those who do not achieve pCR.
PMID: 30733496 [PubMed - in process]
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Therapeutic targeting of HER2-CB2R heteromers in HER2-positive breast cancer.
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Therapeutic targeting of HER2-CB2R heteromers in HER2-positive breast cancer.
Proc Natl Acad Sci U S A. 2019 Feb 07;:
Authors: Blasco-Benito S, Moreno E, Seijo-Vila M, Tundidor I, Andradas C, Caffarel MM, Caro-Villalobos M, Urigüen L, Diez-Alarcia R, Moreno-Bueno G, Hernández L, Manso L, Homar-Ruano P, McCormick PJ, Bibic L, Bernadó-Morales C, Arribas J, Canals M, Casadó V, Canela EI, Guzmán M, Pérez-Gómez E, Sánchez C
Abstract
Although human epidermal growth factor receptor 2 (HER2)-targeted therapies have dramatically improved the clinical outcome of HER2-positive breast cancer patients, innate and acquired resistance remains an important clinical challenge. New therapeutic approaches and diagnostic tools for identification, stratification, and treatment of patients at higher risk of resistance and recurrence are therefore warranted. Here, we unveil a mechanism controlling the oncogenic activity of HER2: heteromerization with the cannabinoid receptor CB2R. We show that HER2 physically interacts with CB2R in breast cancer cells, and that the expression of these heteromers correlates with poor patient prognosis. The cannabinoid Δ9-tetrahydrocannabinol (THC) disrupts HER2-CB2R complexes by selectively binding to CB2R, which leads to (i) the inactivation of HER2 through disruption of HER2-HER2 homodimers, and (ii) the subsequent degradation of HER2 by the proteasome via the E3 ligase c-CBL. This in turn triggers antitumor responses in vitro and in vivo. Selective targeting of CB2R transmembrane region 5 mimicked THC effects. Together, these findings define HER2-CB2R heteromers as new potential targets for antitumor therapies and biomarkers with prognostic value in HER2-positive breast cancer.
PMID: 30733293 [PubMed - as supplied by publisher]
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The Role of Radiology in Intimate Partner Violence.
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The Role of Radiology in Intimate Partner Violence.
Radiology. 2019 Feb 05;:190057
Authors: Flores EJ, Narayan AK
PMID: 30735471 [PubMed - as supplied by publisher]
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Which Is Better for Characterizing Disease Activity in Axial Spondyloarthritis: Diffusion MRI or T2-weighted/STIR MRI?
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Which Is Better for Characterizing Disease Activity in Axial Spondyloarthritis: Diffusion MRI or T2-weighted/STIR MRI?
Radiology. 2019 Feb 05;:190019
Authors: Guermazi A, Roemer FW
PMID: 30735464 [PubMed - as supplied by publisher]
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Pediatric CT in Adult Facilities: Banging the Drum for Radiation Dose Management.
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Pediatric CT in Adult Facilities: Banging the Drum for Radiation Dose Management.
Radiology. 2019 Feb 05;:190016
Authors: Strouse PJ
PMID: 30735090 [PubMed - as supplied by publisher]
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Barley β-glucan accelerates wound healing by favoring migration versus proliferation of human dermal fibroblasts.
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Barley β-glucan accelerates wound healing by favoring migration versus proliferation of human dermal fibroblasts.
Carbohydr Polym. 2019 Apr 15;210:389-398
Authors: Fusté NP, Guasch M, Guillen P, Anerillas C, Cemeli T, Pedraza N, Ferrezuelo F, Encinas M, Moralejo M, Garí E
Abstract
β-Glucans are considered candidates for the medication in different human pathologies. In this work, we have purified β-glucan from a selected barley line and tested their effects in primary human dermal fibroblasts. Unexpectedly, we have observed that this compound promoted a short-transitory proliferation arrest at 24 h after its addition on the medium. We have determined that this transitory arrest was dependent on the cell-cycle regulator protein Retinoblastoma. Moreover, dermal fibroblasts increase their migration capacities at 24 h after barley β-glucan addition. Also, we have described that barley β-glucan strongly reduced the ability of fibroblasts to attach and to spread on cell plates. Our data indicates that barley β-glucan signal induces an early response in HDF cells favoring migration versus proliferation. This feature is consistent with our observation that the topical addition of our barley β-glucan in vivo accelerates the wound closure in mouse skin.
PMID: 30732776 [PubMed - in process]
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JNK-dependent cell cycle stalling in G2 promotes survival and senescence-like phenotypes in tissue stress.
JNK-dependent cell cycle stalling in G2 promotes survival and senescence-like phenotypes in tissue stress.
Elife. 2019 Feb 08;8:
Authors: Cosolo A, Jaiswal J, Csordás G, Grass I, Uhlirova M, Classen AK
Abstract
The restoration of homeostasis after tissue damage relies on proper spatial-temporal control of damage-induced apoptosis and compensatory proliferation. In Drosophila imaginal discs these processes are coordinated by the stress response pathway JNK. We demonstrate that JNK signaling induces a dose-dependent extension of G2 in tissue damage and tumors, resulting in either transient stalling or a prolonged but reversible cell cycle arrest. G2-stalling is mediated by downregulation of the G2/M-specific phosphatase String(Stg)/Cdc25. Ectopic expression of stg is sufficient to suppress G2-stalling and reveals roles for stalling in survival, proliferation and paracrine signaling. G2-stalling protects cells from JNK-induced apoptosis, but under chronic conditions, reduces proliferative potential of JNK-signaling cells while promoting non-autonomous proliferation. Thus, transient cell cycle stalling in G2 has key roles in wound healing but becomes detrimental upon chronic JNK overstimulation, with important implications for chronic wound healing pathologies or tumorigenic transformation.
PMID: 30735120 [PubMed - as supplied by publisher]
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Inhibitory Effect of (2R)-1-(1-Benzofuran-2-yl)-N-propylpentan-2-amine on Lung Adenocarcinoma.
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Inhibitory Effect of (2R)-1-(1-Benzofuran-2-yl)-N-propylpentan-2-amine on Lung Adenocarcinoma.
Pathol Oncol Res. 2019 Feb 08;:
Authors: Mervai Z, Reszegi A, Miklya I, Knoll J, Schaff Z, Kovalszky I, Baghy K
Abstract
BPAP is a potent enhancer substance with catecholaminergic and serotoninergic activity in the brain. It was discovered that it is also effective against certain types of experimental cancers, showing the most promising results in case of lung cancer. That is why we tested its efficacy in two different doses in a newly developed EGFR wild type mouse lung adenocarcinoma xenograft model. Experiments were conducted on FVB/N and SCID mouse strains treated with low and high dose of BPAP. Body weight, survival, and tumor volumes were recorded. Furthermore, the activity of major signaling pathways of NSCLC such as MAPK and Akt/mTOR as well as cell cycle regulation were determined. Significant inhibition of tumor growth was exerted by both doses, but the mechanism of action was different. High dose directly inhibited, whereas low dose activated the main signaling pathways. Exposure to low dose BPAP resulted in elevated activity of the mTOR pathway together with p16INK-induced cell cycle arrest, a typical feature of geroconversion, a senescent state characterized by loss of cell proliferation. Finally the events culminated in cell cycle inhibition point in case of both doses mirrored by the decrease of cyclin D1, CDK4 and PCNA. In addition, BPAP treatment had a beneficial effect on bodyweight suggesting that the compound at least in part is able to compensate the cancer-related wasting. In view of the low toxicity and confirmed antitumor effect of BPAP against experimental lung adenocarcinoma, this novel compound deserves further attention.
PMID: 30734151 [PubMed - as supplied by publisher]
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Growth inhibition and apoptosis in colorectal cancer cells induced by Vitamin D-Nanoemulsion (NVD): involvement of Wnt/β-catenin and other signal transduction pathways.
| Related Articles |
Growth inhibition and apoptosis in colorectal cancer cells induced by Vitamin D-Nanoemulsion (NVD): involvement of Wnt/β-catenin and other signal transduction pathways.
Cell Biosci. 2019;9:15
Authors: Razak S, Afsar T, Almajwal A, Alam I, Jahan S
Abstract
Background: More than the two decades, the question of whether vitamin D has a role in cancer frequency, development, and death has been premeditated in detail. Colorectal, breast, and prostate cancers have been a scrupulous spot of center, altogether, these three malignancies report for approximately 35% of cancer cases and 20% of cancer demises in the United States, and as such are a chief public health apprehension. The aim was to evaluate antitumor activity of Vitamin D-Nanoemulsion (NVD) in colorectal cancer cell lines and HCT116 xenograft model in a comprehensive approach.
Methods: Two human colorectal cancer cell lines HCT116 and HT29 (gained from College of Pharmacy, King Saud University, KSA were grown. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazoliumbromide protocol were performed to show the impact of NVD and β-catenin inhibitor (FH535) on the viability of HCT116 and HT29 cell lines. Apoptosis/cell cycle assay was performed. Analysis was done with a FACScan (Becton-Dickinson, NJ). About 10,000 cells per sample were harvested and Histograms of DNA were analyzed with ModiFitLT software (verity Software House, ME, USA). Western blotting and RT-PCR were performed for protein and gene expression respectively in in vitro and in vivo.
Results: We found that NVD induced cytotoxicity in colorectal cells in a dose-dependent manner and time dependent approach. Further, our data validated that NVD administration of human colorectal cancer HCT116 and HT29 cells resulted in cell growth arrest, alteration in molecules regulating cell cycle operative in the G2 phase of the cell cycle and apoptosis in a dose dependent approach. Further our results concluded that NVD administration decreases expression of β-catenin gene, AKT gene and Survivin gene and protein expression in in vitro and in vivo.
Conclusion: Our findings suggest that targeting β-catenin gene may encourage the alterations of cell cycle and cell cycle regulators. Wnt/β-catenin signaling pathway possibly takes part in the genesis and progression of colorectal cancer cells through regulating cell cycle and the expression of cell cycle regulators.
PMID: 30733856 [PubMed]
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In vitro cytotoxicity and anticancer effects of citral nanostructured lipid carrier on MDA MBA-231 human breast cancer cells.
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In vitro cytotoxicity and anticancer effects of citral nanostructured lipid carrier on MDA MBA-231 human breast cancer cells.
Sci Rep. 2019 Feb 07;9(1):1614
Authors: Nordin N, Yeap SK, Rahman HS, Zamberi NR, Abu N, Mohamad NE, How CW, Masarudin MJ, Abdullah R, Alitheen NB
Abstract
Very recently, we postulated that the incorporation of citral into nanostructured lipid carrier (NLC-Citral) improves solubility and delivery of the citral without toxic effects in vivo. Thus, the objective of this study is to evaluate anti-cancer effects of NLC-Citral in MDA MB-231 cells in vitro through the Annexin V, cell cycle, JC-1 and fluorometric assays. Additionally, this study is aimed to effects of NLC-Citral in reducing the tumor weight and size in 4T1 induced murine breast cancer model. Results showed that NLC-Citral induced apoptosis and G2/M arrest in MDA MB-231 cells. Furthermore, a prominent anti-metastatic ability of NLC-Citral was demonstrated in vitro using scratch, migration and invasion assays. A significant reduction of migrated and invaded cells was observed in the NLC-Citral treated MDA MB-231 cells. To further evaluate the apoptotic and anti-metastatic mechanism of NLC-Citral at the molecular level, microarray-based gene expression and proteomic profiling were conducted. Based on the result obtained, NLC-Citral was found to regulate several important signaling pathways related to cancer development such as apoptosis, cell cycle, and metastasis signaling pathways. Additionally, gene expression analysis was validated through the targeted RNA sequencing and real-time polymerase chain reaction. In conclusion, the NLC-Citral inhibited the proliferation of breast cancer cells in vitro, majorly through the induction of apoptosis, anti-metastasis, anti-angiogenesis potentials, and reducing the tumor weight and size without altering the therapeutic effects of citral.
PMID: 30733560 [PubMed - in process]
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Evaluation of cationic channel TRPV2 as a novel biomarker and therapeutic target in Leukemia-Implications concerning the resolution of pulmonary inflammation.
| Related Articles |
Evaluation of cationic channel TRPV2 as a novel biomarker and therapeutic target in Leukemia-Implications concerning the resolution of pulmonary inflammation.
Sci Rep. 2019 Feb 07;9(1):1554
Authors: Siveen KS, Prabhu KS, Parray AS, Merhi M, Arredouani A, Chikri M, Uddin S, Dermime S, Mohammad RM, Steinhoff M, Janahi IA, Azizi F
Abstract
Patients treated during leukemia face the risk of complications including pulmonary dysfunction that may result from infiltration of leukemic blast cells (LBCs) into lung parenchyma and interstitium. In LBCs, we demonstrated that transient receptor potential vanilloid type 2 channel (TRPV2), reputed for its role in inflammatory processes, exhibited oncogenic activity associated with alteration of its molecular expression profile. TRPV2 was overexpressed in LBCs compared to normal human peripheral blood mononuclear cells (PBMCs). Additionally, functional full length isoform and nonfunctional short form pore-less variant of TRPV2 protein were up-regulated and down-regulated respectively in LBCs. However, the opposite was found in PBMCs. TRPV2 silencing or pharmacological targeting by Tranilast (TL) or SKF96365 (SKF) triggered caspace-mediated apoptosis and cell cycle arrest. TL and SKF inhibited chemotactic peptide fMLP-induced response linked to TRPV2 Ca2+ activity, and down-regulated expression of surface marker CD38 involved in leukemia and lung airway inflammation. Challenging lung airway epithelial cells (AECs) with LBCs decreased (by more than 50%) transepithelial resistance (TER) denoting barrier function alteration. Importantly, TL prevented such loss in TER. Therefore, TRPV2 merits further exploration as a pharmacodynamic biomarker for leukemia patients (with pulmonary inflammation) who might be suitable for a novel [adjuvant] therapeutic strategy based on TL.
PMID: 30733502 [PubMed - in process]
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Polysaccharides as potential anticancer agents-A review of their progress.
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Polysaccharides as potential anticancer agents-A review of their progress.
Carbohydr Polym. 2019 Apr 15;210:412-428
Authors: Khan T, Date A, Chawda H, Patel K
Abstract
Cancer is one of the most common diseases seen in developed countries, with over 1.6 million new cases estimated in 2017, in the US alone. The current chemotherapeutic drugs available for the therapeutic management of cancer are associated with major adverse effects like alopecia, anemia, immunodeficiency, fatigue, peripheral neuropathy, fertility issues and neurological problems, to name a few of them. Polysaccharides have emerged as potential chemical entities exhibiting good anticancer activity across a variety of cancer cell lines and can be developed as alternatives of existing cancer chemotherapeutic agents, possessing selective activity against tumor cells with minimal toxic side-effects. Polysaccharides isolated from plants, fungi, microorganisms and marine sources have been reported to act on malignant cells, mainly via induction of apoptosis. They act via DNA damage, cell cycle arrest, disruption of mitochondrial membrane and production of nitric oxide, to kill cancer cells and prevent metastasis. This review focuses on the polysaccharides studied in the last five years, their proposed mechanism of action, and their anti-cancer activity in comparison to the drugs used in conventional anticancer chemotherapeutic regimen.
PMID: 30732778 [PubMed - in process]
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The induction of Maspin expression by a glucosamine-derivative has an antiproliferative activity in prostate cancer cell lines.
 | Related Articles |
The induction of Maspin expression by a glucosamine-derivative has an antiproliferative activity in prostate cancer cell lines.
Chem Biol Interact. 2019 Feb 25;300:63-72
Authors: Cocchiola R, Lopreiato M, Guazzo R, de Santi MM, Eufemi M, Scandurra R, Scotto d'Abusco A
Abstract
Mammary serine protease inhibitor or Maspin has been characterized as a class II tumor suppressor gene in several cancer types, among them prostate cancer (CaP). Androgen ablation is an effective therapy for CaP, but with short-term effectiveness, thus new therapeutic strategies are actively sought. The present study is aimed to explore the effects of a glucosamine derivative, 2-(N-Carbobenzyloxy)l-phenylalanylamido-2-deoxy-β-d-glucose (NCPA), on two CaP cell lines, PC3 and LNCaP. In particular we analyzed the impact of NCPA on Maspin production, cell viability and cell cycle progression and apoptosis/necrosis pathway activation in PC3 and LNCaP cell lines. NCPA is able to stimulate Maspin production in PC3 and not in LNCaP cell lines. NCPA blocks the PC3 cell cycle in G1 phase, by inhibiting Cyclin D1 production and induces the apoptosis, therefore interfering with aggressiveness of this androgen-insensitive cell line. Moreover, NCPA is able to induce the expression of Maspin in LNCaP cell line treated with androgen receptor inhibitor, Bicalutamide, and in turn to stimulate the apoptosis of these cells. These findings suggest that NCPA, stimulating the endogenous production of a tumor suppressor protein, could be useful in the design of new therapeutic strategies for treatment of CaP.
PMID: 30641060 [PubMed - indexed for MEDLINE]
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Mitotic progression, arrest, exit or death relies on centromere structural integrity, rather than de novo transcription.
 | Related Articles |
Mitotic progression, arrest, exit or death relies on centromere structural integrity, rather than de novo transcription.
Elife. 2018 08 06;7:
Authors: Novais-Cruz M, Alba Abad M, van IJcken WF, Galjart N, Jeyaprakash AA, Maiato H, Ferrás C
Abstract
Recent studies have challenged the prevailing dogma that transcription is repressed during mitosis. Transcription was also proposed to sustain a robust spindle assembly checkpoint (SAC) response. Here, we used live-cell imaging of human cells, RNA-seq and qPCR to investigate the requirement for de novo transcription during mitosis. Under conditions of persistently unattached kinetochores, transcription inhibition with actinomycin D, or treatment with other DNA-intercalating drugs, delocalized the chromosomal passenger complex (CPC) protein Aurora B from centromeres, compromising SAC signaling and cell fate. However, we were unable to detect significant changes in mitotic transcript levels. Moreover, inhibition of transcription independently of DNA intercalation had no effect on Aurora B centromeric localization, SAC response, mitotic progression, exit or death. Mechanistically, we show that DNA intercalating agents reduce the interaction of the CPC with nucleosomes. Thus, mitotic progression, arrest, exit or death is determined by centromere structural integrity, rather than de novo transcription.
PMID: 30080136 [PubMed - indexed for MEDLINE]
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The design, synthesis and evaluation of selenium-containing 4-anilinoquinazoline hybrids as anticancer agents and a study of their mechanism.
 | Related Articles |
The design, synthesis and evaluation of selenium-containing 4-anilinoquinazoline hybrids as anticancer agents and a study of their mechanism.
Org Biomol Chem. 2018 07 07;16(25):4701-4714
Authors: An B, Zhang S, Hu J, Pan T, Huang L, Tang JC, Li X, Chan ASC
Abstract
Inhibition of tubulin polymerization is one of the significant strategies in the treatment of cancer. Inspired by the excellent antitumor activity of EP128495 and the beneficial biological activities of selenium compounds, a series of new selenium-containing 4-anilinoquinazoline hybrids were synthesized and evaluated as tubulin polymerization inhibitors. An anti-proliferative activity assay showed that most of the compounds inhibited human sensitive cancer cells at low nanomolar concentrations. A mechanism study revealed that the optimal compound 5a disrupted microtubule dynamics, decreased the mitochondrial membrane potential and arrested HeLa cells in the G2/M phase, finally resulting in cellular apoptosis.
PMID: 29900452 [PubMed - indexed for MEDLINE]
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MRI estimates of brown adipose tissue in children – Associations to adiposity, osteocalcin, and thigh muscle volume
Publication date: Available online 8 February 2019
Source: Magnetic Resonance Imaging
Author(s): Jonathan Andersson, Josefine Roswall, Emma Kjellberg, Håkan Ahlström, Jovanna Dahlgren, Joel Kullberg
Abstract
Context
Brown adipose tissue is of metabolic interest. The tissue is however poorly explored in children.
Methods
Sixty-three 7-year old subjects from the Swedish birth-cohort Halland Health and Growth Study were recruited. Care was taken to include both normal weight and overweight children, but the subjects were otherwise healthy. Only children born full term were included.
Water-fat separated whole-body MRI scans, anthropometric measurements, and measurements of fasting glucose and levels of energy homeostasis related hormones, including the insulin-sensitizer osteocalcin, were performed. The fat fraction (FF) and effective transverse relaxation time (T2*) of suspected brown adipose tissue in the cervical-supraclavicular-axillary fat depot (sBAT) and the FFs of abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) were measured. Volumes of sBAT, abdominal VAT and SAT, and thigh muscle volumes were measured.
Results
The FF in the sBAT depot was lower than in VAT and SAT for all children. In linear correlations including sex and age as explanatory variables, sBAT FF correlated positively with all measures of adiposity (p < 0.01), except for VAT FF and weight, positively with sBAT T2* (p = 0.036), and negatively with osteocalcin (p = 0.017). When adding measures of adiposity as explanatory variables, sBAT FF also correlated negatively with thigh muscle volume (p < 0.01).
Conclusions
Whole-body water-fat MRI of children allows for measurements of sBAT. The FF of sBAT was lower than that of VAT and SAT, indicating presence of BAT. Future studies could confirm whether the observed correlations corresponds to a hormonally active BAT.
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Microvascular fluorescence in spinal cord repair.
Microvascular fluorescence in spinal cord repair.
World Neurosurg. 2019 Feb 05;:
Authors: Mayorga-Buiza MJ, Rivero-Garvia M, Márquez-Rivas J
Abstract
The release of the placode and reconstruction of the myelomeningocele preserving the maximum of neural tissue is a challenge for the neurosurgeons. Vascular fluorescence with indocyanine green and / or fluorescein allows to observe the microvascularization of the spinal cord and adequately identify viable tissue.
PMID: 30735880 [PubMed - as supplied by publisher]
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Safety, accuracy, and cost effectiveness of bedside bolt external ventricular drains (EVDs) in comparison to tunnelled EVDs inserted in theatres.
Safety, accuracy, and cost effectiveness of bedside bolt external ventricular drains (EVDs) in comparison to tunnelled EVDs inserted in theatres.
World Neurosurg. 2019 Feb 05;:
Authors: Roach J, Gaastra B, Bulters D, Shtaya A
Abstract
OBJECTIVE: External ventricular drain (EVD) placement is frequently required in neurosurgical patients to divert CSF and monitor intracranial pressure. The usual practise is the tunnelled EVD technique performed in operating theatres. EVD insertion through a bolt in intensive care is also described. We employ both practices in our institute. Herein, we compare the indications, accuracy, safety and costs of the two techniques.
METHODS: Retrospective cohort study of a prospectively maintained EVD data-base of all patients undergoing first frontal EVD placement between Jan 2010-Dec 2015. Those with preceding CSF infection were excluded. We compared bolt EVD with tunnelled EVD techniques in terms of accuracy of EVD tip location by analysing CT scans to grade catheter tip location as optimal (ipsilateral frontal horn) or otherwise suboptimal, and complications that include infection and revision rates.
RESULTS: 579 eligible patients aged 3 months to 84 years were identified. 430 had tunnelled EVDs and 149 bolt EVDs. The most frequent diagnosis was intracranial haemorrhage (73% bolt vs 50.4% tunnelled group (p<0.001)). Other diagnoses included tumour (4.7% bolt vs 19.1% tunnelled (p<0.001)), traumatic brain injury (17.5% bolt vs 17.4% tunnelled). In the bolt EVD group 66.4% of EVD tips were optimal, compared to 61.0% in the tunnelled group (p=0.33). Infection was confirmed in 15 (10.0%) bolt EVDs compared to 61 (14.2%) tunnelled EVDs (p=0.2). Each bolt EVD kit costs £260 while placing a tunnelled one in theatre costs £1316.
CONCLUSIONS: Bedside bolt EVD placement is safe, accurate and cost effective in selective patients with haemorrhage related hydrocephalus.
PMID: 30735879 [PubMed - as supplied by publisher]
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Dynamic fusion process in the anterior cervical discectomy and fusion with self-locking stand-alone cages.
Dynamic fusion process in the anterior cervical discectomy and fusion with self-locking stand-alone cages.
World Neurosurg. 2019 Feb 05;:
Authors: Xiong Y, Xu L, Bi LY, Yang JZ, Wang FX, Qu Y, Zhao ZY, Yang YD, Zhao DY, Li CH, Yu X
Abstract
BACKGROUND: Self-locking stand-alone cages can achieve satisfactory clinical results and fusion rate. However, there have been no reports on the causes and relationship of different fusion state. This study is to classify the different fusion state of the index level and to explore the potential contributing factors and links of them.
METHODS: From Jun.2008 to Oct.2011, 42 patients underwent ACDF with MC+ cages. More than 5 years` follow-up were reviewed. The fusion state, the relevant clinical and radiological records were reviewed retrospectively.
RESULTS: At the last follow-up, the fusion proportion of type I, II, III, IV was 11.7%, 16.9%, 26.9% and 42.9%, respectively. The overall fusion rate was 97.4%. For all the fused types, significant improvement for the VAS, JOA and NDI scores was found at the last follow-up (P < 0.05). However, there were no significant differences between the four types (P > 0.05). For SVA, type IV was significantly larger than that of type I, II and III (P < 0.05). And for ROM, type III was significantly larger than that of type II and IV (P < 0.05).
CONCLUSIONS: For the ACDF with self-locking stand-alone cages, the fusion of the index level seems to be a progressive dynamic process during the mid-term follow-up, which may be influenced by the location of the cage, the SVA of the index level and the global ROM of the cervical spine. Satisfactory clinical results could be achieved by all the fused types.
PMID: 30735878 [PubMed - as supplied by publisher]
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Time dependent bi-directional neuroprotection by Adenosine 2A receptor in Experimental Traumatic Brain Injury.
Time dependent bi-directional neuroprotection by Adenosine 2A receptor in Experimental Traumatic Brain Injury.
World Neurosurg. 2019 Feb 05;:
Authors: Velayutham P, Murthy M, Babu KS
Abstract
BACKGROUND: Traumatic Brain Injury (TBI) results in both focal and diffuse brain pathologies that are exacerbated severely after initial injury. Due to this disease complexity in nature, there is still no effective therapeutic measure aimed directly at these pathological processes. We developed a clinically relevant model of TBI and tested bidirectional neuroprotective role of adenosine 2A receptors (A2AR) at different time window periods.
METHODS: Animals (Wistar Rats) were divided into four treatment groups- Sham, TBI, A2AR agonist (CGS-21680) and A2AR antagonist (SCH-58261) with four post TBI time windows (15mins, 1, 12 and 24hrs). A2AR agonist and antagonist effects were tested with neurological functional score (NFS), levels of cAMP, Interleukin-1β, oxidative stress-antioxidant markers and caspase-3.
RESULTS: A2AR agonist treated group showed significant NFS improvement after 15mins and 1hr post TBI compared to TBI group, but no improvement observed at 12 and 24hrs. Interestingly, A2AR antagonists showed no NFS improvement at 15mins and 1hr while significant improvement observed at 12 and 24hrs. Significant neuroprotective effect with A2AR agonist were observed with cAMP, IL-1β, oxidative stress markers, catalase and caspase-3 levels at 15mins and 1hr post TBI. A2AR antagonist showed no effect at these time intervals but showed protective effect at 12 and 24hrs post TBI.
CONCLUSIONS: A2AR agonist showed beneficial neuroprotective effect at early stages of post TBI periods while A2AR antagonist showed at later stages of post TBI. This suggests that A2AR agonist and antagonist to be used depending on the time window at which TBI has occurred.
PMID: 30735877 [PubMed - as supplied by publisher]
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Retropharyngeal granulation: A delayed complication of anterior cervical discectomy and fusion in C2-3.
Retropharyngeal granulation: A delayed complication of anterior cervical discectomy and fusion in C2-3.
World Neurosurg. 2019 Feb 05;:
Authors: Kim JH, Lee SK, Hong JH, Moon BJ, Lee JK
Abstract
INTRODUCTION: A 26-year-old man presented with acute quadriparesis owing to a traffic accident. A computed tomography scan revealed a hangman fracture and locking of the left facet joint at C2-3. Magnetic resonance imaging showed a high signal change of the spinal cord on T2-weighted image and hemorrhage in the C2-3 level. An emergency closed reduction after anterior cervical discectomy and fusion were performed for spinal stability and decompression of the dural sac. Five months postoperatively, C1-2-3 posterior wiring using an iliac bone graft with Brook's method was performed due to non-union of C2-3. After using the posterior cervical approach, the patient began complaining about the difficulty in swallowing. A 5 × 2 × 1-cm-sized posterior pharyngeal wall mass was detected on an endoscopic examination. Despite conservative management, the retropharyngeal mass progressed and dysphagia worsened, so the retropharyngeal wall granulation mass was resected by a laryngologist. Despite removal of the granulation mass, dysphagia and throat discomfort persisted for about 2 years. The plate and screws were removed considering their possible correlation with the granulation tissue. One month after plate removal, the retropharyngeal granulation tissue resolved almost spontaneously. At the last follow-up, the radiological examination showed well-fused C1-2-3 with good alignment. The patient had no residual neurological deficits or dysphagia.
CONCLUSION: Retropharyngeal granulation can occur as a late complication associated with plate fixation following anterior cervical discectomy and fusion. Recurrent retropharyngeal wall granulation caused by plate irritation might only be resolved after plate and screw removal.
PMID: 30735876 [PubMed - as supplied by publisher]
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Curative embolization of arteriovenous malformations.
Curative embolization of arteriovenous malformations.
World Neurosurg. 2019 Feb 05;:
Authors: Zaki Ghali MG, Kan P, Britz GW
Abstract
Arteriovenous malformations have a significant cumulative risk for hemorrhage. Treatment options include observation, microsurgical resection, stereotactic radiosurgery, embolization, and multimodal treatment. Treatment selection and timing are based upon AVM features including size, location in eloquent versus non-eloquent parenchyma, pattern of venous drainage, surgical access, rupture status, and prior treatments. Spetzler-Martin grading is the most commonly used classification system used to select treatment, with grades I and II lesions amenable to surgical resection alone, grade III lesions typically treated via a multimodal approach entailing pre-operative embolization followed by microsurgical resection, and grades IV and V lesions generally observed unless ruptured. Embolization in the treatment of AVMs is thus most commonly used as a pre-operative or, occasionally, pre-radiosurgical adjunct. The concept of curative AVM embolization is an attractive one which has emerged within the past few decades, with increasing clinical evidence for its safety and efficacy in recent years. Obliteration rates for curative AVM embolization will be improved by innovation in endovascular techniques and technologies.
PMID: 30735875 [PubMed - as supplied by publisher]
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Antiplatelet Medication and Operative Subdural Hematomas: A Retrospective Cohort Study Evaluating Reoperation Rates.
Antiplatelet Medication and Operative Subdural Hematomas: A Retrospective Cohort Study Evaluating Reoperation Rates.
World Neurosurg. 2019 Feb 05;:
Authors: Foreman PM, Mooney J, Ilyas A, Agee B, Vivekanandan S, Fong RP, Okor MO, Riley KO, Griessenauer CJ
Abstract
BACKGROUND: Antiplatelet therapy is common and complicates the operative management of subdural hematomas (SDH). The risk of reoperation inferred by antiplatelet medication and the ability of platelet transfusion to reduce hemorrhagic complications in patients presenting with antiplatelet associated SDHs is poorly defined.
METHODS: We performed a retrospective review of consecutive patients treated with craniotomy or craniectomy for evacuation of an acute or mixed density SDH between 2012-2017 at two academic institutions. Exclusion criteria included: anticoagulant therapy, thrombocytopenia, and/or INR > 1.3. Clinical and radiographic data was collected; primary endpoint was reoperation within 30 days. Logistic regression models were used to identify predictors of reoperation.
RESULTS: A total of 195 patients were included: 86 patients on antiplatelet medication and 109 with no antithrombotic history. Overall, 24 (12.3%) of patients required a reoperation. Reoperation rate in patients on antiplatelet medication was not significantly different than those not on antithrombotics (14.0% vs 11.0%, p = 0.53). Patients taking antiplatelet medication were significantly older, more likely to have medical comorbidities, and more likely to receive preoperative platelet transfusion (36.0% vs 3.7%, p < 0.001). Of patients taking antiplatelet medications, there was no difference in reoperation rate between those patients receiving preoperative platelet transfusion and those not receiving transfusion (16.1% vs 12.7%, p = 0.75).
CONCLUSIONS: Antiplatelet medication was not a significant predictor of reoperation following evacuation of an acute or mixed density SDH. In patients on antiplatelet medication, preoperative platelet transfusion did not reduce reoperation rates.
PMID: 30735874 [PubMed - as supplied by publisher]
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Long term outcome and health related quality of life of elderly patients after meningioma surgery.
Long term outcome and health related quality of life of elderly patients after meningioma surgery.
World Neurosurg. 2019 Feb 05;:
Authors: Timmer M, Seibl-Leven M, Wittenstein K, Grau S, Stavrinou P, Röhn G, Krischek B, Goldbrunner R
Abstract
OBJECTIVE: The incidence of meningiomas is increasing with age. As the median age for the diagnosis is 65 years, general health condition, co-morbidity and procedural risks are influencing the postoperative functional outcome. Aim of our study was to assess the long term impairments of health related quality of life (HRQOL) after meningioma resection in different age groups of elderly patients.
METHODS: We therefore analyzed the HRQOL of 133 patients older than 54 years by time of surgery who underwent surgical meningioma resection between 2004 and 2010. The median age was 67.3 ± 7.4 years. The average time interval between surgery and interview was 3.8 ±2.5 years. Six different age groups, each compromising 5 years of age, were established. Patients were interviewed with the SF36 questionnaire and compared to general population values. For statistical analysis Kruskal-Wallis with subsequent Mann-Whitney U test were used.
RESULTS: We found significant lower levels of physical function, vitality, social role function, mental health, general health perception and significant higher levels of pain when comparing the older groups (especially from 75-79 years) with younger patients from 55-59 years of age. The physical component summary showed a steadily and stepwise decline from younger patients to older ones. However, most significant differences in HRQOL were age unrelated but correlated with co-morbidity.
CONCLUSION: Our findings suggest that both, the KPS- and ASA-scores have a strong impact on long term QoL especially in higher ages after meningioma resection. These data should be a substantial part of the presurgical decision making process.
PMID: 30735873 [PubMed - as supplied by publisher]
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Intracranial inflammatory myofibroblastic tumor with negative expression of anaplastic lymphoma kinase: a case report and review of the literature.
Intracranial inflammatory myofibroblastic tumor with negative expression of anaplastic lymphoma kinase: a case report and review of the literature.
World Neurosurg. 2019 Feb 05;:
Authors: Wang X, Chen Y, Wu X, Zhang H
Abstract
Inflammatory myofibroblastic tumor (IMT) is an indolent tumor mainly affecting children and young adults. As a rare mesenchymal tumor with unknown etiology and pathogenesis, IMT has a predilection for lung and abdominopelvic region. Previous literature featuring on IMT in the central nervous system (IMT-CNS) was rare. The clinical symptoms and radiological features of IMT-CNS are not specific, and therefore the diagnosis is predominately based on the histopathological and immunohistochemical analysis of the specimen. We herein present a case of a 21-year-old woman who complained of bilateral blurred vision for 15 days. The head magnetic resonance imaging (MRI) demonstrated a round-shaped and irregular lesion located in the right frontal lobe. The boundary of the lesion was clear and lesion was homogeneously enhanced. Peripheral edema of the lesion was observed and the mass effect was obvious. Supratentorial craniotomy tumor resection was performed. Histopathological and immunohistochemical analysis revealed IMT which had negative expression of anaplastic lymphoma kinase (ALK). Remission of her symptoms was observed and no recurrence was recorded during a 6-month follow-up.
PMID: 30735872 [PubMed - as supplied by publisher]
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Future Oncology; +24 new citations
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Merkel Cell Polyoma Viral Load and Intratumoral CD8+ Lymphocyte Infiltration Predict Overall Survival in Patients With Merkel Cell Carcinoma.
| Related Articles |
Merkel Cell Polyoma Viral Load and Intratumoral CD8+ Lymphocyte Infiltration Predict Overall Survival in Patients With Merkel Cell Carcinoma.
Front Oncol. 2019;9:20
Authors: von der Grün J, Winkelmann R, Meissner M, Wieland U, Silling S, Martin D, Fokas E, Rödel C, Rödel F, Balermpas P
Abstract
Introduction: Merkel cell carcinoma (MCC) is linked to the presence of clonally integrated Merkel cell polyomavirus (MCPyV) in up to 80% of the cases. The aim of the study was to determine the prognostic value of baseline MCPyV viral load and lymphocytic infiltration. Methods: MCPyV DNA prevalence, integration status and viral load were determined by specific quantitative real-time PCR in surgical specimens obtained from 49 patients with MCC treated with (n = 22, 45%) or without postoperative radiotherapy (RT). CD8+ tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) status were assessed using immunohistochemistry. MCPyV characteristics and immune marker expression were correlated with clinicopathological factors and overall survival (OS). Results: Median age at diagnosis was 74 (range, 42-100); 51% of the patients were female. One-, three, and five-year OS rates were 83.8, 58.6, and 47.1%, respectively. A positive MCPyV status was associated with female gender (p = 0.042). Tumor localization (head/arms vs. trunk) positively correlated with PD-L1 status (p = 0.011) and combined CD8/PD-L1 expression (p = 0.038). Overall CD8+ infiltration was inversely associated with N-stage (p = 0.048). Stromal TILs correlated significantly with both PD-L1 expression (p = 0.010) and N-stage (p = 0.037). A high viral load (>median) was significantly associated with worse OS (p = 0.029) and high intratumoral CD8+ infiltration with improved OS for the entire cohort (p = 0.045). Conclusion: These data provide important insight on the role of MCPy DNA viral load and TILs in the context of PD-L1 in patients with Merkel cell carcinoma. Future clinical studies should aim to explore the effect of PD-1/PD-L1 immune-checkpoint inhibitors in combination with existing radiotherapy approaches.
PMID: 30733932 [PubMed]
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Successful preoperative diagnosis of heterotopic pancreas in the duodenum.
Successful preoperative diagnosis of heterotopic pancreas in the duodenum.
Int J Surg Case Rep. 2019 Jan 30;55:125-128
Authors: Chin KM, Tan DMY, Chan NHL, Goh BKP
Abstract
INTRODUCTION: Heterotopic pancreas (HP) is a relatively rare entity occurring in approximately 5% of the general population. It most commonly presents as an asymptomatic mass incidentally picked up on unrelated scans. HP most commonly occurs intra-abdominally, but has been known to occur in extra-abdominal sites such as the lung and brain. It is widely considered to bear little to no malignant potential. Difficulty and ambiguity in the diagnosis of HP commonly results in interventional dilemma and delay.
PRESENTATION OF CASE: We present a case of uncomplicated HP that was ultimately treated conservatively.
DISCUSSION: A literature review is made of the typical workup in a patient with suspected HP, and the characteristic radiological and endoscopic findings commonly used for diagnosis of this rare condition. A succinct summary of management guidelines for HP is reviewed.
CONCLUSION: HP is most commonly an incidental finding. Ambiguity surrounding its diagnosis commonly gives rise to interventional dilemma and delay. The gold standard for diagnosis remains that of EUS and FNA with histological confirmation. This report has been written in concordance with the SCARE criteria Agha et al. [1].
PMID: 30735965 [PubMed - as supplied by publisher]
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Renal protection in sepsis: Is hypertonic sodium (lactate) the solution?
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Exosomes Derived From Bone Mesenchymal Stem Cells Ameliorate Early Inflammatory Responses Following Traumatic Brain Injury.
| Related Articles |
Exosomes Derived From Bone Mesenchymal Stem Cells Ameliorate Early Inflammatory Responses Following Traumatic Brain Injury.
Front Neurosci. 2019;13:14
Authors: Ni H, Yang S, Siaw-Debrah F, Hu J, Wu K, He Z, Yang J, Pan S, Lin X, Ye H, Xu Z, Wang F, Jin K, Zhuge Q, Huang L
Abstract
Traumatic brain injury (TBI) is a leading cause of mortality and disability worldwide. Although treatment guidelines have been developed, no best treatment option or medicine for this condition exists. Recently, mesenchymal stem cells (MSCs)-derived exosomes have shown lots of promise for the treatment of brain disorders, with some results highlighting the neuroprotective effects through neurogenesis and angiogenesis after TBI. However, studies focusing on the role of exosomes in the early stages of neuroinflammation post-TBI are not sufficient. In this study, we investigated the role of bone mesenchymal stem cells (BMSCs)-exosomes in attenuating neuroinflammation at an early stage post-TBI and explored the potential regulatory neuroprotective mechanism. We administered 30 μg protein of BMSCs-exosomes or an equal volume of phosphate-buffered saline (PBS) via the retro-orbital route into C57BL/6 male mice 15 min after controlled cortical impact (CCI)-induced TBI. The results showed that the administration of BMSCs-exosomes reduced the lesion size and improved the neurobehavioral performance assessed by modified Neurological Severity Score (mNSS) and rotarod test. In addition, BMSCs-exosomes inhibited the expression of proapoptosis protein Bcl-2-associated X protein (BAX) and proinflammation cytokines, tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β, while enhancing the expression of the anti-apoptosis protein B-cell lymphoma 2 (BCL-2). Furthermore, BMSCs-exosomes modulated microglia/macrophage polarization by downregulating the expression of inducible nitric oxide synthase (INOS) and upregulating the expression of clusters of differentiation 206 (CD206) and arginase-1 (Arg1). In summary, our result shows that BMSCs-exosomes serve a neuroprotective function by inhibiting early neuroinflammation in TBI mice through modulating the polarization of microglia/macrophages. Further research into this may serve as a potential therapeutic strategy for the future treatment of TBI.
PMID: 30733666 [PubMed]
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