Oncogenic mutations in the monomeric Casitas B-lineage lymphoma (Cbl) gene have been found in many tumors, but their significance remains largely unknown. Several human c-Cbl (CBL) structures have recently been solved, depicting the protein at different stages of its activation cycle and thus providing mechanistic insight underlying how stability—activity tradeoffs in cancer-related proteins—may influence disease onset and progression. In this study, we computationally modeled the effects of missense cancer mutations on structures representing four stages of the CBL activation cycle to identify driver mutations that affect CBL stability, binding, and activity. We found that recurrent, homozygous, and leukemia-specific mutations had greater destabilizing effects on CBL states than random noncancer mutations. We further tested the ability of these computational models, assessing the changes in CBL stability and its binding to ubiquitin-conjugating enzyme E2, by performing blind CBL-mediated EGFR ubiquitination assays in cells. Experimental CBL ubiquitin ligase activity was in agreement with the predicted changes in CBL stability and, to a lesser extent, with CBL-E2 binding affinity. Two thirds of all experimentally tested mutations affected the ubiquitin ligase activity by either destabilizing CBL or disrupting CBL-E2 binding, whereas about one-third of tested mutations were found to be neutral. Collectively, our findings demonstrate that computational methods incorporating multiple protein conformations and stability and binding affinity evaluations can successfully predict the functional consequences of cancer mutations on protein activity, and provide a proof of concept for mutations in CBL. Cancer Res; 76(3); 561–71. ©2015 AACR.
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Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Κυριακή 31 Ιανουαρίου 2016
Mutations Affect Multiple Stages of CBL Activation Cycle
Master Regulators of Follicular Lymphoma Transformation
Follicular lymphoma, the most common indolent subtype of non-Hodgkin lymphoma, is associated with a relatively long overall survival rate ranging from 6 to 10 years from the time of diagnosis. However, in 20% to 60% of follicular lymphoma patients, transformation to aggressive diffuse large B-cell lymphoma (DLBCL) reduces median survival to only 1.2 years. The specific functional and genetic determinants of follicular lymphoma transformation remain elusive, and genomic alterations underlying disease advancement have only been identified for a subset of cases. Therefore, to identify candidate drivers of follicular lymphoma transformation, we performed systematic analysis of a B-cell–specific regulatory model exhibiting follicular lymphoma transformation signatures using the Master Regulator Inference algorithm (MARINa). This analysis revealed FOXM1, TFDP1, ATF5, HMGA1, and NFYB to be candidate master regulators (MR) contributing to disease progression. Accordingly, validation was achieved through synthetic lethality assays in which RNAi-mediated silencing of MRs individually or in combination reduced the viability of (14;18)-positive DLBCL (t-DLBCL) cells. Furthermore, specific combinations of small-molecule compounds targeting synergistic MR pairs induced loss of viability in t-DLBCL cells. Collectively, our findings indicate that MR analysis is a valuable method for identifying bona fide contributors to follicular lymphoma transformation and may therefore guide the selection of compounds to be used in combinatorial treatment strategies. Cancer Res; 76(3); 664–74. ©2015 AACR.
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Bridging the divide: a model-data approach to Polar & Alpine Microbiology
Advances in microbial ecology in the cryosphere continue to be driven by empirical approaches including field sampling and laboratory-based analyses. Although mathematical models are commonly used to investigate the physical dynamics of Polar and Alpine regions, they are rarely applied in microbial studies. Yet, integrating modelling approaches with ongoing observational and laboratory-based work is ideally suited to Polar and Alpine microbial ecosystems given their harsh environmental and biogeochemical characteristics, simple trophic structures, distinct seasonality, often difficult accessibility, geographical expansiveness, and susceptibility to accelerated climate changes. In this opinion paper, we explain how mathematical modelling ideally complements field and laboratory-based analysis. We thus argue that mathematical modelling is a powerful tool for the investigation of these extreme environments and that fully integrated, interdisciplinary model-data approaches could help the Polar and Alpine microbiology community address some of the great research challenges of the 21st century (e.g. assessing global significance, response to climate change). However, a better integration of field and laboratory work with model design and calibration/validation, as well as a stronger focus on quantitative information is required to advance models that can be used to make predictions and upscale processes and fluxes beyond what can be captured by observations alone.
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Microscale distribution of virioplankton and heterotrophic bacteria in the Bohai Sea
In light of limited research in the relationship between the microscale distribution and dynamic changes of microplankton in the shallow Bohai Sea, here, we used flow cytometry to analyze samples collected from the Bohai Sea channel in winter and summer. Results showed that both the average of viral abundance (VA) and bacterial abundance (BA) were lower in winter (3.61 x 107 cells/mL and 1.84 x 106 cells/mL, respectively) than in summer (7.47 x 107 cells/mL and 5.05 x 106 cells/mL, respectively). At all 16 stations, VA was one order of magnitude greater than BA, with a positive relationship between each other. In the horizontal distribution, variations in VA and BA followed a similar trend, and both were obviously higher near-shore than offshore. In the vertical distribution, variations in both VA and BA did not show a clear relationship with water depth. VA and BA in summer were 2.1 and 2.7 times those in winter, respectively. Spearman correlation analysis showed that both VA and BA were correlated with the concentration of PO4-P in winter (positive) and NO3-N in summer (negative). Additionally, BA showed a negative correlation with salinity. It is clear that the microscale distribution of these two microbes in the Bohai Sea is related to seasonal variation and nutrient availability.
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High-throughput quantification of antibiotic resistance genes from an urban wastewater treatment plant
Antibiotic resistance among bacteria is a growing problem worldwide and wastewater treatment plants have been considered as one of the major contributors to the dissemination of antibiotic resistance to the environment. There is lack of comprehensive quantitative molecular data on extensive number of ARGs in different seasons with sampling strategy that would cover both incoming and outgoing water together with the excess sludge that is removed from the process. In order to fill that gap we present a highly parallel quantitative analysis of antibiotic resistance genes and horizontal gene transfer potential over four seasons at an urban wastewater treatment plant using a high-throughput qPCR array. All analyzed transposases and 2/3 of primer sets targeting ARGs were detected in the wastewater. The relative abundance of most of the genes was highest in influent and lower in effluent water and sludge. The resistance profiles of the samples cluster by sample location with a shift from raw influent through the final effluents and dried sludge to the sediments. Wastewater discharge enriched only few genes, namely Tn25 type transposase gene and clinical class 1 integrons, in the sediment near the discharge pipe, but those enriched genes may indicate potential for horizontal gene transfer.
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Microbial diversity in European alpine permafrost and active layers
Permafrost represents a largely understudied genetic resource. Thawing of permafrost with global warming will not only promote microbial carbon turnover with direct feedback on greenhouse gases, but also unlock an unknown microbial diversity. Pioneering metagenomic efforts have shed light on the permafrost microbiome in polar regions, but temperate mountain permafrost is largely understudied. We applied a unique experimental design coupled to high-throughput sequencing of ribosomal markers to characterize the microbiota at the long-term alpine permafrost study site Muot-da-Barba-Peider in eastern Switzerland with an approximate radiocarbon age of 12,000 years. Compared to the active layers, the permafrost community was more diverse and enriched with members of the superphylum Patescibacteria (OD1, TM7, GN02, OP11). These understudied phyla with no cultured representatives proposedly feature small streamlined genomes with reduced metabolic capabilities, adaptations to anaerobic fermentative metabolisms, and potential ectosymbiotic lifestyles. The permafrost microbiota was also enriched with yeasts and lichenized fungi known to harbour various structural and functional adaptation mechanisms to survive under extreme sub-zero conditions. These data yield an unprecedented view on microbial life in temperate mountain permafrost, which is increasingly important for understanding the biological dynamics of permafrost in order to anticipate potential ecological trajectories in a warming world.
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Establishing a cellular FRET-based fluorescence plate reader assay to monitor proNGF-induced cross-linking of sortilin and the neurotrophin receptor p75(NTR).
| Related Articles |
Establishing a cellular FRET-based fluorescence plate reader assay to monitor proNGF-induced cross-linking of sortilin and the neurotrophin receptor p75(NTR).
Int J Biochem Mol Biol. 2015;6(2):17-25
Authors: Skeldal S, Kjaergaard MM, Alwasel S, Nyengaard JR
Abstract
Whereas the proform of the nerve growth factor (proNGF) is crucial for eliminating superfluous cells during neuronal development it also promotes apoptosis following brain trauma and neuronal injury. The apoptotic signal is elicited upon formation of a trimeric receptor complex also containing the vps10p domain receptor sortilin and the neurotrophin receptor p75(NTR). However, proNGF-induced receptor complex formation has been difficult to directly assess other than by western blotting. We here describe a fluorescence resonance energy transfer (FRET) based fluorescence plate reader assay to monitor the interaction between fluorescently tagged sortilin and p75(NTR) in live cells. The method is based on a standard fluorescent plate reader found in many biochemical laboratories and the results are evaluated using a microscopy-based quantified sensitized acceptor emission FRET approach making use of a pair of FRET standard constructs. As a result, the effect of proNGF on the interaction between sortilin and p75(NTR) can be evaluated in live cells allowing for screening and selection of therapeutic compounds interfering with proNGF-induced cell death.
PMID: 26823987 [PubMed]
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Body Image attitudes of Premenopausal and Perimenopausal women in Nigeria: association with Physical Activity Level
2016-01-31T19-14-04Z
Source: Journal of Behavioral Health
Omoyemi Olubunmi Ogwumike, Ade Fatai Adeniyi, Priscilla Utibe Ukpe.
Background: Body image is a multidimensional construct which comprises of perceptual -body size estimation and appearance as well as attitudinal- relating to feelings and attitudes towards ones own body. For menopausal women, weight gain is a common occurrence and these body composition changes may influence how a woman feels about the way her body looks. Concerns about body image in menopausal women may sometimes lead to dissatisfaction with their bodies. Additionally, the great pressure for a perfect body may influence either positively or negatively womens involvement in physical activity. Objectives: This study assessed body image attitude of a sample of premenopausal and perimenopausal women in Nigeria and their physical activity level. Methods: The multidimensional Body-Self Relations Questionnaire-Appearance Scale (MBSRQ-AS) was used to evaluate appearance satisfaction, body image attitudes and satisfaction while the International Physical Activity Questionnaire was used to evaluate PA level. Data were summarized using descriptive statistics, and analyzed using Chi-square while significance level was set at 0.05. Results: Participants were 392 women aged 42.5±6.0 years and all reported positive body image attitude. Premenopausal women reported higher scores in most domains of the MBSRQ-AS while perimenopausal women reported higher scores on the Overweight Preoccupation and Self-Classified Weight. Majority reported moderate to high PA level. Significant associations were observed between PA level and scores on appearance evaluation (p=0.02) and overweight preoccupation (p=0.01) for premenopausal women while perimenopausal women reported significant association between PA level and scores for appearance orientation (p=0.00), overweight preoccupation (p=0.00) and self-classified weight (p=0.01). Conclusions: Body image attitude appeared to have had a positive impact on PA level. It may be imperative for women in the menopausal transition to maintain a physically active lifestyle to enhance a positive body image.
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Does Retirement Promote Healthy Behaviors in Young Elderly Korean People?
2016-01-31T19-14-04Z
Source: Journal of Behavioral Health
Jinhee Kim, Seung-Eun Cha, Ichiro Kawachi, Sunmin Lee.
Research Highlights The study sought to examine the association between retirement and health behaviors in South Korea Study adopted stress theory framework to assess the relationship between retirement and health behavior of Korean young elderly, specifically. Gender differences were noted in the relationship between retirement and health behaviors. Retired men were less likely to engage in heavy smoking or drinking than employed men Retired men and women were more likely to engage in physical activity than employed individuals Retired women were more likely to be overweight than employed women
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Comment on the report of Juneja A. et al.
2016-01-31T19-14-04Z
Source: Journal of Behavioral Health
Elif Yalcin, Suna Kose.
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Alcaligenes faecalis line inoculation with swarming
A line inoculation was done with Alcaligenes faecalis and incubated for 48 hrs at 37 degree's C. Swarming/spreading could be seen form the inoculation line. Note: Small contaminate also seen on the plate.
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Pseudomonas aeruginosa with pigment
A line inoculation was done with Pseudomonas aeruginosa. After 48 hrs incubation at 37 degrees C incubation the blue/green diffusible pigment pyocanin could be seen around the organism. There was also the characteristic grape smell.
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More Fungus
After several weeks of heavy rains several different mushroom species were seen in the leaf litter and shade of a cedar tree in Santa Cruz, CA. The fungus was yellow/orange, undulating appearance, with what looked like rough bumps on the outer edges with the inside being smooth.
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Monthly News Roundup - January 2016
Merck's Once-Daily Zepatier for Hepatitis C Wins Approval Hepatitis C virus (HCV) affects over 3 millions Americans, and may lead to liver impairment, cirrhosis or even liver failure. In January, the U.S. Food and Drug Administration (FDA)...
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First Titan SPORT demo
Source: Titan Medical, MDTMag
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Efficacious Discriminant Analysis (Classifier) Measures for End Users
Many problem domains utilize discriminant analysis, for example, classification, prediction, and diagnoses, by applying artificial intelligence and machine learning. However, the results are rarely perfect and errors can cause significant losses. Hence, end users are best served when they have performance information relevant to their need. Starting with the most basic questions, this study considers eight summary statistics often seen in the literature and evaluates their end user efficacy. Results lead to proposed criteria necessary for end user efficacious summary statistics. Testing the same eight summary statistics shows that none satisfy all of the criteria. Hence, two criteria-compliant summary statistics are introduced. To show how end users can benefit, measure utility is demonstrated on two problems. A key finding of this study is that researchers can make their test outcomes more relevant to end users with minor changes in their analyses and presentation.
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Firefighter battling PTSD: 'I didn't want to shut my eyes'
Scott Geiselhart is now traveling to fire departments across Minnesota speaking about suicide prevention and awareness education.
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Firefighter battling PTSD: 'I didn't want to shut my eyes'
Scott Geiselhart is now traveling to fire departments across Minnesota speaking about suicide prevention and awareness education.
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Multi-target Chromogenic Whole-mount In Situ Hybridization for Comparing Gene Expression Domains in Drosophila Embryos
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Isolation of CD 90+ Fibroblast/Myofibroblasts from Human Frozen Gastrointestinal Specimens
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Firefighter battling PTSD: 'I didn't want to shut my eyes'
Scott Geiselhart is now traveling to fire departments across Minnesota speaking about suicide prevention and awareness education.
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Firefighter battling PTSD: 'I didn't want to shut my eyes'
Scott Geiselhart is now traveling to fire departments across Minnesota speaking about suicide prevention and awareness education.
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TWiV 374: Discordance in B
Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove,
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Zika virus
The rapid spread of Zika virus through the Americas, together with the association of infection with microcephaly and Guillain-Barré syndrome, have propelled this previously ignored virus into the limelight. What is this virus and where did it come from?
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Repeated Electroacupuncture Persistently Elevates Adenosine and Ameliorates Collagen-Induced Arthritis in Rats
The aim of this paper was to investigate the effect of repeated electroacupuncture (EA) over 21 days on the adenosine concentration in peripheral blood of rats with collagen-induced arthritis (CIA). Wistar rats were divided into three groups of 6 animals each: sham-control, CIA-control, and CIA-EA. We determined the adenosine concentration in peripheral blood and assessed pathological changes of ankle joints. Quantitative reverse-transcription-polymerase chain reaction was used to determine mRNA levels of ecto-5′-nucleotidase (CD73), adenosine deaminase (ADA), and tumor necrosis factor-alpha (TNF-α). Immunohistochemical staining was used to detect expression of ADA and CD73 in synovial tissue. Repeated EA treatment on CIA resulted in the persistence of high concentrations of adenosine in peripheral blood, significantly reduced pathological scores, TNF-α mRNA concentrations, and synovial hyperplasia. Importantly, EA treatment led to a significant increase in CD73 mRNA levels in peripheral blood but was associated with a decrease of CD73 immunostaining in synovial tissue. In addition, EA treatment resulted in a significant decrease of both ADA mRNA levels in peripheral blood and ADA immunostaining in synovial tissue. Thus, repeated EA treatment exerts an anti-inflammatory and immunoregulatory effect on CIA by increasing the concentration of adenosine. The mechanism of EA action may involve the modulation of CD73 and ADA expression levels.
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Advanced Glycation End Products Induce Obesity and Hepatosteatosis in CD-1 Wild-Type Mice
AGEs are a heterogeneous group of molecules formed from the nonenzymatic reaction of reducing sugars with free amino groups of proteins, lipids, and/or nucleic acids. AGEs have been shown to play a role in various conditions including cardiovascular disease and diabetes. In this study, we hypothesized that AGEs play a role in the "multiple hit hypothesis" of nonalcoholic fatty liver disease (NAFLD) and contribute to the pathogenesis of hepatosteatosis. We measured the effects of various mouse chows containing high or low AGE in the presence of high or low fat content on mouse weight and epididymal fat pads. We also measured the effects of these chows on the inflammatory response by measuring cytokine levels and myeloperoxidase activity levels on liver supernatants. We observed significant differences in weight gain and epididymal fat pad weights in the high AGE-high fat (HAGE-HF) versus the other groups. Leptin, TNF-α, IL-6, and myeloperoxidase (MPO) levels were significantly higher in the HAGE-HF group. We conclude that a diet containing high AGEs in the presence of high fat induces weight gain and hepatosteatosis in CD-1 mice. This may represent a model to study the role of AGEs in the pathogenesis of hepatosteatosis and steatohepatitis.
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Methanolic Extract of Ceplukan Leaf (Physalis minima L.) Attenuates Ventricular Fibrosis through Inhibition of TNF-α in Ovariectomized Rats
The increase of heart failure prevalence on menopausal women was correlated with the decrease of estrogen level. The aim of this study is to investigate the effects of ceplukan leaf (Physalis minima L.), which contains phytoestrogen physalin and withanolides, on ventricular TNF-α level and fibrosis in ovariectomized rats. Wistar rats were divided into six groups (control (—); OVX 5: 5-week ovariectomy (OVX); OVX 9: 9-week ovariectomy; treatments I, II, and III: 9-weeks OVX + 4-week ceplukan leaf's methanolic extract doses 500, 1500, and 2500 mg/kgBW, resp.). TNF-α levels were measured with ELISA. Fibrosis was counted as blue colored tissues percentage using Masson's Trichrome staining. This study showed that prolonged hypoestrogen increases ventricular fibrosis (). Ceplukan leaf treatment also resulted in a decrease of ventricular fibrosis and TNF-α level in dose dependent manner compared to without treatment group (). Furthermore, the TNF-α level was normalized in 2500 mg/kgBW Physalis minima L. () treatment. The reduction of fibrosis positively correlated with TNF-α level (, ). Methanolic extract of ceplukan leaf decreases ventricular fibrosis through the inhibition of ventricular TNF-α level in ovariectomized rats.
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Behavioral Periodicity Detection from 24 h Wrist Accelerometry and Associations with Cardiometabolic Risk and Health-Related Quality of Life
Periodicities (repeating patterns) are observed in many human behaviors. Their strength may capture untapped patterns that incorporate sleep, sedentary, and active behaviors into a single metric indicative of better health. We present a framework to detect periodicities from longitudinal wrist-worn accelerometry data. GENEActiv accelerometer data were collected from 20 participants (17 men, 3 women, aged 35–65) continuously for (range: 13.9 to 102.0) consecutive days. Cardiometabolic risk biomarkers and health-related quality of life metrics were assessed at baseline. Periodograms were constructed to determine patterns emergent from the accelerometer data. Periodicity strength was calculated using circular autocorrelations for time-lagged windows. The most notable periodicity was at 24 h, indicating a circadian rest-activity cycle; however, its strength varied significantly across participants. Periodicity strength was most consistently associated with LDL-cholesterol ('s = 0.40–0.79, 's
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Infective Exacerbation of Pasteurella multocida
An 89-year-old lady presented with a one-day history of shortness of breath as well as a cough productive of brown sputum. Her medical history was significant for chronic obstructive pulmonary disease (COPD). She was in severe type one respiratory failure and blood tests revealed markedly raised inflammatory markers; however her chest X-ray was clear. On examination there was bronchial breathing with widespread crepitations and wheeze. She was treated as per an infective exacerbation of COPD. Subsequent blood cultures grew Pasteurella multocida, a common commensal in the oropharynx of domesticated animals. The patient was then asked about any contact with animals, after which she revealed she had a dog and was bitten on her left hand the day before admission. We should not forget to enquire about recent history of injuries or animal bites when patients present acutely unwell. She made a complete recovery after treatment with penicillin.
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Protective Effects of L-Malate against Myocardial Ischemia/Reperfusion Injury in Rats
Objective. To investigate the protective effects of L-malate against myocardial ischemia/reperfusion (I/R) injury in rats. Methods. Male Sprague-Dawley rats were randomly assigned to the following groups: sham (sham), an ischemia/reperfusion (I/R) model group (model), an DMF pretreated group (DMF), and 5 L-malate pretreated groups (15, 60, 120, 240, or 480 mg/kg, gavage) before inducing myocardial ischemia. Plasma LDH, cTn-I, TNF-, hs-CRP, SOD, and GSH-PX were measured 3 h later I/R. Areas of myocardial infarction were measured; hemodynamic parameters during I/R were recorded. Hearts were harvested and Western blot was used to quantify Nrf2, Keap1, HO-1, and NQO-1 expression in the myocardium. Results. L-malate significantly reduced LDH and cTn-I release, reduced myocardial infarct size, inhibited expression of inflammatory cytokines, and partially preserved heart function, as well as increasing antioxidant activity after myocardial I/R injury. Western blot confirmed that L-malate reduced Kelch-like ECH-associated protein 1 in ischemic myocardial tissue, upregulated expression of Nrf2 and Nrf2 nuclear translocation, and increased expression of heme oxygenase-1 and NAD(P)H:quinone oxidoreductase 1, which are major targets of Nrf2. Conclusions. L-malate may protect against myocardial I/R injury in rats and this may be associated with activation of the Nrf2/Keap1 antioxidant pathway.
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Downregulation of Mitofusin 2 in Placenta Is Related to Preeclampsia
Background. Mitofusin 2 (Mfn2) is a novel mitochondrial protein that is implicated in cellular proliferation and metabolism; however, the role of Mfn2 in preeclampsia (PE) remains unknown. This study aimed to explore the relationship between Mfn2 and PE. Method. Preeclamptic and normal pregnancies were enrolled in a comparative study. The expression of Mfn2 in placenta was detected by qRT-PCR. And the mitochondrial function was detected by ATP assay. Then TEV-1 cells were cultured in hypoxic conditions. mRNA and protein expressions of Mfn2 were detected by qRT-PCR and western blot separately. Cells' viability was detected by MTT. And the mitochondrial function was detected by ATP and mitochondrial membrane potential (MMP) assay. We further knocked down the Mfn2 gene in TEV-1 cells and evaluated the cells' viability. Results. Mfn2 and ATP expressions were significantly decreased in preeclamptic placentae compared to normal placentae. Mfn2 expression level and the viability of TEV-1 cells were reduced during hypoxic conditions. TEV-1 cells' viability, ATP, and MMP levels were also significantly decreased after knockdown of the Mfn2 gene. Conclusions. These results suggest that defects in Mfn2 could cause mitochondrial dysfunction and decrease trophoblastic cells' viability. Therefore, Mfn2 may be functionally involved in the pathogenesis of PE.
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Compressed Sensing/Sparse-Recovery Approach for Improved Range Resolution in Narrow-Band Radar
A compressed sensing/sparse-recovery procedure is adopted to obtain enhanced range resolution capability from the processing of data acquired with narrow-band SFCW radars. A mathematical formulation for the proposed approach is reported and validity limitations are fully discussed, by demonstrating the ability to identify a great number of targets, up to 20, in the range direction. Both numerical and experimental validations are presented, by assuming also noise conditions. The proposed method can be usefully applied for the accurate detection of parameters with very small variations, such as those involved in the monitoring of soil deformations or biological objects.
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Sensitivities of Two Zebrafish TRPA1 Paralogs to Chemical and Thermal Stimuli Analyzed in Heterologous Expression Systems.
Sensitivities of Two Zebrafish TRPA1 Paralogs to Chemical and Thermal Stimuli Analyzed in Heterologous Expression Systems.
Chem Senses. 2016 Jan 30;
Authors: Oda M, Kurogi M, Kubo Y, Saitoh O
Abstract
Transient receptor potential A1 (TRPA1) is the only member of the mouse, chick, and frog TRPA family, whereas 2 paralogs (zTRPA1a and zTRPA1b) are present in zebrafish. We herein investigated functional differences in the 2 zebrafish TRPA1s. HEK293T cells were used as heterologous expression systems, and the sensitivities of these cells to 4 chemical irritants (allyl isothiocyanate [AITC], caffeine, auto-oxidized epigallocatechin gallate [EGCG], and hydrogen peroxide [H2O2]) were compared with Ca(2+) imaging techniques. Sensitivities to the activators for AITC, oxidized EGCG, and H2O2 were higher in cells expressing zTRPA1a than in those expressing zTRPA1b, whereas caffeine appeared to activate both cells equally. We also characterized the thermal sensitivity of Xenopus oocytes expressing each TRPA1 electrophysiologically using a 2-electrode voltage clamp. Although endogenous currents induced by a cold stimulation were observed in control oocytes in some batches, oocytes expressing zTRPA1b showed significantly stronger cold- and heat-induced responses. However, significant thermal activation was not observed in oocytes expressing zTRPA1a. The results obtained using in vitro expression systems suggest that zTRPA1a is specialized for chemical sensing, whereas zTRPA1b responds to thermal stimuli. Furthermore, characterization of the chimeric molecule of TRPA1a and 1b revealed the importance of the N-terminal region in chemical and thermal sensing by zTRPA1s.
PMID: 26826723 [PubMed - as supplied by publisher]
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Perceptual and Brain Response to Odors Is Associated with Body Mass Index and Postprandial Total Ghrelin Reactivity to a Meal.
Perceptual and Brain Response to Odors Is Associated with Body Mass Index and Postprandial Total Ghrelin Reactivity to a Meal.
Chem Senses. 2016 Jan 28;
Authors: Sun X, Veldhuizen MG, Babbs AE, Sinha R, Small DM
Abstract
Animal studies have shown that olfactory sensitivity is greater when fasted than when fed. However, human research has generated inconsistent results. One possible explanation for these conflicting findings is metabolic health. Many metabolic peptides, including ghrelin, are moderated by adiposity and influence olfaction and olfactory-guided behaviors. We tested whether the effect of a meal on the perceived intensity of suprathreshold chemosensory stimuli is influenced by body mass index and/or metabolic response to a meal. We found that overweight or obese (n = 13), but not healthy weight (n = 20) subjects perceived odors, but not flavored solutions, as more intense when hungry than when sated. This effect was correlated with reduced postprandial total ghrelin suppression (n = 23) and differential brain response to odors in the cerebellum, as measured with functional magnetic resonance imaging. In contrast, it was unrelated to circulating leptin, glucose, insulin, triglycerides, or free fatty acids; or to odor pleasantness or sniffing (n = 24). These findings demonstrate that the effect of a meal on suprathreshold odor intensity perception is associated with metabolic measures such as body weight and total ghrelin reactivity, supporting endocrine influences on olfactory perception.
PMID: 26826114 [PubMed - as supplied by publisher]
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Identification of P450 Oxidoreductase as a Major Determinant of Sensitivity to Hypoxia-Activated Prodrugs.
| Related Articles |
Identification of P450 Oxidoreductase as a Major Determinant of Sensitivity to Hypoxia-Activated Prodrugs.
Cancer Res. 2015 Oct 1;75(19):4211-23
Authors: Hunter FW, Young RJ, Shalev Z, Vellanki RN, Wang J, Gu Y, Joshi N, Sreebhavan S, Weinreb I, Goldstein DP, Moffat J, Ketela T, Brown KR, Koritzinsky M, Solomon B, Rischin D, Wilson WR, Wouters BG
Abstract
Hypoxia is a prevalent feature of many tumors contributing to disease progression and treatment resistance, and therefore constitutes an attractive therapeutic target. Several hypoxia-activated prodrugs (HAP) have been developed, including the phase III candidate TH-302 (evofosfamide) and the preclinical agent SN30000, which is an optimized analogue of the well-studied HAP tirapazamine. Experience with this therapeutic class highlights an urgent need to identify biomarkers of HAP sensitivity, including enzymes responsible for prodrug activation during hypoxia. Using genome-scale shRNA screens and a high-representation library enriched for oxidoreductases, we identified the flavoprotein P450 (cytochrome) oxidoreductase (POR) as the predominant determinant of sensitivity to SN30000 in three different genetic backgrounds. No other genes consistently modified SN30000 sensitivity, even within a POR-negative background. Knockdown or genetic knockout of POR reduced SN30000 reductive metabolism and clonogenic cell death and similarly reduced sensitivity to TH-302 under hypoxia. A retrospective evaluation of head and neck squamous cell carcinomas showed heterogeneous POR expression and suggested a possible relationship between human papillomavirus status and HAP sensitivity. Taken together, our study identifies POR as a potential predictive biomarker of HAP sensitivity that should be explored during the clinical development of SN30000, TH-302, and other hypoxia-directed agents.
PMID: 26297733 [PubMed - indexed for MEDLINE]
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Retention efficacy and release of radioiodine in fume hoods.
Retention efficacy and release of radioiodine in fume hoods.
J Environ Radioact. 2016 Jan 26;
Authors: Schomäcker K, Fischer T, Zimmermanns B, Bregulla J, Sudbrock F, Prante O, Drzezga A
Abstract
Procedures to determine the release of hazardous gaseous substances including radioactive iodine are covered by different norms such as the European standard EN 14175 and the German national standard DIN 25466. The detection of sulphur hexafluoride (SF6) is required to comply with the prescribed methodology. The detection limit of this test is 4.5·10(-7) mol/m(3) in exhaust air. This detection limit would represent a very high activity in the region of 0.27 TBq/m(3) leading to an unacceptable risk. We therefore developed a test using a filter system, consisting of a combination of filters capable of separating various chemical forms of airborne radioiodine. Air samples were collected directly in front of the fume hood and in the laboratory beside two different fume hoods of a similar construction with a final activated carbon filter for retention of radioiodine. Particular attention was therefore paid to air samples taken after passage over the filters. Significant differences in the degree of retention of iodine were found between the two fume hoods investigated. In one test a malfunction of the fume hood was demonstrated. In this case 0.148 × 10(-3)% of the total released activity per m(3) air was found 1 cm in front of the hood sash. A remarkably high fraction of the activity released in the fume hood (1.3 × 10(-3)%/m(3) air) was measured after the activated carbon filter. In the ambient air, values of up to 8.6 × 10(-6)% pro m(3) laboratory air sampled were measured, despite a 6-8-fold air exchange. The selected procedure is a factor of 10(11) (Schomäcker et al., 2001) more sensitive than the standard recommended methods (EN 14175). The standard test prescribed by the DIN/EN failed to reveal any inadequacy in the protective function of the radionuclide hood with respect to radioiodine retention.
PMID: 26825260 [PubMed - as supplied by publisher]
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Choroidal Metastasis of Papillary Thyroid Carcinoma Demonstrated on SPECT-CT.
Choroidal Metastasis of Papillary Thyroid Carcinoma Demonstrated on SPECT-CT.
Clin Nucl Med. 2016 Jan 28;
Authors: Torun N, Reyhan M, Yapar AF, Karatas M
Abstract
We report a 68-year-old woman with papillary thyroid carcinoma metastasizing to choroid. The choroid metastasis was diagnosed with SPECT-CT and then was treated with high-dose radioactive iodine therapy.
PMID: 26825205 [PubMed - as supplied by publisher]
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The miR-146b-3p/PAX8/NIS Regulatory Circuit Modulates the Differentiation Phenotype and Function of Thyroid Cells during Carcinogenesis.
| Related Articles |
The miR-146b-3p/PAX8/NIS Regulatory Circuit Modulates the Differentiation Phenotype and Function of Thyroid Cells during Carcinogenesis.
Cancer Res. 2015 Oct 1;75(19):4119-30
Authors: Riesco-Eizaguirre G, Wert-Lamas L, Perales-Patón J, Sastre-Perona A, Fernández LP, Santisteban P
Abstract
The presence of differentiated thyroid cells in thyroid cancer is critical for the antitumor response to radioactive iodide treatment, and loss of the differentiated phenotype is a key hallmark of iodide-refractory metastatic disease. The role of microRNAs (miRNA) in fine-tuning gene expression has become a major regulatory mechanism by which developmental and pathologic processes occur. In this study, we performed next-generation sequencing and expression analysis of eight papillary thyroid carcinomas (PTC) to comprehensively characterize miRNAs involved in loss of differentiation. We found that only a small set of abundant miRNAs is differentially expressed between PTC tissue and normal tissue from the same patient. In addition, we integrated computational prediction of potential targets and mRNA sequencing and identified a master miRNA regulatory network involved in essential biologic processes such as thyroid differentiation. Both mature products of mir-146b (miR-146b-5p and -3p) were among the most abundantly expressed miRNAs in tumors. Specifically, we found that miR-146b-3p binds to the 3'-untranslated region of PAX8 and sodium/iodide symporter (NIS), leading to impaired protein translation and a subsequent reduction in iodide uptake. Furthermore, our findings show that miR-146b and PAX8 regulate each other and share common target genes, thus highlighting a novel regulatory circuit that governs the differentiated phenotype of PTC. In conclusion, our study has uncovered the existence of a miR-146b-3p/PAX8/NIS regulatory circuit that may be exploited therapeutically to modulate thyroid cell differentiation and iodide uptake for improved treatment of advanced thyroid cancer.
PMID: 26282166 [PubMed - indexed for MEDLINE]
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Oncogenic PI3K mutations are as common as AKT1 and SMO mutations in meningioma.
Oncogenic PI3K mutations are as common as AKT1 and SMO mutations in meningioma.
Neuro Oncol. 2016 Jan 28;
Authors: Abedalthagafi M, Bi WL, Aizer AA, Merrill PH, Brewster R, Agarwalla PK, Listewnik ML, Dias-Santagata D, Thorner AR, Van Hummelen P, Brastianos PK, Reardon DA, Wen PY, Al-Mefty O, Ramkissoon SH, Folkerth RD, Ligon KL, Ligon AH, Alexander BM, Dunn IF, Beroukhim R, Santagata S
Abstract
BACKGROUND: Meningiomas are the most common primary intracranial tumor in adults. Identification of SMO and AKT1 mutations in meningiomas has raised the possibility of targeted therapies for some patients. The frequency of such mutations in clinical cohorts and the presence of other actionable mutations in meningiomas are important to define.
METHODS: We used high-resolution array-comparative genomic hybridization to prospectively characterize copy-number changes in 150 meningiomas and then characterized these samples for mutations in AKT1, KLF4, NF2, PIK3CA, SMO, and TRAF7.
RESULTS: Similar to prior reports, we identified AKT1 and SMO mutations in a subset of non-NF2-mutant meningiomas (ie, ∼9% and ∼6%, respectively). Notably, we detected oncogenic mutations in PIK3CA in ∼7% of non-NF2-mutant meningiomas. AKT1, SMO, and PIK3CA mutations were mutually exclusive. AKT1, KLF4, and PIK3CA mutations often co-occurred with mutations in TRAF7. PIK3CA-mutant meningiomas showed limited chromosomal instability and were enriched in the skull base.
CONCLUSION: This work identifies PI3K signaling as an important target for precision medicine trials in meningioma patients.
PMID: 26826201 [PubMed - as supplied by publisher]
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Bulbar Paralysis and Facial Paralysis due to Metastatic Hepatocellular Carcinoma: A Case Report and Literature Review.
Bulbar Paralysis and Facial Paralysis due to Metastatic Hepatocellular Carcinoma: A Case Report and Literature Review.
Medicine (Baltimore). 2016 Jan;95(4):e2632
Authors: Liu M, Liu S, Liu B, Liu B, Guo L, Wang X, Wang Q, Yang S, Dong L
Abstract
Skull-base metastasis (SBM) from hepatocellular carcinoma (HCC) is extremely rare, and multiple cranial nerve paralysis due to SBM from HCC is also rare. We report a case of bulbar and facial paralysis due to SBM from HCC.A 46-year-old Chinese man presented with a hepatic right lobe lesion that was detected during a routine physical examination. After several failed attempts to treat the primary tumor and bone metastases, neurological examination revealed left VII, IX, X, and XI cranial nerve paralysis. Computed tomography of the skull base subsequently revealed a large mass that had destroyed the left occipital and temporal bones and invaded the adjacent structure. After radiotherapy (27 Gy, 9 fractions), the patient experienced relief from his pain, and the cranial nerve dysfunction regressed. However, the patient ultimately died, due to the tumor's progression.Radiotherapy is usually the best option to relieve pain and achieve regression of cranial nerve dysfunction in cases of SBM from HCC, although early treatment is needed to achieve optimal outcomes. The present case helps expand our understanding regarding this rare metastatic pathway and indicates that improved awareness of SBM in clinical practice can help facilitate timely and appropriate treatment.
PMID: 26825921 [PubMed - in process]
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The Extended Subfrontal and Fronto-Orbito-Zygomatic Approach in Skull Base Meningioma Surgery: Clinical, Radiologic, and Cosmetic Outcome.
The Extended Subfrontal and Fronto-Orbito-Zygomatic Approach in Skull Base Meningioma Surgery: Clinical, Radiologic, and Cosmetic Outcome.
J Craniofac Surg. 2016 Jan 28;
Authors: Soleman J, Leiggener C, Schlaeppi AJ, Kienzler J, Fathi AR, Fandino J
Abstract
OBJECTIVE: To review the outcome and cosmetic results of patients undergoing extended subfrontal and fronto-orbito-zygomatic craniotomy for resection of skull base meningiomas.
METHODS: All surgeries were performed in cooperation with an oral and maxillofacial surgeon between 2006 and 2012. Clinical presentation, surgical techniques and complications, cosmetic, clinical, and radiologic outcomes are presented.
RESULTS: This study included 25 consecutive patients with 26 operations. Total and subtotal tumor removal was obtained in 19 (73.1%) and 7 (26.9%) patients, respectively. Permanent postoperative complications were seen in 5 (19.2%) patients. Eight of 10 patients with preoperative visual impairment showed recovery at 6 months follow-up. Anosmia was improved in 50% and no worsening was seen in any case of hyposmia. All patients showed improved or complete correction of exophthalmos, cognitive deficits, and epilepsy. One patient (3.8%) developed a postoperative ptosis. No mortality was documented. All patients reported a favorable cosmetic satisfactory score over 6 (8.67 ± 1.6). Tumor recurrence rate was 7.7% (n = 2).
CONCLUSIONS: The extended subfrontal and fronto-orbito-zygomatic approach, used for resection of meningiomas located in the orbita and the skull base can provide better visibility of the tumor. In addition, these approaches lead to highly satisfying cosmetic and clinical results.
PMID: 26825741 [PubMed - as supplied by publisher]
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Facial Paralysis Secondary to Extensive Perineural Spread of Adenocarcinoma of the Parotid Gland Identified by PET/CT.
Facial Paralysis Secondary to Extensive Perineural Spread of Adenocarcinoma of the Parotid Gland Identified by PET/CT.
Clin Nucl Med. 2016 Jan 28;
Authors: Achong DM, Zloty M
Abstract
Brain MRI in an 82-year-old man with presumed Bell's palsy revealed a clinically unsuspected right parotid gland mass but no other acute findings. Biopsy revealed poorly differentiated adenocarcinoma. Staging F-FDG PET/CT revealed an FDG-avid parotid mass, abnormal FDG uptake along the course of the facial nerve from mass to skull base, and multiple FDG-avid right level II neck lymph nodes and hepatic metastases. The PET/CT findings and prolonged clinical course suggest that diffuse perineural spread of tumor from a smoldering parotid neoplasm, and not idiopathic Bell's palsy, was responsible for the patient's facial paralysis.
PMID: 26825200 [PubMed - as supplied by publisher]
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Rectal carcinoid tumor metastasis to a skull base meningioma.
Rectal carcinoid tumor metastasis to a skull base meningioma.
Neuroradiol J. 2016 Jan 29;
Authors: Bhojwani N, Huang J, Gupta A, Badve C, Cohen ML, Wolansky LJ
Abstract
Carcinoid tumors are rare, slow-growing neuroendocrine tumors that most frequently develop in the gastrointestinal tract or lungs and have high potential for metastasis. Metastasis to the brain is rare, but to another intracranial tumor is extremely rare. Of the intracranial tumors, meningiomas are the most common to host metastases, which may be related to its rich vascularity and E-cadherin expression. We describe the case of a 65-year-old female with active chemotherapy-treated neuroendocrine carcinoma who presented with left-sided facial numbness, headaches, and blurry vision. Initial imaging revealed a 1 cm irregular dural-based left petrous apex mass suggestive of a meningioma that was re-imaged four months later as a rapidly enlarging, extra-axial, mass extending into the cavernous sinus, effacing Meckel's cave that resembled a trigeminal schwannoma. Pathology revealed a carcinoid tumor metastatic to meningioma. While the mass displayed characteristic imaging findings of a schwannoma, rapid growth in the setting of known active malignancy should prompt the clinician to consider mixed pathology from metastatic disease or a more aggressive meningioma.
PMID: 26825133 [PubMed - as supplied by publisher]
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Effects of the SLCO1B1 *1 and SLCO1B1 *5 polymorphisms on IL-6 and IL-10 levels in patients under pravastatin treatment prior to inguinal hernia repair.
Effects of the SLCO1B1 *1 and SLCO1B1 *5 polymorphisms on IL-6 and IL-10 levels in patients under pravastatin treatment prior to inguinal hernia repair.
Int J Surg. 2016 Jan 27;
Authors: Martha Irazema CR, Ivan DE, Luz Margarita BR, José GE, Mario RF
Abstract
BACKGROUND: Different genetic variants in the SLCO1B1 gene have been shown to have functional importance in individual variability in pravastatin pharmacokinetics, resulting in different inflammatory responses to surgical inguinal hernia repair. The aim of this study was to determine IL-6 and IL-10 serum concentrations in the presence and absence of the SLCO1B1*1 and SLCO1B1*5 polymorphisms in patients under pravastatin treatment that underwent inguinal hernia repair.
METHODS: The study included 26 subjects that were under pravastatin treatment (40 mg/day) at least 1 month prior to inguinal hernia repair open technique. All the subjects were genotyped for the SLCO1B1*1 and SLCO1B1*5 polymorphisms through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and their preoperative and postoperative serum IL-6 and IL-10 levels were quantified through the ELISA technique. The IL-6 and IL-10 levels were analyzed in the presence or absence of the mutated polymorphism for SLCO1B1*1 and SLCO1B1*5.
RESULTS: The SLCO1B1*1 polymorphism had a frequency of 38.5% and the SLCO1B1*5 polymorphism had a frequency of 19.2%. The preoperative and postoperative serum concentrations of IL-6 were 0.252 pg/ml ± 0.19 and 0.206 pg/ml ± 0.20, respectively, with a p=0.525, whereas the preoperative and postoperative serum concentrations for IL-10 were 4.943 pg/ml ±3.13 and 4.611 pg/ml ± 3.01, respectively, with a p=0.004.
CONCLUSIONS: The patients under pravastatin treatment presented with lower postoperative IL-10 levels with respect to the baseline concentration (p=0.004), regardless of the presence or absence of the two polymorphisms.
PMID: 26826613 [PubMed - as supplied by publisher]
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Laparoscopic cholecystectomy during pregnancy: A systematic review.
Laparoscopic cholecystectomy during pregnancy: A systematic review.
Int J Surg. 2016 Jan 27;
Authors: Nasioudis D, Tsilimigras D, Economopoulos KP
Abstract
BACKGROUND: The incidence of symptomatic biliary disease during pregnancy ranges from 0.05 to 8%. Cholecystectomy is one of the common operations performed during pregnancy and laparoscopic approach has gained popularity as an attractive alternative to open surgery.
METHODS: In order to evaluate the safety, feasibility, outcomes and technical aspects of laparoscopic cholecystectomy during pregnancy a comprehensive search of Medline and Cohrane Library databases was conducted.
RESULTS: Fifty-one studies were deemed eligible, in which laparoscopic cholecystectomy was attempted in 590 patients. The majority of the procedures (70.7%) were performed during the second trimester. Intraoperative and postoperative complications were observed in 3.5% and 4% of the study population. Conversion rate to open surgery was 2.2%. Fetal loss rate and preterm delivery rate were 0.4% and 5.7% respectively.
CONCLUSION: Laparoscopic cholecystectomy seems to be a safe alternative to open surgery during pregnancy.
PMID: 26826612 [PubMed - as supplied by publisher]
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Elements: in this month's issue.
Elements: in this month's issue.
QJM. 2016 Feb;109(2):77
Authors: Donnelly SC
PMID: 26826727 [PubMed - as supplied by publisher]
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Epidemiology of Birth Defects Based on a Birth Defect Surveillance System from 2005 to 2014 in Hunan Province, China
by Donghua Xie, Tubao Yang, Zhiyu Liu, Hua Wang
ObjectiveTo describe the epidemiology of birth defects (BDs) in perinatal infants in Hunan Province, China, between 2005 and 2014.
MethodsThe BD surveillance data of perinatal infants (for stillbirth, dead fetus or live birth between 28 weeks of gestation and 7 days after birth) were collected from 52 registered hospitals of Hunan between 2005 and 2014. The prevalence rates of BDs with 95% confidence interval (CI) and crude odds ratio (ORs) were calculated to examine the associations of infant gender, maternal age, and region (urban vs rural) with BDs.
ResultsFrom 2005 to 2014, there were a total of 925413 perinatal infants of which 17753 had BDs, with the average prevalence of 191.84 per 10000 PIs (perinatal infants), showing a significant uptrend. The risks of BDs are higher in urban areas versus rural areas (OR = 1.20), in male infants versus female infants (OR = 1.19), and in mothers above age 35 versus those below age 35 (OR = 1.24). The main five types of BDs are Congenital heart defects (CHD), Other malformation of external ear (OMEE), Polydactyly, Congenital malformation of kidney (CMK), and Congenital talipes equinovarus (CTE). From 2005 to 2014, the prevalence rates (per 10000 PIs) of CHD and CMK increased significantly from 22.56 to 74 (OR = 3.29, 95%CI: 2.65–4.11) and from 7.61 to 14.62 (OR = 1.92, 95%CI:1.30–2.84), respectively; the prevalence rates of congenital hydrocephalus and neural tube defects (NTDs) decreased significantly from 11.8 to 5.29 (OR = 0.45, 95%CI: 0.31–0.65) and from 7.87 to 1.74 (OR = 0.22, 95%CI: 0.13–0.38), respectively.
ConclusionsThe prevalence rates of specific BDs in perinatal infants in Hunan have changed in the last decade. Urban pregnant women, male perinatal infants, and mothers above age 35 present different prevalence rates of BDs. Wider use of new diagnosis technology, improving the ability of monitoring, strengthening the publicity and education are important to reduce the prevalence of BDs.
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Anomalous left main coronary artery detected by CT angiography.
Anomalous left main coronary artery detected by CT angiography.
Surg Radiol Anat. 2016 Jan 29;
Authors: Forte E, Inglese M, Infante T, Schiano C, Napoli C, Soricelli A, Salvatore M, Tedeschi C
Abstract
The growing improvements of computed tomography have made this technique more and more available for cardiac evaluation. Coronary artery anomalies (CAAs) are often incidental findings in subjects with suspected coronary artery disease (CAD) undergoing coronary angiography or computed tomography coronary angiography (CTCA). In some cases, CAAs can be clinically relevant so their identification could change radically patient management and treatment. We report the case of a 68-year-old male patient with known CAD and associated anomalous origination of the left coronary artery from the opposite sinus.
PMID: 26825295 [PubMed - as supplied by publisher]
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Hemifacial spasm associated with contralateral foramen magnum meningioma: case report.
Hemifacial spasm associated with contralateral foramen magnum meningioma: case report.
World Neurosurg. 2016 Jan 27;
Authors: Matsuda M, Akutsu H, Yamamoto T, Ishikawa E, Matsumura A
PMID: 26826538 [PubMed - as supplied by publisher]
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Functional outcome of the facial nerve after surgery for vestibular schwannoma: Prediction of acceptable long-term facial nerve function based on immediate post-operative facial palsy.
Functional outcome of the facial nerve after surgery for vestibular schwannoma: Prediction of acceptable long-term facial nerve function based on immediate post-operative facial palsy.
World Neurosurg. 2016 Jan 27;
Authors: Lee S, Seol HJ, Park K, Lee JI, Nam DH, Kong DS, Cho YS
Abstract
OBJECTIVE: We examined the relationship between immediate post-operative facial palsy and later, and identified treatment strategy for VS considering long-term outcomes of facial nerve function and tumor control.
METHODS: 385 patients who underwent surgery in a single institution were reviewed retrospectively. 12 NF patients, 6 with pre-operative radiosurgery, and 14 with multiple surgeries were excluded. The generalized estimating equation method was used to show the correlation between immediate and later post-operative facial palsy, and to identify the cut-off grade of immediate post-operative facial palsy.
RESULTS: The tumor control for 1-year, 3-year, and 5-year were 88.7%, 83.9%, and 80.0%. Facial functional preservation above H-B grade 1, 2 was achieved in 47.9% of patients immediate post-operatively, 50.1% after 1 month, and 74.5% after >2 years. The immediate post-operative facial palsy grade showed a statistically significant relationship with the facial palsy grade on long-term follow-up (P < 0.001). An H-B grade 3 immediate facial palsy was identified as the cut-off grade that showed the most significant relationship between the grade of immediate post-operative facial palsy and the grades above the cut-off (H-B grade 1, 2, and 3) on long-term follow-up (P < 0.001).
CONCLUSION: Immediate post-operative facial palsy grade can predict the facial palsy at long-term follow-up, that is immediate post-operative H-B grade 3 is the lowest tolerable grade that guarantees functional improvement on long-term follow-up. Planned facial nerve preservation surgery followed by radiosurgery is thought to be optimal treatment in VS patients for both tumor control and facial nerve function.
PMID: 26826537 [PubMed - as supplied by publisher]
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Σάββατο 30 Ιανουαρίου 2016
Reports of perceptual distortion of the face are common in patients with different types of chronic oro-facial pain
Summary
Anecdotally, chronic oro-facial pain patients may perceive the painful face area as 'swollen'. Because there are no clinical signs, these self-reported 'illusions' may represent perceptual distortions and can be speculated to contribute to the maintenance of oro-facial pain. This descriptive study investigated whether chronic oro-facial pain patients experience perceptual distortions – a kind of body image disruption. Sixty patients were consecutively recruited to fill in questionnaires regarding i) pain experience, ii) self-reports of perceptual distortion and iii) psychological condition. Perceptual distortions were examined in the total group and in three diagnostic subgroups: i) painful post-traumatic trigeminal neuropathy (PPTN), ii) painful temporomandibular disorder (TMD) or iii) persistent idiopathic facial pain (PIFP). A large proportion of oro-facial pain patients reported perceptual distortions of the face (55·0%). In the diagnostic subgroups, perceptual distortions were most pronounced in PPTN patients (81·5%) but with no significant group differences. In the total group of chronic oro-facial pain patients, the present pain intensity explained 16·9% of the variance in magnitude of the perceptual distortions (R2 = 16·9, F(31) = 6·3, P = 0·017). This study demonstrates that many chronic oro-facial pain patients may experience perceptual distortions. Future studies may clarify the mechanisms underlying perceptual distortions, which may point towards new complementary strategies for the management of chronic oro-facial pain.
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"Int J Clin Exp Pathol"[jour]; +229 new citations
229 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 2016/01/30
PubMed comprises more than 24 million 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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"Int J Clin Exp Pathol"[jour]; +229 new citations
229 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 2016/01/30
PubMed comprises more than 24 million 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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Reduced germinal center follicular helper T cells but normal follicular regulatory T cells in the tonsils of a patient with a mutation in the PI3KR1 gene
Publication date: Available online 28 January 2016
Source:Clinical Immunology
Author(s): Roberta Di Fonte, Manuela Baronio, Alessandro Plebani, Vassilios Lougaris, Georgia Fousteri
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Cover_spine
Publication date: January–February 2016
Source:Cancer Genetics, Volume 209, Issues 1–2
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Editorial Board
Publication date: January–February 2016
Source:Cancer Genetics, Volume 209, Issues 1–2
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Table of Contents
Publication date: January–February 2016
Source:Cancer Genetics, Volume 209, Issues 1–2
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Meta-analysis of the efficacy of lansoprazole and omeprazole for the treatment of H.pylori-associated duodenal ulcer.
| Related Articles |
Meta-analysis of the efficacy of lansoprazole and omeprazole for the treatment of H.pylori-associated duodenal ulcer.
Int J Physiol Pathophysiol Pharmacol. 2015;7(3):158-64
Authors: Zeng Y, Ye Y, Liang D, Guo C, Li L
Abstract
OBJECTIVE: To conduct a systematic evaluation of the efficacy of lansoprazole and omeprazole for the treatment of Helicobacter pylori-associated duodenal ulcer.
METHODS: Online databases, including CHKD, VIP, China Info, the National Digital Library of China, Google Scholar, PubMed, Lippincott Williams & Wilkins, and Wiley Online Library were searched for related studies. The quality of the studies was evaluated in accordance with the Cochrane Handbook for Systematic Reviews of Interventions, and relevant information was extracted from them. The studies were subjected to meta-analysis using RevMan5.3 software, and qualitative analysis was performed for studies, in which the data could not be merged.
RESULTS: A total of nine randomized controlled trials (RCTs) were included, all of which presented the possibility of bias. Meta-analysis showed no significant differences between patients treated with lansoprazole combinations and omeprazole combinations in terms of DU healing rate (RR = 1.04, 95% CI = 0.99~1.09, P = 0.93). There were significant differences between those treated by lansoprazole combination and omeprazole combination in terms of HP eradication rate (RR = 1.09, 95% CI = 1.01~1.18, P = 0.04), and there was no serious adverse reaction during the treatment process for both lansoprazole and omeprazole.
CONCLUSION: Lansoprazole and omeprazole exhibit similar efficacy in the treatment of Helicobacter pylori associated duodenal ulcers.
PMID: 26823965 [PubMed]
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Cross interaction of melanocortinergic and dopaminergic systems in neural modulation.
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Cross interaction of melanocortinergic and dopaminergic systems in neural modulation.
Int J Physiol Pathophysiol Pharmacol. 2015;7(3):152-7
Authors: He ZG, Liu BW, Xiang HB
Abstract
Melanocortinergic and dopaminergic systems are widely distributed in the CNS and have been established as a crucial regulatory component in diverse physiological functions. The pharmacology of both melanocortinergic and dopaminergic systems including their individual receptors, signaling mechanisms, agonists and antagonists has been extensively studied. Several lines of evidence showed that there existed a cross interaction between the receptors of melanocortinergic and dopaminergic systems. The data available at present had expanded our understanding of melanocortinergic and dopaminergic system interaction in neural modulation, which will be main discussed in this paper.
PMID: 26823964 [PubMed]
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Effects of electroacupuncture on cognitive function in rats with Parkinson's disease.
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Effects of electroacupuncture on cognitive function in rats with Parkinson's disease.
Int J Physiol Pathophysiol Pharmacol. 2015;7(3):145-51
Authors: Shen X, Xie YY, Chen C, Wang XP
Abstract
This study was designed to illustrate the effects of electroacupuncture on cognitive function in rats with Parkinson's disease (PD). The PD model was established by injecting 6-OHDA into the rat brain. Rats with PD were then subjected to electroacupuncture and levodopa treatment for 2 weeks. The level of choline acetyltransferase (ChAT) activity in rat brain homogenates was assessed, for the cerebral cholinergic system is a major chemical pathway consisting of cognitive functions. Immunohistochemistry was applied to observe ChAT expression in the rat hippocampus and corpus striatum. The effects of electroacupuncture on cognitive function were comprehensively assessed in PD rats using Y-maze test. Compared with model control group, electroacupuncture group were apparently improved in learning & memory abilities, and ChAT activity was elevated, and apoptosis was reduced in the rat hippocampus and corpus striatum. No significant differences in learning & memory abilities and ChAT activity were detected between electroacupuncture and levodopa groups. Electroacupuncture remarkably improved cognition in PD rats, and its mechanisms are possibly associated with protecting cholinergic neurons in the central nervous system and elevating ChAT activity, and also might suitable dosage of levodopa protect physiologically the cognitive function in PD rats.
PMID: 26823963 [PubMed]
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Chronic intermittent voluntary alcohol drinking induces hyperalgesia in Sprague-Dawley rats.
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Chronic intermittent voluntary alcohol drinking induces hyperalgesia in Sprague-Dawley rats.
Int J Physiol Pathophysiol Pharmacol. 2015;7(3):136-44
Authors: Fu R, Gregor D, Peng Z, Li J, Bekker A, Ye J
Abstract
The mechanisms of hyperalgesia in alcoholics are not completely clear, and the development of animal models would therefore be necessary in investigating the underlying changes. Several studies including our own have demonstrated that the intermittent access to 20% ethanol two-bottle choice procedure (IA2BC) promotes escalation of drinking, and induces physical dependence in the Sprague-Dawley (SD) rat, one of the strains most commonly used in preclinical alcohol research. In this study, we investigated whether the IA2BC procedure could produce hyperalgesia in SD rats. We show here that, the SD rats in the IA2BC procedure significantly escalated their drinking within 8 weeks, which is consistent with other studies. Starting from 8 weeks of repeated chronic drinking, the mechanical and thermal sensitivity was significantly increased. During withdrawal, there were noticeable physical dependence signs, including tail stiffness and lower limb flexion, which started at 4 hours and lasted for more than 3 days after ethanol removal. Importantly, during withdrawal, the mechanical and thermal sensitivity was further increased, which started at 12 hours and lasted for more than seven days after ethanol removal. These results suggest that utilizing the SD rat under the IA2BC procedure could be a useful animal model with heuristic value for exploring the mechanisms underlying hyperalgesia induced by chronic alcohol abuse.
PMID: 26823962 [PubMed]
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Age-related attenuation of parasympathetic control of the heart in mice.
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Age-related attenuation of parasympathetic control of the heart in mice.
Int J Physiol Pathophysiol Pharmacol. 2015;7(3):126-35
Authors: Freeling JL, Li Y
Abstract
The autonomic nervous system maintains homeostasis through the balance of the sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS). Especially evident in the heart, maintenance of this balance is important for the control of heart rate, conduction, and contractility. It is known that aging, similar to various cardiovascular diseases, results in an increase in SNS activity and a decrease in PSNS activity, which may contribute to age-related cardiac dysfunction and remodeling. Intracardiac ganglia relay and integrate the PSNS signals to the heart. Therefore, this study investigated whether altered function of intracardiac ganglia is involved in age-related parasympathetic dysfunction and the potential role of the major cholinergic components of intracardiac ganglionic transmission in the process. This study utilized two age groups of mice, the younger mice at 1-2.5 months of age, and the older mice at 11-12 months of age. The results show that the older mice exhibit diminishment of both baroreflex sensitivity and response to rostral-severed vagal stimulation but preserved response to administration of muscarinic acetylcholine receptor agonist, bethanechol. Analysis of whole atrial lysate revealed significant diminishments in choline acetyltransferase (ChAT) and the upper band of vesicular acetylcholine transporter (VAchT). In contrast, the upper band of the high affinity choline transporter (CHT) was significantly upregulated in the older group. Further analysis showed that the soluble but not insoluble fraction of CHT protein is significantly increased in the older group. This implicates a potential reduction of acetylcholine synthesis and/or release and an improper compensatory change of CHT may be responsible for the PSNS dysfunction exhibited in this model.
PMID: 26823961 [PubMed]
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The PI3Kδ inhibitor idelalisib suppresses liver and lung cellular respiration.
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The PI3Kδ inhibitor idelalisib suppresses liver and lung cellular respiration.
Int J Physiol Pathophysiol Pharmacol. 2015;7(3):115-25
Authors: Hammadi SA, Almarzooqi S, Abdul-Kader HM, Saraswathiamma D, Souid AK
Abstract
Idelalisib (an inhibitor of phosphatidylinositol-3-kinase-delta) is approved for treatment of B-cell malignancies, with a Boxed Warning concerning potentially fatal hepatic, lung, and intestinal toxicities. The mechanisms of these tissue-specific adverse events have yet to be elucidated. This in vitro study investigated whether these effects could be attributed, at least in part, to altered cellular bioenergetics. A phosphorescence analyzer was used to measure cellular mitochondrial O2 consumption (kc , µM O2 min(-1) mg(-1)) in C57BL/6 mouse organs in the presence of 10 µM idelalisib or dimethyl-sulfoxide. Idelalisib significantly reduced the rate of cellular respiration in liver and lung fragments by 20% and 27%, respectively. Respiration in intestinal, thymic, and kidney fragments was unaffected. Idelalisib did not alter respiratory chain activities in mitochondria isolated from the liver and did not induce hepatocyte death. Thus, the drug mildly lowers liver and lung cellular respiration, an effect that may contribute to toxicities observed in these organs.
PMID: 26823960 [PubMed]
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Determinants of admission to inpatient rehabilitation among acute-care survivors of hypoxic-ischemic brain injury: A prospective population-wide cohort study
Publication date: Available online 30 January 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): David Stock, Cassandra Cowie, Vincy Chan, Nora Cullen, Angela Colantonio
ObjectivesTo investigate demographic and acute care clinical determinants of admission to inpatient rehabilitation (IR) among hypoxic-ischemic brain injury (HIBI) patients who survive the initial acute care episode.DesignPopulation-wide prospective cohort study using Canadian Institutes for Health Information administrative health data from Ontario, Canada. All patients who survived their HIBI acute care episode during the study period remained eligible for the outcome, admission to inpatient rehabilitation, for one year post acute care discharge.SettingOntario, Canada acute care.ParticipantsWe included all HIBI patients using International Classification of Diseases-Tenth Revision codes (ICD-10-CA) recorded at acute care admission who were 20 years or older (n=599) and discharged from acute care between 2002 and 2010 fiscal years, inclusive. Six were excluded from analyses due to missing data.InterventionsNot Applicable.Main Outcome MeasureAdmission to inpatient rehabilitationResultsOf HIBI survivors admitted to IR within one year of acute care discharge (n=169), the majority (56.2%) had an IR admitting diagnosis indicating "anoxic brain damage". Younger age, male sex, lower comorbidity burden, longer length of stay of preceding acute care episode and shorter duration in special care were most predictive of admission to IR in multivariable regression models. Females had an almost 2-fold lower incidence of admission to IR (Risk Ratio (RR): 0.62; 95% CI: 0.46-0.84).ConclusionOlder age, higher comorbidity burden, and shorter lengths of stay and delayed discharge from acute care are associated with lower incidence of IR admission for HIBI patients. That females are almost 2-fold less likely to receive rehabilitation requires further investigation.
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The effect of manual lymphatic drainage following total knee arthroplasty: a randomized controlled trial
Publication date: Available online 30 January 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Claude Pichonnaz, Jean-Philippe Bassin, Estelle Lécureux, Guillaume Christe, Damien Currat, Kamiar Aminian, Brigitte M. Jolles
ObjectiveTo evaluate the effects of manual lymph drainage (MLD) on knee swelling and the swelling's assumed consequences following total knee arthroplasty (TKA).DesignRandomized controlled trial.SettingPrimary care hospital.ParticipantsTwo groups of 30 patients were randomized before TKA surgery (65% ♀, age 70.7±8.8 y.o., weight 77.8±11.3 kg., size 1.64±0.08 m., BMI 29.9±4.1 kg·m−2)InterventionParticipants received either five treatments of MLD or a placebo, added to rehabilitation, in between the second (D2) and the seventh (D7) postsurgical days.Outcome MeasuresSwelling was measured by blinded evaluators before surgery, at D2, D7 and 3 months (3M) using bioimpedance spectroscopy and volume. Secondary outcomes were active and passive ROM, pain, knee function and gait parameters.ResultsAt D7 and 3M, no outcome was significantly different between groups, except for the knee passive flexion contracture at 3M which was smaller and less frequent in the MLD group (–2.6° [95%CI -5.0° to -0.21], P=0.04; absolute risk reduction 26.6% [95% CI 0.9 to 52.3%]; NNT = 4). Pain decreased between 5.8 and 8.2 mm on the VAS immediately after MLD, which was significant after four out of five MLD treatments.ConclusionThe MLD applied early following TKA surgery did not reduce swelling. It reduced pain immediately after treatment. Further studies, should investigate if the positive effect of MLD on knee extension is replicable.
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Manual Tactile Test Predicts Sensorimotor Control Capability of Hands for Patients with Peripheral Nerve Injury
Publication date: Available online 30 January 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Hsiu-Yun Hsu, Shyh-Jou Shieh, Ta-Shen Kuan, Hsiu-Ching Yang, Fong-Chin Su, Haw-Yen Chiu, Li-Chieh Kuo
ObjectiveTo comprehend the merits of a Manual Tactile Test (MTT) in assessing hand sensorimotor functions, this study explores the relationships among three subtests along with the precision pinch performances for patients with peripheral nerve injuries (PNI). In addition, to understand the accuracy of the MTT, this study also constructs the sensitivity and specificity of this test for PNI patients.DesignCase-control studies.SettingHospital and local community.ParticipantsTwenty-eight PNI patients were recruited, along with age-, gender-, and handedness-matched healthy controls.InterventionNot applicable.Main Outcome MeasuresThe Semmes-Weinstein monofilament (SWM), moving and static two-point discrimination (2PD), roughness differentiation, stereognosis and barognosis subtests of the MTT, as well as precision pinch performance, were used to examine the sensory and sensorimotor status of the hand.ResultsThe worst results in all sensibility tests were found for the PNI patients (p<0.001) in comparison with the controls. Multiple linear regression analysis showed the MTT was a better indicator for predicting the sensorimotor capacity of the hands in the PNI patients (r2=0.189, p=0.003) than the traditional test (r2=0.088, p=0.051). The results of receiver operating characteristic curve estimation show that the area under the curve (AUC) was 0.968 and 0.959 for the roughness differentiation and stereognosis subtests, respectively, and was 0.853 for the barognosis subtest, thus revealing the accuracy of the MTT in assessing sensorimotor status for PNI patients.ConclusionsThis study indicates that the MTT is highly accurate and a significant predictor of sensorimotor performance in the hands of PNI patients. The MTT could thus help clinicians obtain a better understanding of the sensorimotor and functional status of the hand with nerve injuries.
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Enhanced gefitinib-induced repression of the EGFR pathway by ATM kinase inhibition in non-small cell lung cancer cells
Summary
The epidermal growth factor receptor (EGFR) tyrosine kinase signaling pathways regulate cellular activities. EGFR tyrosine kinase inhibitors (EGFR-TKIs) repress the EGFR pathway constitutively activated by somatic EGFR gene mutations and have drastically improved the prognosis of non-small cell lung cancer (NSCLC) patients. However, still there are some problems, including resistance, remain to be solved. Recently, the combination therapy with EGFR-TKIs and cytotoxic agents has been shown to improve the prognosis of NSCLC patients. To enhance the anti-cancer effects of EGFR-TKIs, we examined the crosstalk of the EGFR pathways with Ataxia telangiectasia-mutated (ATM) signaling pathways. ATM is a key protein kinase in the DNA damage response and is known to phosphorylate Akt, an EGFR downstream factor. We found that the combination of an ATM inhibitor, KU55933, and an EGFR-TKI, gefitinib, resulted in synergistic cell growth inhibition and induction of apoptosis in NSCLC cell lines carrying the sensitive EGFR mutation. We also found that KU55933 enhanced the gefitinib-dependent repression of the phosphorylation of EGFR and/or its downstream factors. ATM inhibition may facilitate the gefitinib-dependent repression of the phosphorylation of EGFR and/or its downstream factors, to exert anti-cancer effects against NSCLC cells with the sensitive EGFR mutation.
This article is protected by copyright. All rights reserved.
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Drug screening and grouping by sensitivity with a panel of primary cultured cancer spheroids derived from endometrial cancer
Summary
Several molecular targeting drugs are being evaluated for endometrial cancer; selecting patients whose cancers are sensitive to these agents is of paramount importance. Previously, we developed the cancer tissue-originated spheroid method for primary cancer cells taken from patients' tumors as well as patient-derived xenografts. In this study, we successfully prepared and cultured cancer tissue-originated spheroids from endometrial cancers. Characteristics of the original tumors were well retained in cancer tissue-originated spheroids including morphology and expression of p53 or neuroendocrine markers. We screened 79 molecular targeting drugs using two cancer tissue-originated spheroid lines derived from endometrioid adenocarcinoma Grade 3 and serous adenocarcinoma. Among several hits, we focused on an mTORC1 inhibitor, everolimus and a survivin inhibitor, YM155. When sensitivity to everolimus or YM155 was assessed in 12 or 11 cancer tissue-originated spheroids, respectively, from different endometrial cancer patients, the sensitivity varied substantially. The cancer tissue-originated spheroids sensitive to everolimus showed remarkable suppression of proliferation. The phosphorylation status of the mTORC1 downstream molecules before and after everolimus treatment did not predict the effect of the drug. On the other hand, the cancer tissue-originated spheroids sensitive to YM155 showed remarkable cell death. The effect of YM155 was also confirmed in vivo. The histological type correlated with YM155 sensitivity; non-endometrioid adenocarcinomas were sensitive and endometrioid adenocarcinomas were resistant. Non-canonical autophagic cell death was the most likely cause of cell death in a sensitive cancer tissue-originated spheroid. Thus, sensitivity assays using cancer tissue-originated spheroid from endometrial cancers may be useful for screening drugs and finding biomarkers.
This article is protected by copyright. All rights reserved.
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Zero in the brain: a voxel-based lesion–symptom mapping study in right hemisphere damaged patients
Publication date: Available online 29 January 2016
Source:Cortex
Author(s): Silvia Benavides-Varela, Laura Passarini, Brian Butterworth, Giuseppe Rolma, Francesca Burgio, Marco Pitteri, Francesca Meneghello, Tim Shallice, Carlo Semenza
Transcoding numerals containing zero is more problematic than transcoding numbers formed by non-zero digits. However, it is currently unknown whether this is due to zeros requiring brain areas other than those traditionally associated with number representation. Here we hypothesize that transcoding zeros entails visuo-spatial and integrative processes typically associated with the right hemisphere. The investigation involved 22 right-brain-damaged patients and 20 healthy controls who completed tests of reading and writing Arabic numbers. As expected, the most significant deficit among patients involved a failure to cope with zeros. Moreover, a voxel-based lesion–symptom mapping analysis showed that the most common zero-errors were maximally associated to the right insula which was previously related to sensorimotor integration, attention, and response selection, yet for the first time linked to transcoding processes. Error categories involving other digits corresponded to the so-called Neglect errors, which however, constituted only about 10% of the total reading and 3% of the writing mistakes made by the patients. We argue that damage to the right hemisphere impairs the mechanism of parsing, and the ability to set-up empty-slot structures required for processing zeros in complex numbers; moreover, we suggest that the brain areas located in proximity to the right insula play a role in the integration of the information resulting from the temporary application of transcoding procedures.
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A two-level model of interindividual anatomo-functional variability of the brain and its implications for neurosurgery
Publication date: Available online 29 January 2016
Source:Cortex
Author(s): Hugues Duffau
The classical dogma of localizationism implicitly resulted in the principle of a similar brain functional anatomy between individuals, as for example the pars opercularis of the left "dominant" hemisphere corresponding to the speech area. This fixed "single brain" model led neurosurgeons to define a set of "eloquent" areas, for which injury would induce severe and persistent neurological worsening, making their surgical resections impossible. Therefore, numerous patients with a cerebral lesion justifying surgery were a priori not selected for resection and lost a chance to be treated. In fact, advances in brain mapping showed a considerable interindividual variability explained by a networking organization of the brain, in which one function is not underpinned by one specific region, but by interactions between dynamic large-scale delocalized sub-circuits. Indeed, using non-invasive neuroimaging, a variability of both structural and functional anatomy was demonstrated in healthy volunteers. Moreover, intraoperative electrical stimulation mapping of cortex and white matter tracts in awake patients who underwent surgery for tumor or epilepsy also showed an important anatomo-functional variability. However, a remarkable observation is that this variability is huge at the cortical level, while it is very low at the subcortical level. Based upon these intrasurgical findings, the goal of this review is to propose a two-level model of interindividual variability (high cortical variation, low subcortical variation), breaking with the traditional rigid workframe, and making neurosurgery in traditionnally presumed "eloquent" areas feasible without permanent deficits, on condition nonetheless to preserve the "invariant common core" of the brain.
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Reducing pain by moving? A commentary on Ferrè et al. 2013
Publication date: Available online 29 January 2016
Source:Cortex
Author(s): Lucian M. Macrea, Gianluca Macauda, Giovanni Bertolini, Dominik Straumann, Peter Brugger, Konrad Maurer, Antonella Palla, Bigna Lenggenhager
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Altered resting-state whole-brain functional networks of neonates with intrauterine growth restriction
Publication date: Available online 29 January 2016
Source:Cortex
Author(s): Dafnis Batalle, Emma Muñoz-Moreno, Cristian Tornador, Nuria Bargallo, Gustavo Deco, Elisenda Eixarch, Eduard Gratacos
The feasibility to use functional MRI (fMRI) during natural sleep to assess low-frequency basal brain activity fluctuations in human neonates has been demonstrated, although its potential to characterise pathologies of prenatal origin has not yet been exploited. In the present study, we used intrauterine growth restriction (IUGR) as a model of altered neurodevelopment due to prenatal condition to show the suitability of brain networks to characterise functional brain organisation at neonatal age. Particularly, we analysed resting-state fMRI signal of 20 neonates with IUGR and 13 controls, obtaining whole-brain functional networks based on correlations of BOLD signal in 90 grey matter regions of an anatomical atlas (AAL). Characterisation of the networks obtained with graph theoretical features showed increased network infrastructure and raw efficiencies but reduced efficiency after normalisation, demonstrating hyper-connected but sub-optimally organised IUGR functional brain networks. Significant association of network features with neurobehavioral scores was also found. Further assessment of spatiotemporal dynamics displayed alterations into features associated to frontal, cingulate and lingual cortices. These findings show the capacity of functional brain networks to characterise brain reorganisation from an early age, and their potential to develop biomarkers of altered neurodevelopment.
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Irradiation with narrowband-ultraviolet B suppresses phorbol ester-induced up-regulation of H1 receptor mRNA in HeLa cells.
Irradiation with narrowband-ultraviolet B suppresses phorbol ester-induced up-regulation of H1 receptor mRNA in HeLa cells.
Acta Otolaryngol. 2016 Jan 29;:1-5
Authors: Kitamura Y, Mizuguchi H, Okamoto K, Kitayama M, Fujii T, Fujioka A, Matsushita T, Mukai T, Kubo Y, Kubo N, Fukui H, Takeda N
Abstract
Conclusion These findings suggest that low dose irradiation with 310 nm NB-UVB specifically suppressed the up-regulation of H1R gene expression without inducing apoptosis and that UVB of shorter or longer wavelength than 310 nm NB-UVB had no such effects. Objective To develop a narrowband-ultraviolet B(NB-UVB) phototherapy for allergic rhinitis, this study investigated the effects of irradiation with NB-UVB at wavelength of 310 nm on phorbol-12-myristate-13-acetate (PMA)-induced up-regulation of histamine H1 receptor (H1R) mRNA in HeLa cells. Methods The mRNA levels of H1R in HeLa cells were measured using real-time RT-PCR. Apoptosis were evaluated with DNA fragmentation assay. Results PMA induced a significant increase in H1R mRNA expression in HeLa cells. Irradiation with 305 nm UVB and 310 nm NB-UVB, but not with 315 nm UVB at doses of 200 and 300 mJ/cm(2) significantly suppressed PMA-induced up-regulation of H1R mRNA. At a dose of 200 mJ/cm(2), irradiation with 305 nm UVB, but not with 310 nm NB-UVB, induced apoptosis, although exposure of the cells to both 305 and 310 nm UVB induced apoptosis at a dose of 300 mJ/cm(2) after PMA treatment in HeLa cells. Conversely, irradiation with 315 nm UVB at doses of 200 and 300 mJ/cm(2) did not induce apoptosis.
PMID: 26824787 [PubMed - as supplied by publisher]
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Degeneration of stria vascularis in age-related hearing loss; a corrosion cast study in a mouse model.
Degeneration of stria vascularis in age-related hearing loss; a corrosion cast study in a mouse model.
Acta Otolaryngol. 2016 Jan 29;:1-6
Authors: Carraro M, Harrison RV
Abstract
Conclusion With age, in a mouse model, degenerative changes to the capillaries of the stria vascularis are observed. These range from a narrowing of vessel lumen to complete degeneration of strial vessels. Other vascular beds in the cochlea are relatively unchanged with age. Strial capillaries at the cochlear base are significantly more affected than those in mid-apical turns. Objectives Previous work suggests that age-related hearing loss is associated with degenerative changes to cochlear vasculature; the term strial presbyacusis is often cited. This study reports on vascular changes observed in a murine model of presbyacusis, analyzed using corrosion cast techniques. Methods A novel corrosion cast technique was developed to compare cochlear vasculature in control mice (non-presbycusic, CD1) and old (> 6 months) C57BL/6 animals. ABR measures indicated a significant age-related threshold elevation in the C57BL/6 mice. Cochlear vascular casts were imaged using scanning electron microscopy, and vessel degeneration was quantified by measuring capillary diameters. Results Corrosion casts of cochlear vasculature in 6-12 month old C57BL/6 mice reveal significant degeneration of stria vascularis. Other capillary beds (spiral ligament and the spiral limbus) appear unchanged. Comparison of strial capillary diameters reveals significantly more damage in basal/lower-turn regions compared with the cochlear mid-turn.
PMID: 26824717 [PubMed - as supplied by publisher]
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