Immunopanning Purification and Culture of Retinal Ganglion Cells from Mouse

Publication date: Available online 21 February 2018
Source:Journal of Neuroscience Methods
Author(s): Lijun Fang, Tianwen Huang, Catherine Tsilfidis




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Designing GABA-Edited Magnetic Resonance Spectroscopy Studies: Considerations of Scan Duration, Signal-To-Noise Ratio and Sample Size

Publication date: Available online 21 February 2018
Source:Journal of Neuroscience Methods
Author(s): Mark Mikkelsen, Rachelle S. Loo, Nicolaas A.J. Puts, Richard A.E. Edden, Ashley D. Harris
BackgroundThe relationships between scan duration, signal-to-noise ratio (SNR) and sample size must be considered and understood to design optimal GABA-edited magnetic resonance spectroscopy (MRS) studies.New methodSimulations investigated the effects of signal averaging on SNR, measurement error and group-level variance against a known ground truth. Relative root mean square errors (measurement error) and coefficients of variation (group-level variance) were calculated. GABA-edited data from 18 participants acquired from five voxels were used to examine the relationships between scan duration, SNR and quantitative outcomes in vivo. These relationships were then used to determine the sample sizes required to observe different effect sizes.ResultsIn both simulated and in vivo data, SNR increased with the square root of the number of averages. Both measurement error and group-level variance were shown to follow an inverse-square-root function, indicating no significant impact of cumulative artifacts. Comparisons between the first two-thirds of the data and the full dataset showed no statistical difference in group-level variance. There was, however, some variability across the five voxels depending on SNR, which impacted the sample sizes needed to detect group differences in specific brain regions.Comparison with Existing methodsTypical scan durations can be reduced if taking into account a statistically acceptable amount of variance and the magnitudes of predicted effects.ConclusionsWhile scan duration in GABA-edited MRS has typically been considered in terms of SNR, it is more appropriate to think in terms of the amount of measurement error and group-level variance that provides sufficient statistical power.



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High Frequency Oscillations in Epileptic Rodents: Are We Doing It Right?

Publication date: Available online 21 February 2018
Source:Journal of Neuroscience Methods
Author(s): Maxime Lévesque, Siyan Wang, Jean Gotman, Massimo Avoli
BackgroundThe detection of high-frequency oscillations (HFOs, ripples: 80–200 Hz, fast ripples: 250–500 Hz) is often based on considering ripples or fast ripples in isolation; overlapping ripples and fast ripples are excluded from further analysis. Here, we studied overlapping HFOs during spontaneous seizures in pilocarpine-treated animals.New methodSpontaneous seizures (n = 6 animals) presented with either hypersynchronous- (HYP, n = 18) or low-voltage fast-onset (LVF, n = 21) pattern. Ripples and fast ripples overlapping by more than 30% were analysed.ResultsOverlapping HFOs could show a unimodal power spectrum between 80 to 500 Hz (n = 188, 58.9%) or a bimodal power spectrum, with peaks in power between 80–200 Hz and between 250–500 Hz (n = 131, 41.1%,). Overlapping HFOs occurred at higher rates during HYP seizures compared to the pre-ictal period in seizure onset zones (p < 0.001) and regions of secondary spread (p < 0.001). When comparing HYP and LVF seizures, we found that overlapping HFOs occurred at higher rates before LVF seizures (p < 0.05) compared to HYP seizures but, during the ictal period, HYP seizures showed higher rates of overlapping HFOs than LVF seizures (p < 0.001).Comparison with existing methodsWe have analysed overlapping ripples and fast ripples shortly before and during seizures.ConclusionsAlthough overlapping ripples and fast ripples represent a minority of HFOs, they may provide additional information on the excitability of neuronal networks that generate seizures in animal models and patients presenting with mesial temporal lobe epilepsy.



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Expressional analysis of APLNR, an essential gene for cancer immunotherapy, in colon and prostate cancers

Publication date: Available online 22 February 2018
Source:Pathology - Research and Practice
Author(s): Nam Jin Yoo, Min Sung Kim, Ju Hwa Lee, Chang Hyeok An, Sug Hyung Lee




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The degree of overlap between the follicular dendritic cell meshwork and tumor cells in mantle cell lymphoma is associated with prognosis

Publication date: Available online 21 February 2018
Source:Pathology - Research and Practice
Author(s): Weihua Hou, Ping Wei, Jianlan Xie, Yuanyuan Zheng, Yanlin Zhang, Xiaoge Zhou
This study concerning mantle cell lymphoma (MCL) investigated retrospectively an association between patient prognosis and the percentage of the total number of lymphoma cells found in the follicular dendritic cell (FDC) meshwork, that is, the degree of overlap of lymphoma cells. Two hundred and nine MCL patients were apportioned to grades I–III, in which the CD21-positive FDC meshwork covered ≤50%, 51%-89%, and ≥90% of the tumor area, respectively. Significant differences among the grades (all, P < 0.01) were found in the following: duration of disease (from onset of clinical manifestation to diagnosis); clinical staging; extranodal involvement (non-lymphoid organs); histological subtype; and Ki-67 proliferation index (PI). After removing the aggressive variants, the overall survival rates of grade I (n = 92) and II (n = 57) patients were similar. The overall survival rates of grade III (n = 46) patients differed from that of grade I + II patients (P < 0.01). The grades negatively correlated with the Ki-67 PI value (r = −0.234, P = 0.001). At each grade the OSR of patients with Ki-67 PI ≤30% was similar to that of patients with Ki-67 >30%. In the Ki-67 PI ≤30% group, the OSRs of the patients differed significantly among the grades. In the Ki-67 >30% group the OSRs of the grades were similar. The results of multivariate Cox regression analysis showed that the degree of overlap, age and Ki-67 PI was the independent prognostic factors of the OSRs of MCL patients. Our data suggests that MCL patients in whom there was a high degree of overlap between the FDC meshwork and tumor area have a better clinical prognosis. The degree of overlap correlates well with the Ki-67 PI, which can be used to predict the prognosis of patients.



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Intradepartmental Consultations in Surgical Pathology: Review of a Standardized Process and Factors Influencing Consultation Rates and Practices in an Academic and Community Hospital Setting

Publication date: Available online 21 February 2018
Source:Pathology - Research and Practice
Author(s): Emily A. Goebel, Helen Ettler, Joanna C. Walsh
Intradepartmental consultations (ICs) are important for quality assurance (QA) and ensuring diagnostic accuracy in surgical pathology. Few studies have reviewed pathologist factors that influence IC rates. Our study reviews IC data and factors that influence both formal (written) and informal (verbal) consultation practices among pathologists in academic and community hospital settings. Formal IC records from the academic hospital were collected and academic and community pathologists were invited to complete a survey about their IC practices. All centers had a formalized process for documenting ICs; however, 92% of academic and 90% of community pathologists also requested informal IC. The top reasons for selecting a particular colleague for IC was perceived level of expertise; however, interpersonal relationships and office proximity had a greater impact on informal IC practice. Top reasons for requesting a formal IC were mandatory (subspecialty defined) consultation and uncertainty regarding pathological findings. Advice on wording was a common reason for informal IC. Written documentation of IC aids in QA and determination of IC metrics; however, informal, undocumented ICs still occur. Reasons for IC and choice of consulting pathologist are multifactorial, and identifying these can help target quality improvement initiatives.



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Bex1 attenuates neuronal apoptosis in rat intracerebral hemorrhage model

Publication date: Available online 21 February 2018
Source:Pathology - Research and Practice
Author(s): Mingqing He, Yueju Wang, Jiabing Shen, Chengwei Duan, Xiang Lu, Jianzhong Li
Brain expressed x-linked gene 1 (Bex1) which is at high levels in several populations of central nervous system (CNS) neurons, belongs to a family of small proteins of unknown function, playing roles as adaptors or modulators of intracellular signaling pathways. But its distribution and function in CNS remains unclear. Neuronal apoptosis is the major pathogenesis in secondary brain injury of intracerebral hemorrhage (ICH). In this study, the roles of Bex1 were explored in the pathophysiology of ICH. Western blot, immunohistochemistry, and immunofluorescence showed that obvious up-regulation of Bex1 in neurons adjacent to the hematoma after ICH. Furthermore, the increase of Bex1 expression was accompanied by the enhanced expression of Bax and active caspase-3, and decreased expression of B-cell lymphoma 2 (Bcl-2) following ICH. The in vitro study using Bex1 siRNA transfection in hemin-exposed PC12 cells suggested that Bex1 exerted anti-apoptotic function. Therefore, Bex1 may play the neuronal anti-apoptosis role following ICH, implying a novel molecular target for the therapy of ICH.



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Protective effects of Schisandrin on high glucose-induced changes of RhoA and eNOS activity in human umbilical vein endothelial cells

Publication date: Available online 21 February 2018
Source:Pathology - Research and Practice
Author(s): Rong-Jin Zhang, Hui-Yao Hao, Qing-Juan Liu, Hong-Ye Zuo, Ying-Na Chang, Zhong-Ji Zhi, Peng-Peng Guo, Yong-Mei Hao
Schisandrin, derived from the Chinese medicinal herb Schisandra chinensis, has been found to confer protective effects on circulation systems. But the underlying molecular mechanisms remain unclear. The aim of this study was to investigate the effects of a high level of glucose on RhoA and eNOS activity in human umbilical vein endothelial cells(HUVECs) and how Schisandrin plays a role in mediating these effects. To find the optimal treatment time, HUVECs were cultured at a high glucose concentration (30 mM) for different lengths of time (0, 12, 24, and 48 hours). Subsequently, the cells were randomized into five groups: a normal group, a high glucose group, and three high glucose groups that were given different doses (5, 10, and 20 μM) of Schisandrin. The cells were pretreated with Schisandrin for 24 hours before stimulation with high glucose. The morphology of HUVECs in the various groups was assessed under a light microscope. Immunocytochemical staining was used to detect the level of p-MYPT1 expression. The levels of RhoA activity were determined using the RhoA Activation Assay Biochem Kit. The levels of eNOS activity were examined using a nitrate reduction test. The results showed that in the high glucose group, the activity of RhoA was increased and the activity of eNOS was reduced, thus decreasing the secretion of NO. However, after pretreatment with Schisandrin (10, 20 μM), the activity of RhoA was inhibited and the activity of eNOS increased, which led to an increase in NO production compared with the high glucose group. There was no evident difference between the 5 μM Schisandrin group and the high glucose group. Taken together, these findings indicate that Schisandrin can improve the function of endothelial cells by lowering the activity of RhoA/Rho kinase and raising both the activity of eNOS and the production of NO.



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Role of upregulated miR-136-5p in lung adenocarcinoma: a study of 1242 samples utilizing bioinformatics analysis

Publication date: Available online 22 February 2018
Source:Pathology - Research and Practice
Author(s): Tian-tian Li, Xiang Gao, Li Gao, Bin-liang Gan, Zu-cheng Xie, Jing-jing Zeng, Gang Chen
BackgroundIt is generally acknowledged that miRNAs play pivotal roles in the initiation and development of cancer. The aim of the current study is to investigate the clinicopathological role of miR-136-5p in lung adenocarcinoma and its underlying molecular mechanism.Materials and methodsData of a cohort of 1242 samples were provided by the Gene Expression Omnibus and The Cancer Genome Atlas to evaluate miR-136-5p expression in lung adenocarcinoma. A comprehensive meta-analysis integrating the expression data from all sources was performed, followed by a summary receiver operating curve plotted to appraise the upregulated expression of miR-136-5p in lung adenocarcinoma. Candidate targets of miR-136-5p were launched by the intersection of differentially expressed genes in The Cancer Genome Atlas and genes predicted by 12 web-based platforms. Then, hub genes were illustrated by a protein-protein interaction network. Furthermore, Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and Protein Analysis Through Evolutionary Relationships analyses of potential target genes were carried out via bioinformatics tools.ResultsMiR-136-5p expression was upregulated in lung adenocarcinoma versus normal tissues (standard mean difference = 0.43, 95% confidence interval: 0.27-0.58). The summary receiver operating characteristic curve further verified the upregulation of miR-136-5p in lung adenocarcinoma (area under curve = 0.7459). A total of 311 candidate target genes of miR-136-5p were gathered to create a protein-protein interaction network. Molecular mechanism analysis unveiled the potential miR-136-5p target genes participated in cell adhesion molecules, focal adhesion, complement and coagulation cascades and blood coagulation.ConclusionMiR-136-5p is overexpressed in lung adenocarcinoma and is involved in the molecular mechanism of lung adenocarcinoma via suppressing the expressions of downstream targets, especially claudin-18, sialophorin and syndecan 2 that participate in cell adhesion.



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Brain-derived neurotrophic factor induces angiogenin secretion and nuclear translocation in human umbilical vein endothelial cells

Publication date: Available online 21 February 2018
Source:Pathology - Research and Practice
Author(s): Ayako Mori, Yusuke Nishioka, Mai Yamada, Yuka Nishibata, Sakiko Masuda, Utano Tomaru, Naoyuki Honma, Takanori Moriyama, Akihiro Ishizu
Brain-derived neurotrophic factor (BDNF) is a well-known humoral protein that induces growth of neurons. Recent studies have suggested that BDNF could act as an angiogenesis inducer similar to vascular endothelial growth factor (VEGF). Angiogenin is a strong mediator of angiogenesis. It has particular characteristics both as a secreted protein and a transcription factor. After being incorporated into the cytoplasm, angiogenin is immediately transferred to the nucleus and then mediates the angiogenic effects of angiogenesis inducers, including VEGF. The aim of this study is to determine the association between BDNF and angiogenin. At first, we determined the secretion of angiogenin from human umbilical vein endothelial cells (HUVEC) induced by BDNF with enzyme-linked immunosorbent assay. Next, we determined BDNF-induced nuclear translocation of angiogenin by immunofluorescent staining. In addition, we examined the mRNA expression of angiogenin in HUVEC before and after BDNF stimulation by quantitative reverse transcriptase-polymerase chain reaction. As a result, we noted that BDNF induced angiogenin secretion and nuclear translocation without an increase in the mRNA expression in HUVEC. Furthermore, we demonstrated that BDNF-induced HUVEC proliferation was significantly suppressed when neomycin, a specific inhibitor of nuclear translocation of angiogenin, was administered. These findings indicate that nuclear translocation of angiogenin is critically involved in BDNF-induced proliferation of HUVEC. In conclusion, angiogenin contributes to angiogenesis induced by BDNF.



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Local delievery of thalidomide to inhibit neointima formation in rat model with artery injury

Publication date: Available online 21 February 2018
Source:Pathology - Research and Practice
Author(s): Shougang Sun, Quan Zhang, Qiongying Wang, Qiang Wu, Guangli Xu, Peng Chang, Hao Hu, Feng Bai
ObjectiveTo observe the effect of local administration of thalidomide on neointimal formation after balloon-induced carotid artery injury in rats.MethodsForty-eight male Sprague-Dawley rats were randomly divided into 3 groups (n = 16): Sham operation group (group A), alone operation group (group B) and Thalidomide group (group C). The carotid arteries of group B and group C were injured by a conventional percutaneous transluminal coronary angioplasty (PTCA) balloon catheter. Group C was treated by local delivery of thalidomide, and group B did not receive thalidomide. The arteries of group A were not injured. Seven and 14 days after balloon injury, rats were sacrificed. Serum concentrations of vascular endothelial growth factor (VEGF) and tumor necrosis factor-α (TNF-α) were measured using enzyme-linked immunosorbent assay (ELISA). Neointima area, lumen area, macrophage infiltration and local expression of VEGF were measured using morphometric and immunohistochemical analyses. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was used to examine VEGF mRNA expression.ResultsThe VEGF levels were significantly increased in group B than in group C at 7 days (4.82 ± 0.17 pg/ml vs 0.98 ± 0.1 pg/mL, P < 0.01) and 14 days (6.3 ± 0.16 pg/ml vs 1.03 ± 0.09 pg/mL, P < 0.01). The TNF-α levels were also significantly increased in group B than in group C at 7 days (83 ± 1.01 pg/mL vs 76.37 ± 0.75 pg/mL, P < 0.01) and 14 days (84.06 ± 1.11 pg/mL vs 78.46 ± 0.94 pg/mL, P < 0.01). However, the area of neointimal formation was significantly reduced in group C than in group B at 14 days (0.07± 0.01 mm² vs 0.12± 0.04 mm², P < 0.01). Macrophage infiltration and local expression of VEGF in the injured arteries were significantly reduced in group C than in group B at 14 days. VEGF mRNA expression was significantly reduced in Group C than in group B at 14 days (6.3 ± 0.16 vs 1.02 ± 0.1, P < 0.01).ConclusionsThalidomide, which is a specific VEGF inhibitor, significantly inhibited neointimal hyperplasia and vascular restenosis after balloon injury to the carotid artery in rats, thus potentially providing a novel method for the prevention and treatment of restenosis, especially in-stent restenosis.



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Indoleamine 2, 3-dioxygenase and B7-H1 expressions as prognostic and follow-up markers in human pancreatic carcinoma

Publication date: Available online 21 February 2018
Source:Pathology - Research and Practice
Author(s): Liancai Wang, Qingyong Ma, Deyu Li, Senmao Mu, Yong Li, Yafeng Wang, Pengfei Shi, Haibo Yu, Chunhui Gao, Kun Guo, Zhuoli Zhang
This study was to test hypotheses that indoleamine 2, 3-dioxygenase and B7-H1 expressions can be used as prognostic markers in human pancreatic carcinoma (PC). Ninety-five patients were recruited who had undergone radical surgical resection for PC. IDO and B7-H1 expressions in PC tissue specimens were evaluated by immunohistochemistry (IHC) techniques. The clinical and pathological features of these specimens were analyzed.IDO positive, B7-H1 positive, and combined IDO/B7-H1 positive tumors exhibited significant correlations with lymphocytic infiltration, perineural invasion, TNM status, and pathologic grade (p < 0.05), which tended to show strong correlations with malignant progression of PC. Also, IDO correlated with diabetes mellitus (DM) and HAD scale and B7-H1 correlated with smoke (p < 0.05). In addition, the correlation analysis indicated that IDO had a positive correlation with B7-H1 (p < 0.05). Moreover, the results showed that a combination of IDO and B7-H1 expressions could serve as independent prognostic marker after adjusting by Cox proportional hazards regression models (p < 0.05). IDO and B7-H1 expressions were observed in patient with PC tissues and are important markers for PC malignant progression. A combination of IDO and B7-H1 expression can be served as an independent prognostic marker for PC.



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Detection of the DICER1 hotspot mutation alongside immunohistochemical analysis may provide a better diagnostic measure for ovarian Sertoli-Leydig cell

Publication date: Available online 21 February 2018
Source:Pathology - Research and Practice
Author(s): Xiaobo Zhang, Danhua Shen, Ying Wang
BackgroundTo evaluate the clinicopathological and histopathological characteristics of ovarian Sertoli-Leydig cell tumors (SLCTs) in relation to differential diagnosis, and patient prognosis.MethodsA review of clinical data, pathological morphology and immunohistochemical analysis of SLCTs were performed in 18 SLCTs patients. The DICER1 gene mutation was assessed in eight cases that were obtained from in-house surgical resections.ResultsAmong 18 SLCTs patients, three cases had well-differentiated tumors, 8 cases had moderately-differentiated tumors, and the remaining 7 cases had poorly-differentiated tumors. Among the moderately-differentiated tumors, three cases occurred coincidently with other diseases – one case occurred with endometrial carcinoma (grade I), and two cases with endometrial carcinoma of the ovary (grade 2 and grade 3). Immunohistochemical staining for α-inhibin, calretinin, and FOXL2 was positive in all the biopsies tested. The intensity of staining varied depending on the percentage of Sertoli cells and the primitive gonad interstitial composition. DICER1 mutations were detected in three of eight cases that were evaluated and were significantly more in low age range patients (P < 0.05). The initial symptoms of these three cases were sexual changes and elevation of androgen levels. The follow-up time in this study ranged from 3 to 87 months with the mean follow-up time of 29.1 months. Prognosis was generally favorable. There was no recurrence or metastasis in any patient, except for one case with recurrence of endometrial carcinoma.ConclusionThe clinical presentation of SLCTs can be both varied and complex. Pathological examination is imperative for both diagnostic and prognostic grading. Immunohistochemical stain of α-inhibin, FOXL2, and calretinin and genetic testing for DICER1 mutations will be more potent for differential diagnosis.



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MicroRNA-30d/JAG1 axis modulates pulmonary fibrosis through Notch signaling pathway

Publication date: Available online 21 February 2018
Source:Pathology - Research and Practice
Author(s): Silin Zhao, Xuefei Xiao, Shuang Sun, Da Li, Wei Wang, Yan Fu, Fuyuan Fan
Pulmonary fibrosis (PF) is a fibroproliferative disease which can finally end up fatal lung failure. PF is characterized by abnormal proliferation of fibroblast, dysregulated fibroblast differentiation to myofibroblast and disorganized collagen and extracellular matrix (ECM) production, deposition and degradation. JAG1/Notch signaling has been reported to play a key role in tissue fibrosis including PF. Herein, we confirmed the abnormal upregulation of JAG1 mRNA expression and protein levels in PF tissue specimens; JAG1 knockdown reduced TGF-β1-induced α-SMA and Collagen I protein levels. From the aspect of miRNA regulation, we searched for candidate miRNAs which might target JAG1 to inhibit its expression. Among the selected miRNAs, miR-30d expression was downregulated in PF tissues; miR-30d overexpression attenuated TGF-β1-induced primary normal human lung fibroblast (NHLF) proliferation, as well as α-SMA and Collagen I protein levels. Through directly binding to the 3′-UTR of JAG1, miR-30d significantly inhibited JAG1 mRNA expression and protein level. Furthermore, JAG1 overexpression partially reversed the effect of miR-30d on NHLF proliferation and α-SMA and Collagen I proteins upon TGF-β1 stimulation; miR-30d could suppress TGF-β1 function on NHLFs through blocking JAG1/Notch signaling. Rescuing miR-30d expression to suppress TGF-β1-induced activation of JAG1/Notch signaling may present a promising strategy for PF treatment.



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Metastasis-associated protein 1 (MTA1) in gastric cancer tissues is positively associated with poorer prognosis

Publication date: Available online 21 February 2018
Source:Pathology - Research and Practice
Author(s): Zhen-ye Lv, Zhong-Sheng Zhao, Zai-Yuan Ye, Yuan-Yu Wang, Hui-Ju Wang, Qiong Yang
BackgroundThe present study examined the clinical significance of metastasis-associated protein 1 (MTA1) in the progression and patient survival of gastric cancer.MethodsParaffin-embedded resected tissues of gastric cancer mucosa (n = 436) and adjacent normal mucosa (n = 92) were assessed immunohistochemically for MTA1 protein, and scored according to the percentage of cells positively stained for MTA1 combined with stain intensity. Associations between MTA1 staining scores and clinicopathological factors, including survival time, were evaluated.ResultsThe staining scores for MTA1 were significantly higher in gastric cancer tissues than in matched normal tissues. MTA1 scores positively correlated with tumor size, depth of invasion, presence of lymph node metastasis, lymphatic involvement, venous invasion, distal metastasis, and advanced clinical staging. Patients with high MTA1 scores in gastric cancer tissues had a significantly lower five-year survival rate compared with patients with low MTA1 scores. The multivariate analysis indicated that MTA1 protein levels in resected gastric cancer tissues, as reflected by immunohistochemical staining, are an independent prognostic index of gastric carcinoma (P < 0.01).ConclusionMTA1 immunopositivity was significantly associated with progression of gastric cancer, and may be helpful in gastric cancer prognosis.



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Corrigendum to “Hippocampus and amygdala volumes from magnetic resonance images in children: Assessing accuracy of FreeSurfer and FSL against manual segmentation”[NeuroImage 129 (2016) 1–14]

Publication date: June 2018
Source:NeuroImage, Volume 173
Author(s): Dorothee Schoemaker, Claudia Buss, Kevin Head, Curt A. Sandman, Elysia P. Davis, M. Mallar Chakravarty, Serge Gauthier, Jens C. Pruessner




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Editorial-ozone and plant life: the Italian state-of-the-art

http://ift.tt/2FlRfe1

Biological responses of aquatic organisms and assessment water contamination and ecotoxicity

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Directed Interaction Between Monkey Premotor and Posterior Parietal Cortex During Motor-Goal Retrieval from Working Memory

Abstract

Goal-directed behavior requires cognitive control of action, putatively by means of frontal-lobe impact on posterior brain areas. We investigated frontoparietal directed interaction (DI) in monkeys during memory-guided rule-based reaches, to test if DI supports motor-goal selection or working memory (WM) processes. We computed DI between the parietal reach region (PRR) and dorsal premotor cortex (PMd) with a Granger-causality measure of intracortical local field potentials (LFP). LFP mostly in the beta (12–32 Hz) and low-frequency (f≤10Hz) ranges contributed to DI. During movement withholding, beta-band activity in PRR had a Granger-causal effect on PMd independent of WM content. Complementary, low-frequency PMd activity had a transient Granger-causing effect on PRR specifically during WM retrieval of spatial motor goals, while no DI was associated with preliminary motor-goal selection. Our results support the idea that premotor and posterior parietal cortices interact functionally to achieve cognitive control during goal-directed behavior, in particular, that frontal-to-parietal interaction occurs during retrieval of motor-goal information from spatial WM.

http://ift.tt/2EKuzXL

Subset of Cortical Layer 6b Neurons Selectively Innervates Higher Order Thalamic Nuclei in Mice

Abstract

The thalamus receives input from 3 distinct cortical layers, but input from only 2 of these has been well characterized. We therefore investigated whether the third input, derived from layer 6b, is more similar to the projections from layer 6a or layer 5. We studied the projections of a restricted population of deep layer 6 cells ("layer 6b cells") taking advantage of the transgenic mouse Tg(Drd1a-cre)FK164Gsat/Mmucd (Drd1a-Cre), that selectively expresses Cre-recombinase in a subpopulation of layer 6b neurons across the entire cortical mantle. At P8, 18% of layer 6b neurons are labeled with Drd1a-Cre::tdTomato in somatosensory cortex (SS), and some co-express known layer 6b markers. Using Cre-dependent viral tracing, we identified topographical projections to higher order thalamic nuclei. VGluT1+ synapses formed by labeled layer 6b projections were found in posterior thalamic nucleus (Po) but not in the (pre)thalamic reticular nucleus (TRN). The lack of TRN collaterals was confirmed with single-cell tracing from SS. Transmission electron microscopy comparison of terminal varicosities from layer 5 and layer 6b axons in Po showed that L6b varicosities are markedly smaller and simpler than the majority from L5. Our results suggest that L6b projections to the thalamus are distinct from both L5 and L6a projections.

http://ift.tt/2CAJ2Qe

Age-dependent skin texture analysis and evaluation using mobile camera image

Abstract

Background/Purpose

The aim of this study was to evaluate skin condition, expensive equipment is required, continuous skin care is difficult. Therefore, we obtain the skin image using mobile camera, and propose a new algorithm that easily and simply extracts skin features.

Methods

We analyze skin features, extracting the wrinkle length, cell area, and the number of cells. To get accurate skin features, we obtain a new skin binary image, and apply Watershed segmentation to it. So, we improve the accuracy of skin analysis. Therefore, we compare and analyze the degree of matching distribution of wrinkles, the shape of the cell, etc., using similarity between the ground truth and the proposed algorithm result image.

Results

We extract skin surface features using a mobile camera image, and verify the change in skin features with age. Also, we demonstrate the superiority of the proposed algorithm through the similarity between the ground truth and proposed result image.

Conclusion

The proposed method in this study shows that the skin surface can be quantitatively evaluated by the similarity with ground truth. We also propose a method to diagnose and manage individual skin condition using a mobile camera in real life.

http://ift.tt/2BGA7Qq

Editorial Board

Publication date: June 2018
Source:Journal of Environmental Radioactivity, Volume 186





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Journal of Environmental Radioactivity special issue: II International Conference on Radioecological Concentration Processes. (50 years later)

Publication date: June 2018
Source:Journal of Environmental Radioactivity, Volume 186
Author(s): Rafael Garcia-Tenorio, Elis Holm
An international conference on Radioecological Concentration Processes was held in Seville, Spain, 6–9 November 2016 at the Centro Nacional de Aceleradores. It was attended by 160 participants from 35 different countries. This was the 2nd conference on this item since 1966, 50 years ago. The conference covered aspects of radiological important radionuclides on terrestrial, marine and freshwater environments and has allowed obtaining a clear picture of the status of the Radioecology as a consolidated discipline in the 21st century.



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Comparison of radiocesium concentration changes in leguminous and non-leguminous herbaceous plants observed after the Fukushima Dai-ichi Nuclear Power Plant accident

Publication date: June 2018
Source:Journal of Environmental Radioactivity, Volume 186
Author(s): Shigeo Uchida, Keiko Tagami
Transfer of radiocesium from soil to crops is an important pathway for human intake. In the period from one to two years after the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, food monitoring results showed that radiocesium concentrations in soybean (a legume) were higher than those in other annual agricultural crops; in these crops, root uptake is the major pathway of radiocesium from soil to plant. However, it was not clear whether or not leguminous and non-leguminous herbaceous plants have different Cs uptake abilities from the same soil because crop sample collection fields were different. In this study, therefore, we compared the concentrations of ¹³⁷Cs in seven herbaceous plant species including two leguminous plants (Trifolium pratense L. and Vicia sativa L.) collected in 2012–2016 from the same sampling field in Chiba, Japan that had been affected by the FDNPP accident fallout. Among these species, Petasites japonicus (Siebold & Zucc.) Maxim. showed the highest ¹³⁷Cs concentration in 2012–2016. The correlation factor between all concentration data for ¹³⁷Cs and those for ⁴⁰K in these seven plants was R = 0.54 (p < 0.001) by t-test, thus potassium uptake ability by species would affect radiocesium uptake; however, for each species, no correlation between ¹³⁷Cs and ⁴⁰K was found. Interestingly, ⁴⁰K concentrations in T. pratense, V. sativa and Poaceae family plants did not differ significantly, but ¹³⁷Cs data in the Poaceae family plants were significantly lower than those in T. pratense (p < 0.001) and V. sativa (p = 0.017). The results indicated that leguminous species would have higher ¹³⁷Cs uptake ability than Poaceae family plants.



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Transfer parameters for ICRP's Reference Animals and Plants in a terrestrial Mediterranean ecosystem

Publication date: June 2018
Source:Journal of Environmental Radioactivity, Volume 186
Author(s): J. Guillén, N.A. Beresford, A. Baeza, M. Izquierdo, M.D. Wood, A. Salas, A. Muñoz-Serrano, J.M. Corrales-Vázquez, J.G. Muñoz-Muñoz
A system for the radiological protection of the environment (or wildlife) based on Reference Animals and Plants (RAPs) has been suggested by the International Commission on Radiological Protection (ICRP). To assess whole-body activity concentrations for RAPs and the resultant internal dose rates, transfer parameters are required. However, transfer values specifically for the taxonomic families defined for the RAPs are often sparse and furthermore can be extremely site dependent. There is also a considerable geographical bias within available transfer data, with few data for Mediterranean ecosystems. In the present work, stable element concentrations (I, Li, Be, B, Na, Mg, Al, P, S, K. Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Rb, Sr, Mo, Ag, Cd, Cs, Ba, Tl, Pb and U) in terrestrial RAPs, and the corresponding whole-body concentration ratios, CRwo, were determined in two different Mediterranean ecosystems: a Pinewood and a Dehesa (grassland with disperse tree cover). The RAPs considered in the Pinewood ecosystem were Pine Tree and Wild Grass; whereas in the Dehesa ecosystem those considered were Deer, Rat, Earthworm, Bee, Frog, Duck and Wild Grass. The CRwo values estimated from these data are compared to those reported in international compilations and databases.



http://ift.tt/2xCpo8i

Natural attenuation of Fukushima-derived radiocesium in soils due to its vertical and lateral migration

Publication date: June 2018
Source:Journal of Environmental Radioactivity, Volume 186
Author(s): A. Konoplev, V. Golosov, Y. Wakiyama, T. Takase, V. Yoschenko, T. Yoshihara, O. Parenyuk, A. Cresswell, M. Ivanov, M. Carradine, K. Nanba, Y. Onda
Processes of vertical and lateral migration lead to gradual reduction in contamination of catchment soil, particularly its top layer. The reduction can be considered as natural attenuation. This, in turn, results in a gradual decrease of radiocesium activity concentrations in the surface runoff and river water, in both dissolved and particulate forms. The purpose of this research is to study the dynamics of Fukushima-derived radiocesium in undisturbed soils and floodplain deposits exposed to erosion and sedimentation during floods. Combined observations of radiocesium vertical distribution in soil and sediment deposition on artificial lawn-grass mats on the Niida River floodplain allowed us to estimate both annual mean sediment accumulation rates and maximum sedimentation rates corresponding to an extreme flood event during Tropical Storm Etau, 6-11 September 2015. Dose rates were reduced considerably for floodplain sections with high sedimentation because the top soil layer with high radionuclide contamination was eroded and/or buried under cleaner fresh sediments produced mostly due to bank erosion and sediments movements. Rate constants of natural attenuation on the sites of the Takase River and floodplain of Niida River was found to be in range 0.2–0.4 year⁻¹. For the site in the lower reach of the Niida River, collimated shield dose readings from soil surfaces slightly increased during the period of observation from February to July 2016. Generally, due to more precipitation, steeper slopes, higher temperatures and increased biological activities in soils, self-purification of radioactive contamination in Fukushima associated with vertical and lateral radionuclide migration is faster than in Chernobyl. In many cases, monitored natural attenuation along with appropriate restrictions seems to be optimal option for water remediation in Fukushima contaminated areas.



http://ift.tt/2eGyxli

Radioecological modelling of Polonium-210 and Caesium-137 in lichen-reindeer-man and top predators

Publication date: June 2018
Source:Journal of Environmental Radioactivity, Volume 186
Author(s): Bertil R.R. Persson, Runhild Gjelsvik, Elis Holm
This work deals with analysis and modelling of the radionuclides ²¹⁰Pb and²¹⁰Po in the food-chain lichen-reindeer-man in addition to ²¹⁰Po and ¹³⁷Cs in top predators. By using the methods of Partial Least Square Regression (PLSR) the atmospheric deposition of ²¹⁰Pb and ²¹⁰Po is predicted at the sample locations. Dynamic modelling of the activity concentration with differential equations is fitted to the sample data. Reindeer lichen consumption, gastrointestinal absorption, organ distribution and elimination is derived from information in the literature. Dynamic modelling of transfer of ²¹⁰Pb and ²¹⁰Po to reindeer meat, liver and bone from lichen consumption, fitted well with data from Sweden and Finland from 1966 to 1971. The activity concentration of ²¹⁰Pb in the skeleton in man is modelled by using the results of studying the kinetics of lead in skeleton and blood in lead-workers after end of occupational exposure. The result of modelling ²¹⁰Pb and ²¹⁰Po activity in skeleton matched well with concentrations of ²¹⁰Pb and ²¹⁰Po in teeth from reindeer-breeders and autopsy bone samples in Finland.The results of ²¹⁰Po and ¹³⁷Cs in different tissues of wolf, wolverine and lynx previously published, are analysed with multivariate data processing methods such as Principal Component Analysis PCA, and modelled with the method of Projection to Latent Structures, PLS, or Partial Least Square Regression PLSR.

Graphical abstract

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Estimation of air-to-grass mass interception factors for iodine

Publication date: June 2018
Source:Journal of Environmental Radioactivity, Volume 186
Author(s): N. Karunakara, P. Ujwal, I. Yashodhara, K. Sudeep Kumara, M.P. Mohan, K. Bhaskar Shenoy, P.V. Geetha, B.N. Dileep, Joshi P. James, P.M. Ravi
Air-to-grass mass interception factors for radionuclide are important basic input parameter for the estimation of radiation dose to the public around a nuclear power plant. In this paper, we present the determination of air-to- grass mass interception factors for iodine using a 2 m × 2 m × 2 m (l × b × h) size environmental chamber. The temperature, humidity, and rainfall inside the environmental chamber was controlled to required values to simulate different environmental conditions. Grass (Pennisetum purpureum, Schum), grown in pots, was kept inside the environmental chamber and stable iodine in elemental form was sublimed quickly inside the chamber to simulate an accidental release of iodine to the environment. The concentration of iodine in the air was measured periodically by drawing air through a bubbling setup, containing 1% sodium carbonate solution. The mass interception factor for dry deposition varied in the range of 0.25–7.7 m² kg⁻¹ with mean value of 2.2 m² kg⁻¹ with respect to fresh weight of grass, and that due to wet deposition varied in the range of 0.6–4.8 m² kg⁻¹ with mean value of 2.3 m² kg⁻¹. The mass interception factor was inversely correlated with the total iodine deposited through dry deposition as well as with the rainfall.



http://ift.tt/2Gvy2px

Application of bomb- and Chernobyl-derived radiocaesium for reconstructing changes in erosion rates and sediment fluxes from croplands in areas of European Russia with different levels of Chernobyl fallout

Publication date: June 2018
Source:Journal of Environmental Radioactivity, Volume 186
Author(s): V.N. Golosov, D.E. Walling, A.V. Konoplev, M.M. Ivanov, A.G. Sharifullin




http://ift.tt/2Fk3Hea

Challenges associated with the behaviour of radioactive particles in the environment

Publication date: June 2018
Source:Journal of Environmental Radioactivity, Volume 186
Author(s): Brit Salbu, Valery Kashparov, Ole Christian Lind, Rafael Garcia-Tenorio, Mathew P. Johansen, David P. Child, Per Roos, Carlos Sancho
A series of different nuclear sources associated with the nuclear weapon and fuel cycles have contributed to the release of radioactive particles to the environment. Following nuclear weapon tests, safety tests, conventional destruction of weapons, reactor explosions and fires, a major fraction of released refractory radionuclides such as uranium (U) and plutonium (Pu) were present as entities ranging from sub microns to fragments. Furthermore, radioactive particles and colloids have been released from reprocessing facilities and civil reactors, from radioactive waste dumped at sea, and from NORM sites. Thus, whenever refractory radionuclides are released to the environment following nuclear events, radioactive particles should be expected.Results from many years of research have shown that particle characteristics such as elemental composition depend on the source, while characteristics such as particle size distribution, structure, and oxidation state influencing ecosystem transfer depend also on the release scenarios. When radioactive particles are deposited in the environment, weathering processes occur and associated radionuclides are subsequently mobilized, changing the apparent Kd. Thus, particles retained in soils or sediments are unevenly distributed, and dissolution of radionuclides from particles may be partial. For areas affected by particle contamination, the inventories can therefore be underestimated, and impact and risk assessments may suffer from unacceptable large uncertainties if radioactive particles are ignored. To integrate radioactive particles into environmental impact assessments, key challenges include the linking of particle characteristics to specific sources, to ecosystem transfer, and to uptake and retention in biological systems. To elucidate these issues, the EC-funded COMET and RATE projects and the IAEA Coordinated Research Program on particles have revisited selected contaminated sites and archive samples. This COMET position paper summarizes new knowledge on key sources that have contributed to particle releases, including particle characteristics based on advanced techniques, with emphasis on particle weathering processes as well as on heterogeneities in biological samples to evaluate potential uptake and retention of radioactive particles.



http://ift.tt/2Gw46cX

Accelerator Mass Spectrometry (AMS) in Radioecology

Publication date: June 2018
Source:Journal of Environmental Radioactivity, Volume 186
Author(s): M. García-León
Accelerator Mass Spectrometry (AMS) provides with an excellent sensitivity for the determination of radionuclides in the environment. In fact, conventional radiometric techniques can hardly compete with AMS in the solution of many problems involving the measurement of very low levels of radioactivity in Nature. For that reason, during the last years AMS has become a powerful tool for Radioecology studies.In this paper a review is done on the evolution of AMS applications to the measurement of environmental radioactivity and, therefore, its contribution to the understanding of radionuclide behavior in Nature. For that, the advantages of using AMS to determine key nuclides as ¹²⁹I, ¹⁴C, Pu-isotopes and others in different natural compartments will be discussed. The content of the paper is illustrated with the contributions to these studies of the Spanish National Center for Accelerators (CNA) AMS systems.



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Pacific Proving Grounds radioisotope imprint in the Philippine Sea sediments

Publication date: June 2018
Source:Journal of Environmental Radioactivity, Volume 186
Author(s): Daniela Pittauer, Per Roos, Jixin Qiao, Walter Geibert, Marcus Elvert, Helmut W. Fischer
Radionuclide concentrations were studied in sediment cores taken at the continental slope of the Philippine Sea off Mindanao Island in the equatorial Western Pacific. High resolution deposition records of anthropogenic radionuclides were collected at this site. Excess ²¹⁰Pb together with excess ²²⁸Th and anthropogenic radionuclides provided information about accumulation rates. Concentrations of Am and Pu isotopes were detected by gamma spectrometry, alpha spectrometry and ICP-MS. The Pu ratios indicate a high portion (minimum of 60%) of Pu from the Pacific Proving Grounds (PPG). This implies that the transport of PPG derived plutonium with the Mindanao Current southward is similarly effective as the previously known transport towards the north with the Kuroshio Current. The record is compared to other studies from northwest Pacific marginal seas and Lombok basin in the Indonesian Archipelago. The sediment core top was found to contain a 6 cm thick layer dominated by terrestrial organic matter, which was interpreted as a result of the 2012 Typhoon Pablo-related fast deposition.



http://ift.tt/2Gyel0m

Phase II Trial of Carboplatin, 5-FU and Cetuximab in Elderly Fit (no Frailty) Patients With Recurrent/Metastatic HNSCC

Condition:   Metastatic or Recurrent Head and Neck Squamous Cell Cancer
Intervention:   Drug: Carbo, 5FU, Cetuximab
Sponsors:   Groupe Oncologie Radiotherapie Tete et Cou;   Gustave Roussy, Cancer Campus, Grand Paris
Recruiting

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Perceptual Boundaries Cause Mnemonic Trade-Offs Between Local Boundary Processing and Across-Trial Associative Binding.

Author: Heusser, Andrew C.; Ezzyat, Youssef; Shiff, Ilana; Davachi, Lila

DOI: 10.1037/xlm0000503

Publication Date: POST AUTHOR CORRECTIONS, 19 February 2018

http://ift.tt/2EX5GXX

Multiscale Deep Neural Networks based analysis of FDG-PET images for the Early Diagnosis of Alzheimer’s Disease

Publication date: Available online 21 February 2018
Source:Medical Image Analysis
Author(s): Donghuan Lu, Karteek Popuri, Gavin Weiguang Ding, Rakesh Balachandar, Mirza Faisal Beg
Alzheimer's Disease (AD) is one of the most common neurodegenerative diseases with a commonly seen prodromal mild cognitive impairment (MCI) phase where memory loss is the main complaint progressively worsening with behavior issues and poor self-care. However, not all individuals clinically diagnosed with MCI progress to AD. A fraction of subjects with MCI either progress to non-AD dementia or remain stable at the MCI stage without progressing to dementia. Although a curative treatment of AD is currently unavailable, it is extremely important to correctly identify the individuals in the MCI phase that will go on to develop AD so that they may benefit from a curative treatment when one becomes available in the near future. At the same time, it would be highly desirable to also correctly identify those in the MCI phase that do not have AD pathology so they may be spared from unnecessary pharmocologic interventions that, at best, may provide them no benefit, and at worse, could further harm them with adverse side-effects. Additionally, it may be easier and simpler to identify the cause of the cognitive impairment in these non-AD cases, and hence proper identification of prodromal AD will be of benefit to these individuals as well.Fluorodeoxy glucose positron emission tomography (FDG-PET) captures the metabolic activity of the brain, and this imaging modality has been reported to identify changes related to AD prior to the onset of structural changes. Prior work on designing classifier using FDG-PET imaging has been promising. Since deep-learning has recently emerged as a powerful tool to mine features and use them for accurate labeling of the group membership of given images, we propose a novel deep-learning framework using FDG-PET metabolism imaging to identify subjects at the MCI stage with presymptomatic AD and discriminate them from other subjects with MCI (non-AD / non-progressive). Our multiscale deep neural network obtained 82.51 % accuracy of classification just using measures from a single modality (FDG-PET metabolism data) outperforming other comparable FDG-PET classifiers published in the recent literature.

Graphical abstract

http://ift.tt/2oorGAZ

The Decomposition of Deformation: new metrics to enhance shape analysis in medical imaging.

Publication date: Available online 21 February 2018
Source:Medical Image Analysis
Author(s): Valerio Varano, Paolo Piras, Stefano Gabriele, Luciano Teresi, Paola Nardinocchi, Ian L. Dryden, Concetta Torromeo, Paolo E. Puddu
In landmarks-based Shape Analysis size is measured, in most cases, with Centroid Size. Changes in shape are decomposed in affine and non affine components. Furthermore the non affine component can be in turn decomposed in a series of local deformations (partial warps). If the extent of deformation between two shapes is small, the difference between centroid size and m-Volume increment is barely appreciable. In medical imaging applied to soft tissues bodies can undergo very large deformations, involving large changes in size. The cardiac example, analyzed in the present paper, shows changes in m-Volume that can reach the 60%. We show here that standard Geometric Morphometrics tools (landmarks, Thin Plate Spline, and related decomposition of the deformation) can be generalized to better describe the very large deformations of biological tissues, without losing a synthetic description. In particular, the classical decomposition of the space tangent to the shape space in affine and non affine components is enriched to include also the change in size, in order to give a complete description of the tangent space to the size-and-shape space. The proposed generalization is formulated by means of a new Riemannian metric describing the change in size as change in m-Volume rather than change in Centroid Size. This leads to a redefinition of some aspects of the Kendall's size-and-shape space without losing Kendall's original formulation. This new formulation is discussed by means of simulated examples using 2D and 3D platonic shapes as well as a real example from clinical 3D echocardiographic data. We demonstrate that our decomposition based approaches discriminate very effectively healthy subjects from patients affected by Hypertrophic Cardiomyopathy.

Graphical abstract

http://ift.tt/2CebSdr

A Survey of Methods for 3D Histology Reconstruction

Publication date: Available online 21 February 2018
Source:Medical Image Analysis
Author(s): Jonas Pichat, Juan Eugenio Iglesias, Tarek Yousry, Sébastien Ourselin, Marc Modat
Histology permits the observation of otherwise invisible structures of the internal topography of a specimen. Although it enables the investigation of tissues at a cellular level, it is invasive and breaks topology due to cutting. Three-dimensional (3D) reconstruction was thus introduced to overcome the limitations of single-section studies in a dimensional scope. It finds its roots in embryology, where it enabled the visualisation of spatial relationships of developing systems and organs, and extended to biomedicine, where the observation of individual, stained sections provided only partial understanding of normal and abnormal tissues. However, despite bringing visual awareness, recovering realistic reconstructions is elusive without prior knowledge about the tissue shape.3D medical imaging made such structural ground truths available. In addition, combining non-invasive imaging with histology unveiled invaluable opportunities to relate macroscopic information to the underlying microscopic properties of tissues through the establishment of spatial correspondences; image registration is one technique that permits the automation of such a process and we describe reconstruction methods that rely on it. It is thereby possible to recover the original topology of histology and lost relationships, gain insight into what affects the signals used to construct medical images (and characterise them), or build high resolution anatomical atlases.This paper reviews almost three decades of methods for 3D histology reconstruction from serial sections, used in the study of many different types of tissue. We first summarise the process that produces digitised sections from a tissue specimen in order to understand the peculiarity of the data, the associated artefacts and some possible ways to minimise them. We then successively describe methods for 3D histology reconstruction without and with the help of 3D medical imaging, along with methods of validation and some applications. We finally attempt to identify the trends and challenges that the field is facing, many of which are derived from the cross-disciplinary nature of the problem as it involves the collaboration between physicists, histologists, computer scientists and physicians.

Graphical abstract

http://ift.tt/2onVHAU

Fully-Automated Alignment of 3D Fetal Brain Ultrasound to a Canonical Reference Space using Multi-Task Learning

Publication date: Available online 21 February 2018
Source:Medical Image Analysis
Author(s): Ana I.L. Namburete, Weidi Xie, Mohammad Yaqub, Andrew Zisserman, J. Alison Noble
Methods for aligning 3D fetal neurosonography images must be robust to (i) intensity variations, (ii) anatomical and age-specific differences within the fetal population, and (iii) the variations in fetal position. To this end, we propose a multi-task fully convolutional neural network (FCN) architecture to address the problem of 3D fetal brain localization, structural segmentation, and alignment to a referential coordinate system. Instead of treating these tasks as independent problems, we optimize the network by simultaneously learning features shared within the input data pertaining to the correlated tasks, and later branching out into task-specific output streams. Brain alignment is achieved by defining a parametric coordinate system based on skull boundaries, location of the eye sockets, and head pose, as predicted from intracranial structures. This information is used to estimate an affine transformation to align a volumetric image to the skull-based coordinate system. Co-alignment of 140 fetal ultrasound volumes (age range: 26.0 ± 4.4 weeks) was achieved with high brain overlap and low eye localization error, regardless of gestational age or head size. The automatically co-aligned volumes show good structural correspondence between fetal anatomies.

Graphical abstract

http://ift.tt/2ogQN9r

The role of trophoblastic epigenetic reprogrammation in benign tumor cells on malignant progression: a mollecular hypothesis

Publication date: Available online 21 February 2018
Source:Medical Hypotheses
Author(s): Kevin Doello
Cancer tissues and placental ones share many properties such as invasiveness, metastasis and local immunosuppressive effects. The goal of the present article is to hypothesize a theory about cancer origin that links placental and cancerous tissues at mollecular level. This hypothesis explain that cancer origin could be due to low hypoxic conditions in the peripheral zones of benign tumors which might up-regulate the expression of IGF2, and, consequently, trophoblastic genes. In fact, many phenotypic characteristics and molecular markers are shared between these two cell types (cancerous and trophoblastics ones), providing evidences to support this hypothesis. As a consequence, it could be interesting to demonstrate whether cancer start with a cellular reprogramation towards a trophoblastic fate in order to design new antitumoral strategies focused on this fact.



http://ift.tt/2ohFqhH

Potential role of lipoic acid as a chelator in prevention and treatment of gadolinium brain retention

Publication date: Available online 21 February 2018
Source:Medical Hypotheses
Author(s): Ashkan Heshmatzadeh Behzadi, Ajay Gupta, Martin R. Prince




http://ift.tt/2BH26zm

Plasma creatine as a marker of mitochondrial dysfunction

Publication date: Available online 21 February 2018
Source:Medical Hypotheses
Author(s): Sergej M. Ostojic
Mitochondrial dysfunction (MD) is a complex pathophysiological phenomenon, linked with many inherited and acquired diseases. A clinical evaluation of MD requires rather extensive approach, while no gold-standard circulating biomarker has been established so far. Partly produced in mitochondria, creatine thus might be considered as a sensible compound of mitochondrial bioenergetics. Increased plasma creatine perhaps is linked with MD, illustrating disturbances in its utilization in the stressed organelle.



http://ift.tt/2CdDQG3

Preoperative gastric lavage in gastric cancer patients undergoing surgical, endoscopic or minimally invasive treatment: an oncological measure preventing peritoneal spillage of intragastric cancer cells and development of related metastases

Publication date: Available online 21 February 2018
Source:Medical Hypotheses
Author(s): Edoardo Virgilio, Genoveffa Balducci, Paolo Mercantini, Enrico Giarnieri, Maria Rosaria Giovagnoli, Monica Montagnini, Antonella Proietti, Rosaria D'Urso, Marco Cavallini
In addition to classical metastatic pathways, recently gastric cancer was described having an alternative route called "endoluminal exfoliation". Provisional analyses demonstrated, in fact, this kind of shedding is associated with several clinico-pathological features indicative of aggressive behavior and resulted to be an independent prognostic factor entailing poor prognosis. Compared with non-sowing counterparts, in fact, patients affected with exfoliating early and advanced gastric carcinomas met with shorter overall survival, disease free survival, progression free survival and time to tumor progression. In spite of these interesting results, however, the clinico-pathological and oncological significance of this unconventional metastatic route is still to be clarified. Such an investigation is further urged by the increasing widespread employment of minimally invasive treatments for gastric cancer which include a wide spectrum of intragastric interventions and maneuvers. Indeed, endoscopic mucosal resection, endoscopic submucosal dissection, endoscopic full-thickness resection, intragastric laparoscopic surgery and hybrid procedures all take place inside of the stomach. However, iatrogenic perforations can occur during execution of these treatments leading to spillage of malignant cells from gastric to the peritoneal cavity or trocar insertion sites. Furthermore, many other gastric conditions and interventions can collide with endogastric presence of floating cancer cells: spontaneous ulceration or perforation, laparotomy surgery, gastrointestinal occlusion, diverticula. Viability, migration and intraluminal transportability of the intragastric floating cancer cells represents another original and intriguing topic. All these considerations led us to entertain the hypothesis that removing the exfoliated cancer cells from the gastric lumen could save patients from the dreaded potential risk of spillage. Performing gastric lavage before starting any kind of tumor intervention could be the most appropriate procedure to adopt with prophylactic intent. Should our speculation prove to be clinically significant, preoperative gastric lavage should be pointed out as a simple but cogent method useful for preventing oncological mishaps such as spillage of gastric cancer cells and development of related recurrences or metastases.



http://ift.tt/2omv7b6

Comparison of Two Different Ultrasound Devices Using Strain Elastography Technology in the Diagnosis of Breast Lesions Related to the Histologic Results

Publication date: Available online 22 February 2018
Source:Ultrasound in Medicine & Biology
Author(s): André Farrokh, Fritz Schaefer, Friedrich Degenhardt, Nicolai Maass
This study was conducted to provide evidence that elastograms of two different devices and different manufacturers using the same technical approach provide the same diagnoses. A total of 110 breast lesions were prospectively analysed by two experts in ultrasound, using the strain elastography function from two different manufacturers (Hitachi HI-RTE, Hitachi Medical Systems, Wiesbaden, Germany; and Siemens eSie Touch, Siemens Medical Systems, Erlangen, Germany). Results were compared with the histopathologic results. Applying the Bowker test of symmetry, no statistically significant difference between the two elastography functions of these two devices was found (p = 0.120). The Cohen's kappa of k = 0.591 showed moderate strength of agreement between the two elastograms. The two examiners yielded moderate strength of agreement analysing the elastograms (Hitachi HI-RTE, k = 0.478; Siemens eSie Touch, k = 0.441). In conclusion, evidence is provided that elastograms of the same lesion generated by two different ultrasound devices equipped with a strain elastography function do not significantly differ.



http://ift.tt/2ooW26q

Orthogonal B-Mode Evaluation of Common Carotid Artery Plaques Reveals the Absence of Outward Remodeling

Publication date: Available online 21 February 2018
Source:Ultrasound in Medicine & Biology
Author(s): J. Steinbuch, F.H.B.M. Schreuder, K.D. Reesink, A.P.G. Hoeks, W.H. Mess
To properly assess morphologic and dynamic parameters of arteries and plaques, we propose the concept of orthogonal distance measurements, that is, measurements made perpendicular to the local lumen axis rather than along the ultrasound beam (vertical direction for a linear array). The aim of this study was to compare orthogonal and vertical artery and lumen diameters at the site of a plaque in the common carotid artery (CCA). Moreover, we investigated the interrelationship of orthogonal diameters and plaque size and the association of artery parameters with plaque echogenicity. In 29 patients, we acquired a longitudinal B-mode ultrasound recording of plaques at the posterior CCA wall. After semi-automatic segmentation of end-diastolic frames, diameters were extracted orthogonally along the lumen axis. To establish inter-observer variability of diameters obtained at the location of maximal plaque thickness, a second observer repeated the analysis (subset N = 21). Orthogonal adventitia–adventitia and lumen diameters could be determined with good precision (coefficient of variation: 1%–5%. However, the precision of the change in lumen diameter from diastole to systole (distension) at the site of the plaque was poor (21%–50%). The orthogonal lumen diameter was significantly smaller than the vertical lumen diameter (p < 0.001). Surprisingly, the plaques did not cause outward remodeling, that is, a local increase in adventitia–adventitia distance at the site of the plaque. The intra- and inter-observer precision of diastolic–systolic plaque compression was poor and of the same order as the standard deviation of plaque compression. The orthogonal relative lumen distension was significantly lower for echogenic plaques, indicating a higher stiffness, than for echolucent plaques (p < 0.01). In conclusion, we illustrated the feasibility of extracting orthogonal CCA and plaque dimensions, albeit that the proposed approach is inadequate to quantify plaque compression.



http://ift.tt/2CcJs3s

Shear Wave Speed Estimation Using Reverberant Shear Wave Fields: Implementation and Feasibility Studies

Publication date: Available online 21 February 2018
Source:Ultrasound in Medicine & Biology
Author(s): Juvenal Ormachea, Benjamin Castaneda, Kevin J. Parker
Elastography is a modality that estimates tissue stiffness and, thus, provides useful information for clinical diagnosis. Attention has focused on the measurement of shear wave propagation; however, many methods assume shear wave propagation is unidirectional and aligned with the lateral imaging direction. Any deviations from the assumed propagation result in biased estimates of shear wave speed. To address these challenges, directional filters have been applied to isolate shear waves with different propagation directions. Recently, a new method was proposed for tissue stiffness estimation involving creation of a reverberant shear wave field propagating in all directions within the medium. These reverberant conditions lead to simple solutions, facile implementation and rapid viscoelasticity estimation of local tissue. In this work, this new approach based on reverberant shear waves was evaluated and compared with another well-known elastography technique using two calibrated elastic and viscoelastic phantoms. Additionally, the clinical feasibility of this technique was analyzed by assessing shear wave speed in human liver and breast tissues, in vivo. The results indicate that it is possible to estimate the viscoelastic properties in each scanned medium. Moreover, a better approach to estimation of shear wave speed was obtained when only the phase information was taken from the reverberant waves, which is equivalent to setting all magnitudes within the bandpass equal to unity: an idealization of a perfectly isotropic reverberant shear wave field.



http://ift.tt/2BHK2VM

Radiation Biology and Circulating Tumor Cells

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Brian Marples, Scott M. Welford




http://ift.tt/2sKtdqn

In Regard to Kumar et al

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Pervin Hurmuz, Mustafa Cengiz, Faruk Zorlu, Fadil Akyol




http://ift.tt/2EVUIC9

Radiation Therapy in a Time of Disaster

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Sue S. Yom, Anthony L. Zietman




http://ift.tt/2sNfteu

Puerto Rico: After María

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Angélica Pérez-Andújar




http://ift.tt/2EYpYk4

Issue Highlights

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4





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When Disaster Strikes: Mitigating the Adverse Impact on Head and Neck Cancer Patients

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Sue S. Yom, Paul M. Harari




http://ift.tt/2sK8ClZ

Radiation Necrosis and White Matter Lesions in Pediatric Patients With Brain Tumors Treated With Pencil Beam Scanning Proton Therapy

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Beat Bojaxhiu, Frank Ahlhelm, Marc Walser, Lorenzo Placidi, Ulrike Kliebsch, Lorentzos Mikroutsikos, Petra Morach, Alessandra Bolsi, Tony Lomax, Alessia Pica, Damien C. Weber
PurposeTo assess the rate of radiation necrosis (RN) and white matter lesions (WMLs) in pediatric patients with primary brain tumors treated with pencil beam scanning (PBS) proton therapy (PT) with or without concomitant chemotherapy at the PSI.Methods and MaterialsBetween 1999 and 2015, 171 pediatric patients (age <18 years) were treated with PT. Median age at diagnosis was 3.3 years (range, 0.3-17.0 years), and the median delivered dose was 54 Gy (relative biological effectiveness) (range, 40.0–74.1 Gy). Radiation necrosis and WMLs were defined as a new area of abnormal signal intensity on T2-weighted images or increased signal intensity on T2-weighted images, and contrast enhancement on T1 occurring in the brain parenchyma included in the radiation treatment field, which did not demonstrate any abnormality before PT. Radiation necrosis and WMLs were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up period for the surviving patients was 49.8 months (range, 5.9-194.7 months).ResultsTwenty-nine patients (17%) developed RN at a median time of 5 months (range, 1-26 months), most of them (n = 17; 59%) being asymptomatic (grade 1). Grade 2, 4, and 5 toxicities occurred in 8, 2, and 2 patients, respectively. Eighteen patients (11%) developed WMLs at a median time of 14.5 months (range, 2-62 months), most of them (n = 13; 72%) being asymptomatic (grade 1). White matter lesion grade 2 and 3 toxicities occurred in 4 and 1 patient(s), respectively. The 5-year RN-free and WML-free survival was 83% and 87%, respectively. In univariate analysis, neoadjuvant (P = .025) or any (P = .03) chemotherapy, hydrocephalus before PT (P = .035), and ependymoma (P = .026) histology were significant predictors of RN.ConclusionsChildren treated with PT demonstrated a low prevalence of symptomatic RN (7%) or WML (3%) compared with similar cohorts treated with either proton or photon radiation therapy. Chemotherapy, ependymomal tumors and hydrocephalus as an initial symptom were significant risk factors for RN.



http://ift.tt/2EZGVL6

Role of Overall Treatment Time in the Management of Prostate Cancer Patients: How to Manage Unscheduled Treatment Interruptions

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Howard M. Sandler




http://ift.tt/2sIFHPf

Radiation Oncology in the Face of Natural Disaster: The Experience of Houston Methodist Hospital

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Matthew Mireles, Ramiro Pino, Bin S. Teh, Andrew Farach, Adrienne Joseph, E. Brian Butler




http://ift.tt/2EWIuZV

Radiation Oncology and Related Oncology Fields in the Face of the 2011 “Triple Disaster” in Fukushima, Japan

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Akihiko Ozaki, Masaharu Tsubokura




http://ift.tt/2sM8fHG

Meetings

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4





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Our Role in Radiation Disaster Preparedness

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Andrew L. Salner




http://ift.tt/2sJEtTM

Hippocampal Sparing During Craniospinal Irradiation: What Did We Learn About the Incidence of Perihippocampus Metastases?

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Laetitia Padovani, Frédérique Chapon, Nicolas André, Mohamed Boucekine, Anne Geoffray, Franck Bourdeau, Julien Masliah-Planchon, Line Claude, Aymeri Huchet, Anne Laprie, Stephane Supiot, Bernard Coche-Dequéant, Christine Kerr, Claire Alapetite, Julie Leseur, Tandat Nguyen, Sophie Chapet, Valerie Bernier, Pierre-Yves Bondiau, Georges Noel, Jean Louis Habrand, Stephanie Bolle, François Doz, Christelle Dufour, Xavier Muracciole, Christian Carrie
PurposeTo identify the incidence of patients with perihippocampal metastases to assess the risk of brain relapse when sparing the hippocampal area. Medulloblastoma (MB) represents 20% of pediatric brain tumors. For high-risk MB patients, the 3- to 5-year event-free survival rate has recently improved from 50% to >76%. Many survivors, however, experience neurocognitive side effects. Several retrospective studies of patients receiving whole brain irradiation (WBI) have suggested a relationship between the radiation dose to the hippocampus and neurocognitive decline. The hippocampal avoidance-WBI (HA-WBI) approach could partially reduce neurocognitive impairment in children treated for high-risk MB.Methods and MaterialsFrom 2008 to 2011, 51 patients with high-risk MB were treated according to the French trial primitive neuroectodermal tumor HR+5. Hippocampal contouring was manually generated on 3-dimensional magnetic resonance images according to the Radiation Therapy Oncology Group 0933 atlas. The distribution of metastases was assessed relative to the hippocampus: 0 to 5 mm for the first perihippocampal area and 5 to 15 mm for the rest of the perihippocampal area.ResultsThe median patient age was 8.79 years (33% female). After a follow-up of 2.4 years, 43 patients were alive; 28 had had brain metastasis at diagnosis and 2 at relapse, with 16% in the first perihippocampal area and 43% in the rest of the perihippocampal area. Of the 18 patients without brain metastases at diagnosis, including M1 patients, none developed secondary lesions within the first or the rest of the perihippocampal area, after receiving 36 Gy. No clinical or biological factor was significantly associated with the development of perihippocampal metastases.ConclusionsOur results suggest the HA-WBI strategy should be evaluated for the subgroup of high-risk MB patients without metastatic disease.



http://ift.tt/2EVUniR

CTV Guidance for Head and Neck Cancers

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Beth M. Beadle, Carryn M. Anderson




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Phase 1 Dose Escalation Trial of Ipilimumab and Stereotactic Body Radiation Therapy in Metastatic Melanoma

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Nora Sundahl, Katrien De Wolf, Vibeke Kruse, Annabel Meireson, Dries Reynders, Els Goetghebeur, Mireille Van Gele, Reinhart Speeckaert, Benjamin Hennart, Lieve Brochez, Piet Ost
PurposeTo report the results of a phase 1 trial evaluating the safety of the ipilimumab/radiation therapy combination in patients with metastatic melanoma.Patients and MethodsThirteen patients with metastatic melanoma were enrolled. Trial treatment consisted of 4 cycles of ipilimumab in combination with concurrent dose-escalated high-dose radiation therapy to 1 lesion administered before the third cycle of ipilimumab.ResultsGrade 3 or 4 ipilimumab-related adverse events occurred in 25% of patients. The maximum tolerated radiation therapy dose was not reached. Local control of the irradiated lesions was achieved in 11 of 12 irradiated patients (1 patient had progressive disease before irradiation and dropped out of the trial). Evaluation of the nonirradiated lesions demonstrated that 3 of 13 patients experienced clinical benefit, with 1 patient developing a partial response and 2 patients having confirmed stable disease. Immunomonitoring data showed that in patients without clinical benefit, factors linked to immunotolerance increased early after the initiation of ipilimumab, suggesting that early initiation of radiation therapy might be more effective if combined with ipilimumab.ConclusionsOur findings suggest that the combination of ipilimumab and high-dose radiation therapy is feasible and safe.



http://ift.tt/2sLYadB

Decision-Making Strategy for Rectal Cancer Management Using Radiation Therapy for Elderly or Comorbid Patients

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Shang-Jui Wang, Lara Hathout, Usha Malhotra, Nell Maloney-Patel, Sarah Kilic, Elizabeth Poplin, Salma K. Jabbour
Rectal cancer predominantly affects patients older than 70 years, with peak incidence at age 80 to 85 years. However, the standard treatment paradigm for rectal cancer oftentimes cannot be feasibly applied to these patients owing to frailty or comorbid conditions. There are currently little information and no treatment guidelines to help direct therapy for patients who are elderly and/or have significant comorbidities, because most are not included or specifically studied in clinical trials. More recently various alternative treatment options have been brought to light that may potentially be utilized in this group of patients. This critical review examines the available literature on alternative therapies for rectal cancer and proposes a treatment algorithm to help guide clinicians in treatment decision making for elderly and comorbid patients.



http://ift.tt/2EUWEuB

Location-allocation model for external beam radiotherapy as an example of an evidence-based management tool implemented in healthcare sector in Poland

Publication date: Available online 21 February 2018
Source:Radiotherapy and Oncology
Author(s): Adam Michał Czerwiński, Barbara Więckowska
Background and purposeExternal beam radiotherapy (EBRT) is one of three key treatment modalities of cancer patients. Its utilisation and outcomes depend on a plethora of variables, one of which is the distance a patient must travel to undergo the treatment. The relation between distance and utilisation is clearly visible in Poland. At the same time no strategic investment plan is observed. This work proposes a method of resolving these two issues.Materials and methodsWe propose a mixed-integer linear programming model that aims to optimise the distribution of linear accelerators among selected locations in such a way that a patient's journey to the nearest EBRT is as short as possible. The optimisation is done with observance of international guidelines concerning EBRT capacity. With the use of proposed theoretical framework, we develop a national, strategic plan for linear accelerator investments.ResultsAccording to model assumptions decentralisation of EBRT, together with new equipment purchases, is required to ensure optimal access to EBRT.ConclusionsThe results were incorporated into Healthcare Needs Maps for Poland. The plan based on the results of this study, implemented by 2025, should deal with the most pressing concerns of Polish EBRT.



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Comparison of cortical responses to the activation of retina by visual stimulation and transcorneal electrical stimulation

Publication date: Available online 21 February 2018
Source:Brain Stimulation
Author(s): Pengcheng Sun, Heng Li, Zhuofan Lu, Xiaofan Su, Zengguang Ma, Jianpin Chen, Liming Li, Chuanqing Zhou, Yao Chen, Xinyu Chai
BackgroundElectrical stimulation has been widely used in many ophthalmic diseases to modulate neuronal activities or restore partial visual function. Due to the different processing pathways and mechanisms, responses to visual and electrical stimulation in the primary visual cortex and higher visual areas might be different. This differences would shed some light on the properties of cortical responses evoked by electrical stimulation.ObjectiveThis study's goal was to directly compare the cortical responses evoked by visual and electrical stimulation and investigate the cortical processing of visual information and extrinsic electrical signal.MethodsOptical imaging of intrinsic signals (OIS) was used to probe the cortical hemodynamic responses in 11 cats. Transcorneal electrical stimulation (TES) through an ERG-jet contact lens electrode was used to activate visual cortices. Full-field and peripheral drifting gratings were used as the visual stimuli.ResultsThe response latency evoked by TES was shorter than that responding to visual stimulation (VS). Cortical responses evoked by VS were retinotopically organized, which was consistent with previous studies. On the other hand, the cortical region activated by TES was preferentially located in the secondary visual cortex (Area 18), while the primary visual cortex (Area 17) was activated by a higher current intensity. Compared with the full-field VS, the cortical response in Area 18 to TES with a current intensity above 1.2 mA was significantly stronger.ConclusionAccording to our results, we hypothesized that the cortical processing of TES was influenced by the distribution of the electrical field in the retina and the activating threshold of different retinal ganglion cells.



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Environmental enrichment decreases avoidance responses in the elevated T-maze and delta FosB immunoreactivity in anxiety-related brain regions

Publication date: 15 May 2018
Source:Behavioural Brain Research, Volume 344
Author(s): Danielle A. Lopes, Thaissa M.O. Souza, José S. de Andrade, Mariana F.S. Silva, Hanna K.M. Antunes, Luciana Le Sueur-Maluf, Isabel C. Céspedes, Milena B. Viana
Environmental enrichment (EE) is an animal management technique, which seems to improve adaptation to the experimental conditions of housing in laboratory animals. Previous studies have pointed to different beneficial effects of the procedure in the treatment of several disorders, including psychiatric conditions such as depression. The anxiolytic effects induced by EE, on the other hand, are not as clear. In fact, it has been proposed that EE acts as a mild stressor agent. To better understand the relationship of EE with anxiety-related responses, the present study exposed rats to one week of EE and subsequently tested these animals in the inhibitory avoidance and escape tasks of the elevated T-maze (ETM). In clinical terms, these responses have been respectively related to generalized anxiety and panic disorder. All animals were tested in an open field, immediately after the ETM, for locomotor activity assessment. Additionally, analysis of delta FosB protein immunoreactivity (FosB-ir) was used to map areas activated by EE exposure and plasma corticosterone measurements were performed. The results obtained demonstrate that exposure to EE for one week impaired avoidance responses, an anxiolytic-like effect, without altering escape reactions. Also, in animals submitted to the avoidance task EE exposure decreased FosB-ir in the cingulate cortex, dorsolateral and intermediate lateral septum, hippocampus (cornus of Ammon), anterior and dorsomedial hypothalamus, medial and basolateral amygdala and ventral region of the dorsal raphe nucleus. Although no behavioral differences were observed in animals submitted to the escape task, EE exposure also decreased FosB-ir in the cingulate cortex, hippocampus (dentate gyrus), lateral amygdala, paraventricular, anterior and ventromedial hypothalamus, dorsomedial periaqueductal gray and ventral and dorsal region of the dorsal raphe. No changes in corticosterone levels, however, were observed. These results contribute to a better understanding of the effects of EE on anxiety.



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The role of intraamygdaloid neurotensin and dopamine interaction in conditioned place preference

Publication date: 15 May 2018
Source:Behavioural Brain Research, Volume 344
Author(s): K. László, L. Péczely, A. Kovács, O. Zagoracz, T. Ollmann, E. Kertes, V. Kállai, B. Csetényi, Z. Karádi, L. Lénárd
Tridecapeptide Neurotensin (NT) is widely distributed in the central nervous system where it acts as a neurotransmitter and neuromodulator. The central nucleus of amygdala (CeA), part of the limbic system, plays an important role in learning, memory, anxiety and reinforcing mechanisms. Our previous data showed that NT microinjected into the CeA has positive reinforcing properties. We supposed that these effects might be due to modulations of the mesolimbic dopamine system. The aim of our study was to examine in the CeA the possible effects of NT and dopamine interaction on reinforcement by conditioned place preference test.Male Wistar rats were microinjected bilaterally with 100 ng NT or 2 μg D1 dopamine receptor antagonist alone, or D1 dopamine antagonist 15 min before 100 ng NT treatment or vehicle solution into the CeA. Other animals received 4 μg D2 dopamine receptor antagonist Sulpiride alone, or administration of D2 dopamine receptor antagonist 15 min before 100 ng NT treatment or vehicle solution into the CeA.Rats that received 100 ng NT spent significantly more time in the treatment quadrant during the test session. Pre-treatment with the D1 dopamine antagonist, blocked the effects of NT. D2 dopamine receptor antagonist pretreatment could prevent the positive reinforcing effects of NT as well. Antagonists themselves did not influence the place preference.Our results show that the rewarding effect of NT can be due to the modulation of DA system, since its effects could be blocked by either D1 dopamine or D2 dopamine antagonist preteatment.



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Fluctuations of extracellular glucose and lactate in the mouse primary visual cortex during visual stimulation

Publication date: 15 May 2018
Source:Behavioural Brain Research, Volume 344
Author(s): Alexandria Béland-Millar, Claude Messier
We measured the extracellular glucose and lactate in the primary visual cortex in the CD-1 mouse using electrochemical electrodes. To gain some additional information on brain metabolism, we examined the impact of systemic injections of lactate and fructose on the brain extracellular glucose and lactate changes observed during visual stimulation. We found that simple stimulation using a flashlight produced a decrease in visual cortex extracellular glucose and an increase in extracellular lactate. Similar results were observed following visual stimulation with an animated movie without soundtrack or the presentation of a novel object. Specificity of these observations was confirmed by the absence of extracellular glucose and lactate changes when the mice were presented a second time with the same object. Previous experiments have shown that systemic injections of fructose and lactate lead to an increase in blood lactate but no change in blood glucose while they both increase brain extracellular glucose but they do not increase brain extracellular lactate. When mice were visually stimulated after they had received these injections, we found that lactate, and to a slightly lesser degree fructose, both reduced the amplitude of the changes in extracellular glucose and lactate that accompanied visual stimulation. Thus, neural activation leads to an increase in extracellular lactate and a decrease in extracellular glucose. Novelty, attentional resources and availability of metabolic fuels modulate these fluctuations. The observations are consistent with a modified view of brain metabolism that takes into account the blood and brain glucose availability.



http://ift.tt/2CD1Kq7

Predicting cognitive decline with deep learning of brain metabolism and amyloid imaging

Publication date: 15 May 2018
Source:Behavioural Brain Research, Volume 344
Author(s): Hongyoon Choi, Kyong Hwan Jin
For effective treatment of Alzheimer's disease (AD), it is important to identify subjects who are most likely to exhibit rapid cognitive decline. We aimed to develop an automatic image interpretation system based on a deep convolutional neural network (CNN) which can accurately predict future cognitive decline in mild cognitive impairment (MCI) patients using flurodeoxyglucose and florbetapir positron emission tomography (PET). PET images of 139 patients with AD, 171 patients with MCI and 182 normal subjects obtained from Alzheimer's Disease Neuroimaging Initiative database were used. Deep CNN was trained using 3-dimensional PET volumes of AD and normal controls as inputs. Manually defined image feature extraction such as quantification using predefined region-of-interests was unnecessary for our approach. Furthermore, it used minimally processed images without spatial normalization which has been commonly used in conventional quantitative analyses. Cognitive outcome of MCI subjects was predicted using this network. The prediction accuracy of the conversion of mild cognitive impairment to AD was compared with the conventional feature-based quantification approach. Accuracy of prediction (84.2%) for conversion to AD in MCI patients outperformed conventional feature-based quantification approaches. ROC analyses revealed that performance of CNN-based approach was significantly higher than that of the conventional quantification methods (p < 0.05). Output scores of the network were strongly correlated with the longitudinal change in cognitive measurements (p < 0.05). These results show the feasibility of deep learning as a practical tool for developing predictive neuroimaging biomarker.



http://ift.tt/2EKuS4M

Age-related validity and reliability of the Dutch Little Developmental Coordination Disorder Questionnaire (LDCDQ-NL)

Publication date: Available online 21 February 2018
Source:Research in Developmental Disabilities
Author(s): Marja Cantell, Suzanne Houwen, Marina Schoemaker
BackgroundEarly recognition of children at risk of Developmental Coordination Disorder (DCD) is important, but variability in motor development in preschool children affects the validity of instruments to reliably detect children at risk of DCD.AimsTo investigate the age-related validity and reliability of the Dutch version of the Little Developmental Coordination Disorder Questionnaire (LDCDQ-NL).Methods and proceduresTwo hundred and sixty 3- to 5-year old children were recruited in the Netherlands. Parents filled out the LDCDQ-NL and children were assessed with the Movement Assessment Battery for Children-2 Test (MABC-2 Test). Internal consistency of the LDCDQ-NL was determined by Cronbach's alpha. Construct validity was investigated using factor analysis. Concurrent validity was measured by calculating correlations between the LDCDQ-NL and MABC-2. Receiver Operating Characteristics (ROC) were calculated to assess discriminant validity.Outcomes and resultsInternal consistency of the LDCDQ-NL was 0.91. Factor analysis resulted in three factors (Fine motor skills, Locomotor skills, Ball skills). Correlation between the LDCDQ-NL and MABC-2 Test increased with increasing age. With a sensitivity of 80%, specificity increased with age.Conclusions and implicationsThe LDCDQ-NL is a reliable and valid screening instrument for 4- and 5-year old Dutch children; concurrent and discriminant validity are low for 3-year olds.



http://ift.tt/2GycTei

Testosterone Complex and Non-Steroidal Ligands of Human Aromatase

Publication date: Available online 21 February 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Debashis Ghosh, Chinaza Egbuta, Jessica Lo
Cytochrome P450 aromatase (AROM) catalyzes the biosynthesis of estrogen from androgen. Previously crystal structures of human AROM in complex with the substrate androstenedione, and inhibitors exemestane, as well as the newly designed steroidal compounds, have been reported. Here we report the first crystal structure of testosterone complex of human placental AROM. Testosterone binds at the androgen-specific heme distal pocket. The polar and hydrophobic interactions with the surrounding residues resemble the interactions observed for other ligands. The heme proximal region comprises the intermolecular interface in AROM, and also the putative interaction surface of its redox partner cytochrome P450 reductase. Unreported previously, the proximal region is characterized by a large surface cavity, unlike most known P450's. Using five best X-ray data sets from androstenedione and testosterone complexes of AROM, we now unequivocally show the presence of an unexplained ligand electron density inside the proximal cavity. The density is interpreted as ordered five ethylene glycol units of polyethylene glycols used as a solvent for steroids and also in crystallization. Interestingly, polyethylene glycol exhibits weak inhibition of AROM enzyme activity in a time dependent manner. Besides its critical role in the redox partner coupling and electron transfer process, the proximal cavity possibly serves as the interaction site for other molecules that may have regulatory effects on AROM activity. In addition, the new data also reveal a previously unidentified water channel linking the active site to the lipid interface. The channel could be the predicted passage for water molecules involved in catalysis.

Graphical abstract

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Hypothalamic Sensing of Bile Acids, a Gut Feeling

Publication date: Available online 21 February 2018
Source:Trends in Endocrinology & Metabolism
Author(s): Allison W. Xu
Bile acids facilitate dietary fat absorption upon release into the small intestine after a meal. A recent study by Liu and colleagues identifies a gut–brain axis wherein bile acids signal an energy-replete state to hypothalamic AgRP neurons via activation of neuronal FGF receptors, which orchestrate whole-body glucose metabolism.



http://ift.tt/2CAcKVq

FISH-ing Novel Dynamic Modes of Glucocorticoid-Induced Chromatin Reorganization

Publication date: Available online 21 February 2018
Source:Trends in Endocrinology & Metabolism
Author(s): Felicity E. Stubbs, Benjamin P. Flynn, Becky L. Conway-Campbell
In a recent study, Jubb et al. used 3D DNA FISH to assess glucocorticoid-induced 'chromatin decompaction' at multiple loci. Determinants of the specificity, speed, and duration of this phenomenon further enhance our understanding of how the glucocorticoid receptor (GR) dynamically alters chromatin accessibility during acute-phase transcriptional regulation and beyond.



http://ift.tt/2HCmMsI

Editorial overview: Innate immunity: The finely tuned STING of innate immunity

Publication date: Available online 20 February 2018
Source:Current Opinion in Immunology
Author(s): Gwendalyn J .Randolph




http://ift.tt/2FjUpig

Erratum to “Overcoming multiple gastrointestinal barriers by bilayer modified hollow mesoporous silica nanocarriers” [Acta Biomater. 65 (2017) 405–416]

Publication date: Available online 21 February 2018
Source:Acta Biomaterialia
Author(s): Ying Wang, Yating Zhao, Yu Cui, Qinfu Zhao, Qiang Zhang, Sara Musetti, Karina A. Kinghorn, Siling Wang




http://ift.tt/2EJ0ALQ

Stapled truncated orexin peptides as orexin receptor agonists

Publication date: Available online 21 February 2018
Source:Peptides
Author(s): Lasse Karhu, Janne Weisell, Pauli M. Turunen, Teppo O. Leino, Henri Pätsi, Henri Xhaard, Jyrki P. Kukkonen, Erik A.A. Wallén
The peptides orexin-A and -B, the endogenous agonists of the orexin receptors, have similar 19-amino-acid C-termini which retain full maximum response as truncated peptides with only marginally reduced potency, while further N-terminal truncations successively reduce the activity. The peptides have been suggested to bind in an α‐helical conformation, and truncation beyond a certain critical length is likely to disrupt the overall helical structure. In this study, we set out to stabilize the α‐helical conformation of orexin‐A15–33 via peptide stapling at four different sites. At a suggested hinge region, we varied the length of the cross-linker as well as replaced the staple with two α-aminoisobutyric acid residues. Modifications close to the peptide C‐terminus, which is crucial for activity, were not allowed. However, central and N‐terminal modifications yielded bioactive peptides, albeit with decreased potencies. This provides evidence that the orexin receptors can accommodate and be activated by α-helical peptides. The decrease in potency is likely linked to a stabilization of suboptimal peptide conformation or blocking of peptide backbone–receptor interactions at the hinge region by the helical stabilization or the modified amino acids.



http://ift.tt/2sKfD6d

Impact of pictorial warning labels on tobacco products among patients attending outpatient department of a dental college in Bangalore city: A cross-sectional study

N Vanishree, RR Narayan, N Naveen, D Bullapa, D Vignesh, NM P Raveendran

Indian Journal of Cancer 2017 54(2):461-466

AIM: The aim of this study is to assess the knowledge, attitude, and impact of pictorial warnings present on tobacco packets among patients attending outpatient department of a dental college of Bangalore city. MATERIALS AND METHODS: A cross-sectional study was conducted among 419 patients through convenience sampling, using a structured close-ended questionnaire containing 35 questions. The participants were approached and invited to participate voluntarily. The data obtained were analyzed using descriptive statistics, Chi-square test and ANOVA. RESULTS: Mean age of the participants was 28.1 ± 7.06 years. Out of total 419 participants, 62.8% were tobacco users. About 40.6% of the participants had average knowledge and only 22.9% had positive attitude regarding the pictorial warnings. Nearly 77.9% of tobacco users had previously attempted decreased frequency of tobacco use and 63.7% had tried quitting the habit. The difference was statistically significant (P < 0.05 Chi-square test and ANOVA). CONCLUSION: The present study revealed that most of study participants have noticed the warnings on tobacco products, and most of them believe that they could understand warning labels. This study also showed that most of study participants believed that pictorial health warnings create awareness about probable health hazards of tobacco use and that these pictorial presentations on tobacco packs positively assist in reducing or quitting tobacco smoking.

http://ift.tt/2EXMCZW

Neoadjuvant chemotherapy for unresectable oral cancers: Optimizing outcomes?

T Puri

Indian Journal of Cancer 2017 54(2):394-396



http://ift.tt/2sIpSbj

From the new editors.....

Indian Journal of Cancer 2017 54(2):393-393



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Clinico-pathological profile of colorectal cancer in first two decades of life: A retrospective analysis from tertiary health center

D Sharma, G Singh

Indian Journal of Cancer 2017 54(2):397-400

AIM: This retrospective observational study was done to analyze age, gender, site of primary tumor and histological characterstics in patients of colorectal carcinoma in the first two decades of life. MATERIAL AND METHOD: A total of 373 patients of colorectal patients were registered in the Department of Radiation Oncology from January 2010 to December 2015. Patients who were <20 years of age were analyzed for clinicopathological characteristic. RESULTS: In our study, a total of 29 out of 373 patients (7.75%) were ≤20 years. Male to female distribution was 2.2:1. Younger age group presented with advanced Stage III and IV 58.62% and 10.34% patients, respectively. Only 9 (30.5%) patients were of Stage I and II. The most common involved site was rectum in 21 (72.41%) patients, followed by rectosigmoid involvement in 5 (17.24%). CONCLUSIONS: Colorectal carcinoma in young adults is usually locally advanced or metastatic. Therefore, the diagnosis of CRC should be done at early and curable stage. Bleeding per rectum in a younger age group should not be ignored but must be properly evaluated.

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