In vivo magnetic resonance imaging investigating the development of experimental brain metastases due to triple negative breast cancer

Abstract

Triple negative breast cancer (TNBC), when associated with poor outcome, is aggressive in nature with a high incidence of brain metastasis and the shortest median overall patient survival after brain metastasis development compared to all other breast cancer subtypes. As therapies that control primary cancer and extracranial metastatic sites improve, the incidence of brain metastases is increasing and the management of patients with breast cancer brain metastases continues to be a significant clinical challenge. Mouse models have been developed to permit in depth evaluation of breast cancer metastasis to the brain. In this study, we compare the efficiency and metastatic potential of two experimental mouse models of TNBC. Longitudinal MRI analysis and end point histology were used to quantify initial cell arrest as well as the number and volume of metastases that developed in mouse brain over time. We showed significant differences in MRI appearance, tumor progression and model efficiency between the syngeneic 4T1-BR5 model and the xenogeneic 231-BR model. Since TNBC does not respond to many standard breast cancer treatments and TNBC brain metastases lack effective targeted therapies, these preclinical TNBC models represent invaluable tools for the assessment of novel systemic therapeutic approaches. Further pursuits of therapeutics designed to bypass the blood tumor barrier and permit access to the brain parenchyma and metastatic cells within the brain will be paramount in the fight to control and treat lethal metastatic cancer.

http://ift.tt/2kdxu0u

Reduced proliferation and colony formation of head and neck squamous cell carcinoma (HNSCC) after dual targeting of EGFR and hedgehog pathways

Abstract

Purpose

The hedgehog signalling pathway (Hh) is frequently active in head and neck squamous cell carcinoma (HNSCC). Overexpressed Hh associates with poor prognosis. The Hh inhibitor vismodegib targets smoothened, and based on molecular data, may prevent resistance to EGFR targeting.

Methods

To elucidate potential roles of vismodegib in HNSCC therapy, its sole effects and those combined with cisplatin, docetaxel, and cetuximab on HNSCC cell lines were assessed by MTT metabolisation and BrdU incorporation. Colony formation (CF) of primary HNSCC cells was studied utilizing the FLAVINO-protocol. Combinatory effects were analysed regarding antagonism, additivity or synergism. Associations between the ex vivo detected mode of action of vismodegib with other treatments related to patient characteristics were assessed and progression-free survival (PFS) in patient groups compared using Kaplan–Meier curves.

Results

Vismodegib suppressed BrdU incorporation significantly stronger than MTT turnover; CF was significantly inhibited at ≥20 µM vismodegib while concentrations <20 µM acted hormetic. Combining 20 µM vismodegib plus docetaxel (T), cisplatin (P), and cetuximab (E), additively enhanced anti-tumoral activity in HNSCC samples from patients with superior PFS highlighting a potential role for ex-vivo testing of this combination for use as a prognostic classifier.

Conclusion

We provide ex-vivo evidence for vismodegib's potential in HNSCC therapies, especially if combined with cetuximab, cisplatin and docetaxel.

http://ift.tt/2iXbce9

Soil compaction effects on soil health and cropproductivity: an overview

Abstract

Soil compaction causes substantial reduction in agriculture productivity and has always been of great distress for farmers. Intensive agriculture seems to be more crucial in causing compaction. High mechanical load, less crop diversification, intensive grazing, and irrigation methods lead to soil compaction. It is further exasperated when these factors are accompanied with low organic matter, animal trampling, engine vibrations, and tillage at high moisture contents. Soil compaction increases soil bulk density and soil strength, while decreases porosity, aggregate stability index, soil hydraulic conductivity, and nutrient availability, thus reduces soil health. Consequently, it lowers crop performance via stunted aboveground growth coupled with reduced root growth. This paper reviews the potential causes of compaction and its consequences that have been published in last two decades. Various morphological and physiological alterations in plant as result of soil compaction have also been discussed in this review.

http://ift.tt/2jJZMyq

Adsorption of nickel ions by oleate-modified magnetic iron oxide nanoparticles

Abstract

In this work, magnetic nanoparticles of iron oxide (MNPs) were synthesized, and then the surface was recovered with an oleate double layer in order to investigate the ability of this material to adsorb nickel ions. First, the solution chemistry of oleate ions was investigated in order to determine the critical micellar concentration (CMC) value and the arrangements of ions above the CMC. Then, the synthesized oleate-modified MNP was characterized (TEM, DLS, XRD, FTIR, zeta potential, magnetometry). Finally, adsorption experiments were carried out as a function of pH and as a function of nickel concentration in 0.1 g L⁻¹ suspensions of oleate-modified MNP. The results show that CMC of oleate ranges from 1 to 2.5∙10⁻³ mol L⁻¹. Above CMC, arrangement of oleate ions as droplets, vesicles, or micelles depends on pH and influences the average size and solution absorbance. Potentiometric titrations allowed determining a pKa value of 7.8 for sodium oleate. The high stability in aqueous suspensions and characterization of oleate-modified MNP confirm that oleate ions are arranged as a bilayer coating at the surface of MNP. Retention of nickel was found to be highly dependent on pH, with a maximum adsorption (90%) beginning from pH = 7.5. The sorption isotherms were well fitted with the Langmuir model and the maximum nickel adsorption capacities were found to be 44 and 80 mg g⁻¹ for pH = 6.8 and 7.2, respectively. The efficient removal of nickel combined with the magnetic properties of the NMP make the oleate-modified MNP an interesting water purification tool.

http://ift.tt/2j4wCtg

Biochemical and physiological responses of halophilic nanophytoplankton ( Dunaliella salina ) from exposure to xeno-estrogen 17α-ethinylestradiol

Abstract

The environmental impacts of various pollutants on the entire levels of organisms are under investigation. Among these pollutants, endocrine-disrupting compounds (EDCs) present a serious hazard, even though the environmental significance of these compounds remains basically unknown. To drop some light on this field, we assessed the effects of a 11-day exposure of 17α-ethinylestradiol (EE2) on the growth, metabolic content, antioxidant response, oxidative stress, and genetic damage of Dunaliella salina, isolated from Tunisian biotopes. The results showed that at 10 ng L⁻¹, EE2 could stimulate the growth of D. salina and increase its cellular content of photosynthetic pigments and metabolites; however, it did not significantly increase the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) or the level of malondialdehyde (MDA) and hydrogen peroxide (H₂O₂). In contrast, exposure to high levels of EE2 concentrations significantly inhibited the growth of D. salina (P < 0.05), decreased the cellular content of photosynthetic pigments, increased the cellular content of all of the metabolites and the SOD activity, and inhibited CAT and GPx activities. Nevertheless, the balance between oxidant and antioxidant enzymes was disrupted because H₂O₂ content along with MDA content simultaneously increased. Contrary to expected results, DNA damage (strand breaks) decreased after the exposure of algae to EE2. The results of this study suggest that EE2 toxicity could result in environmental impacts with consequences on the whole aquatic community.

Graphical abstract

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Association between heavy metal and metalloid levels in topsoil and cancer mortality in Spain

Abstract

Spatio-temporal cancer mortality studies in Spain have revealed patterns for some tumours which display a distribution that is similar across the sexes and persists over time. Such characteristics would be common to tumours that shared risk factors, including the geochemical composition of the soil. The aim of this study was to assess the possible association between heavy metal and metalloid levels in topsoil (upper soil horizon) and cancer mortality in mainland Spain. Ecological cancer mortality study at a municipal level, covering 861,440 cancer deaths (27 different tumour locations) in 7917 Spanish mainland towns, from 1999 to 2008. The elements included in this analysis were Al, As, Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn. Topsoil levels (partial extraction) were determined by ICP-MS at 13,317 sampling points. For the analysis, the data on the topsoil composition have been transformed by the centred logratio (clr-transformation). Principal factor analysis was performed to obtain independent latent factors for the transformed variables. To estimate the effect of heavy metal levels in topsoil composition on mortality, we fitted Besag, York and Mollié models, which included each town's factor scores as the explanatory variable. Integrated Nested Laplace Approximation (INLA) was used as a tool for Bayesian inference. All results were adjusted for sociodemographic variables. The results showed an association between trace contents of heavy metals and metalloids in topsoil and mortality due to tumours of the digestive system in mainland Spain. This association was observed in both sexes, something that would support the hypothesis that the incorporation of heavy metals into the trophic chain might be playing a role in the aetiology of some types of cancer. Topsoil composition and the presence of potentially toxic elements in trace concentrations might be an additional component in the aetiology of some types of cancer, and go some way to determine the ensuing geographic differences in mortality in Spain. The results support the interest of inclusion of heavy metal levels in topsoil as a hypothesis in analytical epidemiological studies using biological markers of exposure to heavy metals and metalloids.

http://ift.tt/2jhsS5g

Heavy metals and nutrients (carbon, nitrogen, and phosphorus) in sediments: relationships to land uses, environmental risks, and management

Abstract

Management of sediments in polluted rivers requires an inventory of sediment quantities as well as their nutrient and metal contents and the chemical forms of pollutants. We investigated the influence of three major land uses (i.e., orange plantation—OP, OP + residential + industrial—OPRI, and residential + industrial—RI) on the quality of surface sediments (0–20 cm below water/sediment interface) at the Sanyang Wetland (China). The total contents of metals (As, Cd, Cr, Cu, Ni, Pb, and Zn) and nutrients (C, N, and P) as well as metal speciation in sediments were examined. GIS technology was used to estimate the volume of sediments needed to calculate the amounts of stored nutrients and metals in sediments. The surface sediments in the 3.2-km² study area contain more than 2800 Mg C, 200 Mg N, and 100 Mg P. OPRI and RI land uses contribute more total C, N, P, Zn, and Cd to sediments than OP land use. High contents of C, N, and P may provide options to recycle the sediments as fertilizer but must be used with caution due to high levels of metals. Total Cd in sediments is at an order of magnitude (up to 59 mg kg−1) higher than the Level III criterion in the Chinese Environmental Quality Standards for Soil. Sediments in all land uses have very high risks due to >50% exchangeable + carbonate-bound Zn, Ni, and Cd. It is suggested that toxicity tests be conducted to better assess the environmental risks associated with any potential use of sediments.

http://ift.tt/2j4yLVM

The nexus of oil consumption, CO 2 emissions and economic growth in China, Japan and South Korea

Abstract

This article attempts to explore the nexus between oil consumption, economic growth and carbon dioxide (CO₂) emissions in three East Asian oil importing countries (i.e. China, South Korea and Japan) over the period 1980–2013, by using the Granger causality, Johansen cointegration test, Generalised Impulse Response functions (GIRF) and variance decompositions. The empirical findings provide evidence for the existence of a long-run relationship between oil consumption and economic growth in China and Japan. The results also point to a uni-directional causality from running from oil consumption to economic growth in China and Japan, and from oil consumption to CO₂ emissions in South Korea. The overall results of GIRF reveal that while economic growth in China and South Korea shows a positive response to oil consumption, this variable responses negatively to the same shock in Japan. In addition, oil consumption spikes cause a negative response of CO₂ emissions in Japan and China, as well as a U-shape response in South Korea.

http://ift.tt/2iWZIHO

Cadherin-11 as a therapeutic target in chronic, inflammatory rheumatic diseases

Publication date: Available online 21 January 2017
Source:Clinical Immunology
Author(s): Petros P. Sfikakis, Nikolaos I. Vlachogiannis, Panagiotis F. Christopoulos
Cadherin-11 has been identified as a key regulator of synovial architecture mediating contact between Fibroblast-like Synoviocytes and organization in the lining layer. A central role for cadherin-11 has also been suggested in the formation of the rheumatoid pannus. Therapeutic targeting of cadherin-11 results in amelioration of autoimmune experimental arthritis, as well as of experimental fibrosis. In addition, cadherin-11 expression is upregulated in the synovium of patients with chronic inflammatory arthritis, whereas detection of cadherin-11 mRNA transcripts in the peripheral blood has been associated with more severe disease phenotypes in two prototypic conditions of chronic joint inflammation and fibrosis, namely, rheumatoid arthritis and systemic sclerosis, respectively. Currently, a monoclonal antibody against cadherin-11 is in early phases of clinical trials in patients with rheumatoid arthritis. Herein, we review the current knowledge regarding the potential role of cadherin-11 in pathogenesis, as well as a biomarker and therapeutic target in chronic inflammatory rheumatic diseases.



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Development of a model to predict the 10-year cumulative risk of second primary cancer among cancer survivors

Publication date: April 2017
Source:Cancer Epidemiology, Volume 47
Author(s): Marie Moitry, Michel Velten, Brigitte Trétarre, Simona Bara, Laetitia Daubisse-Marliac, Bénédicte Lapôtre-Ledoux, Xavier Troussard, Florence Molinié, Karine Ligier, Anne-Sophie Woronoff, Véronique Bouvier, Marc Colonna, Delphine Klein, Anne-Valérie Guizard, Jérémie Jégu
BackgroundTo develop a prediction model to quantify the cumulative risk of Second Primary Cancer (SPC) among cancer patients given that they survive their disease.MethodsA cohort of 293,435 patients based on data from twelve French cancer registries was analyzed. For five first cancer sites, SPC incidence rates were estimated using Poisson regression models. The cumulative risks of SPC were computed for different follow-up times. For comparison purpose, the same method was used to estimate the probability of cancer in the general population.ResultsIn this population-based cohort, 27,320 patients presented with a SPC. The cumulative risk of SPC varied depending on first cancer site, with a 10-year cumulative probability of SPC ranging from 6.2% for women with breast cancer to 44.0% for men with head and neck cancer. Compared with the general population, the 10-year cumulative risk of SPC was dramatically elevated for tobacco-related first cancers, with an increase of +7.3% for men aged 55 to 64 with a first lung cancer and +35.6% for men aged 45 to 54 with a first head and neck cancer. Lower differences were observed among patients diagnosed with a first prostate cancer (+5.5% among men aged 55 to 64), colorectal (+4.1% for women aged 55 to 64 and +6.3% for men aged 55 to 64), and breast (+2.0% among females aged 75 and older) cancers.ConclusionThis study provides physicians with a practical estimate to assess the risk of SPC of their patients more accurately.



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Les néoplasies intra-épithéliales bowénoïdes HPV-induites du pénis

Publication date: Available online 20 January 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): J.-.N. Dauendorffer, B. Cavelier Balloy, M. Bagot, C. Renaud-Vilmer




http://ift.tt/2jZAIRG

Splenic Enlargement and Bone Marrow Hyperplasia in Patients Receiving Trastuzumab-Emtansine for Metastatic Breast Cancer

Abstract

Background

An association between trastuzumab-emtansine (T-DM1) and splenic enlargement is reported in preclinical data, and has been noted anecdotally in patients receiving T-DM1 at our institution. Use of whole-body MRI examinations (WB-MRI) allows for detailed bone marrow assessment and semi-automated splenic volume calculations.

Objective

To retrospectively evaluate changes in splenic volume versus evidence of bone marrow hyperplasia and/or changes in portal venous pressure in patients receiving T-DM1 for metastatic breast cancer.

Patients and Methods

Twelve metastatic breast cancer patients underwent 29 WB-MRIs before and during T-DM1 therapy. Splenic volume, portal vein diameter, bone marrow diffusion-weighted normalised signal intensity (nSI), quantitative water diffusivity (apparent diffusion coefficient, ADC) and fat fraction (rF%) were measured and correlated.

Results

Splenic volume increases were observed in 92% of patients. Mean splenic volume increased from 144 cm³ (95% CI 110–177 cm³) to 209 cm³ (95% CI 161–257 cm³) on T-DM1 therapy (p = 0.006). Splenic volume increases correlated with treatment duration (r² = 0.43). Bone marrow hyperplasia was evidenced by an increase in bone marrow nSI (3.5 to 4.8, p = 0.12), and decreases in rF% (64.3% to 57.3%, p = 0.12) and ADC (655 μm²/s to 543 μm²/s, p = 0.11). No changes to portal vein diameter were seen.

Conclusions

Previously unreported increases in splenic volume and bone marrow hyperplasia are observed on WB-MRI in patients on T-DM1 therapy. Caution must be applied to avoid misinterpreting T-DM1-induced bone marrow hyperplasia as diffuse disease progression in bone.

http://ift.tt/2jj4a4B

CXCR4 antagonist AMD3100 reverses the neurogenesis promoted by enriched environment and suppresses long-term seizure activity in adult rats of temporal lobe epilepsy

Publication date: 30 March 2017
Source:Behavioural Brain Research, Volume 322, Part A
Author(s): Zhike Zhou, Tingting Liu, Xiaoyu Sun, Xiaopeng Mu, Gang Zhu, Ting Xiao, Mei Zhao, Chuansheng Zhao
It has been showed that enriched environment (EE) enhances the hippocampal neurogenesis and improves the cognitive impairments, accompanied by the increased expressions of stromal cell-derived factor-1 (SDF-1) in adult rats of temporal lobe epilepsy (TLE). We examined whether the enhanced neurogenesis and improved cognitive functions induced by EE following seizures were mediated by SDF-1/CXCR4 pathway. Therefore, we investigated the effects of the EE combined with CXCR4 antagonist AMD3100 on neurogenesis, cognitive functions and the long-term seizure activity in the TLE model. Adult rats were randomly assigned as control rats, rats treated with EE, rats subjected to status epilepticus (SE), post-SE rats treated with EE, AMD3100 or EE combined with AMD3100 respectively. We used immunofluorescence staining to analyze the hippocampal neurogenesis and Nissl staining to evaluate hippocampal damage. Electroencephalography was used to measure the frequency and mean duration of spontaneous seizures. Cognitive function was evaluated by Morris water maze test. EE treatment significantly, as well as improved cognitive impairments and decreased long-term seizure activity, and that these effects might be mediated through SDF-1/CXCR4 pathway during the chronic stage of TLE. Although AMD3100 reversed the effect of EE on neurogenesis, it did not abolish the cognitive improvement induced by EE following seizures. More importantly, EE combined with AMD3100 treatment significantly suppressed long-term seizure activity, which provided promising evidences to treat TLE.



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Effect of ZBD-2 on chronic pain, depressive-like behaviors, and recovery of motor function following spinal cord injury in mice

Publication date: 30 March 2017
Source:Behavioural Brain Research, Volume 322, Part A
Author(s): Xiao-ming Li, Jia Meng, Lin tao Li, Ting Guo, Liu-kun Yang, Qi-xin Shi, Xu-bo Li, Yong Chen, Qi Yang, Jian-ning Zhao
In addition to debilitating sensory and motor deficits, patients with spinal cord injury (SCI) may experience chronic hyperpathic pain (SCI-pain). Recent studies have revealed that translocator protein (TSPO) is involved in repairing neural cells as well as reducing anxiety and depression. However, the role of TSPO in SCI-pain and pain-induced depression remains unknown. The present study aimed to determine the effects of a new TSPO ligand, ZBD-2, on SCI-pain and consequent pain-induced depressive-like behaviors in mice. Treatment with ZBD-2 at either dose significantly attenuated the symptoms of chronic SCI-pain and pain-induced depressive-like behaviors. ZBD-2 reversed SCI-induced elevation of serum corticosterone levels, an index of hyper-activation of the hypothalamic–pituitary–adrenal (HPA) axis. Additionally, administration of ZBD-2 inhibited decreases in the expression of synaptic plasticity-related signaling proteins, including brain-derived neurotrophic factor (BDNF) and cyclic AMP-responsive element binding protein (CREB). Moreover, ZBD-2 administration reversed chronic, SCI-induced gliocyte activation at the lesion site. Therefore, ZBD-2 may improve chronic SCI-pain and pain-induced depressive-like behaviors via suppression of gliocyte activation and restoration of the synaptic plasticity-related signaling systems.



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Modulation on brain gray matter activity and white matter integrity by APOE ε4 risk gene in cognitively intact elderly: A multimodal neuroimaging study

Publication date: 30 March 2017
Source:Behavioural Brain Research, Volume 322, Part A
Author(s): Suping Cai, Yuanyuan Jiang, Yubo Wang, Xiaoming Wu, Junchan Ren, Min Seob Lee, Sunghoon Lee, Liyu Huang
Apolipoprotein E (APOE) ε4 allele is the genetic risk factor with the most established evidence for sporadic Alzheimer's disease. Previous neuroimaging studies have demonstrated insufficiently consistent functional and structural changes among healthy APOE ε4 carriers when compared to non-carriers. Here, in a cognitively intact elderly group (a total of 110: 45 APOE ε4 carriers, 65 non-carriers), we aimed to investigate the potential role of APOE ε4 in the modulation of grey matter activity, white matter integrity, and brain morphology before the development of clinically significant symptoms and signs, by methods of: amplitude of low frequency fluctuations and regional homogeneity analysis based on resting state fMRI, and fiber tractography approach based on diffusion tensor imaging. Our results revealed that compared to non-carriers, APOE ε4 carriers showed: (1) an inconsistent pattern of activity change in the default mode network, including increased gray matter activity in anterior cingulate cortex and medial prefrontal cortex and decreased activity in precuneus; (2) lower mean diffusivity (MD) in fibers of corona radiata and corpus callosum, and lower axial diffusivity in genu of corpus callosum; and (3) significant positive correlation between the MD value of the right superior corona radiate and gross white matter volume; significant negative correlation between the MD value of the right superior corona radiate and Mini-Mental State Examination (MMSE) score. Our results suggested that APOE ε4 gene can modulate gray matter activity and white matter integrity in cognitive and memory related regions, even before any clinical or neuropsychic symtoms or signs of imminent disease.



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Virtual reality conditioned place preference using monetary reward

Publication date: 30 March 2017
Source:Behavioural Brain Research, Volume 322, Part A
Author(s): Emma Childs, Robert S. Astur, Harriet de Wit
Computerized tasks based on conditioned place preference (CPP) methodology offer the opportunity to study learning mechanisms involved in conditioned reward in humans. In this study, we examined acquisition and extinction of a CPP for virtual environments associated with monetary reward ($).Healthy men and women (N=57) completed a computerized CPP task in which they controlled an avatar within a virtual environment. On day 1, subjects completed 6 conditioning trials in which one room was paired with high $ and another with low $. Acquisition of place conditioning was assessed by measuring the time spent in each room during an exploration test of the virtual environments and using self-reported ratings of room liking and preference. Twenty-four hours later, retention and extinction of CPP were assessed during 4 successive exploration tests of the virtual environments.Participants exhibited a place preference for (spent significantly more time in) the virtual room paired with high $ over the one paired with low $ (p=0.015). They also reported that they preferred the high $ room (p<0.001) and liked it significantly more than the low $ room (p<0.001). However, these preferences were short-lived: 24h later subjects did not exhibit a behavioral or subjective preference for the high $ room.These findings show that individuals exhibit transient behavioral and subjective preferences for a virtual environment paired with monetary reward. Variations on this task may be useful to study mechanisms and brain substrates involved in conditioned reward and to examine the influence of drugs upon appetitive conditioning.



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The effects of neonatal amygdala or hippocampus lesions on adult social behavior

Publication date: 30 March 2017
Source:Behavioural Brain Research, Volume 322, Part A
Author(s): Eliza Bliss-Moreau, Gilda Moadab, Anthony Santistevan, David G. Amaral
The present report details the final phase of a longitudinal evaluation of the social behavior in a cohort of adult rhesus monkeys that received bilateral neurotoxic lesions of the amygdala or hippocampus, or sham operations at 2 weeks of age. Results were compared to previous studies in which adult animals received amygdala lesions and were tested in a similar fashion. Social testing with four novel interaction partners occurred when the animals were between 7 and 8 years of age. Experimental animals interacted with two male and two female partners in two conditions – one in which physical access was restricted (the constrained social access condition) and a second in which physical access was unrestricted (the unconstrained social access condition). Across conditions and interaction partners, there were no significant effects of lesion condition on the frequency or duration of social interactions. As a group, the hippocampus-lesioned animals generated the greatest number of communicative signals during the constrained social access condition. Amygdala-lesioned animals generated more frequent stress-related behaviors and were less exploratory. Amygdala and hippocampus-lesioned animals demonstrated greater numbers of stereotypies than control animals. Subtle, lesion-based differences in the sequencing of behaviors were observed. These findings suggest that alterations of adult social behavior are much less prominent when damage to the amygdala occurs early in life rather than in adulthood.



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Unraveling the Role of Ataxin-2 in Metabolism

Publication date: Available online 21 January 2017
Source:Trends in Endocrinology & Metabolism
Author(s): Sara Carmo-Silva, Clevio Nobrega, Luís Pereira de Almeida, Claudia Cavadas
Ataxin-2 is a polyglutamine protein implicated in several biological processes such as RNA metabolism and cytoskeleton reorganization. Ataxin-2 is highly expressed in various tissues including the hypothalamus, a brain region that controls food intake and energy balance. Ataxin-2 expression is influenced by nutritional status. Emerging studies discussed here now show that ataxin-2 deficiency correlates with insulin resistance and dyslipidemia, an action mediated via the mTOR pathway, suggesting that ataxin-2 might play key roles in metabolic homeostasis including body weight regulation, insulin sensitivity, and cellular stress responses. In this review we also discuss the relevance of ataxin-2 in the hypothalamic regulation of energy balance, and its potential as a therapeutic target in metabolic disorders such as obesity.



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Reply to Vinson et al.

Publication date: Available online 20 January 2017
Source:The Journal of Emergency Medicine
Author(s): Adam J. Singer




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Hemorrhagic Pericardial Cyst Diagnosis Accelerated by Emergency Physician Echocardiography: A Case Report

Publication date: Available online 20 January 2017
Source:The Journal of Emergency Medicine
Author(s): Michael F. Yip, Brooks M. Walsh
BackgroundThe differential diagnosis for chest pain in the emergency department is broad and includes both benign and life-threatening conditions–with pericardial cyst as a rare example. Emergency physician-performed point-of-care focused cardiac ultrasound (FOCUS) is increasingly recognized as a useful modality in the evaluation of patients with chest pain.Case ReportWe report a case of hemorrhagic pericardial cyst in a young woman presenting with chest pain in which findings on FOCUS contradicted findings on chest x-ray study and thus, accelerated diagnosis and definitive treatment. We also comment on epidemiology, pathophysiology, clinical presentation, diagnosis, and management of this uncommon, potentially fatal cause of chest pain.Why Should an Emergency Physician Be Aware of This?This case report aims to bring an uncommon case to the attention of emergency providers and emphasize the importance of facility with FOCUS. Although definitive diagnosis and management were not accomplished at the bedside in this case, an abnormal finding on FOCUS prompted further investigation and timely treatment.



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