Industrial fortification of maize flour and corn meal with at least iron has been practiced for many years in several countries in the Americas and Africa, where these ingredients are used in the preparation of many common national dishes.
http://ift.tt/2iNi2r3
Παρασκευή 30 Δεκεμβρίου 2016
WHO Guideline: Fortification of Maize Flour and Corn Meal with Vitamins and Minerals.
The Neurobiology of Human Attachments
Source:Trends in Cognitive Sciences
Author(s): Ruth Feldman
Attachment bonds are a defining feature of mammals. A conceptual framework on human attachments is presented, integrating insights from animal research with neuroimaging studies. Four mammalian bonds are described, including parent–infant, pair–bonds, peers, and conspecifics, all built upon systems shaped by maternal provisions during sensitive periods, and evolution from rodents to humans is detailed. Bonding is underpinned by crosstalk of oxytocin and dopamine in striatum, combining motivation and vigor with social focus, and their time sensitivity/pulsatility enables reorganization of neural networks. Humans' representation-based attachments are characterized by biobehavioral synchrony and integrate subcortical with cortical networks implicated in reward/motivation, embodied simulation, and mentalization. The neurobiology of love may open perspectives on the 'situated' brain and initiate dialog between science and humanities, arts, and clinical wisdom.
http://ift.tt/2iMzGqK
Adult neurogenesis beyond the niche: its potential for driving brain plasticity
Source:Current Opinion in Neurobiology, Volume 42
Author(s): Kurt A Sailor, Alejandro F Schinder, Pierre-Marie Lledo
Adult neurogenesis emerges as a tremendous form of plasticity with the continuous addition and loss of neurons in the adult brain. It is unclear how preexisting adult circuits generated during development are capable of modifying existing connections to accommodate the thousands of new synapses formed and exchanged each day. Here we first make parallels with sensory deprivation studies and its ability to induce preexisting non-neurogenic adult circuits to undergo massive reorganization. We then review recent studies that show high structural and synaptic plasticity in circuits directly connected to adult-born neurons. Finally, we propose future directions in the field to decipher how host circuits can accommodate new neuron integration and to determine the impact of adult neurogenesis on global brain plasticity.
http://ift.tt/2hwCsQ2
Modeling interactions and toxicity of Cu-Zn mixtures to zebrafish larvae
Publication date: April 2017
Source:Ecotoxicology and Environmental Safety, Volume 138
Author(s): Yongfei Gao, Jianfeng Feng, Cancan Wang, Lin Zhu
Quantitative predictions of metal-metal interactions and toxicity in aquatic organisms meet a unique challenge. Accumulation and toxicity of Cu and Zn mixtures in zebrafish larvae has been quantified in binary metal system with variable combinatorial concentrations in order to understand the interactions between essential trace metals and assess availability of the toxicokinetic-toxicodynamic (TK-TD) model which simulated the uptake of metals over time as well as metal toxicity after 24h of exposure. Competitive uptake experiments showed a straightforward antagonistic competition, as would be predicted by Michaelis–Menten competitive equilibrium model. Zn uptake decreased significantly in the presence of Cu2+ concentrations higher than 10−6M. Cu2+ was shown to compete strongly with Zn for uptake, having a higher affinity constant to biotic ligand (BL) sites (KCuBL=105.42M−1) than Zn (KZnBL=104.13M−1). TK-TD model considering potential metal-metal antagonism interactions showed good predictive power in predicting accumulation and toxicity of Cu-Zn mixtures in zebrafish larvae with the high coefficient of determination (r2) and significant level (p). In particular, with the elevated Zn concentrations in mixtures, the TD model showed better predictive power in predicting toxicity of 10−6M Cu concentration in Cu-Zn mixtures. The TK-TD analysis provided some new insights into the interactive mechanism of binary Cu and Zn exposure in aquatic animals and may have important implications for our understanding of quantitative predictions of metal-metal interactions and toxicity in a field where animals are simultaneously exposed to several metals.
http://ift.tt/2ixtl3k
Photophysics, TiO2 sensitization and photovoltaic performance of Zn-ProtoporphyrinIX
Publication date: 15 April 2017
Source:Journal of Molecular Structure, Volume 1134
Author(s): Venkatesan Srinivasan, Nagaraj Pavithra, Sambandam Anandan, Madhavan Jaccob, Arunkumar Kathiravan
Chlorophylls are playing an important role in natural photosynthesis. Hence, in the present investigation, a chlorophyll analogue Zn-Protoporphyrin IX (ZnPPIX) was selected for dye sensitized solar cell applications. The properties of ZnPPIX were fully investigated by optical spectroscopy, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), density functional theory (DFT) calculations, electrochemical and photovoltaic measurements. The optical and electrochemical HOMO-LUMO gaps were consistent with those estimated by PBE functional. The nature of the binding of ZnPPIX onto the TiO2 surface was investigated using ATR-FTIR and XPS measurements. The amount of adsorbed ZnPPIX on TiO2 surface was reasonably fit using the Langmuir adsorption isotherm, with a binding constant value of 25,800 M−1. The power conversion efficiency of ZnPPIX is smaller than those of reference cell under the optimized conditions (η = 0.6% for ZnPPIX; η = 6.3% for N3).
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http://ift.tt/2hzGISd
Influence of Camellia sinensis extract on Zinc Oxide nanoparticle green synthesis
Publication date: 15 April 2017
Source:Journal of Molecular Structure, Volume 1134
Author(s): O.J. Nava, P.A. Luque, C.M. Gómez-Gutiérrez, A.R. Vilchis-Nestor, A. Castro-Beltrán, M.L. Mota-González, A. Olivas
This work addresses low cost, non-toxic green synthesis of Zinc Oxide nanoparticles prepared using different amounts of Camellia sinensis extract. The Synthesized material was studied and characterized through Fourier transform infrared spectroscopy (FTIR), x-ray diffraction (XRD), transmission electron microscopy (TEM). The Zinc Oxide nanoparticles presented the desired ZnO bond at 618 cm−1, demonstrated growth in a purely hexagonal Wurtzite crystal structure, and, depending on the amount of extract used, they presented different size and shape homogeneity. The photocatalytic activity of the obtained Zinc Oxide nanoparticles was studied. The photocatalytic degradation studies were done at a 1:1 M ratio of methylene blue to Zinc Oxide nanoparticles under UV light. The obtained results presented a better degradation rate than commercially available Zinc Oxide nanoparticles.
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http://ift.tt/2hzAnGg
Heteroleptic complexes of Zn(II) based on 1-(5-bromo-2-hydroxybenzylidene)-4-phenylthiosemicarbazide: Synthesis, structural characterization, theoretical studies and antibacterial activity
Publication date: 15 April 2017
Source:Journal of Molecular Structure, Volume 1134
Author(s): Mohammad Azarkish, Alireza Akbari, Tahereh Sedaghat, Jim Simpson
Four new ternary complexes, [ZnL (2,2′-bipy)] (1), Zn2L2(4,4′-bipy)] (2), [ZnL(Imd)]·H2O (3) and [ZnL3(MeImd)] (4), have been synthesized from the reaction of Zn(II) acetate with 1-(5-bromo-2-hydroxybenzylidene)-4-phenylthiosemicarbazide (H2L) in the presence of a heterocyclic base, 2,2′-bipyridine, 4,4′-bipyridine, imidazole or 2-methylimidazole, as an auxiliary ligand. The complexes have been investigated by elemental analysis and FT-IR, UV–Vis and 1HNMR spectroscopy. These data show that the thiosemicarbazone acts as a tridentate dianionic ligand and coordinates via the thiol group, imine nitrogen, and phenolic oxygen. The coordination sphere was completed by the nitrogen atom(s) of the secondary ligand. The structure of 1 was also confirmed by X-ray crystallography and shown to be a five coordinate complex with coordination geometry between the square-pyramidal and trigonal-bipyramidal. Density functional theory (DFT) calculations including geometry optimization, vibrational frequencies and electronic absorptions have been performed for 1 with the B3LYP functional at the TZP(6-311G*) basis set using the Gaussian 03 or ADF 2009 packages. The optimization calculation showed that the crystallographically determined geometry parameters can be reproduced with that basis set. Experimental IR frequencies and calculated vibration frequencies also support each other. The in vitro antibacterial activities of the ligand and complexes have been evaluated against Gram-positive (B. subtilis and S. aureus) and Gram-negative (P. aeruginosa) bacteria and compared with the standard antibacterial drugs. The results reveal that all of the complexes show much better activity in comparison to the individual thiosemoicarbazone ligand (H2L), against all bacterial strains used, with complex 3 showing the most promising results.
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http://ift.tt/2hzvnkU
Elevated CO2 levels increase the toxicity of ZnO nanoparticles to goldfish (Carassius auratus) in a water-sediment ecosystem
Publication date: 5 April 2017
Source:Journal of Hazardous Materials, Volume 327
Author(s): Ying Yin, Zhengxue Hu, Wenchao Du, Fuxun Ai, Rong Ji, Jorge L. Gardea-Torresdey, Hongyan Guo
Concerns about the environmental safety of metal-based nanoparticles (MNPs) in aquatic ecosystems are increasing. Simultaneously, elevated atmospheric CO2 levels are a serious problem worldwide, making it possible for the combined exposure of MNPs and elevated CO2 to the ecosystem. Here we studied the toxicity of nZnO to goldfish in a water-sediment ecosystem using open-top chambers flushed with ambient (400±10μL/L) or elevated (600±10μL/L) CO2 for 30days. We measured the content of Zn in suspension and fish, and analyzed physiological and biochemical changes in fish tissues. Results showed that elevated CO2 increased the Zn content in suspension by reducing the pH value of water and consequently enhanced the bioavailability and toxicity of nZnO. Elevated CO2 led to higher accumulation of Zn in fish tissues (increased by 43.3%, 86.4% and 22.5% in liver, brain and muscle, respectively) when compared to ambient. Elevated CO2 also intensified the oxidative damage to fish induced by nZnO, resulting in higher ROS intensity, greater contents of MDA and MT and lower GSH content in liver and brain. Our results suggest that more studies in natural ecosystems are needed to better understand the fate and toxicity of nanoparticles in future CO2 levels.
http://ift.tt/2hzB2I1
The Cogne magnetite deposit (Western Alps, Italy): A Late Jurassic seafloor ultramafic-hosted hydrothermal system?
Publication date: April 2017
Source:Ore Geology Reviews, Volume 83
Author(s): Luca Toffolo, Paolo Nimis, Silvana Martin, Simone Tumiati, Wolfgang Bach
The Cogne magnetite deposit (Western Alps, Italy) is the largest in a series of apatite and sulphide-free magnetite orebodies that are hosted in serpentinites belonging to western Alpine ophiolitic units. The nearly endmember composition of magnetite, which is unusual for an ultramafic setting, and the relatively high tonnage of the deposit (18·106tonnes at 45–50wt% Fe) make Cogne an intriguing case study to explore magnetite-forming processes in ophiolites. The Cogne magnetite shows variable textures, including nodular ores, veins and fine-grained disseminations in serpentinites after mantle peridotites and totally serpentinized melt-impregnated peridotites (troctolites). An increase in Co/Ni ratio from magnetite-poor serpentinized peridotites (0.05) to nodular magnetite ores (>1) is observed. Trace element analyses of magnetite from different sites and lithologies by laser-ablation inductively-coupled mass spectrometry indicate that magnetites have typical hydrothermal compositions, characterized by high Mg and Mn (median values up to ∼24,100 and ∼5000ppm, respectively), and low Cr, Ti and V (median values up to ∼30, ∼570 and ∼60ppm, respectively). Moreover, the variations in trace element compositions distinguish magnetite that is hydrothermal fluid-controlled [highest (Mg, Mn, Co, Zn)/Ni ratios] from magnetite whose composition is affected by host-rock chemistry (highest Ni±Ti±V). U-Th-Pb dating of magnetite-associated uraninite constrains the formation of the deposit to the Late Jurassic (ca. 150Ma), during an advanced stage of the opening of the Alpine Tethys. Thermodynamic modelling of fluid-rock interactions indicates that fluids produced by seawater–peridotite or seawater–Fe-gabbro are not sufficiently Fe-rich to account for the formation of the Cogne deposit. This suggests that fractionation processes such as phase separation were critical to generate hydrothermal fluids capable to precipitate large amounts of magnetite in various types of ultramafic host-rocks. The oceanic setting and geochemical and mineralogical similarities with some modern ultramafic-hosted volcanogenic massive sulphide deposits on mid-ocean ridges suggest that the exposed mineralized section at Cogne may represent the deep segment of a seafloor, high-temperature (∼300–400°C) hydrothermal system. The occurrence of similar magnetite enrichments in present-day oceanic settings could contribute to explain the presence of significant magnetic anomalies centred on active and inactive ultramafic-hosted hydrothermal fields.
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Gene expression profiling reveals genes and transcription factors associated with dilated and ischemic cardiomyopathies
Publication date: Available online 29 December 2016
Source:Pathology - Research and Practice
Author(s): Aiqing Qiao, Zhenying Zhao, Hui Zhang, Zhenyu Sun, Xiao Cui
AimsDilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) can cause heart failure, and this study aims to identify genes and transcription factors (TFs) associated with DCM and ICM.MethodsGene expression dataset GSE42955 was generated from GEO database, and it contained 12 DCM, 12 ICM, and 5 control samples. Differentially expressed genes (DEGs) were identified between DCM (or ICM) and controls. Gene functions were investigated, and their associations were analyzed using Enrichmentmap plugin in Cytoscape. Protein-protein interactions (PPIs) between DEGs were determined, and DEGs with high degree were defined as key DEGs. Potential TFs of key DEGs were predicted using iRegulon plugin. Common DEGs were found, and their functional interactions were investigated using GeneMANIA.ResultsA total of 362 and 300 DEGs were respectively identified for DCM and ICM in comparison with controls, and these DEGs mainly participated in similar functions about extracellular region, membrane, immune process, and defense response. PPI networks were respectively constructed for DCM and ICM, and 26 key DEGs (e.g. CXCL10, IL6, TLR3, and VCAM1) were found, which might be targeted by 35 TFs (e.g. IRF1). Besides, 47 common up-regulated DEGs were found, which participated in 14 pathways like Apoptosis, Collagen formation, as well as 127 common down-regulated DEGs that involved in 20 pathways like Adaptive immune system, Interferon γ signaling (e.g. IRF1, VCAM1), and Toll-like receptor signaling pathway (e.g. CXCL10, IL6, TLR3).ConclusionDCM and ICM may share similar mechanism, and TFs (e.g. IRF1) play crucial roles in their development via regulating gene expression.
http://ift.tt/2hTzZjH
Elevated expression of microRNA-19a predicts a poor prognosis in patients with osteosarcoma
Publication date: Available online 29 December 2016
Source:Pathology - Research and Practice
Author(s): Pingzhou Zou, Jian Ding, Shiping Fu
MicroRNA (miR)-19a, a member of the miR-17-92 cluster, functions as an oncomiRNA in multiple kinds of cancers. However, its involvement in human osteosarcomas remains unclear. In this study, to analyze the expression pattern of miR-19a and to investigate its clinical implication in human osteosarcomas, quantitative reverse-transcription polymerase chain reaction was performed to detect expression levels of miR-19a in 166 self-pairs of osteosarcoma and noncancerous bone tissues. Associations between miR-19a expression and various clinicopathological parameters and patients' prognosis of osteosarcomas were further evaluated. As a results, miR-19a expression in osteosarcoma tissues was significantly higher than that in corresponding noncancerous bone tissues (P<0.001). Osteosarcoma patients with high miR-19a expression more frequently had large tumor size (P=0.03), advanced clinical stage (P=0.01), positive distant metastasis (P=0.008) and poor response to chemotherapy (P=0.01) than those with low miR-19a expression. Additionally, kaplan-Meier analysis showed that both overall and disease-free survivals of osteosarcoma patients with high miR-19a expression were shorter than those with low miR-19a expression (both P<0.001). Further multivariate analysis identified miR-19a expression as an independent prognostic factor for both overall (P=0.001) and disease-free (P=0.006) survivals. In conclusion, the aberrant expression of miR-19a may play a crucial role in development and progression of human osteosarcomas. MiR-19a may act as a novel prognostic marker for patients with this malignancy.
http://ift.tt/2hBT11M
Clinicopathologic characteristics of young patients with gallbladder cancer
Publication date: Available online 29 December 2016
Source:Pathology - Research and Practice
Author(s): Sung-Im Do, Hyoun Wook Lee, Jin Hee Sohn, Kyungeun Kim
Gallbladder cancer is the most common biliary tract cancer and the fifth most common cancer of the digestive system. However, the clinicopathologic features of gallbladder cancer in young Korean patients have not been studied. This study included 101 consecutive cases of gallbladder cancer that underwent cholecystectomy at Kangbuk Samsung Hospital from December 1990 to March 2011. The patients were divided into two groups by age at initial diagnosis of gallbladder cancer: a young patient group aged less than 45 years and an old patient group aged 45 or older. The young patient group included 10 patients with mean age of 38 (range, 29 to 44 years). Compared with the old patient group, the young patient group showed polypoid tumor appearance (p=0.014), lower pT stage (p=0.023), more frequent adenoma background (p=0.009), and less frequent dysplasia in remaining mucosa (p=0.001). The disease-related survival rate after 13.5 months was significantly more favorable for the young patients. Gallbladder cancers in young Korean patients have distinct clinicopathologic features of a high frequency of cancer arising in adenoma, rare association with intestinal metaplasia and dysplasia, and a favorable patient's prognosis. These findings suggest that the adenoma-carcinoma pathway could contribute more to gallbladder cancer carcinogenesis in young Korean patients than the metaplasia-dysplasia-carcinoma pathway.
http://ift.tt/2hTBm1N
Application of Whole Exome Sequencing in Elucidating the Phenotype and Genotype Spectrum of Junctional Epidermolysis Bullosa: A Preliminary Experience of a Tertiary Care Centre in India
Publication date: Available online 29 December 2016
Source:Journal of Dermatological Science
Author(s): Vamsi K Yenamandra, Shamsudheen K Vellarikkal, Manoj Kumar, Madhumita R Chowdhury, Rijith Jayarajan, Ankit Verma, Vinod Scaria, Sridhar Sivasubbu, Subrata B. Ray, Amit K Dinda, Madhulika Kabra, Punit Kaur, Vinod K Sharma, Gomathy Sethuraman
BackgroundJunctional epidermolysis bullosa (JEB) is a diverse group of genodermatoses associated with extreme skin fragility. Despite several well-characterized genetic studies, molecular diagnosis of this heterogeneous group is still challenging. Recent advances in the field of genomics have seen the successful implementation of whole exome sequencing (WES) as a fast and efficient diagnostic strategy in several genodermatoses.ObjectiveIn view of the scarcity and need of molecular studies for JEB in India, we sought to explore the potential of WES in understanding the mutational spectrum of this rare, in certain subtypes lethal, sub-group of EB.MethodsWES was performed using genomic DNA from each case of EB, followed by massively parallel sequencing. Resulting reads were mapped to the human reference genome hg19. Sanger sequencing subsequently confirmed the potentially pathogenic mutations.ResultsOverall, four unrelated families (6 patients) of JEB with a highly variable clinical presentation including a rare case of LOC syndrome were studied. WES revealed 4 variations in 3 genes (LAMA3, LAMB3 and COL17A1) that are implicated in JEB. None of the variations were recurrent. In addition we proposed the probable molecular consequence of a missense mutation on the structure-function relationship of lamininβ3 protein through computational modeling studies.ConclusionsBeing the first report documenting the phenotype-genotype correlations of JEB patients from India, our preliminary experience with WES is clearly encouraging and serves as a nidus for future large-scale molecular studies to actively identify and understand JEB patients in Indian population.
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Serum level of interleukin-6 is increased in nivolumab-associated psoriasiform dermatitis and tumor necrosis factor-α is a biomarker of nivolumab recativity
Publication date: Available online 29 December 2016
Source:Journal of Dermatological Science
Author(s): Ryota Tanaka, Naoko Okiyama, Mari Okune, Yosuke Ishitsuka, Rei Watanabe, Junichi Furuta, Mikio Ohtsuka, Atsushi Otsuka, Hiroshi Maruyama, Yasuhiro Fujisawa, Manabu Fujimoto
http://ift.tt/2ipa5YM
Nick-initiated homologous recombination: Protecting the genome, one strand at a time
Publication date: Available online 29 December 2016
Source:DNA Repair
Author(s): Lianne E.M. Vriend, Przemek M. Krawczyk
Homologous recombination (HR) is an essential, widely conserved mechanism that utilizes a template for accurate repair of DNA breaks. Some early HR models, developed over five decades ago, anticipated single-strand breaks (nicks) as initiating lesions. Subsequent studies favored a more double-strand break (DSB)-centered view of HR initiation and at present this pathway is primarily considered to be associated with DSB repair. However, mounting evidence suggests that nicks can indeed initiate HR directly, without first being converted to DSBs. Moreover, recent studies reported on novel branches of nick-initiated HR (nickHR) that rely on single-, rather than double-stranded repair templates and that are characterized by mechanistically and genetically unique properties. The physiological significance of nickHR is not well documented, but its high-fidelity nature and low mutagenic potential are relevant in recently developed, precise gene editing approaches. Here, we review evidence for stimulation of HR by nicks, as well as the data on the interactions of nickHR with other DNA repair pathways and mechanistic properties. We conclude that nickHR is a bona-fide pathway for nick repair, sharing the molecular machinery with the canonical HR but nevertheless characterized by unique properties that secure its inclusion in DNA repair models and warrant future investigations.
http://ift.tt/2hBWeyx
Polarity Reversal by Centrosome Repositioning Primes Cell Scattering during Epithelial-to-Mesenchymal Transition
Publication date: Available online 29 December 2016
Source:Developmental Cell
Author(s): Mithila Burute, Magali Prioux, Guillaume Blin, Sandrine Truchet, Gaëlle Letort, Qingzong Tseng, Thomas Bessy, Sally Lowell, Joanne Young, Odile Filhol, Manuel Théry
During epithelial-to-mesenchymal transition (EMT), cells lining the tissue periphery break up their cohesion to migrate within the tissue. This dramatic reorganization involves a poorly characterized reorientation of the apicobasal polarity of static epithelial cells into the front-rear polarity of migrating mesenchymal cells. To investigate the spatial coordination of intracellular reorganization with morphological changes, we monitored centrosome positioning during EMT in vivo, in developing mouse embryos and mammary gland, and in vitro, in cultured 3D cell aggregates and micropatterned cell doublets. In all conditions, centrosomes moved from their off-centered position next to intercellular junctions toward extracellular matrix adhesions on the opposite side of the nucleus, resulting in an effective internal polarity reversal. This move appeared to be supported by controlled microtubule network disassembly. Sequential release of cell confinement using dynamic micropatterns, and modulation of microtubule dynamics, confirmed that centrosome repositioning was responsible for further cell disengagement and scattering.
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Teaser
During epithelial-to-mesenchymal transition, epithelial cells migrate into the underlying interstitial tissues. Burute et al. show that this movement is enabled by a reversal of cell polarity. This reversal results from centrosome displacement from intercellular junctions to the cell center in response to controlled microtubule disassembly.http://ift.tt/2hTp09Q
Exosomal MicroRNA Transport from Salivary Mesenchyme Regulates Epithelial Progenitor Expansion during Organogenesis
Publication date: Available online 29 December 2016
Source:Developmental Cell
Author(s): Toru Hayashi, Isabelle M.A. Lombaert, Belinda R. Hauser, Vaishali N. Patel, Matthew P. Hoffman
Epithelial-mesenchymal interactions involve fundamental communication between tissues during organogenesis and are primarily regulated by growth factors and extracellular matrix. It is unclear whether RNA-containing exosomes are mobile genetic signals regulating epithelial-mesenchymal interactions. Here we identify that exosomes loaded with mesenchyme-specific mature microRNA contribute mobile genetic signals from mesenchyme to epithelium. The mature mesenchymal miR-133b-3p, loaded into exosomes, was transported from mesenchyme to the salivary epithelium, which did not express primary miR-133b-3p. Knockdown of miR-133b-3p in culture decreased endbud morphogenesis, reduced proliferation of epithelial KIT+ progenitors, and increased expression of a target gene, Disco-interacting protein 2 homolog B (Dip2b). DIP2B, which is involved in DNA methylation, was localized with 5-methylcytosine in the prophase nucleus of a subset of KIT+ progenitors during mitosis. In summary, exosomal transport of miR-133b-3p from mesenchyme to epithelium decreases DIP2B, which may function as an epigenetic regulator of genes responsible for KIT+ progenitor expansion during organogenesis.
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Epithelial-mesenchymal interactions are critical for salivary gland development. Hayashi et al. show that miRNA-containing exosomes produced by mesenchyme are transported to the epithelium, where they regulate KIT+ progenitor cell proliferation. A specific mesenchymal miRNA (miR-133b-3p) targets DIP2B, which is involved in DNA methylation, thus regulating progenitor cell expansion during organogenesis.http://ift.tt/2hTkQPy
The APC/C Coordinates Retinal Differentiation with G1 Arrest through the Nek2-Dependent Modulation of Wingless Signaling
Publication date: Available online 29 December 2016
Source:Developmental Cell
Author(s): Torcato Martins, Francesco Meghini, Francesca Florio, Yuu Kimata
The cell cycle is coordinated with differentiation during animal development. Here we report a cell-cycle-independent developmental role for a master cell-cycle regulator, the anaphase-promoting complex or cyclosome (APC/C), in the regulation of cell fate through modulation of Wingless (Wg) signaling. The APC/C controls both cell-cycle progression and postmitotic processes through ubiquitin-dependent proteolysis. Through an RNAi screen in the developing Drosophila eye, we found that partial APC/C inactivation severely inhibits retinal differentiation independently of cell-cycle defects. The differentiation inhibition coincides with hyperactivation of Wg signaling caused by the accumulation of a Wg modulator, Drosophila Nek2 (dNek2). The APC/C degrades dNek2 upon synchronous G1 arrest prior to differentiation, which allows retinal differentiation through local suppression of Wg signaling. We also provide evidence that decapentaplegic signaling may posttranslationally regulate this APC/C function. Thus, the APC/C coordinates cell-fate determination with the cell cycle through the modulation of developmental signaling pathways.
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Martins et al. discovered a cell-cycle-independent function of the APC/C ubiquitin ligase in Drosophila eye development. They show that the APC/C controls retinal differentiation by locally suppressing Wingless signaling through the destruction of Nek2. Thus, the APC/C coordinates developmental signaling activity with the cell cycle.http://ift.tt/2hToetw
APC/CFzr/Cdh1-Dependent Regulation of Planar Cell Polarity Establishment via Nek2 Kinase Acting on Dishevelled
Publication date: Available online 29 December 2016
Source:Developmental Cell
Author(s): Ursula Weber, Marek Mlodzik
The Anaphase-Promoting Complex/Cyclosome (APC/C) is an E3 ubiquitin ligase, well known for its role in cell-cycle progression. However, it has been linked to additional functions, mainly in neuronal contexts, when using the co-activator Cdh1/Fzr. Here, our data indicate a post-mitotic requirement for the APC/CFzr/Cdh1 in epithelial cell patterning and planar cell polarity (PCP) in Drosophila. PCP signaling is critical for development by establishing cellular asymmetries and orientation within the plane of an epithelium, via differential localization of distinct complexes of core PCP factors. Loss of APC/C function leads to reduced levels of Dishevelled (Dsh), a core PCP factor. The effect of APC/C on Dsh is mediated by Nek2 kinase, which can phosphorylate Dsh and is a direct APC/CFzr/Cdh1 substrate. We have thus uncovered a pathway of regulation whereby APC/CFzr/Cdh1 negatively regulates Nek2, which negatively regulates Dsh, to ensure its proper stoichiometric requirement and localization during PCP establishment.
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Anaphase-Promoting Complex/Cyclosome (APC/C) is an E3 ubiquitin ligase known for its role in cell-cycle progression. Weber and Mlodzik identify a post-mitotic APC/C function in planar cell polarity establishment in Drosophila. The APC/C regulates levels of the Nek2 kinase, which regulates Dsh localization/levels via phosphorylation and targeting to the proteasome.http://ift.tt/2hTuzoE
Long-Term High-Resolution Imaging of Developing C. elegans Larvae with Microfluidics
Publication date: Available online 29 December 2016
Source:Developmental Cell
Author(s): Wolfgang Keil, Lena M. Kutscher, Shai Shaham, Eric D. Siggia
Long-term studies of Caenorhabditis elegans larval development traditionally require tedious manual observations because larvae must move to develop, and existing immobilization techniques either perturb development or are unsuited for young larvae. Here, we present a simple microfluidic device to simultaneously follow development of ten C. elegans larvae at high spatiotemporal resolution from hatching to adulthood (∼3 days). Animals grown in microchambers are periodically immobilized by compression to allow high-quality imaging of even weak fluorescence signals. Using the device, we obtain cell-cycle statistics for C. elegans vulval development, a paradigm for organogenesis. We combine Nomarski and multichannel fluorescence microscopy to study processes such as cell-fate specification, cell death, and transdifferentiation throughout post-embryonic development. Finally, we generate time-lapse movies of complex neural arborization through automated image registration. Our technique opens the door to quantitative analysis of time-dependent phenomena governing cellular behavior during C. elegans larval development.
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Keil et al. present a microfluidics setup, enabling long-term, high-resolution, time-lapse microscopy of up to ten C. elegans larvae simultaneously. They collect vulval cell-cycle timing statistics, measure intensities of fluorescent transcriptional reporters during cell-fate specification, transdifferentiation, and cell death, and visualize complex neurite outgrowth in automatically registered z stacks.http://ift.tt/2hTwVnR
Kaempferol slows intervertebral disc degeneration by modifying LPS-induced osteogenesis/adipogenesis imbalance and inflammation response in BMSCs
Publication date: February 2017
Source:International Immunopharmacology, Volume 43
Author(s): Jun Zhu, Haoyu Tang, Zhenhua Zhang, Yong Zhang, Chengfeng Qiu, Ling Zhang, Pinge Huang, Feng Li
Intervertebral disc (IVD) degeneration is a common disease that represents a significant cause of socio-economic problems. Bone marrow-derived mesenchymal stem cells (BMSCs) are a potential autologous stem cell source for the nucleus pulposus regeneration. Kaempferol has been reported to exert protective effects against both osteoporosis and obesity. This study explored the effect of kaempferol on BMSCs differentiation and inflammation. The results demonstrated that kaempferol did not show any cytotoxicity at concentrations of 20, 60 and 100μM. Kaempferol enhanced cell viability by counteracting the lipopolysaccharide (LPS)-induced cell apoptosis and increasing cell proliferation. Western blot analysis of mitosis-associated nuclear antigen (Ki67) and proliferation cell nuclear antigen (PCNA) further confirmed the increased effect of kaempferol on LPS-induced decreased viability of BMSCs. Besides, kaempferol elevated LPS-induced reduced level of chondrogenic markers (SOX-9, Collagen II and Aggrecan), decreased the level of matrix-degrading enzymes, i.e., matrix metalloprotease (MMP)-3 and MMP-13, suggesting the osteogenesis of BMSC under kaempferol treatment. On the other hand, kaempferol enhanced LPS-induced decreased expression of lipid catabolism-related genes, i.e., carnitine palmitoyl transferase-1 (CPT-1). Kaempferol also suppressed the expression of lipid anabolism-related genes, i.e., peroxisome proliferators-activated receptor-γ (PPAR-γ). The Oil red O staining further convinced the inhibition effect of kaempferol on BMSCs adipogenesis. In addition, kaempferol alleviated inflammatory by reducing the level of pro-inflammatory cytokines (i.e., interleukin (IL)-6) and increasing anti-inflammatory cytokine (IL-10) via inhibiting the nucleus translocation of nuclear transcription factor (NF)-κB p65. Taken together, our research indicated that kaempferol may serve as a novel target for treatment of IVD degeneration.
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http://ift.tt/2hwjetN
Liver 5-HT7 receptors: A novel regulator target of fibrosis and inflammation-induced chronic liver injury in vivo and in vitro
Publication date: February 2017
Source:International Immunopharmacology, Volume 43
Author(s): Beyzagul Polat, Zekai Halici, Elif Cadirci, Emre Karakus, Yasin Bayir, Abdulmecit Albayrak, Deniz Unal
Background and aimHepatocellular cancer (HCC) is the sixth most common cancer and liver fibrosis is strongly associated with HCC. Treatment options are limited, and preventive strategies should be developed. An important step in the beginning of liver fibrosis is a strong inflammatory response. 5-HT7 is the last recognized member of the serotonin receptor family and is expressed in both central nerve system and peripheral system and have a lot of functions like learning, memory, smooth muscular relaxation, in the control of circadian rhythms and thermoregulation, pain and migraine, schizophrenia, anxiety, cognitive disturbances, and even inflammation.MethodsWe therefore examined the biochemical, histopathological and molecular effects of the 5-HT7 receptor agonist and antagonist on inflammatory liver fibrogenesis in animal models of progressive cirrhosis: a mouse model induced by carbon tetrachloride (CCl4) and in Hep3b cells.Results5-HT7 expression was observed in the liver in vivo and in vitro in CCl4-induced damage. 5-HT7 receptor agonist but not the antagonist reduced liver markers in mice and in Hep3b cells in carbon tetrachloride (CCl4) induced damage. 5-HT7 agonist, but not antagonist, protected liver tissue from oxidative stress in fibrosis. 5-HT7 agonist but not antagonist induces anti-inflammatory, anti-fibrinotic and anti-cytokine features in liver fibrosis in vivo and in vitro.Conclusions5-HT7 receptors have modulatory function and are an up-and-coming pharmacological target in the inflammatory fibrotic process. 5-HT7 receptor agonist LP-44 showed significant hepatoprotective effects against liver fibrosis, and LP-44 might become a useful therapeutic target for chronic liver inflammation and fibrosis.
http://ift.tt/2hwaXGr
Metal-phenolic networks as a versatile platform to engineer nanomaterials and biointerfaces
Publication date: Available online 29 December 2016
Source:Nano Today
Author(s): Hirotaka Ejima, Joseph J. Richardson, Frank Caruso
Surface modification is crucial for conferring novel functionalities to objects and interfaces. However, simple yet versatile strategies for the surface modification of multiple classes of nanomaterials, including biointerfaces, are rare, as the chemical interactions between the surface modifiers and the substrates need to be tailored on a case-by-case basis. Recently, metal-phenolic networks (MPNs) have emerged as a versatile surface modifier based on the universal adherent properties of phenolic molecules, namely the constituent gallol and catechol groups. Additionally, the dynamic interactions between metal ions and phenolic molecules confer additional functionalities to the MPNs, such as stimuli-responsiveness. Given the interest in MPNs for nanomaterial and biointerface engineering, this review aims to provide an overview of the assembly process, physicochemical properties and applications of MPN coatings.
Graphical abstract
http://ift.tt/2inBlH5
miR-29c is implicated in the cardioprotective activity of Panax notoginseng saponins against isoproterenol-induced myocardial fibrogenesis
Publication date: 23 February 2017
Source:Journal of Ethnopharmacology, Volume 198
Author(s): Li Liu, Bingbing Ning, Jingang Cui, Teng Zhang, Yu Chen
Ethnopharmacological relevancePanax notoginseng (Burkill) F.H. Chen (Araliaceae) has a long history of clinical application in China for the treatment of cardiovascular diseases. Panax notoginseng saponins (PNS) have been proven to be the major cardioprotective substances of Panax notoginseng (Burkill) F.H. Chen (Araliaceae).Aim of the studyThe current study further investigated the molecular mechanisms associated with the cardioprotective effect of PNS.Materials and methodsC57BL/6J mice were subject to isoproterenol (ISO)-induced myocardial injury in the absence or presence of PNS treatment. Histological, immunohistochemical and molecular biological approaches were taken to assess the effects of PNS treatment on ISO-induced myocardial injury and ensuing fibrogenesis.ResultsPNS treatment significantly attenuated ISO-induced myocardial injury and fibrosis. The expression of an anti-fibrotic microRNA, miR-29c, was significantly decreased in ISO-challenged mouse hearts. In contrast, PNS treatment resulted in increased cardiac expression of miR-29c. The expression of miR-29c target genes including Collagen (Col) 1a1, Col1a2, Col3a1 and Col5a1, fibrillin 1 (Fbn1) as well as TGFβ1 was significantly increased by ISO, which exhibited decreased expression by PNS intervention.ConclusionsOur results demonstrate for the first time that the cardioprotective effects of PNS could in part implicate increased expression of miR-29c in the heart, which may help increase the understanding of the pharmacological activities of PNS in treating cardiovascular disorders.
Graphical abstract
http://ift.tt/2ikKMnZ
Assessment of scoring systems to describe the position of tracheostomy tubes within the airway - the lunar study
Background: Malposition of tracheostomy tubes is difficult to detect at the bedside and may contribute to eventual device misplacement. Endoscopic examination can be undertaken via tracheoscopic (T-view) or trans-laryngeal (L-view) approach, offering more precise detail regarding positioning within the airway. The aims of this study were to evaluate inter-rater agreement between bespoke T and L view scoring systems and subsequently whether T-views could predict L-views.
Methods: Adult intensive care unit patients with percutaneous or surgical tracheostomies were included and paired T and L-views of their tracheostomy tube within the airway were taken on up to four occasions. Images were later scored by five independent raters using bespoke scoring systems. The primary outcome was to determine the T and L view scoring system with the best inter-rater agreement, defined by weighted kappa and intra-class correlation coefficients. The secondary outcome was to assess agreement between T and L-view scoring systems.
Results: Seventy-one T-views and 43 L-views were obtained from a total of 20 patients. Images were scored by five raters, resulting in 355 T-view scores, 215 L-view scores and 215 paired T and L-view scores for comparison. There was good inter-rater agreement (highest T-view k = 0.84, L-view k = 0.72). There was poor agreement between T and L-view scores for each of the paired images (highest k = 0.25) although extreme-to-extreme misclassification rates remained acceptable.
Conclusions: Whilst our data demonstrated good inter-rater agreement between scoring systems, it is not possible to reliably predict the T-view orientation and position of a tracheostomy tube within the airway from the paired L-view.
Clinical trial registration: NCT01356719
http://ift.tt/2iLUlLD
Intensive care utilization and outcomes after high-risk surgery in Scotland: a population-based cohort study
Background. The optimal perioperative use of intensive care unit (ICU) resources is not yet defined. We sought to determine the effect of ICU admission on perioperative (30 day) and long-term mortality.
Methods. This was an observational study of all surgical patients in Scotland during 2005–7 followed up until 2012. Patient, operative, and care process factors were extracted. The primary outcome was perioperative mortality; secondary outcomes were 1 and 4 yr mortality. Multivariable regression was used to construct a risk prediction model to allow standard-risk and high-risk groups to be defined based on deciles of predicted perioperative mortality risk, and to determine the effect of ICU admission (direct from theatre; indirect after initial care on ward; no ICU admission) on outcome adjusted for confounders.
Results. There were 572 598 patients included. The risk model performed well (c-index 0.92). Perioperative mortality occurred in 1125 (0.2%) in the standard-risk group (n=510 979) and in 3636 (6.4%) in the high-risk group (n=56 785). Patients with no ICU admission within 7 days of surgery had the lowest perioperative mortality (whole cohort 0.7%; high-risk cohort 5.3%). Indirect ICU admission was associated with a higher risk of perioperative mortality when compared with direct admission for the whole cohort (20.9 vs 12.1%; adjusted odds ratio 2.39, 95% confidence interval 2.01–2.84; P<0.01) and for high-risk patients (26.2 vs 17.8%; adjusted odds ratio 1.64, 95% confidence interval 1.37–1.96; P<0.01). Compared with direct ICU admission, indirectly admitted patients had higher severity of illness on admission, required more organ support, and had an increased duration of ICU stay.
Conclusions. Indirect ICU admission was associated with increased mortality and increased requirement for organ support.
Trial registration. UKCRN registry no. 15761.
http://ift.tt/2iLLxWe
Association between day and time of admission to critical care and acute hospital outcome for unplanned admissions to adult general critical care units: cohort study exploring the 'weekend effect
Background. We aimed to identify any association between day and time of admission to critical care and acute hospital outcome.
Methods. We conducted a cohort study using prospectively collected data from the national clinical audit of adult critical care. We included 195 428 unplanned admissions from 212 adult general critical care units in England, Wales and Northern Ireland, between April 1, 2013 and March 31, 2015 in the analysis.
Results. Hourly admission rates for unplanned admissions varied more than three-fold during the 24 h cycle. Overall acute hospital mortality was 26.8%. Before adjustment, acute hospital mortality was similar between weekends and weekdays but was significantly lower for admissions at night compared with the daytime (–3.4%, –3.8 to –3.0%; P<0.001). After adjustment for casemix, there remained no difference between weekends and weekdays (–0.0%, –0.4 to +0.3%; P=0.87) or between nighttime and daytime (–0.2%, –0.5 to +0.1%; P=0.21). Delays in admission were reported for 4.3% of admissions and were slightly more common during weekdays than weekends and in the daytime than at night. Delayed admission was associated with a small increase in acute hospital mortality, but adjusting for this did not affect the estimates of the effect of day and time of admission.
Conclusions. The day of week and time of admission have no influence on patient mortality for unplanned admissions to adult general critical care units within the UK. Ways to improve critical care and hospital systems to minimize delays in admission and potentially improve outcomes need to be ascertained in future research.
http://ift.tt/2ieUPgz
Effect of anaesthesia type on postoperative mortality and morbidities: a matched analysis of the NSQIP database
Background. The anaesthetic technique may influence clinical outcomes, but inherent confounding and small effect sizes makes this challenging to study. We hypothesized that regional anaesthesia (RA) is associated with higher survival and fewer postoperative organ dysfunctions when compared with general anaesthesia (GA).
Methods. We matched surgical procedures and type of anaesthesia using the US National Surgical Quality Improvement database, in which 264,421 received GA and 64,119 received RA. Procedures were matched according to Current Procedural Terminology (CPT) and ASA physical status classification. Our primary outcome was 30-day postoperative mortality and secondary outcomes were hospital length of stay, and postoperative organ system dysfunction. After matching, multiple regression analysis was used to examine associations between anaesthetic type and outcomes, adjusting for covariates.
Results. After matching and adjusting for covariates, type of anaesthesia did not significantly impact 30-day mortality. RA was significantly associated with increased likelihood of early discharge (HR 1.09; P< 0.001), 47% lower odds of intraoperative complications, and 24% lower odds of respiratory complications. RA was also associated with 16% lower odds of developing deep vein thrombosis and 15% lower odds of developing any one postoperative complication (OR 0.85; P < 0.001). There was no evidence of an effect of anaesthesia technique on postoperative MI, stroke, renal complications, pulmonary embolism or peripheral nerve injury.
Conclusions. After adjusting for clinical and patient characteristic confounders, RA was associated with significantly lower odds of several postoperative complications, decreased hospital length of stay, but not mortality when compared with GA.
http://ift.tt/2iLRfr3
Safety of sedation for gastrointestinal endoscopy in a group of university-affiliated hospitals: a prospective cohort study
Background. Service models for gastrointestinal endoscopy sedation must be safe, as endoscopy is the most common procedure performed under sedation in many countries. The aim of this prospective cohort study was to determine the patient risk profile, and incidence of and risk factors for significant unplanned events, in adult patients presenting for gastrointestinal endoscopy in a group of university-affiliated hospitals where most sedation is managed by anaesthetists.
Methods. Patients aged ≥18 yr presenting for elective and emergency gastrointestinal endoscopy under anaesthetist-managed sedation at nine hospitals affiliated with the University of Melbourne, Australia, were included. Outcomes included significant airway obstruction, hypoxia, hypotension and bradycardia; unplanned tracheal intubation; abandoned procedure; advanced life support; prolonged post-procedure stay; unplanned over-night admission and 30-day mortality.
Results. 2,132 patients were included. Fifty percent of patients were aged >60 yr, 50% had a BMI >27 kg m –2, 42% were ASA physical status III-V and 17% were emergency patients. The incidence of significant unplanned events was 23.0% (including significant hypotension 11.8%). Significant unplanned intraoperative events were associated with increasing age, BMI <18.5 kg m –2, ASA physical status III-V, colonoscopy and planned tracheal intubation. Thirty-day mortality was 1.2% (0.2% in electives and 6.0% in emergencies) and was associated with ASA physical status IV-V and emergency status.
Conclusions. Patients presenting for gastrointestinal endoscopy at a group of public university-affiliated hospitals where most sedation is managed by anaesthetists, had a high risk profile and a substantial incidence of significant unplanned intraoperative events and 30-day mortality.
http://ift.tt/2ieZmQa
Medication safety in the operating room: literature and expert-based recommendations
Human error poses significant risk for hospitalized patients causing an estimated 100,000 to 400,000 deaths in the USA annually. Medication errors contribute, with error occurring in 5.3% of medication administrations during surgery. In this study 70.3% of medication errors were deemed preventable. Given the paucity of randomized controlled studies, we undertook a rigorous review of the literature to identify recommendations supported by expert opinions. An extensive literature search pertaining to medication error, medication safety, operating room, and anaesthesia was performed. The National Guidelines Clearinghouse was searched for any anaesthesia or operating room medication safety guidelines.
A total of 74 articles were included. Recommendations were tabulated and assigned points based on a scale revised from a prior study. A total of 138 unique recommendations were identified, with point tallies ranging from 4 to 190. An in-person focus meeting occurred, where the 138 recommendations were reviewed, combined and condensed. A modified Delphi process was used to eliminate items found to be unimportant or those unable to be quantified (e.g. "minimize fatigue"). A total of 35 specific recommendations remained. Adverse events as a result of medication errors occur frequently in the operative setting. There are few rigorous studies to direct medication safety strategies, but this should not lead us to do nothing. The overwhelming consensus regarding best practices should be accepted, and the recommendations implemented. Our list of recommended strategies can hopefully be used to assess local vulnerabilities and institute system solutions.
http://ift.tt/2hyRrMK
Characterization of thin film tandem solar cells by radiofrequency pulsed glow discharge – Time of flight mass spectrometry
Publication date: 1 April 2017
Source:Talanta, Volume 165
Author(s): Beatriz Fernandez, Lara Lobo, Nies Reininghaus, Rosario Pereiro, Alfredo Sanz-Medel
Beside low production costs and the use of nontoxic and abundant raw materials, silicon based thin-film solar cells have the advantage to be built up as multi junction devices like tandem or triple junction solar cells. Silicon thin film modules made of tandem cells with hydrogenated amorphous silicon (a-Si:H) top cell and microcrystalline (μc) Si:H bottom cell are available on the market. In this work, the analytical potential of state-of-the art radiofrequency (rf) pulsed glow discharge (PGD) time of flight mass spectrometry (TOFMS) commercial instrumentation is investigated for depth profiling analysis of tandem-junctions solar cells on 2mm thick glass substrate with 1µm thick ZnO:Al. Depth profile characterization of two thin film tandem photovoltaic devices was compared using millisecond and sub-millisecond rf-PGD regimes, as well as the so-called "low mass mode" available in the commercial instrument used. Two procedures for sample preparation, namely using flat or rough cell substrates, were compared and the distribution of dopant elements (phosphorous, boron and germanium) was investigated in both cases. Experimental results obtained by rf-PGD-TOFMS as well as electrical measurements of the samples showed that a worse depth resolution of dopant elements in the silicon layers (e.g. distribution of boron in a thicker region that suggests a diffusion of this dopant in the coating of the sample) found using a rough sample substrate was related to a higher power conversion efficiency.
Graphical abstract
http://ift.tt/2hTnTHh
Conjugated microporous polymers-based fluorescein for fluorescence detection of 2,4,6-trinitrophenol
Publication date: 1 April 2017
Source:Talanta, Volume 165
Author(s): Tong-Mou Geng, Sai-Nan Ye, Yu Wang, Hai Zhu, Xie Wang, Xue Liu
2,4,6-Trinitrophenol (TNP, also called picric acid, PA) pose a large threat to environmental health, public safety and military security. Conjugated microporous polymers are emerging new fluorescence sensing materials for TNP. In this paper, we report the synthesis of two fluorescein containing conjugated microporous polymers (DTF and TTF) through the palladium catalyzed Sonogashira–Hagihara polycondensation reactions of tetraiodofluorescein sodium salt (TIFA) with 1,4-diethynylbenzene (DEB) or 1,3,5-triethynylbenzene (TEB). DTF and TTF are porous with the BET surface areas of 705 and 712m2g−1 and exhibit high chemical and thermal stabilities. The formation of conjugated polymers with the incorporation of ethynyl groups leads to the fluorescent properties. The fluorescence quenching behaviors of DTF by nitroaromatic analytes in THF suspension are investigated. It is found that the fluorescence of DTF can be effectively quenched by 2,4,6-trinitrophenol over 2-nitrophenol (NP), 4-nitrotoluene (NT), nitrobenzene (NB), phenol (PhOH), p-dichlorobenzene (DClB) and 2,4-dinitrotoluene (DNT) with an SV constant of 2.08×103Lmol−1 and a detection limit of 7.22×10−7molL−1 (0.165mgL−1). In short, the DTF may be a new kind of fluorescence sensing material for detecting TNP.
Graphical abstract
http://ift.tt/2hTeDDe
A supramolecular material for dual-modal imaging and targeted cancer therapy
Publication date: 1 April 2017
Source:Talanta, Volume 165
Author(s): Shanyue Guan, Ruizheng Liang, Chunyang Li, Min Wei
Recently, how to design a formulation system with simultaneous diagnosis and therapy toward cancer has attracted tremendous attention. Herein, a supramolecular material was prepared via a facile method by the co-intercalation of folic acid (FA) and doxorubicin (DOX) into the gallery of Gd3+-doped layered double hydroxides (LDHs), followed by surface adsorption of fluorescein isothiocyanate (FITC). This supramolecular agent was proved to exhibit excellent magnetic resonance imaging (MRI) and fluorescence imaging (FI) behavior, as well as chemotherapy toward cancer (KB cell). The co-intercalated FA enables an efficient and selective drug delivery with good specificity. This work provides a facile approach for the fabrication of a drug formulation with dual-modal imaging and targeted therapy, which could be potentially used in the practical chemotherapy and medical imaging.
Graphical abstract
http://ift.tt/2hTnmFo
State-dependent modulation of functional connectivity in early blind individuals
Source:NeuroImage, Volume 147
Author(s): Maxime Pelland, Pierre Orban, Christian Dansereau, Franco Lepore, Pierre Bellec, Olivier Collignon
Resting-state functional connectivity (RSFC) studies have provided strong evidences that visual deprivation influences the brain's functional architecture. In particular, reduced RSFC coupling between occipital (visual) and temporal (auditory) regions has been reliably observed in early blind individuals (EB) at rest. In contrast, task-dependent activation studies have repeatedly demonstrated enhanced co-activation and connectivity of occipital and temporal regions during auditory processing in EB. To investigate this apparent discrepancy, the functional coupling between temporal and occipital networks at rest was directly compared to that of an auditory task in both EB and sighted controls (SC). Functional brain clusters shared across groups and cognitive states (rest and auditory task) were defined. In EBs, we observed higher occipito-temporal correlations in activity during the task than at rest. The reverse pattern was observed in SC. We also observed higher temporal variability of occipito-temporal RSFC in EB suggesting that occipital regions in this population may play the role of a multiple demand system. Our study reveals how the connectivity profile of sighted and early blind people is differentially influenced by their cognitive state, bridging the gap between previous task-dependent and RSFC studies. Our results also highlight how inferring group-differences in functional brain architecture solely based on resting-state acquisition has to be considered with caution.
http://ift.tt/2ioXgO0
Plasmacytoid dendritic cell distribution and maturation are altered in lupus prone mice prior to the onset of clinical disease
Source:Clinical Immunology
Author(s): Jennifer L. Scott, Jena R. Wirth, Jackie G. EuDaly, Gary S. Gilkeson, Melissa A. Cunningham
Plasmacytoid dendritic cells (pDCs) and their production of type I interferons (IFN) are key pathogenic mediators of systemic lupus erythematosus (SLE). Despite the key role of pDCs in SLE, the mechanism by which pDCs promote disease is not well understood. The first objective for this study was to assess the number and maturation state of pDCs in pre-disease NZM2410 lupus prone mice compared to control mice. Second, we sought to identify mechanisms responsible for the alteration in pDCs in NZM mice prior to onset of clinical disease. We compared the number and percent of pDCs in the spleens and bone marrow (BM) of pre-disease NZM24010 (NZM) mice to C57BL/6 (B6) control mice. In the spleens of pre-disease NZM mice, pDC percent and number were increased. This increase occurs in parallel with a decrease in BM pDC number and percent in the NZM mice. The decrease in BM pDC number suggests the increase in spleen pDCs is a result of altered pDC distribution and not increased production of pDCs in the BM. To determine if pDC developmental potential is altered in lupus prone mice, we cultured BM from NZM and B6 mice in vitro. We found a reduced percentage/number of pDCs developing from the BM of NZM mice compared to B6 mice, which further supports that the increase in pDC number is a result of altered pDC distribution rather than increased pDC production. To better characterize the pDC population, we compared the percentage of mature pDCs in the spleens and BM of NZM mice to controls. In the NZM mice, there is a dramatic reduction in the number of mature pDCs in the BM of NZM mice, suggesting that mature pDCs exit the BM at a higher rate/earlier maturation time compared to healthy mice. We conclude that pDCs contribution to disease pathogenesis in NZM mice may include the alteration of pDC distribution to increase the number of pDCs in the spleen prior to disease onset.
http://ift.tt/2hBHM9S
The Emerging Zika Virus Threat: A Guide for Dermatologists
Abstract
We provide a guide for dermatologists to follow if they encounter patients with a rash and clinical history suspicious of Zika virus infection, including diagnostic testing and management options. We also provide an illustrative case report of a patient from Brazil who was diagnosed with Zika virus infection after presenting with a generalized pruritic rash. One of the most prominent symptoms of Zika virus infection is a cutaneous eruption. As such, it is especially necessary for dermatologists to understand this virus so that they may appropriately recognize this entity as a diagnostic consideration in the clinic. The rash associated with Zika virus infection is most commonly an erythematous maculopapular eruption that presents after an initial 3–4 days of fever, headache, and arthralgia or myalgia. The rash typically lasts for an average of 6 days, and can spread to involve any part of the body, including the face, torso, extremities, palms, and soles.
http://ift.tt/2hTlRXv
Melanoma Perception in People of Color: A Targeted Educational Intervention
Abstract
Background
Although melanoma is more common in non-Hispanic Whites, ethnic minorities face a greater risk of melanoma-related mortality, which may be partially attributed to presentation at atypical sites and a lack of awareness.
Objective
Our objective was to assess the effectiveness of a melanoma educational intervention targeted towards people of color.
Design
Participants received one of two scripted melanoma educational interventions in the summer of 2015. They completed surveys before the intervention, immediately post-intervention, and 2 months post-intervention.
Setting
Dermatology clinic at an academic hospital.
Participants
A consecutive sample of 100 participants who self-identified as African American, Asian, or Hispanic were recruited following their dermatology visit. In total, 70 participants completed the 2-month follow-up questionnaire.
Intervention
The comparison intervention group received an educational intervention using a conventional pamphlet on the 'ABCDEs' (Asymmetry, Borders, Color, Diameter, Evolution) of melanoma. The targeted intervention group received a modified pamphlet that included a skin of color section, the nomenclature "melanoma skin cancer", and an image of an individual performing a skin self-examination with the help of a friend.
Main Outcomes and Measures
Melanoma knowledge, perceived risk for developing melanoma, and skin self-examination practices were assessed through self-reported questionnaires.
Results
Among the 100 participants, 78% self-identified as African American, 11% as Asian, and 11% as Hispanic. Both groups experienced a similar increase in melanoma knowledge that was retained at 2 months. Perceived personal risk for developing melanoma increased more in the targeted intervention group immediately post-intervention (p = 0.015), but this difference no longer existed between the groups at the 2-month follow-up. The targeted intervention group also demonstrated a greater increase in skin self-examinations (p = 0.048) and knowledge of warning signs to look for when examining the skin (p = 0.002) at the 2-month follow-up.
Conclusions and Relevance
The educational intervention targeted towards people of color resulted in increased skin self-examinations. Educational material that is relevant to ethnic minorities may better promote early detection and help to decrease the disparity in melanoma-related morality rates.
Trial Registration
Clinicaltrials.gov registration number NCT02437305.
http://ift.tt/2hBMFjh
Depth versus subdural temporal electrodes revisited: impact on surgical outcome after resective surgery for epilepsy
Source:Clinical Neurophysiology
Author(s): A Valentín, N Hernando, J Moles, D Jimenez-Jimenez, S Mourente, I Malik, RP Selway, G Alarcón
ObjectiveTo study retrospectively the impact of electrode modality (subdural or depth electrodes) during presurgical assessment on surgical outcome after temporal lobectomy.MethodsThe study included 17 patients assessed with depth electrodes and 57 with bitemporal subdural strips.ResultsMRI showed a larger proportion of bilateral pathology in patients undergoing depth recordings (29.41% versus 3.5%, p=0.00069). Among the operated patients, those undergoing depth electrode recordings showed better outcome at one year after surgery (11/12 versus 22/33; p= 0.046). This difference disappears at longest follow up (10/12 versus 22/33; p=0.138). Moreover, the probability of undergoing surgery and having good outcome after assessment with intracranial recordings is higher for the depth electrode group at one-year follow up (11/17 versus 22/57; p= 0.029) but statistical differences decrease to a trend for the longest follow up (10/17 versus 22/57; p= 0.069). No other statistical differences were noted between subdural and depth electrodes. Depth electrodes showed lower complication rates than subdural electrodes.ConclusionBoth depth and subdural electrodes are effective for presurgical assessment of temporal lobe epilepsy.SignificanceAssessment with depth electrodes is associated with slightly increased likelihood of surgery and marginally better surgical outcome at one year follow up which disappears for longer follow up periods. Initial assessment with depth electrodes would have avoided a second implantation in 15% of patients.
http://ift.tt/2iMuXK0
Demonstration of Motor-Related Beta and High Gamma Brain Signals in Subdermal Electroencephalography Recordings
Source:Clinical Neurophysiology
Author(s): Jared D Olson, Jeremiah D Wander, Felix Darvas
http://ift.tt/2hw33Na
The Effect of Saccadic Eye Movements on the Sensor-Level Magnetoencephalogram
Source:Clinical Neurophysiology
Author(s): Timothy J. Gawne, Jeffrey F. Killen, John M. Tracy, Adrienne C. Lahti
ObjectiveWe used a combination of simulation and recordings from human subjects to characterize how saccadic eye movements affect the magnetoencephalogram (MEG).MethodsWe used simulated saccadic eye movements to generate simulated MEG signals. We also recorded the MEG signals from three healthy adults to 5-degree magnitude saccades that were vertical up and down, and horizontal left and right.ResultsThe signal elicited by the rotating eye dipoles is highly dependent on saccade direction, can cover a large area, can sometimes have a non-intuitive trajectory, but does not significantly extend above approximately 30Hz in the frequency domain. In contrast, the saccadic spikes (which are primarily monophasic pulses, but can be biphasic) are highly localized to the lateral frontal regions for all saccade directions, and in the frequency domain extend up past 60 Hz.ConclusionsGamma band saccadic artifact is spatially localized to small regions regardless of saccade direction, but beta band and lower frequency saccadic artifact have broader spatial extents that vary strongly as a function of saccade direction.SignificanceWe have here characterized the MEG saccadic artifact in both the spatial and the frequency domains for saccades of different directions. This could be important in ruling in or ruling out artifact in MEG recordings.
http://ift.tt/2iMmeHD
Value of re-interpretation of controversial EEGs in a tertiary epilepsy clinic
Source:Clinical Neurophysiology
Author(s): Johan B Arends, Inge van der Linden, Saskia C Ebus, Mariëtte H Debeij, W Boudewijn Gunning, Machiel J Zwarts
ObjectiveDiagnostic value and efficacy of re-interpretation of previous EEGs in 100 patients admitted to a tertiary epilepsy center with EEG results conflicting with the clinical diagnosis after the first visit.MethodsEEGs were reclassified. A matched control group was included to assess the efficiency of the re-interpretation process. Efficacy was assessed by questionnaires and costs as number of technician hours needed.ResultsIn 85 patients the previous EEG conclusion was known. In 43 the conclusion was altered. In 23 the epileptic activity changed from positive to negative (17) or the reverse (6). In 15 the focus changed (7 originally classified as generalized epileptic activity). In 5 the syndrome changed. 57% Of the re-interpretation group needed no extra EEG afterwards.96% Of the re-interpretations were considered useful by requesting and 72% by not involved neurologists.The average time per EEG technologist per patient was 8,81 hours in controls and 5,40 in the re-interpretation group.ConclusionsIn 43 from the 85 patients (51%) re-interpretation of 'controversial' EEGs led to a different opinion. The re-interpretations were useful and less time consuming, compared to new EEGs in controls.SignificanceRe-interpretation of 'controversial' EEGs is useful and cost effective.
http://ift.tt/2hw2EKG
Interrater Reliability of Visually Evaluated High Frequency Oscillations
Source:Clinical Neurophysiology
Author(s): Aaron M Spring, Daniel J Pittman, Yahya Aghakhani, Jeffrey Jirsch, Neelan Pillay, Luis E Bello-Espinosa, Colin Josephson, Paolo Federico
ObjectiveHigh frequency oscillations (HFOs) and interictal epileptiform discharges (IEDs) have been shown to be markers of epileptogenic regions. However, there is currently no 'gold standard' for identifying HFOs. Accordingly, we aimed to formally characterize the interrater reliability of HFO markings to validate the current practices.MethodsA morphology detector was implemented to detect events (candidate HFOs, lower-threshold events, and distractors) from the intracranial EEG (iEEG) of ten patients. Six electroencephalographers visually evaluated these events for the presence of HFOs and IEDs. Interrater reliability was calculated using pairwise Cohen's Kappa (κ) and intraclass correlation coefficients (ICC).ResultsThe HFO evaluation distributions were significantly different for most pairs of reviewers (p < 0.05; 11/15 pairs). Interrater reliability was poor for HFOs alone (κmean = 0.403; ICC = 0.401) and HFO+IEDs (κmean = 0.568; ICC = 0.570).ConclusionsThe current practice of using two visual reviewers to identify HFOs is prone to bias arising from the poor agreement between reviewers, limiting the extrinsic validity of studies using these markers.SignificanceThe poor interrater reliability underlines the need for a framework to reconcile the important findings of existing studies. The present epoched design is an ideal candidate for the implementation of such a framework.
http://ift.tt/2iMt1RR
Pain perception in patients with chronic disorders of consciousness: what can limbic system tell us?
Source:Clinical Neurophysiology
Author(s): Rocco Salvatore Calabrò, Antonino Naro, Alfredo Manuli, Antonino Leo, Rosaria De Luca, Viviana Lo Buono, Margherita Russo, Alessia Bramanti, Placido Bramanti
ObjectiveAlthough it is believed that patients with Unresponsive Wakefulness Syndrome (UWS) do not feel pain, recent neuroimaging and neurophysiologic studies have demonstrated some residual traces of nociceptive processing.MethodsTo confirm this growing evidence, we evaluated 21 patients suffering from chronic disorders of consciousness (DOC) (both UWS, n=11, and minimally conscious state –MCS-, n=10), using an Event-Related Potential (ERP) Low-Resolution Brain Electromagnetic Tomography (LORETA) approach, based on nociceptive repeated laser stimulation (RLS). We delivered laser stimuli to the dorsum of both hands and analysed the γ-band LORETA activations and the ERP γ-power magnitude induced by laser stimulation, as well as the heart rate variability (HRV).ResultsWe found partially preserved cortical activations and ERP γ-power magnitude in all MCS and two UWS individuals. These effects were paralleled by a purposeful behaviour, and a reduced HRV concerning nociceptive stimulation, whereas the two UWS individuals showed no more than reflex behaviours, besides a strong limbic activation.ConclusionsSome UWS patients may somehow perceive the affective components of nociceptive stimulation.Significancethe diagnosis of functional locked-in syndrome should be taken into account when dealing with DOC differential diagnosis.
http://ift.tt/2hvMAsq
MUNIX in the clinic in ALS: MUNE comes of age
Source:Clinical Neurophysiology
Author(s): Michael Swash
http://ift.tt/2hw123n
GABAAergic dysfunction in the olivary-cerebellar-brainstem network may cause eye oscillations and body tremor
Source:Clinical Neurophysiology
Author(s): Elena Pretegiani, Francesca Rosini, Raffaele Rocchi, Federica Ginanneschi, Claudia Vinciguerra, Lance M. Optican, Alessandra Rufa
http://ift.tt/2iMdam6
Polyglycerol-based organic-inorganic hybrid adhesive with high early strength
Publication date: 5 March 2017
Source:Materials & Design, Volume 117
Author(s): Zhengpeng Yang, Xuefeng Zhang, Xuan Liu, Xuemao Guan, Chunjing Zhang, Yutao Niu
The rapid achievement of high strength adhesive is of ever increasing importance for underground construction. Herein, a simple and effective strategy to make an adhesive in a "high early strength" way was based on excellent crosslinking and synergistic interactions among tripolyglycerol, waterglass and polyaryl polymethylene isocyanate (PAPI). The resultant organic-inorganic hybrid adhesive with three-dimensional interpenetrating network structure showed an excellent mechanical performance, the compressive strength could reach more than 50 and 60MPa after curing for 2 and 4h, respectively. The adhesive was mainly composed of amorphous polyurethane and crystalline polysilicic acid/NaHCO3 composite, and its probable formation mechanism was proposed. Furthermore, the adhesive was thermally stable below 260°C and presented a favorable adhesion performance for dry/wet sands with various sizes. This work may open a simple and convenient avenue for the preparation of organic-inorganic hybrid adhesive with high early strength.
Graphical abstract
http://ift.tt/2hBAgeQ
Hydrophilic polymer vasculopathy with coinciding pseudoxanthoma elasticum-like changes in an amputated toe.
Abstract
For the past decades, hydrophilic polymer gel coating have been widely used on endovascular devices to decrease friction and to aid with binding and delivering of medications in drug eluting stents. In the recent years, hydrophilic polymer emboli disease has been recognized as an iatrogenic adverse effect which has led to considerable morbidity and mortality of patients. This under-recognized embolic phenomenon now has reproducible pathognomonic histologic findings. Small to medium sized blood vessels are occluded with basophilic, amorphous, non-refractile, non-polarizable, whirled aggregates of foreign body material. Depending on the affected organ, the patients have variable symptomatology, from livedo racemosa, gangrene of extremities to cardiac arrhythmias, hemiparesis, stroke and death. Here, we present a unique case of hydrophilic polymer vasculopathy six years post endovascular procedure with coinciding pseudoxanthoma elasticum-like changes. As the literature has seen increased reporting of individual cases and case series documenting the patients' diverse symptomatology; hydrophilic polymer vasculopathy should be entertained sooner in the patient's differential diagnosis.
http://ift.tt/2hBwMcj
Comparison of radon doses based on different radon monitoring approaches
Source:Journal of Environmental Radioactivity, Volumes 169–170
Author(s): Janja Vaupotič, Nataša Smrekar, Zora S. Žunić
In 43 places (23 schools, 3 kindergartens, 16 offices and one dwelling), indoor radon has been monitored as an intercomparison experiment, using α-scintillation cells (SC – Jožef Stefan Institute, Slovenia), various kinds of solid state nuclear track detectors (KfK – Karlsruhe Institute of Technology, Germany; UFO – National Institute of Radiological Sciences, Chiba, Japan; RET – University College Dublin, Ireland) and active electronic devices (EQF, Sarad, Germany). At the same place, the radon levels and, consequently, the effective doses obtained with different radon devices differed substantially (by a factor of 2 or more), and no regularity was observed as regards which detector would show a higher or lower dose.
http://ift.tt/2iwALny
Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity
Publication date: Available online 29 December 2016
Source:Cell Metabolism
Author(s): Danielle M. Friend, Kavya Devarakonda, Timothy J. O'Neal, Miguel Skirzewski, Ioannis Papazoglou, Alanna R. Kaplan, Jeih-San Liow, Juen Guo, Sushil G. Rane, Marcelo Rubinstein, Veronica A. Alvarez, Kevin D. Hall, Alexxai V. Kravitz
Obesity is associated with physical inactivity, which exacerbates the health consequences of weight gain. However, the mechanisms that mediate this association are unknown. We hypothesized that deficits in dopamine signaling contribute to physical inactivity in obesity. To investigate this, we quantified multiple aspects of dopamine signaling in lean and obese mice. We found that D2-type receptor (D2R) binding in the striatum, but not D1-type receptor binding or dopamine levels, was reduced in obese mice. Genetically removing D2Rs from striatal medium spiny neurons was sufficient to reduce motor activity in lean mice, whereas restoring Gi signaling in these neurons increased activity in obese mice. Surprisingly, although mice with low D2Rs were less active, they were not more vulnerable to diet-induced weight gain than control mice. We conclude that deficits in striatal D2R signaling contribute to physical inactivity in obesity, but inactivity is more a consequence than a cause of obesity.
Graphical abstract
Teaser
Friend et al. show that diet-induced obesity causes deficits in striatal D2-type dopamine receptor (D2R) binding and reductions in physical activity. However, the decrease in physical activity appears to be more a consequence than a cause of weight gain in mice.http://ift.tt/2hT0J3O
SREBP1 Contributes to Resolution of Pro-inflammatory TLR4 Signaling by Reprogramming Fatty Acid Metabolism
Publication date: Available online 29 December 2016
Source:Cell Metabolism
Author(s): Yumiko Oishi, Nathanael J. Spann, Verena M. Link, Evan D. Muse, Tobias Strid, Chantle Edillor, Matthew J. Kolar, Takashi Matsuzaka, Sumio Hayakawa, Jenhan Tao, Minna U. Kaikkonen, Aaron F. Carlin, Michael T. Lam, Ichiro Manabe, Hitoshi Shimano, Alan Saghatelian, Christopher K. Glass
Macrophages play pivotal roles in both the induction and resolution phases of inflammatory processes. Macrophages have been shown to synthesize anti-inflammatory fatty acids in an LXR-dependent manner, but whether the production of these species contributes to the resolution phase of inflammatory responses has not been established. Here, we identify a biphasic program of gene expression that drives production of anti-inflammatory fatty acids 12–24 hr following TLR4 activation and contributes to downregulation of mRNAs encoding pro-inflammatory mediators. Unexpectedly, rather than requiring LXRs, this late program of anti-inflammatory fatty acid biosynthesis is dependent on SREBP1 and results in the uncoupling of NFκB binding from gene activation. In contrast to previously identified roles of SREBP1 in promoting production of IL1β during the induction phase of inflammation, these studies provide evidence that SREBP1 also contributes to the resolution phase of TLR4-induced gene activation by reprogramming macrophage lipid metabolism.
Graphical abstract
Teaser
Oishi and Spann et al. identify a biphasic macrophage gene expression program underlying anti-inflammatory fatty acid production following TLR4 activation. The late anti-inflammatory program is dependent on SREBP1. This is surprising given the known roles of SREBP1 in promoting IL1β production during the induction of inflammation and highlights its dual roles.http://ift.tt/2hT6Sgw
Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks
Publication date: Available online 29 December 2016
Source:Cell Metabolism
Author(s): Ildem Akerman, Zhidong Tu, Anthony Beucher, Delphine M.Y. Rolando, Claire Sauty-Colace, Marion Benazra, Nikolina Nakic, Jialiang Yang, Huan Wang, Lorenzo Pasquali, Ignasi Moran, Javier Garcia-Hurtado, Natalia Castro, Roser Gonzalez-Franco, Andrew F. Stewart, Caroline Bonner, Lorenzo Piemonti, Thierry Berney, Leif Groop, Julie Kerr-Conte, Francois Pattou, Carmen Argmann, Eric Schadt, Philippe Ravassard, Jorge Ferrer
Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate β cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key β cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance. These results implicate lncRNAs in the regulation of β cell-specific transcription factor networks.
Graphical abstract
Teaser
Akerman et al. studied the function of human β cell lncRNAs with RNAi, CRISPRi, and co-expression networks. This revealed β cell lncRNAs and transcription factors that control common regulatory networks. One lncRNA, PLUTO, is downregulated in type 2 diabetes and controls PDX1, encoding a key β cell transcription factor.http://ift.tt/2hT1mu0
Table of Contents & Bacode
Publication date: January–February 2017
Source:Journal of Surgical Education, Volume 74, Issue 1
http://ift.tt/2iwNOVR
Masthead
Publication date: January–February 2017
Source:Journal of Surgical Education, Volume 74, Issue 1
http://ift.tt/2hyzUUP
Individualised Expert Feedback is Not Essential for Improving Basic Clinical Skills Performance in Novice Learners: A Randomized Trial
Publication date: Available online 29 December 2016
Source:Journal of Surgical Education
Author(s): Alexander W. Phillips, Joanna Matthan, Lucy R. Bookless, Ian J. Whitehead, Anantha Madhavan, Paul Rodham, Anna L.R. Porter, Craig I. Nesbitt, Gerard Stansby
ObjectiveTo determine whether unsupervised video feedback (UVF) is as effective as direct expert feedback (DEF) in improving clinical skills performance for medical students learning basic surgical skills—intravenous cannulation, catheterization, and suturing.BackgroundFeedback is a vital component of the learning process, yet great variation persists in its quality, quantity, and methods of delivery. The use of video technology to assist in the provision of feedback has been adopted increasingly.MethodsA prospective, blinded randomized trial comparing DEF, an expert reviewing students' performances with subsequent improvement suggestions, and UVF, students reviewing their own performance with an expert teaching video, was carried out. Medical students received an initial teaching lecture on intravenous cannulation, catheterization, and suturing and were then recorded performing the task. They subsequently received either DEF or UVF before reperforming the task. Students' recordings were additionally scored by 2 blinded experts using a validated proforma.ResultsA total of 71 medical students were recruited. Cannulation scores improved 4.3% with DEF and 9.5% with UVF (p = 0.044), catheterization scores improved 8.7% with DEF and 8.9% with UVF (p = 0.96), and suturing improved 15.6% with DEF and 13.2% with UVF (p = 0.54). Improvement from baseline scores was significant in all cases (p < 0.05).ConclusionVideo-assisted feedback allows a significant improvement in clinical skills for novices. No significant additional benefit was demonstrated from DEF, and a similar improvement can be obtained using a generic expert video and allowing students to review their own performance. This could have significant implications for the design and delivery of such training.
http://ift.tt/2iwzTPy
Racial and Ethnic Diversity of U.S. Plastic Surgery Trainees
Publication date: January–February 2017
Source:Journal of Surgical Education, Volume 74, Issue 1
Author(s): Jason Silvestre, Joseph M. Serletti, Benjamin Chang
BackgroundIncreased diversity of U.S. physicians can improve patient communication and mitigate health disparities for racial minorities. This study analyzes trends in racial and ethnic diversity of plastic surgery residents.MethodsDemographic data of surgical residents, medical students, and integrated plastic surgery residency applicants were obtained from the Association of American Medical Colleges. Data for college students and the general population were obtained from the U.S. Census for comparison with plastic surgery. Interspecialty differences and temporal trends in racial composition were analyzed with chi-square tests.ResultsFrom 1995 to 2014, Asian and Hispanic plastic surgery residents increased nearly 3-fold (7.4%-21.7%, p < 0.001) and 2-fold (4.6%-7.9%, p < 0.001), respectively. African American plastic surgery residents did not increase significantly (3.0%-3.5%, p = 0.129). Relative to the U.S. population, Hispanics (range: 0.1-0.5–fold) and African Americans (range: 0.1-0.4–fold) were underrepresented, whereas Asians (range: 2.2-5.3–fold) were overrepresented in plastic surgery. A "bottleneck" existed in the pipeline of African American and Hispanic plastic surgery residents. Significant differences in racial composition existed between plastic surgery and other surgical disciplines, which varied over time. The percentage of Hispanic (10.6% vs 7.0%, p = 0.402) and African American (6.4% vs 2.1%, p < 0.001) plastic surgery residency applicants exceeded those in residency.ConclusionsHispanics and African Americans are underrepresented in plastic surgery residency relative to whites and Asians. This study underscores the need for greater initiatives to increase diversity in plastic surgery residency.
http://ift.tt/2hyvOMD
Effect of General Anesthesia on Neurodevelopmental Abnormalities in Children Undergoing Treatment of Vascular Anomalies With Laser Surgery: A Retrospective Review.
BACKGROUND: Multiple exposures to general anesthesia may be neurotoxic to the developing brain. This relationship has not been evaluated in children undergoing laser surgery for vascular anomalies. OBJECTIVE: To evaluate the prevalence of neurodevelopmental abnormalities in children who received multiple laser procedures under general anesthesia before the age of 4 years for the treatment of vascular anomalies. METHODS AND MATERIALS: Retrospective chart review of patients with contact of parents for telephone interview. RESULTS: Thirty-three patients were eligible. Average age at the time of survey was 7.8 years. Twenty-three (84.8%) patients were female, with average age at the time of first treatment at 1.9 years. Average number of treatments received before the age of 4 years was 6.7. Anesthetics included inhalational nitrous oxide and isoflurane and intravenous propofol. Seven patients carried one or more of the following diagnoses: attention-deficit hyperactivity disorder (3.0%), anxiety (6.1%), behavioral disorder (3.0%), language disorder (3.0%), speech disorder (3.0%), and motor disorder (6.1%). These prevalence rates are similar to those found in the US population. CONCLUSION: This is the first report on the prevalence of neurodevelopmental disorders in children undergoing multiple laser treatments under general anesthesia. Although the study sample is small, no increased risks when comparing with prevalence rates reported in the literature were noted. (C) 2016 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2hBn7Tg
http://ift.tt/2hBn7Tg
Novel four-sided neural probe fabricated by a thermal lamination process of polymer films
Source:Journal of Neuroscience Methods
Author(s): Soowon Shin, Jae-Hyun Kim, Joonsoo Jeong, Tae Mok Gwon, Seung-Hee Lee, Sung June Kim
BackgroundIdeally, neural probes should have channels with a three-dimensional (3-D) configuration to record the activities of 3-D neural circuits. Many types of 3-D neural probes have been developed; however, most of them were designed as an array of multiple shanks with electrodes located along one side of the shanks.New methodWe developed a novel liquid crystal polymer (LCP)-based neural probe with four-sided electrodes. This probe has electrodes on four sides of the shank, i.e., the front, back and two sidewalls. To generate the proposed configuration of the electrodes, we used a thermal lamination process involving LCP films and laser micromachining.ResultsThe proposed novel four-sided neural probe, was used to successfully perform in vivo multichannel neural recording in the mouse primary somatosensory cortex.Comparison with existing methodThe multichannel neural recording showed that the proposed four-sided neural probe can record spiking activities from a more diverse neuronal population than single-sided probes. This was confirmed by a pairwise Pearson correlation coefficient (Pearson's r) analysis and a cross-correlation analysis.ConclusionThe developed four-sided neural probe can be used to record various signals from a complex neural network.
http://ift.tt/2iogy64
Palisaded Granuloma on the Nose: An Atypical Presentation of Granuloma Annulare.
Granuloma annulare (GA) is a common, asymptomatic dermatosis of unknown etiology. Many variants exist, among them widespread papules, papules in photodistribution, papules marked by tiny crusts ("perforating" GA), patches, plaques, and nodules (subcutaneous GA). The histopathological hallmark is a palisaded histiocytic infiltrate surrounding a central area of degenerated collagen with abundant mucin deposits. We report 2 women who presented with persistent nodules on the nose, which, on histopathological examination, showed a palisaded granuloma. We propose that these cases represent an unusual variant of GA occurring on the nose. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2ieBKeb
http://ift.tt/2ieBKeb
Malignant Melanoma in Association With a Thymic Nevus in a Patient With a Giant Congenital Nevus.
Nevi and melanocytic proliferations are known to appear in multiple extracutaneous sites, including lymph nodes and meninges. We report a case of an anterior mediastinal mass in a patient with a giant congenital nevus and neurofibromatosis type I. Histologically, the tumor was found to be a malignant melanoma in the thymus arising in association with a nevus that involved most of the thymic tissue. There was no sign of cutaneous melanoma on skin examination. We suggest that the tumor originated from the benign nevus in the thymus, a rare extracutaneous location for nevi and malignant melanoma. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2iLdKfQ
http://ift.tt/2iLdKfQ
Tubulopapillary Cystic Adenoma With Apocrine Differentiation: A Unifying Concept for Syringocystadenoma Papilliferum, Apocrine Gland Cyst, and Tubular Papillary Adenoma.
Syringocystadenoma papilliferum (SCAP), apocrine gland cyst (AGC, also called apocrine hidrocystoma or apocrine cystadenoma), and tubular papillary adenoma (TPA) with apocrine differentiation are defined as proliferations of apocrine epithelium with myoepithelial cells. At Sapporo Dermatopathology Institute, we retrieved 308 benign neoplastic lesions diagnosed as SCAP, AGC, or TPA and combinations of these entities. Among the 308 lesions, 202 (66%) exhibited features of only one type, of which 144 (47%) were AGC, 39 (13%) were TPA, and 19 (6%) were SCAP. The other 106 lesions (34%) had features of 2 or more types, including 56 lesions that were AGC + TPA (18%), 2 that were AGC + SCAP (1%), 34 that were TPA + SCAP (11%), and 14 that were AGC + TPA + SCAP (5%). The most frequent site of these lesions was the face (56%), followed by the scalp (13%). Lesions with the features of AGC were more frequently found on the face, especially the periocular region, than at other sites. TPA lesions were more frequent on the face and scalp than at other sites, whereas SCAP lesions were preferentially found on the face, scalp, and trunk. We also retrieved clinicopathological data and other information. We propose a unifying concept for AGC, TPA, and SCAP. Approximately one-third of these lesions are composite entities with the features of 2 or 3 different tumors, and we propose calling such tumors tubulopapillary cystic adenoma with apocrine differentiation. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2iLqFyl
http://ift.tt/2iLqFyl
Distinct cortico-striatal connections with subthalamic nucleus underlie facets of compulsivity
Publication date: Available online 29 December 2016
Source:Cortex
Author(s): Laurel S. Morris, Kwangyeol Baek, Valerie Voon
The capacity to flexibly respond to contextual changes is crucial to adapting to a dynamic environment. Compulsivity, or behavioural inflexibility, consists of heterogeneous subtypes with overlapping yet discrete neural substrates. The subthalamic nucleus (STN) mediates the switch from automatic to controlled processing to slow, break or stop behaviour when necessary. Rodent STN lesions or inactivation are linked with perseveration or repetitive, compulsive responding. However, there are few studies examining the role of latent STN-centric neural networks and compulsive behaviour in healthy individuals. We therefore aimed to characterize the relationship between measures of compulsivity (goal-directed and habit learning, perseveration, and self-reported obsessive – compulsive symptoms) and the intrinsic resting state network of the STN. We scanned 77 healthy controls using a multi-echo resting state functional MRI sequence analyzed using independent components analysis (ME-ICA) with enhanced signal-to-noise ratio to examine small subcortical structures. Goal directed model-based behaviour was associated with higher connectivity of STN with medial orbitofrontal cortex and ventral striatum and more habitual model-free learning was associated with STN connectivity with hippocampus and dorsal anterior cingulate cortex. Perseveration was associated with reduced connectivity between STN and premotor cortex and finally, higher obsessive –compulsive inventory scores were associated with reduced STN connectivity with dorsolateral prefrontal cortex. We highlight unique contributions of diffuse cortico-striatal functional connections with STN in dissociable measures of compulsivity. These findings are relevant to the development of potential biomarkers of treatment response in neurosurgical procedures targeting the STN for neurological and psychiatric disorders.
http://ift.tt/2ieqjn1
Convergence of interoception, emotion, and social cognition: A twofold fMRI meta-analysis and lesion approach
Source:Cortex
Author(s): Federico Adolfi, Blas Couto, Fabian Richter, Jean Decety, Jessica Lopez, Mariano Sigman, Facundo Manes, Agustín Ibáñez
Guided by indirect evidence, recent approaches propose a tripartite crosstalk among interoceptive signaling, emotional regulation, and low-level social cognition. Here we examined the neurocognitive convergence of such domains. First, we performed three meta-analyses of functional magnetic resonance imaging studies to identify which areas are consistently coactivated by these three systems. Multi-level Kernel Density Analysis revealed major overlaps in the right anterior insular and frontotemporal regions (viz., the orbitofrontal and inferior frontal gyri, the amygdala, and mid temporal lobe/subcortical structures). Second, we explored such domains in patients with fronto-insulo-temporal damage. Relative to controls, the patients showed behavioral impairments of interoception, emotional processing, and social cognition, with preservation of other cognitive functions. Convergent results from both studies offer direct support for a model of insular-frontotemporal regions integrating interoception, emotion, and social cognition.
http://ift.tt/2iL9M6T
Πέμπτη 29 Δεκεμβρίου 2016
Three unusual histopathological presentations of angiolymphoid hyperplasia with eosinophilia
Abstract
Angiolymphoid hyperplasia with eosinophilia (ALHE) is a poorly understood benign vasculoproliferative disorder. Histopathologicaly, the lesions are composed of a dermal or subcutaneous proliferation of blood vessels of varying sizes with plump and bland endothelial cells, which often show vacuolization and protrusion of the cytoplasm into the lumen. The vascular proliferation is admixed with a diffuse inflammatory infiltrate composed of lymphocytes, eosinophils, and mast cells. Lymphoid follicles with germinal centers can sometimes be seen. Additionally, fibrosis is a common accompanying feature. Some clinical and histopathological variants of ALHE have already been described in the literature. In this report, we present three rare associations of ALHE that have not been previously described. Case 1 was a 73-year-old woman with a lesion on her right medial thigh. Examination showed ALHE admixed with a chronic lymphocytic leukemic (CLL) infiltrate. Case 2 was a 55-year-old woman with a lesion on her right anterior ankle, which was a syringocystademoma papilliferum coexisting with an ALHE. Case 3 was a 54-year-old man with a lesion on the left medial thigh, which showed overlapping features of IgG4-related disease associated with areas of ALHE. Given these multiple and diverse associations, it seems likely that ALHE may be a reactive rather than neoplastic process.
http://ift.tt/2ieiSft
Cutaneous Extranodal NK/T Cell Lymphoma Mimicking Cellulitis in a HIV Positive Patient without Lymphopenia
Abstract
We present the case of a 28-year-old male with a history of HIV with a 1-month history of a steadily enlarging, firm painful lesion on the right posterior shoulder. The patient was initially treated for cellulitis given his clinical picture. Histopathologic examination revealed an angiocentric and dermal proliferation of markedly atypical lymphoid cells with numerous mitoses and apoptotic bodies along with broad zones of necrosis. Biopsy revealed the presentation to be consistent with NK/T-cell lymphoma. The cutaneous lesions from NK/T-cell lymphoma can often be initially mistaken for cellulitis, therefore this malignancy should be included on the differential in a patient HIV/AIDS.
http://ift.tt/2iLcObs
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Publication date: September 2017 Source: Free Radical Biology and Medicine, Volume 110 Author(s): Lucía Fernández-del-Río, Anish Nag, Elen...
