Cosmetics, Vol. 5, Pages 34: Alkenones as a Promising Green Alternative for Waxes in Cosmetics and Personal Care Products

Cosmetics, Vol. 5, Pages 34: Alkenones as a Promising Green Alternative for Waxes in Cosmetics and Personal Care Products

Cosmetics doi: 10.3390/cosmetics5020034

Authors: Kyle McIntosh Amber Smith Lisa K. Young Michael A. Leitch Amit K. Tiwari Christopher M. Reddy Gregory W. O'Neil Matthew W. Liberatore Mark Chandler Gabriella Baki

The move toward green, sustainable, natural products has been growing in the cosmetic and personal care industry. Ingredients derived from marine organisms and algae are present in many cosmetic products. In this study, a new green ingredient, a wax (i.e., long-chain alkenones) derived from Isochyrsis sp., was evaluated as an alternative for cosmetic waxes. First, the melting point was determined (71.1–77.4 °C), then the alkenones’ thickening capability in five emollients was evaluated and compared to microcrystalline wax and ozokerite. Alkenones were compatible with three emollients and thickened the emollients similarly to the other waxes. Then, lipsticks and lip balms were formulated with and without alkenones. All products remained stable at room temperature for 10 weeks. Lipstick formulated with alkenones was the most resistant to high temperature. Finally, alkenones were compared to three cosmetic thickening waxes in creams. Viscosity, rheology, and stability of the creams were evaluated. All creams had a gel-like behavior. Both viscosity and storage modulus increased in the same order: cream with alkenones < cetyl alcohol < stearic acid < glyceryl monostearate. Overall, alkenones’ performance was comparable to the other three waxes. Alkenones can thus offer a potential green choice as a new cosmetic structuring agent.

https://ift.tt/2sIoOB7

Autophony of eyelid movement is not independent of eyeball movement

https://ift.tt/2Lmhxyl

Improvement in minimal cross-sectional area and nasal-cavity volume occurs in different areas after septoplasty and radiofrequency therapy of inferior turbinates

Abstract

Purpose

Septoplasty and radiofrequency therapy for inferior turbinate hypertrophy (RFIT) are common techniques used to improve nasal patency. Our aim was to compare nasal geometry and function using acoustic rhinometry and peak nasal inspiratory flow (PNIF) in three patients groups undergoing surgery for nasal obstruction, and to investigate if the improvement in minimal cross-sectional area (MCA) and nasal-cavity volume (NCV) occurred in different cavity areas in the groups. Finally, we evaluated the correlation between the objective measurements and the patients' assessment of nasal obstruction (SNO).

Methods

This prospective, observational study investigated 148 patients pre-operatively and 6 months post-operatively. Fifty patients underwent septoplasty (group 1), 51 underwent septoplasty combined with RFIT (group 2), and 47 underwent RFIT alone (group 3). The MCA and NCV were measured at two distances (MCA/NCV_0–3.0 and MCA/NCV_3–5.2), in addition to measuring PNIF and SNO.

Results

Pre-operatively, groups 1 and 2 had narrower MCA_0–3.0 on one side than group 3 (0.31 ± 0.14 and 0.31 ± 0.14) versus (0.40 ± 0.16) cm². Post-operatively, total MCA_0–3.0 and MCA/NCV_3–5.2 increased in group 1. In group 2, MCA/NCV_0–3.0 at the narrow side and total MCA/NCV_3–5.2 increased, while total MCA/NCV_3–5.2 increased in group 3. PNIF improved from 106 ± 49 to 150 ± 57 l/min post-operatively. We found a correlation between increased MCA and NCV and less SNO in the septoplasty group (p < 0.01).

Conclusion

Surgery produced an improvement in MCA and NCV in all groups. The improvement occurred in different areas of the nasal cavity in the patient groups. Both anterior and posterior areas increased in the septoplasty groups, while only the posterior area increased in the RFIT group. PNIF improved in all three patient groups, indicating that surgery produced an improvement in nasal patency.

https://ift.tt/2JrbLyi

Efficiency of Tinospora crispa against Culex quinquefasciatus larva

Abstract

Tinospora crispa stem aqueous extractions for various time durations were determined regarding their total phenolic content and their larvicidal abilities. The results revealed that the total phenolic content in 1-, 3-, 5-, 10-, and 24-h extracts were 8.26, 8.43, 13.57, 12.52, and 12.43 mg/g gallic acid equivalent, respectively. The 5-h extract of T. crispa was evaluated against Culex quinquefasciatus mosquito larva in concentrations 3.125, 6.25, 12.5, and 25 mg/l, by determining the lethal concentration (LC) within 24 h and by histopathological analysis. The 24-h LC₅₀ and LC₉₀ values were 16.95 and 30.12 mg/l, respectively. The histopathological lesions after exposure to 50% of the 24-h LC₅₀ were observed primarily in the midgut of the larva. The lesions observed were for the example epithelial cells lifting from the basement membrane, cell elongation protruding into the lumen, brush border disrupting with absent microvilli, and vesicle appearance. The present study indicated that the aqueous extract of this herb may have a suitable property for a larvicidal natural product and may replace harmful chemical pesticides.

https://ift.tt/2HlsOg3

Scalable long-term extraction of photosynthetic electrons by simple sandwiching of nanoelectrode array with densely-packed algal cell film

Publication date: 15 October 2018
Source:Biosensors and Bioelectronics, Volume 117
Author(s): Yong Jae Kim, JaeHyoung Yun, Seon Il Kim, Hyeonaug Hong, Jun-Hee Park, Jae-Chul Pyun, WonHyoung Ryu
Direct extraction of photosynthetic electrons from the whole photosynthetic cells such as plant cells or algal cells can be highly efficient and sustainable compared to other approaches based on isolated photosynthetic apparatus such as photosystems I, II, and thylakoid membranes. However, insertion of nanoelectrodes (NEs) into individual cells are time-consuming and unsuitable for scale-up processes. We propose simple and efficient insertion of massively-populated NEs into cell films in which algal cells are densely packed in a monolayer. After stacking the cell film over an NE array, gentle pressing of the stack allows a large number of NEs to be inserted into the cells in the cell film. The NE array was fabricated by metal-assisted chemical etching (MAC-etching) followed by additional steps of wet oxidation and oxide etching. The cell film was prepared by mixing highly concentrated algal cells with alginate hydrogel. Photosynthetic currents of up to 106 nA/cm² was achieved without aid of mediators, and the photosynthetic function was maintained for 6 days after NE array insertion into algal cells.



https://ift.tt/2Jc6Xxp

Enhancement of bioelectricity generation via heterologous expression of IrrE in Pseudomonas aeruginosa-inoculated MFCs

Publication date: 15 October 2018
Source:Biosensors and Bioelectronics, Volume 117
Author(s): Jianmei Luo, Tingting Wang, Xiao Li, Yanan Yang, Minghua Zhou, Ming Li, Zhongli Yan
Low electricity power output (EPT) is still the main bottleneck limited the industrial application of microbial fuel cells (MFCs). Herein, EPT enhancement by introducing an exogenous global regulator IrrE derived from Deinococcus radiodurans into electrochemically active bacteria (EAB) was explored using Pseudomonas aeruginosa PAO1 as a model strain, achieving a power density 71% higher than that of the control strain. Moreover, IrrE-expressing strain exhibited a remarkable increase in the total amount of electron shuttles (majorly phenazines compounds) and a little decrease in internal resistance, which should underlie the enhancement in extracellular electron transfer (EET) efficiency and EPT. Strikingly, IrrE significantly affected substrate utilization profiling, improved cell growth characterization and cell tolerance to various stresses. Further quantitative RT-PCR analysis revealed that IrrE led to many differentially expressed genes, which were responsible for phenazines core biosynthesis, biofilm formation, QS systems, transcriptional regulation, glucose metabolism and general stress response. The results substantiated that targeting cellular regulatory network by the introduction of exogenous global regulators could be a facile and promising approach for the enhancement of bioelectricity generation and cell multiple phenotypes, and thus would be of great potential application in the practical MFCs.



https://ift.tt/2HkFP9D

Simultaneous detection and determination of mercury (II) and lead (II) ions through the achievement of novel functional nucleic acid-based biosensors

Publication date: 30 September 2018
Source:Biosensors and Bioelectronics, Volume 116
Author(s): Zahra Khoshbin, Mohammad Reza Housaindokht, Asma Verdian, Mohammad Reza Bozorgmehr
The serious threats of mercury (Hg²⁺) and lead (Pb²⁺) ions for the public health makes it important to achieve the detection methods of the ions with high affinity and specificity. Metal ions usually coexist in some environment and foodstuff or clinical samples. Therefore, it is very necessary to develop a fast and simple method for simultaneous monitoring the amount of metal ions, especially when Hg²⁺ and Pb²⁺ coexist. DNAzyme-based biosensors and aptasensors have been highly regarded for this purpose as two main groups of the functional nucleic acid (FNA)-based biosensors. In this review, we summarize the recent achievements of functional nucleic acid-based biosensors for the simultaneous detection of Hg²⁺ and Pb²⁺ ions in two main optical and electrochemical groups. The tremendous interest in utilizing the various nanomaterials is also highlighted in the fabrication of the FNA-based biosensors. Finally, some results are presented based on the advantages and disadvantages of the studied FNA-based biosensors to compare their validation.



https://ift.tt/2kM6Gmi

Gold nanorod embedded novel 3D graphene nanocomposite for selective bio-capture in rapid detection of Mycobacterium tuberculosis

Publication date: 30 September 2018
Source:Biosensors and Bioelectronics, Volume 116
Author(s): Veeradasan Perumal, Mohamed Shuaib Mohamed Saheed, Norani Muti Mohamed, Mohamed Salleh Mohamed Saheed, Satisvar Sundera Murthe, Subash C.B. Gopinath, Jian-Ming Chiu
Tuberculosis (TB) is a chronic and infectious airborne disease which requires a diagnosing system with high sensitivity and specificity. However, the traditional gold standard method for TB detection remains unreliable with low specificity and sensitivity. Nanostructured composite materials coupled with impedimetric sensing utilised in this study offered a feasible solution. Herein, novel gold (Au) nanorods were synthesized on 3D graphene grown by chemical vapour deposition. The irregularly spaced and rippled morphology of 3D graphene provided a path for Au nanoparticles to self-assemble and form rod-like structures on the surface of the 3D graphene. The formation of Au nanorods were showcased through scanning electron microscopy which revealed the evolution of Au nanoparticle into Au islets. Eventually, it formed nanorods possessing lengths of ~ 150 nm and diameters of ~ 30 nm. The X-ray diffractogram displayed appropriate peaks suitable to defect-free and high crystalline graphene with face centered cubic Au. The strong optical interrelation between Au nanorod and 3D graphene was elucidated by Raman spectroscopy analysis. Furthermore, the anchored Au nanorods on 3D graphene nanocomposite enables feasible bio-capturing on the exposed Au surface on defect free graphene. The impedimetric sensing of DNA sequence from TB on 3D graphene/Au nanocomposite revealed a remarkable wide detection linear range from 10 fM to 0.1 µM, displays the capability of detecting femtomolar DNA concentration. Overall, the novel 3D graphene/Au nanocomposite demonstrated here offers high-performance bio-sensing and opens a new avenue for TB detection.



https://ift.tt/2Hk0WJm

Wearable humidity sensor based on porous graphene network for respiration monitoring

Publication date: 30 September 2018
Source:Biosensors and Bioelectronics, Volume 116
Author(s): Yu Pang, Jinming Jian, Tao Tu, Zhen Yang, Jiang Ling, Yuxing Li, Xuefeng Wang, Yancong Qiao, He Tian, Yi Yang, Tian-Ling Ren
Respiration is as one of the most essential physiological signals, which can be used to monitor human healthcare and activities. Herein, we report a flexible, lightweight and highly conductive porous graphene network as the humidity sensor for respiration monitoring. To enhance the sensing performance, the graphene oxide (GO), poly (3, 4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT: PSS) and Ag colloids (AC) were used to modify the porous graphene. The humidity properties of porous based graphene networks have been investigated at different relative humidity (RH). The porous based graphene sensors exhibit excellent capability of monitoring different breathing patterns including mouse and nose respiration, normal and deep respiration. Besides, the signal variations before and after water intake was recorded by the sensor, which demonstrates the ability to monitor water loss during breathing period. Furthermore, the humidity sensor shows the ability to detect physiological activities including skin moisture, speaking and whistle rhythm, which could be a promising electronic for clinical respiration monitoring.



https://ift.tt/2JcQ3Pl

Multi-subject hierarchical inverse covariance modelling improves estimation of functional brain networks

Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Giles L. Colclough, Mark W. Woolrich, Samuel J. Harrison, Pedro A. Rojas López, Pedro A. Valdes-Sosa, Stephen M. Smith
A Bayesian model for sparse, hierarchical, inver-covariance estimation is presented, and applied to multi-subject functional connectivity estimation in the human brain. It enables simultaneous inference of the strength of connectivity between brain regions at both subject and population level, and is applicable to fMRI, MEG and EEG data. Two versions of the model can encourage sparse connectivity, either using continuous priors to suppress irrelevant connections, or using an explicit description of the network structure to estimate the connection probability between each pair of regions. A large evaluation of this model, and thirteen methods that represent the state of the art of inverse covariance modelling, is conducted using both simulated and resting-state functional imaging datasets. Our novel Bayesian approach has similar performance to the best extant alternative, Ng et al.'s Sparse Group Gaussian Graphical Model algorithm, which also is based on a hierarchical structure. Using data from the Human Connectome Project, we show that these hierarchical models are able to reduce the measurement error in MEG beta-band functional networks by 10%, producing concomitant increases in estimates of the genetic influence on functional connectivity.



https://ift.tt/2xPpQRI

Investigating common coding of observed and executed actions in the monkey brain using cross-modal multi-variate fMRI classification

Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Prosper Agbesi Fiave, Saloni Sharma, Jan Jastorff, Koen Nelissen
Mirror neurons are generally described as a neural substrate hosting shared representations of actions, by simulating or 'mirroring' the actions of others onto the observer's own motor system. Since single neuron recordings are rarely feasible in humans, it has been argued that cross-modal multi-variate pattern analysis (MVPA) of non-invasive fMRI data is a suitable technique to investigate common coding of observed and executed actions, allowing researchers to infer the presence of mirror neurons in the human brain. In an effort to close the gap between monkey electrophysiology and human fMRI data with respect to the mirror neuron system, here we tested this proposal for the first time in the monkey. Rhesus monkeys either performed reach-and-grasp or reach-and-touch motor acts with their right hand in the dark or observed videos of human actors performing similar motor acts. Unimodal decoding showed that both executed or observed motor acts could be decoded from numerous brain regions. Specific portions of rostral parietal, premotor and motor cortices, previously shown to house mirror neurons, in addition to somatosensory regions, yielded significant asymmetric action-specific cross-modal decoding. These results validate the use of cross-modal multi-variate fMRI analyses to probe the representations of own and others' actions in the primate brain and support the proposed mapping of others' actions onto the observer's own motor cortices.



https://ift.tt/2M1xVWq

Focused ultrasound induced opening of the blood-brain barrier disrupts inter-hemispheric resting state functional connectivity in the rat brain

Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Nick Todd, Yongzhi Zhang, Michael Arcaro, Lino Becerra, David Borsook, Margaret Livingstone, Nathan McDannold
Focused ultrasound (FUS) is a technology capable of delivering therapeutic levels of energy through the intact skull to a tightly localized brain region. Combining the FUS pressure wave with intravenously injected microbubbles creates forces on blood vessel walls that open the blood-brain barrier (BBB). This noninvasive and localized opening of the BBB allows for targeted delivery of pharmacological agents into the brain for use in therapeutic development. It is possible to use FUS power levels such that the BBB is opened without damaging local tissues. However, open questions remain related to the effects that FUS-induced BBB opening has on brain function including local physiology and vascular hemodynamics. We evaluated the effects that FUS-induced BBB opening has on resting state functional magnetic resonance imaging (rs-fMRI) metrics. Data from rs-fMRI was acquired in rats that underwent sham FUS BBB vs. FUS BBB opening targeted to the right primary somatosensory cortex hindlimb region (S1HL). FUS BBB opening reduced the functional connectivity between the right S1HL and other sensorimotor regions, including statistically significant reduction of connectivity to the homologous region in the left hemisphere (left S1HL). The effect was observed in all three metrics analyzed: functional connectivity between anatomically defined regions, whole brain voxel-wise correlation maps based on anatomical seeds, and spatial patterns from independent component analysis. Connectivity metrics for other regions where the BBB was not perturbed were not affected. While it is not clear whether the effect is vascular or neuronal in origin, these results suggest that even safe levels of FUS BBB opening have an effect on the physiological processes that drive the signals measured by BOLD fMRI. As such these effects must be accounted for when carrying out studies using fMRI to evaluate the effects of pharmacological agents delivered via FUS-induced BBB opening.



https://ift.tt/2xLOhzm

What if? Neural activity underlying semantic and episodic counterfactual thinking

Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Natasha Parikh, Luka Ruzic, Gregory W. Stewart, R. Nathan Spreng, Felipe De Brigard
Counterfactual thinking (CFT) is the process of mentally simulating alternative versions of known facts. In the past decade, cognitive neuroscientists have begun to uncover the neural underpinnings of CFT, particularly episodic CFT (eCFT), which activates regions in the default network (DN) also activated by episodic memory (eM) recall. However, the engagement of DN regions is different for distinct kinds of eCFT. More plausible counterfactuals and counterfactuals about oneself show stronger activity in DN regions compared to implausible and other- or object-focused counterfactuals. The current study sought to identify a source for this difference in DN activity. Specifically, self-focused counterfactuals may also be more plausible, suggesting that DN core regions are sensitive to the plausibility of a simulation. On the other hand, plausible and self-focused counterfactuals may involve more episodic information than implausible and other-focused counterfactuals, which would imply DN sensitivity to episodic information. In the current study, we compared episodic and semantic counterfactuals generated to be plausible or implausible against episodic and semantic memory reactivation using fMRI. Taking multivariate and univariate approaches, we found that the DN is engaged more during episodic simulations, including eM and all eCFT, than during semantic simulations. Semantic simulations engaged more inferior temporal and lateral occipital regions. The only region that showed strong plausibility effects was the hippocampus, which was significantly engaged for implausible CFT but not for plausible CFT, suggestive of binding more disparate information. Consequences of these findings for the cognitive neuroscience of mental simulation are discussed.



https://ift.tt/2LYmyhV

Signal compartments in ultra-high field multi-echo gradient echo MRI reflect underlying tissue microstructure in the brain

Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Shrinath Kadamangudi, David Reutens, Surabhi Sood, Viktor Vegh
Gradient recalled echo magnetic resonance imaging (GRE-MRI) at ultra-high field holds great promise for new contrast mechanisms and delineation of putative tissue compartments that contribute to the multi-echo GRE-MRI signal may aid structural characterization. Several studies have adopted the three water-pool compartment model to study white matter brain regions, associating individual compartments with myelin, axonal and extracellular water. However, the number and identifiability of GRE-MRI signal compartments has not been fully explored. We undertook this task for human brain imaging data. Multiple echo time GRE-MRI data were acquired in five healthy participants, specific anatomical structures were segmented in each dataset (substantia nigra, caudate, insula, putamen, thalamus, fornix, internal capsule, corpus callosum and cerebrospinal fluid), and the signal fitted with models comprising one to six signal compartments using a complex-valued plane wave formulation. Information criteria and cluster analysis methods were used to ascertain the number of distinct compartments within the signal from each structure and to determine their respective frequency shifts. We identified five principal signal compartments with different relative contributions to each structure's signal. Voxel-based maps of the volume fraction of each of these compartments were generated and demonstrated spatial correlation with brain anatomy.



https://ift.tt/2xPpCdk

Integrating spatial-anatomical regularization and structure sparsity into SVM: Improving interpretation of Alzheimer's disease classification

Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Zhuo Sun, Yuchuan Qiao, Boudewijn P.F. Lelieveldt, Marius Staring
In recent years, machine learning approaches have been successfully applied to the field of neuroimaging for classification and regression tasks. However, many approaches do not give an intuitive relation between the raw features and the diagnosis. Therefore, they are difficult for clinicians to interpret. Moreover, most approaches treat the features extracted from the brain (for example, voxelwise gray matter concentration maps from brain MRI) as independent variables and ignore their spatial and anatomical relations. In this paper, we present a new Support Vector Machine (SVM)-based learning method for the classification of Alzheimer's disease (AD), which integrates spatial-anatomical information. In this way, spatial-neighbor features in the same anatomical region are encouraged to have similar weights in the SVM model. Secondly, we introduce a group lasso penalty to induce structure sparsity, which may help clinicians to assess the key regions involved in the disease. For solving this learning problem, we use an accelerated proximal gradient descent approach. We tested our method on the subset of ADNI data selected by Cuingnet et al. (2011) for Alzheimer's disease classification, as well as on an independent larger dataset from ADNI. Good classification performance is obtained for distinguishing cognitive normals (CN) vs. AD, as well as on distinguishing between various sub-types (e.g. CN vs. Mild Cognitive Impairment). The model trained on Cuignet's dataset for AD vs. CN classification was directly used without re-training to the independent larger dataset. Good performance was achieved, demonstrating the generalizability of the proposed methods. For all experiments, the classification results are comparable or better than the state-of-the-art, while the weight map more clearly indicates the key regions related to Alzheimer's disease.

Graphical abstract

https://ift.tt/2M1xIm6

Disrupted topology of the resting state structural connectome in middle-aged APOE ε4 carriers

Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): L.E. Korthauer, L. Zhan, O. Ajilore, A. Leow, I. Driscoll
The apolipoprotein E (APOE) ε4 allele is the best characterized genetic risk factor for Alzheimer's disease to date. Older APOE ε4 carriers (aged 60 + years) are known to have disrupted structural and functional connectivity, but less is known about APOE-associated network integrity in middle age. The goal of this study was to characterize APOE-related differences in network topology in middle age, as disentangling the early effects of healthy versus pathological aging may aid early detection of Alzheimer's disease and inform treatments. We performed resting state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) in healthy, cognitively normal, middle-aged adults (age 40–60; N = 76, 38 APOE ε4 carriers). Graph theoretical analysis was used to calculate local and global efficiency of 1) a whole brain rs-fMRI network; 2) a whole brain DTI network; and 3) the resting state structural connectome (rsSC), an integrated functional-structural network derived using functional-by-structural hierarchical (FSH) mapping. Our results indicated no APOE ε4-associated differences in network topology of the rs-fMRI or DTI networks alone. However, ε4 carriers had significantly lower global and local efficiency of the integrated rsSC compared to non-carriers. Furthermore, ε4 carriers were less resilient to targeted node failure of the rsSC, which mimics the neuropathological process of Alzheimer's disease. Collectively, these findings suggest that integrating multiple neuroimaging modalities and employing graph theoretical analysis may reveal network-level vulnerabilities that may serve as biomarkers of age-related cognitive decline in middle age, decades before the onset of overt cognitive impairment.



https://ift.tt/2Ji1kd9

A comparison of three fiber tract delineation methods and their impact on white matter analysis

Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Valerie J. Sydnor, Ana María Rivas-Grajales, Amanda E. Lyall, Fan Zhang, Sylvain Bouix, Sarina Karmacharya, Martha E. Shenton, Carl-Fredrik Westin, Nikos Makris, Demian Wassermann, Lauren J. O'Donnell, Marek Kubicki
Diffusion magnetic resonance imaging (dMRI) is an important method for studying white matter connectivity in the brain in vivo in both healthy and clinical populations. Improvements in dMRI tractography algorithms, which reconstruct macroscopic three-dimensional white matter fiber pathways, have allowed for methodological advances in the study of white matter; however, insufficient attention has been paid to comparing post-tractography methods that extract white matter fiber tracts of interest from whole-brain tractography. Here we conduct a comparison of three representative and conceptually distinct approaches to fiber tract delineation: 1) a manual multiple region of interest-based approach, 2) an atlas-based approach, and 3) a groupwise fiber clustering approach, by employing methods that exemplify these approaches to delineate the arcuate fasciculus, the middle longitudinal fasciculus, and the uncinate fasciculus in 10 healthy male subjects. We enable qualitative comparisons across methods, conduct quantitative evaluations of tract volume, tract length, mean fractional anisotropy, and true positive and true negative rates, and report measures of intra-method and inter-method agreement. We discuss methodological similarities and differences between the three approaches and the major advantages and drawbacks of each, and review research and clinical contexts for which each method may be most apposite. Emphasis is given to the means by which different white matter fiber tract delineation approaches may systematically produce variable results, despite utilizing the same input tractography and reliance on similar anatomical knowledge.



https://ift.tt/2LYmpuT

Multidimensional co-segmentation of longitudinal brain MRI ensembles in the presence of a neurodegenerative process

Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Shiri Gordon, Irit Dolgopyat, Itamar Kahn, Tammy Riklin Raviv
MRI Segmentation of a pathological brain poses a significant challenge, as the available anatomical priors that provide top-down information to aid segmentation are inadequate in the presence of abnormalities. This problem is further complicated for longitudinal data capturing impaired brain development or neurodegenerative conditions, since the dynamic of brain atrophies has to be considered as well. For these cases, the absence of compatible annotated training examples renders the commonly used multi-atlas or machine-learning approaches impractical.We present a novel segmentation approach that accounts for the lack of labeled data via multi-region multi-subject co-segmentation (MMCoSeg) of longitudinal MRI sequences. The underlying, unknown anatomy is learned throughout an iterative process, in which the segmentation of a region is supported both by the segmentation of the neighboring regions, which share common boundaries, and by the segmentation of corresponding regions, in the other jointly segmented images. A 4D multi-region atlas that models the spatio-temporal deformations and can be adapted to different subjects undergoing similar degeneration processes is reconstructed concurrently.An inducible mouse model of p25 accumulation (the CK-p25 mouse) that displays key pathological hallmarks of Alzheimer disease (AD) is used as a gold-standard to test the proposed algorithm by providing a conditional control of rapid neurodegeneration. Applying the MMCoSeg to a cohort of CK-p25 mice and littermate controls yields promising segmentation results that demonstrate high compatibility with expertise manual annotations. An extensive comparative analysis with respect to current well-established, atlas-based segmentation methods highlights the advantage of the proposed approach, which provides accurate segmentation of longitudinal brain MRIs in pathological conditions, where only very few annotated examples are available.

Graphical abstract

https://ift.tt/2JgACkV

Generalized Recurrent Neural Network accommodating Dynamic Causal Modeling for functional MRI analysis

Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Yuan Wang, Yao Wang, Yvonne W. Lui
Dynamic Causal Modeling (DCM) is an advanced biophysical model which explicitly describes the entire process from experimental stimuli to functional magnetic resonance imaging (fMRI) signals via neural activity and cerebral hemodynamics. To conduct a DCM study, one needs to represent the experimental stimuli as a compact vector-valued function of time, which is hard in complex tasks such as book reading and natural movie watching. Deep learning provides the state-of-the-art signal representation solution, encoding complex signals into compact dense vectors while preserving the essence of the original signals. There is growing interest in using Recurrent Neural Networks (RNNs), a major family of deep learning techniques, in fMRI modeling. However, the generic RNNs used in existing studies work as black boxes, making the interpretation of results in a neuroscience context difficult and obscure.In this paper, we propose a new biophysically interpretable RNN built on DCM, DCM-RNN. We generalize the vanilla RNN and show that DCM can be cast faithfully as a special form of the generalized RNN. DCM-RNN uses back propagation for parameter estimation. We believe DCM-RNN is a promising tool for neuroscience. It can fit seamlessly into classical DCM studies. We demonstrate face validity of DCM-RNN in two principal applications of DCM: causal brain architecture hypotheses testing and effective connectivity estimation. We also demonstrate construct validity of DCM-RNN in an attention-visual experiment. Moreover, DCM-RNN enables end-to-end training of DCM and representation learning deep neural networks, extending DCM studies to complex tasks.



https://ift.tt/2LYmjDx

Modulation of neuronal oscillatory activity in the beta- and gamma-band is associated with current individual anxiety levels

Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Till R. Schneider, Joerg F. Hipp, Claudia Domnick, Christine Carl, Christian Büchel, Andreas K. Engel
Human faces are among the most salient visual stimuli and act both as socially and emotionally relevant signals. Faces and especially faces with emotional expression receive prioritized processing in the human brain and activate a distributed network of brain areas reflected, e.g., in enhanced oscillatory neuronal activity. However, an inconsistent picture emerged so far regarding neuronal oscillatory activity across different frequency-bands modulated by emotionally and socially relevant stimuli. The individual level of anxiety among healthy populations might be one explanation for these inconsistent findings. Therefore, we tested the hypothesis whether oscillatory neuronal activity is associated with individual anxiety levels during perception of faces with neutral and fearful facial expressions. We recorded neuronal activity using magnetoencephalography (MEG) in 27 healthy participants and determined their individual state anxiety levels. Images of human faces with neutral and fearful expressions, and physically matched visual control stimuli were presented while participants performed a simple color detection task. Spectral analyses revealed that face processing and in particular processing of fearful faces was characterized by enhanced neuronal activity in the theta- and gamma-band and decreased activity in the beta-band in early visual cortex and the fusiform gyrus (FFG). Moreover, the individuals' state anxiety levels correlated positively with the gamma-band response and negatively with the beta response in the FFG and the amygdala. Our results suggest that oscillatory neuronal activity plays an important role in affective face processing and is dependent on the individual level of state anxiety. Our work provides new insights on the role of oscillatory neuronal activity underlying processing of faces.



https://ift.tt/2xKNvCE

Distinct neural circuits support incentivized inhibition

Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Josiah K. Leong, Kelly H. MacNiven, Gregory R. Samanez-Larkin, Brian Knutson
The ability to inhibit responses under high stakes, or "incentivized inhibition," is critical for adaptive impulse control. While previous research indicates that right ventrolateral prefrontal cortical (VLPFC) activity plays a key role in response inhibition, less research has addressed how incentives might influence this circuit. By combining a novel behavioral task, functional magnetic resonance imaging (FMRI), and diffusion-weighted imaging (DWI), we targeted and characterized specific neural circuits that support incentivized inhibition. Behaviorally, large incentives enhanced responses to obtain money, but also reduced response inhibition. Functionally, activity in both right VLPFC and right anterior insula (AIns) predicted successful inhibition for high incentives. Structurally, characterization of a novel white-matter tract connecting the right AIns and VLPFC revealed an association of tract coherence with incentivized inhibition performance. Finally, individual differences in right VLPFC activity statistically mediated the association of right AIns-VLPFC tract coherence with incentivized inhibition performance. These multimodal findings bridge brain structure, brain function, and behavior to clarify how individuals can inhibit impulses, even in the face of high stakes.



https://ift.tt/2M0z94a

Modeling hyperoxia-induced BOLD signal dynamics to estimate cerebral blood flow, volume and mean transit time

Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): M. Ethan MacDonald, Avery J.L. Berman, Erin L. Mazerolle, Rebecca J. Williams, G. Bruce Pike
A new method is proposed for obtaining cerebral perfusion measurements whereby blood oxygen level dependent (BOLD) MRI is used to dynamically monitor hyperoxia-induced changes in the concentration of deoxygenated hemoglobin in the cerebral vasculature. The data is processed using kinetic modeling to yield perfusion metrics, namely: cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). Ten healthy human subjects were continuously imaged with BOLD sequence while a hyperoxic (70% O2) state was interspersed with baseline periods of normoxia. The BOLD time courses were fit with exponential uptake and decay curves and a biophysical model of the BOLD signal was used to estimate oxygen concentration functions. The arterial input function was derived from end-tidal oxygen measurements, and a deconvolution operation between the tissue and arterial concentration functions was used to yield CBF. The venous component of the CBV was calculated from the ratio of the integrals of the estimated tissue and arterial concentration functions. Mean gray and white matter measurements were found to be: 61.6 ± 13.7 and 24.9 ± 4.0 ml 100 g⁻¹ min⁻¹ for CBF; 1.83 ± 0.32 and 1.10 ± 0.19 ml 100 g⁻¹ for venous CBV; and 2.94 ± 0.52 and 3.73 ± 0.60 s for MTT, respectively. We conclude that it is possible to derive CBF, CBV and MTT metrics within expected physiological ranges via analysis of dynamic BOLD fMRI acquired during a period of hyperoxia.



https://ift.tt/2xFHqre

Dorsal and ventral cortices are coupled by cross-frequency interactions during working memory

Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Tzvetan Popov, Ole Jensen, Jan-Mathijs Schoffelen
Oscillatory activity in the alpha and gamma bands is considered key in shaping functional brain architecture. Power increases in the high-frequency gamma band are typically reported in parallel to decreases in the low-frequency alpha band. However, their functional significance and in particular their interactions are not well understood. The present study shows that, in the context of an N-back working memory task, alpha power decreases in the dorsal visual stream are related to gamma power increases in early visual areas. Granger causality analysis revealed directed interregional interactions from dorsal to ventral stream areas, in accordance with task demands. Present results reveal a robust, behaviorally relevant, and architectonically decisive power-to-power relationship between alpha and gamma activity. This relationship suggests that anatomically distant power fluctuations in oscillatory activity can link cerebral network dynamics on trial-by-trial basis during cognitive operations such as working memory.



https://ift.tt/2M25CXA

Concentric radiofrequency arrays to increase the statistical power of resting-state maps in monkeys

Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Kyle M. Gilbert, David J. Schaeffer, Peter Zeman, Jörn Diedrichsen, Stefan Everling, Julio C. Martinez-Trujillo, J. Andrew Pruszynski, Ravi S. Menon
The close homology of monkeys and humans has increased the prevalence of non-human-primate models in functional MRI studies of brain connectivity. To improve upon the attainable resolution in functional MRI studies, a commensurate increase in the sensitivity of the radiofrequency receiver coil is required to avoid a reduction in the statistical power of the analysis. Most receive coils are comprised of multiple loops distributed equidistantly over a surface to produce spatially independent sensitivity profiles. A larger number of smaller elements will in turn provide a higher signal-to-noise ratio (SNR) over the same field of view. As the loops become physically smaller, noise originating from the sample is reduced relative to noise originating from the coil. In this coil-noise-dominated regime, coil elements can have overlapping sensitivity profiles, yet still possess only mildly correlated noise. In this manuscript, we demonstrate that inductively decoupled, concentric coil arrays can improve temporal SNR when operating in the coil-noise-dominated regime—in contrast to what is expected for the more ubiquitous sample-noise-dominated array. A small, thin, 7-channel flexible coil is developed and operated in conjunction with an existing whole-head monkey coil. The mean and maximum noise correlation between the two arrays was 5% and 23%, respectively. When the flex coil was placed over the sensorimotor cortex, the temporal SNR improved by up to 2.3-fold in the peripheral cortex and up to 1.3-fold at a 2- to 3-cm depth within the brain. When the flex coil was placed over the frontal eye fields, resting-state maps showed substantially elevated sensitivity to correlations in the prefrontal cortex (54%), supplementary eye fields (39%), and anterior cingulate cortex (41%). The concentric-coil topology provided a pragmatic and robust means to significantly improve local temporal SNR and the statistical power of functional connectivity maps.

Graphical abstract

https://ift.tt/2xImcJ9

Cyclin A Turns on Bora to Light the Path to Mitosis

Publication date: 4 June 2018
Source:Developmental Cell, Volume 45, Issue 5
Author(s): Ge Zheng, Hongtao Yu
Mitotic entry is an irreversible cell-cycle transition that requires the robust, rapid activation of cyclin-dependent kinase 1 (Cdk1). In this issue of Developmental Cell, Vigneron et al. (2018) identify cyclin A-Cdk1 as the factor triggering mitotic entry through the phosphorylation of Bora, an activator of the kinase Aurora A.

Teaser

Mitotic entry is an irreversible cell-cycle transition that requires the robust, rapid activation of cyclin-dependent kinase 1 (Cdk1). In this issue of Developmental Cell, Vigneron et al. (2018) identify cyclin A-Cdk1 as the factor triggering mitotic entry through the phosphorylation of Bora, an activator of the kinase Aurora A.


https://ift.tt/2kQcpaJ

Melanophores Tune Out the Noise to Make Stripes

Publication date: 4 June 2018
Source:Developmental Cell, Volume 45, Issue 5
Author(s): Larissa B. Patterson, David M. Parichy
Migratory cells derived from the neural crest encounter both local cues and more distant signals as they effect specific morphogenetic outcomes. In this issue of Developmental Cell, Zhang et al. (2018) reveal how zebrafish melanophores use the sheddase Bace2 to "tune out" insulin signaling, thereby allowing stripes to form.

Teaser

Migratory cells derived from the neural crest encounter both local cues and more distant signals as they effect specific morphogenetic outcomes. In this issue of Developmental Cell, Zhang et al. (2018) reveal how zebrafish melanophores use the sheddase Bace2 to "tune out" insulin signaling, thereby allowing stripes to form.


https://ift.tt/2sKtiHw

Integrating into the Rhombomere Community across the Border

Publication date: 4 June 2018
Source:Developmental Cell, Volume 45, Issue 5
Author(s): Taro Kitazawa, Filippo M. Rijli
During early hindbrain development, single neuroepithelial progenitors cross into neighboring rhombomere compartments and switch their molecular identity to match their new position. In this issue of Developmental Cell,Addison et al. (2018) show that this identity switch is mediated by non-cell-autonomous retinoid signaling that ensures a homogeneous segment identity.

Teaser

During early hindbrain development, single neuroepithelial progenitors cross into neighboring rhombomere compartments and switch their molecular identity to match their new position. In this issue of Developmental Cell, Addison et al. (2018) show that this identity switch is mediated by non-cell-autonomous retinoid signaling that ensures a homogeneous segment identity.


https://ift.tt/2kMmAgp

Making a Notch in the Evolution of the Human Cortex

Publication date: 4 June 2018
Source:Developmental Cell, Volume 45, Issue 5
Author(s): Sara Bizzotto, Christopher A. Walsh
The unique structure and function of the human brain ultimately results from the action of evolution on the human genome. In a recent issue of Cell, Fiddes et al. (2018) and Suzuki et al. (2018) describe human-specific NOTCH2 paralogs that enhance neural progenitor proliferation and expand cortical neurogenesis.

Teaser

The unique structure and function of the human brain ultimately results from the action of evolution on the human genome. In a recent issue of Cell, Fiddes et al. (2018) and Suzuki et al. (2018) describe human-specific NOTCH2 paralogs that enhance neural progenitor proliferation and expand cortical neurogenesis.


https://ift.tt/2HjjUQn

Actin Network Discussion during Mitotic Pseudo-Furrowing

Publication date: 4 June 2018
Source:Developmental Cell, Volume 45, Issue 5
Author(s): Florencia di Pietro, Yohanns Bellaïche
Two types of cortical actin networks act during mitotic pseudocleavage furrowing in the Drosophila syncytium, but how they interact has remained elusive. In this issue of Developmental Cell, Zhang et al. (2018) show how these networks shape each other and propose that furrowing is driven by actin polymerization-derived pushing forces.

Teaser

Two types of cortical actin networks act during mitotic pseudocleavage furrowing in the Drosophila syncytium, but how they interact has remained elusive. In this issue of Developmental Cell, Zhang et al. (2018) show how these networks shape each other and propose that furrowing is driven by actin polymerization-derived pushing forces.


https://ift.tt/2kPkk82

Redistribution of Adhesive Forces through Src/FAK Drives Contact Inhibition of Locomotion in Neural Crest

Publication date: 4 June 2018
Source:Developmental Cell, Volume 45, Issue 5
Author(s): Alice Roycroft, András Szabó, Isabel Bahm, Liam Daly, Guillaume Charras, Maddy Parsons, Roberto Mayor
Contact inhibition of locomotion is defined as the behavior of cells to cease migrating in their former direction after colliding with another cell. It has been implicated in multiple developmental processes and its absence has been linked to cancer invasion. Cellular forces are thought to govern this process; however, the exact role of traction through cell-matrix adhesions and tension through cell-cell adhesions during contact inhibition of locomotion remains unknown. Here we use neural crest cells to address this and show that cell-matrix adhesions are rapidly disassembled at the contact between two cells upon collision. This disassembly is dependent upon the formation of N-cadherin-based cell-cell adhesions and driven by Src and FAK activity. We demonstrate that the loss of cell-matrix adhesions near the contact leads to a buildup of tension across the cell-cell contact, a step that is essential to drive cell-cell separation after collision.

Graphical abstract

Teaser

Contact inhibition of locomotion leads to cell separation when they collide during migration. Roycroft et al. examine the role of mechanical force in cell separation and demonstrate that immediately after collision, cell-matrix adhesions are disassembled, leading to a tension buildup across cell-cell contacts that is essential for cell separation.


https://ift.tt/2sEOjDm

A Drosophila Tumor Suppressor Gene Prevents Tonic TNF Signaling through Receptor N-Glycosylation

Publication date: 4 June 2018
Source:Developmental Cell, Volume 45, Issue 5
Author(s): Geert de Vreede, Holly A. Morrison, Alexandra M. Houser, Ryan M. Boileau, Ditte Andersen, Julien Colombani, David Bilder
Drosophila tumor suppressor genes have revealed molecular pathways that control tissue growth, but mechanisms that regulate mitogenic signaling are far from understood. Here we report that the Drosophila TSG tumorous imaginal discs (tid), whose phenotypes were previously attributed to mutations in a DnaJ-like chaperone, are in fact driven by the loss of the N-linked glycosylation pathway component ALG3. tid/alg3 imaginal discs display tissue growth and architecture defects that share characteristics of both neoplastic and hyperplastic mutants. Tumorous growth is driven by inhibited Hippo signaling, induced by excess Jun N-terminal kinase (JNK) activity. We show that ectopic JNK activation is caused by aberrant glycosylation of a single protein, the fly tumor necrosis factor (TNF) receptor homolog, which results in increased binding to the continually circulating TNF. Our results suggest that N-linked glycosylation sets the threshold of TNF receptor signaling by modifying ligand-receptor interactions and that cells may alter this modification to respond appropriately to physiological cues.

Graphical abstract

Teaser

de Vreede et al. correct cloning of a classic Drosophila tumor suppressor gene, showing that it encodes a regulator of N-glycosylation rather than a DnaJ-like chaperone. Appropriate N-glycosylation of the fly TNF receptor limits binding of circulating TNF-α ligand, thus preventing excess JNK-driven signaling that inhibits Hippo signaling and causes tissue overgrowth.


https://ift.tt/2kPkf4e

Vps39 Interacts with Tom40 to Establish One of Two Functionally Distinct Vacuole-Mitochondria Contact Sites

Publication date: 4 June 2018
Source:Developmental Cell, Volume 45, Issue 5
Author(s): Ayelén González Montoro, Kathrin Auffarth, Carina Hönscher, Maria Bohnert, Thomas Becker, Bettina Warscheid, Fulvio Reggiori, Martin van der Laan, Florian Fröhlich, Christian Ungermann
The extensive subcellular network of membrane contact sites plays central roles in organelle biogenesis and communication, yet the precise contributions of the involved machineries remain largely enigmatic. The yeast vacuole forms a membrane contact site with mitochondria, called vacuolar and mitochondrial patch (vCLAMP). Formation of vCLAMPs involves the vacuolar Rab GTPase Ypt7 and the Ypt7-interacting Vps39 subunit of the HOPS tethering complex. Here, we uncover the general preprotein translocase of the outer membrane (TOM) subunit Tom40 as the direct binding partner of Vps39 on mitochondria. We identify Vps39 mutants defective in TOM binding, but functional for HOPS. Cells that cannot form vCLAMPs show reduced growth under stress conditions and impaired survival upon starvation. Unexpectedly, our mutant analysis revealed the existence of two functionally independent vacuole-mitochondria MCSs: one formed by the Ypt7-Vps39-Tom40 tether and a second one by Vps13-Mcp1, which is redundant with ER-mitochondrial contacts formed by ERMES.

Graphical abstract

Teaser

González Montoro et al. show that the vacuole-mitochondria contact site (vCLAMP) is established by interaction of Vps39 with Tom40. Generation of mutants that specifically disrupt this contact revealed its necessity for cell physiology during starvation and show that there are two functionally independent types of vacuole-mitochondrial contact sites.


https://ift.tt/2HlCzuz

Cyclin A-cdk1-Dependent Phosphorylation of Bora Is the Triggering Factor Promoting Mitotic Entry

Publication date: 4 June 2018
Source:Developmental Cell, Volume 45, Issue 5
Author(s): Suzanne Vigneron, Lena Sundermann, Jean-Claude Labbé, Lionel Pintard, Ovidiu Radulescu, Anna Castro, Thierry Lorca
Mitosis is induced by the activation of the cyclin B/cdk1 feedback loop that creates a bistable state. The triggering factor promoting active cyclin B/cdk1 switch has been assigned to cyclin B/cdk1 accumulation during G2. However, this complex is rapidly inactivated by Wee1/Myt1-dependent phosphorylation of cdk1 making unlikely a triggering role of this kinase in mitotic commitment. Here we show that cyclin A/cdk1 kinase is the factor triggering mitosis. Cyclin A/cdk1 phosphorylates Bora to promote Aurora A-dependent Plk1 phosphorylation and activation and mitotic entry. We demonstrate that Bora phosphorylation by cyclin A/cdk1 is both necessary and sufficient for mitotic commitment. Finally, we identify a site in Bora whose phosphorylation by cyclin A/cdk1 is required for mitotic entry. We constructed a mathematical model confirming the essential role of this kinase in mitotic commitment. Overall, our results uncover the molecular mechanism by which cyclin A/cdk1 triggers mitotic entry.

Graphical abstract

Teaser

Mitotic commitment was thought to depend on the accumulation of cyclin B/cdk1 during G2. Vigneron et al. now revise this view by showing that the key event triggering mitotic entry depends instead on cyclin A/cdk1, which phosphorylates Bora, leading to activation of Plk1 and a cyclin B/cdk positive feedback loop.


https://ift.tt/2JbQE3P

Progressive Recruitment of Mesenchymal Progenitors Reveals a Time-Dependent Process of Cell Fate Acquisition in Mouse and Human Nephrogenesis

Publication date: 4 June 2018
Source:Developmental Cell, Volume 45, Issue 5
Author(s): Nils O. Lindström, Guilherme De Sena Brandine, Tracy Tran, Andrew Ransick, Gio Suh, Jinjin Guo, Albert D. Kim, Riana K. Parvez, Seth W. Ruffins, Elisabeth A. Rutledge, Matthew E. Thornton, Brendan Grubbs, Jill A. McMahon, Andrew D. Smith, Andrew P. McMahon
Mammalian nephrons arise from a limited nephron progenitor pool through a reiterative inductive process extending over days (mouse) or weeks (human) of kidney development. Here, we present evidence that human nephron patterning reflects a time-dependent process of recruitment of mesenchymal progenitors into an epithelial nephron precursor. Progressive recruitment predicted from high-resolution image analysis and three-dimensional reconstruction of human nephrogenesis was confirmed through direct visualization and cell fate analysis of mouse kidney organ cultures. Single-cell RNA sequencing of the human nephrogenic niche provided molecular insights into these early patterning processes and predicted developmental trajectories adopted by nephron progenitor cells in forming segment-specific domains of the human nephron. The temporal-recruitment model for nephron polarity and patterning suggested by direct analysis of human kidney development provides a framework for integrating signaling pathways driving mammalian nephrogenesis.

Graphical abstract

Teaser

During kidney development, mammalian nephrons arise from a limited progenitor pool through a reiterative inductive process. Lindström et al. demonstrate that human and mouse nephron patterning involves gradual mesenchymal progenitor cell recruitment into the epithelial nephron precursor. Recruitment timing predicts precursor cell position and eventual fate in functional nephron structures.


https://ift.tt/2sEOaji

Cardiomyocytes Sense Matrix Rigidity through a Combination of Muscle and Non-muscle Myosin Contractions

Publication date: 4 June 2018
Source:Developmental Cell, Volume 45, Issue 5
Author(s): Pragati Pandey, William Hawkes, Junquiang Hu, William Valentine Megone, Julien Gautrot, Narayana Anilkumar, Min Zhang, Liisa Hirvonen, Susan Cox, Elisabeth Ehler, James Hone, Michael Sheetz, Thomas Iskratsch




https://ift.tt/2Jbz6oq

Oncological and functional outcomes of transoral laser surgery for laryngeal carcinoma

Abstract

Introduction

Transoral laser microsurgery (TLM) has become the standard approach for treatment of early-stage laryngeal carcinoma in most institutions due to their good oncological and functional results with few local complications. The purpose of this study was to analyze the oncological and functional results of TLM in the treatment of laryngeal tumors at our Hospital.

Materials and methods

Patients with laryngeal squamous cell carcinoma (LSCC) treated from 1998 to 2013 with TLM with curative intention, and with a minimum follow-up of 24 months, were reviewed.

Results

203 patients with LSCC were included. 195 patients were men (96%) and 8 women (4%), with a mean age of 63 years. The series includes 134 (66%) T1, 40 (20%) T2, and 29 (14%) T3-classified tumors. 116 tumors (57%) were in the glottis, 79 (39%) in the supraglottis and 8 (4%) in the anterior commissure. 16 patients (8%) received adjuvant radiotherapy. Initial local control was obtained in 75.5% of patients. The 5-year overall survival rate was 84% and the 5-year disease-specific survival was 90%. The presence of nodal metastasis (p < 0.001) and the involvement of the surgical margins (p = 0.004) were associated with a lower disease-specific survival in the multivariate analysis. All but three patients with local control of the disease reassumed oral diet, and none were tracheostomy-dependent. The 5-year laryngeal preservation rate was 85%.

Conclusions

TLM is a minimally invasive treatment for early and moderately-advanced laryngeal carcinomas, with good oncologic and functional outcomes, and few complications as well.

https://ift.tt/2LntPXg

Correction to: MiR-760 suppresses non-small cell lung cancer proliferation and metastasis by targeting ROS1

In the original article the authors list and the credit to the corresponding authors were not complete.

https://ift.tt/2HjNRQl

Viral suppression among HIV-infected methadone-maintained patients: The role of ongoing injection drug use and adherence to antiretroviral therapy (ART)

Publication date: October 2018
Source:Addictive Behaviors, Volume 85
Author(s): Roman Shrestha, Michael M. Copenhaver
IntroductionMethadone maintenance therapy (MMT) is associated with improved virologic outcomes, yet no studies have explored factors associated with viral suppression in HIV-infected patients on MMT. Given the critical role of sustained viral suppression in maximizing benefits of antiretroviral therapy (ART), we sought to assess factors associated with viral suppression in patients stabilized on MMT.MethodsA sample of 133 HIV-infected, methadone-maintained patients who reported HIV-risk behaviors were assessed using an audio-computer assisted self-interview (ACASI). Multivariable logistic regression was used to identify significant correlates of viral suppression.ResultsAmong all participants, self-reported HIV risk behaviors were highly prevalent and over 80% had achieved viral suppression. Independent correlates of viral suppression were: having optimal adherence to ART (aOR = 4.883, p = .009), high CD4 count (aOR = 2.483, p = .045), and ongoing injection drug use (aOR = 0.081, p = .036). Furthermore, results revealed a significant interaction effect that involved optimal ART adherence and injection of drug use on viral suppression (aOR = 2.953, p = .029).ConclusionOverall, our findings highlight unaddressed HIV-related treatment challenges faced by certain group of methadone-maintained patients. These findings have significant implications for the HIV treatment as prevention efforts and, thus, indicate the need for comprehensive efforts to promote viral suppression in this risk population.



https://ift.tt/2xJ0LHR

Histology-proven recurrence in the lateral or central neck after systematic neck dissection for medullary thyroid cancer

Abstract

Purpose

To delineate risk factors for, and examine temporal patterns of, histology-proven recurrent medullary thyroid cancer (MTC) after compartment-oriented surgery.

Methods

Multivariate Cox regression on overall, node, and soft tissue infiltrate recurrence per previously dissected neck compartment.

Results

Mean follow-up for the 203 (and 158) patients with central (and ipsilateral lateral) neck dissection was 56.1 months. On multivariate Cox regression, tumor size > 20 mm predicted overall and node recurrence in the central neck, whereas extranodal growth predicted overall and node recurrence in the ipsilateral lateral neck. Extrathyroidal extension alone predicted soft tissue infiltrate recurrence in the central neck, and extranodal growth alone soft tissue infiltrate recurrence in the ipsilateral lateral neck. When analyses were restricted to patients not biochemically cured after initial surgery, only extranodal growth predicted overall and node recurrence in the dissected neck compartments.

Conclusions

Patients not biochemically cured, specifically those with extranodal growth at the initial operation, carry greater risks of node recurrence.

https://ift.tt/2JplWmW

The influence of TAP1 and TAP2 gene polymorphisms on TAP function and its inhibition by viral immune evasion proteins

Publication date: September 2018
Source:Molecular Immunology, Volume 101
Author(s): P. Praest, R.D. Luteijn, I.G.J. Brak-Boer, J. Lanfermeijer, H. Hoelen, L. Ijgosse, A.I. Costa, R.D. Gorham, R.J. Lebbink, E.J.H.J. Wiertz
Herpesviruses encode numerous immune evasion molecules that interfere with the immune system, particularly with certain stages in the MHC class I antigen presentation pathway. In this pathway, the transporter associated with antigen processing (TAP) is a frequent target of viral immune evasion strategies. This ER-resident transporter is composed of the proteins TAP1 and TAP2, and plays a crucial role in the loading of viral peptides onto MHC class I molecules. Several variants of TAP1 and TAP2 occur in the human population, some of which are linked to autoimmune disorders and susceptibility to infections. Here, we assessed the influence of naturally occurring TAP variants on peptide transport and MHC class I expression. In addition, we tested the inhibitory capacity of three viral immune evasion proteins, the TAP inhibitors US6 from human cytomegalovirus, ICP47 from herpes simplex virus type 1 and BNLF2a from Epstein-Barr virus, for a series of TAP1 and TAP2 variants. Our results suggest that these TAP polymorphisms have no or limited effect on peptide transport or MHC class I expression. Furthermore, our study indicates that the herpesvirus-encoded TAP inhibitors target a broad spectrum of TAP variants; inhibition of TAP is not affected by the naturally occurring polymorphisms of TAP tested in this study. Our findings suggest that the long-term coevolution of herpesviruses and their host did not result in selection of inhibitor-resistant TAP variants in the human population.



https://ift.tt/2sGrGhW

The influence of TAP1 and TAP2 gene polymorphisms on TAP function and its inhibition by viral immune evasion proteins

Publication date: September 2018
Source:Molecular Immunology, Volume 101
Author(s): P. Praest, R.D. Luteijn, I.G.J. Brak-Boer, J. Lanfermeijer, H. Hoelen, L. Ijgosse, A.I. Costa, R.D. Gorham, R.J. Lebbink, E.J.H.J. Wiertz
Herpesviruses encode numerous immune evasion molecules that interfere with the immune system, particularly with certain stages in the MHC class I antigen presentation pathway. In this pathway, the transporter associated with antigen processing (TAP) is a frequent target of viral immune evasion strategies. This ER-resident transporter is composed of the proteins TAP1 and TAP2, and plays a crucial role in the loading of viral peptides onto MHC class I molecules. Several variants of TAP1 and TAP2 occur in the human population, some of which are linked to autoimmune disorders and susceptibility to infections. Here, we assessed the influence of naturally occurring TAP variants on peptide transport and MHC class I expression. In addition, we tested the inhibitory capacity of three viral immune evasion proteins, the TAP inhibitors US6 from human cytomegalovirus, ICP47 from herpes simplex virus type 1 and BNLF2a from Epstein-Barr virus, for a series of TAP1 and TAP2 variants. Our results suggest that these TAP polymorphisms have no or limited effect on peptide transport or MHC class I expression. Furthermore, our study indicates that the herpesvirus-encoded TAP inhibitors target a broad spectrum of TAP variants; inhibition of TAP is not affected by the naturally occurring polymorphisms of TAP tested in this study. Our findings suggest that the long-term coevolution of herpesviruses and their host did not result in selection of inhibitor-resistant TAP variants in the human population.



https://ift.tt/2sGrGhW

Deleterious single nucleotide polymorphisms of protein kinase R identified by the computational approach

Publication date: September 2018
Source:Molecular Immunology, Volume 101
Author(s): Anna Maria Melzer, Navaneethan Palanisamy
The human protein kinase R (PKR) recognizes invading RNA viruses and mediates the antiviral immune response by phosphorylating the eukaryotic translation initiation factor 2α (eIF-2α), thus blocking protein translation in infected cells and thus preventing viral replication. The observation that individuals show different degrees of susceptibility to viral infections gives rise to the hypothesis that single nucleotide polymorphisms (SNPs) in the protein kinase R may alter the response to an infection. Using different available servers (e.g. SIFT, PROVEAN, Polyphen2, SNAP2, SNP&GOs, SNP-PhD, I-Mutant Suite), 14 SNPs were identified that were predicted to have deleterious effects on the protein kinase R. Five SNPs, namely D266Y, Y323D, I398 K, Y465C and Y472C, were selected for homology modeling and the generated models were investigated with regard to their secondary structure, residue fluctuations and eIF-2α binding. Analysis with computational tools POLYVIEW-MM, SAAPdap, SRIDE, CMView, elNémo, NMsim and PatchDock revealed structural changes in all mutants yielding a more stable structure at the cost of reduced flexibility (except Y465C) and less conformational freedom compared to the native protein. The conformational changes in the mutant protein structures and the displacement of functional residues from their strategic positions are predicted to affect the functionality of PKR, and consequently will affect the efficiency of the individual's antiviral immune response negatively. This study will aid the physicians in precision medicine field to tailor optimal treatment for the patients.



https://ift.tt/2kQG6Zc

Surgical treatment of pulmonary metastasis in colorectal cancer patients: Current practice and results

Publication date: July 2018
Source:Critical Reviews in Oncology/Hematology, Volume 127
Author(s): Matthieu Zellweger, Etienne Abdelnour-Berchtold, Thorsten Krueger, Hans-Beat Ris, Jean Yannis Perentes, Michel Gonzalez
Colorectal cancer (CRC) is a frequently occurring disease, yet diagnosed at a local stage in only 40% of cases. Lung metastases (LM) appear in 5–15% of patients and, left untreated, carry a very poor prognosis. Some CRC patients may benefit from a potentially curative LM resection, but success and benefit are difficult to predict. We discuss prognostic factors of survival after lung metastasectomy in CRC patients under several scenarios (with/ without prior liver metastases; repetitive pulmonary resections).We reviewed all studies (2005–2015) about pulmonary metastases surgical management with curative intent in CRC patients, with a minimum threshold on the number of patients reported (without prior liver metastases: n ≥ 100; with prior resection of liver metastases: n ≥ 50; repetitive thoracic surgery: n ≥ 30).The picture of the prognostic factors of survival is nuanced: surgical management demonstrates clear successes and steady progress, yet there is no single success criterion; stratification of patients and selection bias impact the conclusions. Surgical management of liver and lung metastases may prolong life or cure CRC patients, provided the lesions are fully resected and patients carefully selected. Repeat lung metastasectomy is a safe approach to treat patients in selected cases.In conclusion, there is no standard for surgical management in CRC patients with pulmonary metastases. Patients with isolated unilateral lung metastasis with normal CEA level and no lymph node involvement benefit the most from surgery. Most series report good results in highly selected patients, but instances of long-term disease-free survival remain exceptional.



https://ift.tt/2kOVuFz

Rediscovering the Orbit of Percutaneous Coronary Intervention After ORBITA.

Author: Bhatt, Deepak L. MD, MPH; Gersh, Bernard J. MB, ChB, DPhil; Steg, Ph. Gabriel MD; Harrington, Robert A. MD; Windecker, Stephan MD

Page: 2427-2429

https://ift.tt/2sB8cuW

Therapeutic Attenuation of Cardiac Remodeling After Acute Myocardial Infarction: A Conversation With Marc A. Pfeffer, MD, PhD.

Author: Pfeffer, Marc A. MD, PhD; Rutherford, John D. MB, ChB

Page: 2430-2434

https://ift.tt/2kMLqN7

Comparison of Reduced-Dose Prasugrel and Standard-Dose Clopidogrel in Elderly Patients With Acute Coronary Syndromes Undergoing Early Percutaneous Revascularization.

Author: Savonitto, Stefano MD; Ferri, Luca A. MD; Piatti, Luigi MD; Grosseto, Daniele MD; Piovaccari, Giancarlo MD; Morici, Nuccia MD; Bossi, Irene MD; Sganzerla, Paolo MD; Tortorella, Giovanni MD; Cacucci, Michele MD; Ferrario, Maurizio MD; Murena, Ernesto MD; Sibilio, Girolamo MD; Tondi, Stefano MD; Toso, Anna MD; Bongioanni, Sergio MD; Ravera, Amelia MD; Corrada, Elena MD; Mariani, Matteo MD; Di Ascenzo, Leonardo MD; Petronio, A. Sonia MD, PhD; Cavallini, Claudio MD; Vitrella, Giancarlo MD; Rogacka, Renata MD; Antonicelli, Roberto MD; Cesana, Bruno M. MD, PhD; De Luca, Leonardo MD; Ottani, Filippo MD; De Luca, Giuseppe MD; Piscione, Federico MD; Moffa, Nadia BSc; De Servi, Stefano MD; on behalf of the Elderly ACS 2 Investigators; Bolognese, Leonardo MD; Bovenzi, Francesco MD; Steffenino, Giuseppe MD; Santilli, Ignazio MD; Bassanelli, Giorgio MD; Sacco, Alice MD; Canziani, Federico MD; Ferri, Marco MD; Lo Jacono, Emilia MD; Canosi, Umberto; Fornaro, Giuseppe; Leoncini, Mario MD; Rosa Conte, Maria MD; Farina, Rosario MD; Stefanin, Catia MD; Di Pede, Francesco MD; Chella, Piersilvio MD; Chiara Nardoni, M. MD; Tamburrini, Paola MD; Trimarco, Bruno MD; Galasso, Gennaro MD; Elia, Raffaele MD; Bolognese, Leonardo MD; Grotti, Simone MD; Bovenzi, Francesco MD; Borrelli, Lucia MD; Tamburino, Corrado MD; Capranzano, Piera MD; Francaviglia, Bruno MD; Campana, Carlo MD; Bonatti, Roberto MD; Martinoni, Alessandro MD; Abate, Fabio MD; Coscarelli, Sebastian MD; Rubartelli, Paolo MD; Villani, Giovanni Q. MD; Rossini, Roberta

Page: 2435-2445

https://ift.tt/2sG0Fv3

Prasugrel in the Elderly.

Author: Bangalore, Sripal MD, MHA

Page: 2446-2449

https://ift.tt/2svaL2q

Pharmacodynamic Effects of Switching From Ticagrelor to Clopidogrel in Patients With Coronary Artery Disease: Results of the SWAP-4 Study.

Author: Franchi, Francesco MD; Rollini, Fabiana MD; Rivas Rios, Jose MD; Rivas, Andrea MD; Agarwal, Malhar MD; Kureti, Megha MD; Nagaraju, Deepa MD; Wali, Mustafa MD; Shaikh, Zubair MD; Briceno, Maryuri MD; Nawaz, Ahmed MD; Moon, Jae Youn MD, PhD; Been, Latonya AAS; Suryadevara, Siva MD; Soffer, Daniel MD; Zenni, Martin M. MD; Bass, Theodore A. MD; Angiolillo, Dominick J. MD, PhD

Page: 2450-2462

https://ift.tt/2HlOqsy

Ventricular Fibrillation Conversion Testing After Implantation of a Subcutaneous Implantable Cardioverter Defibrillator: Report From the National Cardiovascular Data Registry.

Author: Friedman, Daniel J. MD; Parzynski, Craig S. MS; Heist, E. Kevin MD, PhD; Russo, Andrea M. MD; Akar, Joseph G. MD, PhD; Freeman, James V. MD, MPH, MS; Curtis, Jeptha P. MD; Al-Khatib, Sana M. MD, MHS

Page: 2463-2477

https://ift.tt/2kMWU3e

CD301b/MGL2+ Mononuclear Phagocytes Orchestrate Autoimmune Cardiac Valve Inflammation and Fibrosis.

Author: Meier, Lee A. BS, BBmE; Auger, Jennifer L. BA; Engelson, Brianna J. BA; Cowan, Hannah M.; Breed, Elise R. BA; Gonzalez-Torres, Mayra I. BS; Boyer, Joshua D. MS; Verma, Mayank PhD; Marath, Aubyn MBBS, MS; Binstadt, Bryce A. MD, PhD

Page: 2478-2493

https://ift.tt/2HmvVEr

Myeloid Cells Remodel the Mitral Valve.

Author: Cremer, Sebastian MD; Nahrendorf, Matthias MD, PhD

Page: 2494-2496

https://ift.tt/2swNtJF

Targeting Chondroitin Sulfate Glycosaminoglycans to Treat Cardiac Fibrosis in Pathological Remodeling.

Author: Zhao, Rong-Rong PhD; Ackers-Johnson, Matthew PhD; Stenzig, Justus MD, PhD; Chen, Chen PhD; Ding, Tao PhD; Zhou, Yue PhD; Wang, Peipei MD, PhD; Ng, Shi Ling BSc; Li, Peter Y. BSc; Teo, Gavin BSc; Rudd, Pauline M. PhD; Fawcett, James W. MD, PhD; Foo, Roger S.Y. MD, FRCP

Page: 2497-2513

https://ift.tt/2sHbpZN

Risk Stratification of Genetic, Dilated Cardiomyopathies Associated With Neuromuscular Disorders: Role of Cardiac Imaging.

Author: van der Bijl, Pieter MD; Delgado, Victoria MD, PhD; Bootsma, Marianne MD, PhD; Bax, Jeroen J. MD, PhD

Page: 2514-2527

https://ift.tt/2svapsC

Highlights From the Circulation Family of Journals.

Author:

Page: 2528-2533

https://ift.tt/2HhvfjP

From the Literature.

Author: Hampton, Tracy PhD

Page: 2534-2535

https://ift.tt/2kPx3rC

Direct Comparison of the 0/1h and 0/3h Algorithms for Early Rule-Out of Acute Myocardial Infarction.

Author: Badertscher, Patrick MD ,,*; Boeddinghaus, Jasper MD ,,,*; Twerenbold, Raphael MD; Nestelberger, Thomas MD; Wildi, Karin MD; Wussler, Desiree MD; Schwarz, Jonas MD; Puelacher, Christian MD; Rubini Gimenez, Maria MD; Kozhuharov, Nikola MD; du Fay de Lavallaz, Jeanne MD; Cerminara, Sara Elisa MS; Potlukova, Eliska MD; Rentsch, Katharina PhD; Miro, Oscar MD; Lopez, Beatriz MD; Martin-Sanchez, F. Javier MD; Morawiec, Beata MD; Muzyk, Piotr MD; Keller, Dagmar I. MD; Reichlin, Tobias MD; Mueller, Christian MD; for the APACE Investigators; Sabti, Zaid; Strebel, Ivo; Shrestha, Samyut; Flores, Dayana; Freese, Michael; Stelzig, Claudia; Kulangara, Caroline; Meissner, Kathrin; Schaerli, Nicolas; Mueller, Deborah; Yufera Sanchez, Ana; Sazgary, Lorraine; Marbot, Stella; Fuenzalida, Carolina; Calderon, Sofia; Rodriguez Adrada, Esther; Kawecki, Damian; Nowalany-Kozielska, Ewa; Parenica, Jiri; Ganovska, Eva; von Eckardstein, Arnold; Lohrmann, Jens; Kloos, Wanda; Osswald, Stefan; Buser, Andreas; Bingisser, Roland; Geigy, Nicolas

Page: 2536-2538

https://ift.tt/2sB8bqS

Letter by Zhang and Xu Regarding Article, "Clinical Profile and Consequences of Atrial Fibrillation in Hypertrophic Cardiomyopathy".

Author: Zhang, Li MD; Xu, Xiao-mao MD

Page: 2539

https://ift.tt/2kMWTfG

Letter by Wang and Zhao Regarding Article, "Clinical Profile and Consequences of Atrial Fibrillation in Hypertrophic Cardiomyopathy".

Author: Wang, Lei MD; Zhao, Yun-Tao MD, PhD

Page: 2540

https://ift.tt/2sDwnZL

Response by Rowin et al to Letter Regarding Article, "Clinical Profile and Consequences of Atrial Fibrillation in Hypertrophic Cardiomyopathy".

Author: Rowin, Ethan J. MD; Maron, Martin S. MD; Maron, Barry J. MD

Page: 2541-2542

https://ift.tt/2svMt8C

Letter by Sniecinski et al Regarding Article, "Conscious Sedation Versus General Anesthesia for Transcatheter Aortic Valve Replacement: Insights from the National Cardiovascular Data Registry Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry".

Author: Sniecinski, Roman M. MD; Mackensen, G. Burkhard MD, PhD; Kertai, Miklos D. MD, PhD

Page: 2543-2544

https://ift.tt/2HjSUjH

Response by Hyman et al to Letter Regarding Article, "Conscious Sedation Versus General Anesthesia for Transcatheter Aortic Valve Replacement: Insights From the National Cardiovascular Data Registry Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry".

Author: Hyman, Matthew C. MD, PhD; Patel, Prakash A. MD; Giri, Jay MD, MPH

Page: 2545-2546

https://ift.tt/2svMqJY

Letter by Koh Regarding Article, "J Curve in Patients Randomly Assigned to Different Systolic Blood Pressure Targets: An Experimental Approach to an Observational Paradigm".

Author: Koh, Kwang Kon MD, PhD

Page: 2547-2548

https://ift.tt/2HkK45d

Response by Kalkman et al to Letter Regarding Article, "J Curve in Patients Randomly Assigned to Different Systolic Blood Pressure Targets: An Experimental Approach to an Observational Paradigm".

Author: Kalkman, Deborah N. MD; Brouwer, Tom F. MD; van den Born, Bert-Jan H. MD, PhD

Page: 2549-2550

https://ift.tt/2kSdor3

Microbiota and Type 2 immune responses

Kathy D McCoy | Aline Ignacio | Markus B Geuking

https://ift.tt/2JjRyap

All along the watchtower: group 2 innate lymphoid cells in allergic responses

Madelene W Dahlgren | Ari B Molofsky

https://ift.tt/2Jgccbf

Why do proteases mess up with antigen presentation by re-shuffling antigen sequences?

Juliane Liepe | Huib Ovaa | Michele Mishto

https://ift.tt/2Hmvvhl

Parallel imaging compressed sensing for accelerated imaging and improved signal-to-noise ratio in MRI-based postimplant dosimetry of prostate brachytherapy

Publication date: Available online 4 June 2018
Source:Brachytherapy
Author(s): Jeremiah W. Sanders, Hao Song, Steven J. Frank, Tharakeswara Bathala, Aradhana M. Venkatesan, Mitchell Anscher, Chad Tang, Teresa L. Bruno, Wei Wei, Jingfei Ma
PurposeTo investigate the feasibility of using parallel imaging compressed sensing (PICS) to reduce scan time and improve signal-to-noise ratio (SNR) in MRI-based postimplant dosimetry of prostate brachytherapy.Methods and MaterialsTen patients underwent low-dose-rate prostate brachytherapy with radioactive seeds stranded with positive magnetic resonance-signal seed markers and were scanned on a Siemens 1.5T Aera. MRI comprised a fully balanced steady-state free precession sequence with two 18-channel external pelvic array coils with and without a rigid two-channel endorectal coil. The fully sampled data sets were retrospectively subsampled with increasing acceleration factors and reconstructed with parallel imaging and compressed sensing algorithms. The images were assessed in a blinded reader study by board-certified care providers. Rating scores were compared for statistically significant differences between reconstruction types.ResultsImages reconstructed from subsampling up to an acceleration factor of 4 with PICS demonstrated consistently sufficient quality for dosimetry with no apparent loss of SNR, anatomy depiction, or seed/marker conspicuity when compared to the fully sampled images. Images obtained with acceleration factors of 5 or 6 revealed reduced spatial resolution and seed marker contrast. Nevertheless, the reader study revealed that images obtained with an acceleration factor of up to 5 and reconstructed with PICS were adequate-to-good for postimplant dosimetry.ConclusionsCombined parallel imaging and compressed sensing can substantially reduce scan time in fully balanced steady-state free precession imaging of the prostate while maintaining adequate-to-good image quality for postimplant dosimetry. The saved scan time can be used for multiple signal averages and improved SNR, potentially obviating the need for an endorectal coil in MRI-based postimplant dosimetry.



https://ift.tt/2xH9gmN

Health risks of heavy metal exposure through vegetable consumption near a large-scale Pb/Zn smelter in central China

Publication date: 15 October 2018
Source:Ecotoxicology and Environmental Safety, Volume 161
Author(s): Xinyu Li, Zhonggen Li, Che-Jen Lin, Xiangyang Bi, Jinling Liu, Xinbin Feng, Hua Zhang, Ji Chen, Tingting Wu
Smelting of nonferrous metals is an important source of heavy metals in surface soil. The crops/vegetables grown on contaminated soil potentially impose adverse effects on human health. In this study, the contamination level of five heavy metals (Hg, Pb, Zn, Cd and Cu) in ten types of vegetables grown nearby a large scale Pb/Zn smelter in Hunan Province, China and the health risk associated with their consumption are assessed. Based on the data obtained from 52 samples, we find that Pb and Cd contributed to the greatest health risk and leafy vegetables tend to be more contaminated than non-leafy vegetables. Within 4 km radius of the smelter, over 75% of vegetable samples exceeded the national food standard for Pb; over 47% exceeded the Cd standard; and 7% exceeded the Hg standard. Heavy metal concentrations in vegetables measured within the 4 km radius are on average three times more elevated compared to those found at the control area 15 km away. Heavy metals in vegetables have dual sources of root absorption from soil and leaf adsorption from atmosphere. Health risk in terms of the hazard index (HI) at contaminated areas are 3.66 and 3.14 for adults and children, respectively, suggesting adverse health effects would occur. HI for both groups are mainly contributed by Pb (48%) and Cd (40%). Fortunately, vegetable samples collected at the control area are considered safe to consume.

Graphical abstract

https://ift.tt/2LY05Bz

CheckMate 141: 1‐Year Update and Subgroup Analysis of Nivolumab as First‐Line Therapy in Patients with Recurrent/Metastatic Head and Neck Cancer

AbstractNivolumab significantly improved overall survival (OS) vs investigator's choice (IC) of chemotherapy at the primary analysis of randomized, open‐label, phase 3 CheckMate 141 in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). Here, we report that OS benefit with nivolumab was maintained at a minimum follow‐up of 11.4 months. Further, OS benefit with nivolumab vs IC was also noted among patients who received first‐line treatment for R/M SCCHN after progressing on platinum therapy for locally advanced disease in the adjuvant or primary (i.e., with radiation) setting. The Oncologist 2018

https://ift.tt/2swQHN4

Comparative Molecular Analyses of Esophageal Squamous Cell Carcinoma, Esophageal Adenocarcinoma, and Gastric Adenocarcinoma

AbstractBackground.Gastroesophageal cancers are often grouped together even though cancers that originate in the esophagus often exhibit different histological features, geographical distribution, risk factors, and clinical characteristics than those originating in the stomach. Herein, we aimed to compare the molecular characteristics of three different gastroesophageal cancer types: esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and gastric adenocarcinoma (GAC).Subjects, Materials, and Methods.In total, 3,342 gastroesophageal cancers were examined. Next‐generation sequencing was performed on genomic DNA isolated from formalin‐fixed paraffin‐embedded tumor samples using the NextSeq platform. Tumor mutational burden was measured by counting all nonsynonymous missense mutations, and microsatellite instability was examined at over 7,000 target microsatellite loci. Immunohistochemistry and in situ hybridization techniques were also performed.Results.When compared with EAC and GAC, ESCC showed significantly lower mutational rates within APC, ARID1A, CDH1, KRAS, PTEN, and SMAD4, whereas more frequent mutations were observed in BAP1, CDKN2A, FOXO3, KMT2D, MSH6, NOTCH1, RB1, and SETD2. Human epidermal growth receptor 2 (HER2) overexpression was observed in 13% of EAC compared with 6% of GAC and 1% of ESCC (p < .0001). Compared with EAC and GAC, ESCC exhibited higher expression of programmed death‐ligand 1 (PD‐L1) (27.7% vs. 7.5% vs. 7.7%, p < .0001). We observed that FGF3, FGF4, FGF19, CCND1 (co‐localized on 11q13), and FGFR1 were significantly more amplified in ESCC compared with EAC and GAC (p < .0001).Conclusion.Molecular comparisons between ESCC, EAC, and GAC revealed distinct differences between squamous cell carcinomas and adenocarcinomas in each platform tested. Different prevalence of HER2/neu overexpression and amplification, and immune‐related biomarkers between ESCC, EAC, and GAC, suggests different sensitivity to HER2‐targeted therapy and immune checkpoint inhibition. These findings bring into question the validity of grouping patients with EAC and ESCC together in clinical trials and provide insight into molecular features that may represent novel therapeutic targets. The Oncologist 2018

https://ift.tt/2sFPJ0m

The Importance of Distinguishing Sporadic Cancers from Those Related to Cancer Predisposing Germline Mutations

AbstractChoosing the optimal therapy for a patient's cancer has long been based on whether the cancer demonstrates a predictive marker of efficacy. The U.S. Food and Drug Administration (FDA) has now approved use of a targeted therapy based solely on tumor molecular markers (pembrolizumab for tumors with deficient mismatch repair [MMR] and high microsatellite instability [MSI]) and approved another therapy based solely on a germline mutation as the predictive marker of benefit (olaparib for BRCA carriers with ovarian or breast cancer) [New Engl J Med 2017;377:1409–1412, N Engl J Med 2012;366:1382–1392, N Eng J Med 2017;377:523–533].Here, a patient is presented with a molecular diagnosis of Lynch syndrome and with breast cancer. Yet the breast cancer showed proficient expression of the same MMR gene found to be mutated in her germline testing. The case underscores the importance of tumor testing for MMR and MSI and of not assuming that the tumor is related to the Lynch syndrome rather than being sporadic. This is particularly true in patients with cancers (e.g., breast cancer) whose association with Lynch syndrome is not well established.The case presented also underscores the importance of considering next‐generation sequencing of the tumor when the therapies approved are based on a germline mutation being the predictive marker. For example, the FDA‐approved use of the PARP inhibitor olaparib is for ovarian or breast cancers in patients harboring a BRCA germline mutation [N Engl J Med 2012;366:1382–1392, N Eng J Med 2017;377:523–533]. Yet patients with tumors lacking BRCA loss of heterozygosity (LOH) or lacking other evidence of probable loss of normal BRCA gene product expression might be less likely to benefit from PARP inhibitor therapy, because the efficacy of PARP inhibitor therapy in patients with germline BRCA mutations would likely be predicated upon BRCA LOH in their tumors. The Oncologist 2018

https://ift.tt/2swSZMl

Correlation between gonial angle and dynamic tongue collapse in children with snoring/sleep disordered breathing – an exploratory pilot study

Drug induced sleep endoscopy (DISE) is hoped to identify reasons of failure of adenotonsillectomy (AT) in treating pediatric sleep disordered breathing (SDB). Maxillomandibular disproportion has been studied a...

https://ift.tt/2xObMaK

Characterization and quality assessment of recycled post-consumption poly(ethylene terephthalate) (PET)

Abstract

In the present study, the recycled post-consumption polyethylene terephthalate (PET) flakes were investigated as possible raw materials for the production of food packaging. After heating at 220 °C for 1 h, a steaming stage was conducted as a control test to assess the quality of the product. Different samples were characterized by ¹H-NMR, FT-IR, DSC/TGA analysis, viscosity index (VI), and trace metals analysis. The results showed that the recycled post-consumed PET flakes' properties were generally conform to the standard norms of PET except the color of some flakes turned to yellow. Subsequently, a complementary study was undertaken to assess whether the material could be possibly reused for food packaging. For this purpose, rheological, thermal, and mechanical characterizations were performed. The results of the comparative study between the virgin and the recycled PET flakes concluded that the PET recycling affected the rheological properties but did not have any significant effect on their thermal and mechanical characteristics. Hence, it was deduced that the post-consumed PET flakes could be reused as a packaging material except food products.

https://ift.tt/2LZ8YLh

Cross-sectional study on sensitization to mite and cockroach allergen components in allergy patients in the Central European region

The major sources of allergens in the indoor air include house dust mites, dander derived from domestic animals and rodents, cockroach, and several fungi. Mites are the main cause of allergies in some countrie...

https://ift.tt/2sGWAXg

Effect of alumina nano additives into biodiesel-diesel blends on the combustion performance and emission characteristics of a diesel engine with exhaust gas recirculation

Abstract

In the present study, the combined effect of alumina nanoparticles into the Calophyllum inophyllum biodiesel blend and exhaust gas recirculation on the combustion, performance, and emission characteristics of a diesel engine was investigated. The alumina (Al₂O₃) nanoparticles with the mass fraction of 40 ppm were dispersed into the C. inophyllum biodiesel blend (20% of C. inophyllum biodiesel + 80% of diesel (CIB20)) by the ultrasonication process. Further, the exhaust gas recirculation was adopted to control the oxides of nitrogen (NOx) emissions of a diesel engine. The experiments were conducted on a single cylinder diesel engine with the diesel, CIB20, 20% of C. inophyllum biodiesel + 80% of diesel + 40 ppm Al₂O₃ nanoparticles (CIB20ANP40), CIB20 + 20% exhaust gas recirculation (EGR), and CIB20ANP40 + 20% EGR fuel samples at different load conditions. The results reveal that brake thermal efficiency of CIB20ANP40 fuel increased by 5.04 and 7.71% compared to the CIB20 and CIB20ANP40 + 20% EGR fuels, respectively. The addition of alumina nanoparticles to the CIB20 fuel, CO, and hydrocarbon (HC) emissions were was reduced compared to the CIB20 fuel. The smoke opacity was decreased with the addition of alumina nanoparticles to the CIB20 fuel by 7.3% compared to the CIB20 fuel. The NOx emissions for the CIB20ANP40 + 20% EGR fuel was decreased by 36.84, 31.53, and 17.67% compared to the CIB20, CIB20ANP40, and CIB20 + 20% EGR fuel samples at full load condition.

https://ift.tt/2xH2PAe

The response of zooplankton communities to the 2016 extreme hydrological cycle in floodplain lakes connected to the Yangtze River in China

Abstract

The Huayanghe Lakes play an important role in the Yangtze floodplain in China and had extremely high water levels during the summer of 2016. Monitoring data was collected in an effort to understand the impact of this change on the crustacean zooplankton composition and abundance and the biomass variation in the Huayanghe Lakes between a regular hydrological cycle (RHC) and an extreme hydrological cycle (EHC). The crustacean zooplankton community composition, abundance, and biomass in the floodplain lakes were markedly affected by the water-level disturbance. The number of species was lower in the RHC, but the mean density and biomass decreased from 93.84 ± 13.29 ind./L and 6.11 ± 0.89 mg/L, respectively, in the RHC to 66.62 ± 10.88 ind./L and 1.22 ± 0.26 mg/L, respectively, in the EHC. Pearson correlations and redundancy analyses revealed the environmental factors with the most significant impact on the crustacean zooplankton community differed between the RHC and EHC cycles. Little previous information exists on the zooplankton in these lakes, and the present study provides data on the zooplankton composition, abundance, and biomass, both at baseline and in response to hydrological changes.

https://ift.tt/2JbkNQM

Immune checkpoint-mediated myositis and myasthenia gravis: A case report and review of evaluation and management

We present a case of myositis and possible overlapping neuromuscular junction disorder following treatment with nivolumab for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).

https://ift.tt/2LnAlgD

Outcomes in microvascular head and neck reconstruction in the setting of restricted residency hours

Resident duty hour restrictions can limit the frequency of resident flap checks at smaller institutions with "home" call. Institutions are compensating with adjuvant nursing flap checks as well as incorporating technology; however, this management remains controversial.

https://ift.tt/2JvxfKn

Comparison of intratympanic dexamethasone therapy and hyperbaric oxygen therapy for the salvage treatment of refractory high-frequency sudden sensorineural hearing loss

This study aimed to compare the efficacy of intratympanic dexamethasone (ITD) therapy and hyperbaric oxygen(HBO) therapy for the salvage treatment of patients with high-frequency sudden sensorineural hearing loss (SSNHL) after the failure of conventional therapy.

https://ift.tt/2LmD620

Current Insight and Futuristic Vistas of Microbial Transglutaminase in Nutraceutical Industry

Publication date: Available online 4 June 2018
Source:Microbiological Research
Author(s): Syeda Warisul Fatima, Sunil K. Khare
Microbial transglutaminase (MTGase) has become a driving force in the food industry cross-linking the food proteins. MTGase-the nature's molecular glue is recognized to reorient food protein's functional properties without affecting its nutritive value. The scope and approach of this review is to have insight on the action mechanism of MTGase and impact of molecular linkage on functional proteins in various protein moieties in development of innovative features in food production for better consumer's choice and satisfaction. The study covers a wide range of published work across food industries involving innovative use of MTGase, an environment friendly production approach for commercial utilization to get better outcome in terms of culinary delight. The intrinsic biochemical properties and structural information by sequence analysis and clustering validates the mode of reaction mechanism of the biological glue enzyme. The review singles out how the MTGase emerged as a prime choice in ever evolving food industry.



https://ift.tt/2sBJRFa

A computed tomographic analysis of frontal recess cells in association with the development of frontal sinusitis

This study was done to determine frontal recess anatomy cell variations and its association with frontal sinusitis. The incidence of frontal recess cells in the population, the presence of frontal recess cell variations in chronic rhinosinusitis and non-chronic rhinosinusitis and the association of frontal recess cell variation in the development of frontal sinusitis were also assessed.

https://ift.tt/2LicA9V

Role of Complement in a Rat Model of Paclitaxel-Induced Peripheral Neuropathy [INNATE IMMUNITY AND INFLAMMATION]

Chemotherapy-induced peripheral neuropathy (CIPN) is a painful and debilitating side effect of cancer chemotherapy with an unclear pathogenesis. Consequently, the available therapies for this neuropathic pain syndrome are inadequate, leading to a significantly reduced quality of life in many patients. Complement, a key component of the innate immune system, has been associated with neuroinflammation, a potentially important trigger of some types of neuropathic pain. However, the role of complement in CIPN remains unclear. To address this issue, we developed a C3 knockout (KO) rat model and induced CIPN in these KO rats and wild-type littermates via the i.p. administration of paclitaxel, a chemotherapeutic agent associated with CIPN. We then compared the severity of mechanical allodynia, complement activation, and intradermal nerve fiber loss between the groups. We found that 1) i.p. paclitaxel administration activated complement in wild-type rats, 2) paclitaxel-induced mechanical allodynia was significantly reduced in C3 KO rats, and 3) the paclitaxel-induced loss of intradermal nerve fibers was markedly attenuated in C3 KO rats. In in vitro studies, we found that paclitaxel-treated rat neuronal cells activated complement, leading to cellular injury. Our findings demonstrate a previously unknown but pivotal role of complement in CIPN and suggest that complement may be a new target for the development of novel therapeutics to manage this painful disease.

https://ift.tt/2LZTV3F

eIF4E-Binding Proteins 1 and 2 Limit Macrophage Anti-Inflammatory Responses through Translational Repression of IL-10 and Cyclooxygenase-2 [INNATE IMMUNITY AND INFLAMMATION]

Macrophages represent one of the first lines of defense during infections and are essential for resolution of inflammation following pathogen clearance. Rapid activation or suppression of protein synthesis via changes in translational efficiency allows cells of the immune system, including macrophages, to quickly respond to external triggers or cues without de novo mRNA synthesis. The translational repressors eIF4E-binding proteins 4E-BP1 and 4E-BP2 (4E-BP1/2) are central regulators of proinflammatory cytokine synthesis during viral and parasitic infections. However, it remains to be established whether 4E-BP1/2 play a role in translational control of anti-inflammatory responses. By comparing translational efficiencies of immune-related transcripts in macrophages from wild-type and 4E-BP1/2 double-knockout mice, we found that translation of mRNAs encoding two major regulators of inflammation, IL-10 and PG-endoperoxide synthase 2/cyclooxygenase-2, is controlled by 4E-BP1/2. Genetic deletion of 4E-BP1/2 in macrophages increased endogenous IL-10 and PGE₂ protein synthesis in response to TLR4 stimulation and reduced their bactericidal capacity. The molecular mechanism involves enhanced anti-inflammatory gene expression (sIl1ra, Nfil3, Arg1, Serpinb2) owing to upregulation of IL-10–STAT3 and PGE₂–C/EBPβ signaling. These data provide evidence that 4E-BP1/2 limit anti-inflammatory responses in macrophages and suggest that dysregulated activity of 4E-BP1/2 might be involved in reprogramming of the translational and downstream transcriptional landscape of macrophages during pathological conditions, such as infections and cancer.

https://ift.tt/2JgLcIJ

RNF31 Regulates Skin Homeostasis by Protecting Epidermal Keratinocytes from Cell Death [INNATE IMMUNITY AND INFLAMMATION]

Linear ubiquitin chain assembly complex plays an important role in regulating TNF-α signaling activation by modifying target proteins with linear (M1-linked) ubiquitin chains. In this study, we report that the epidermis-specific knockout (KO) of RNF31, the catalytic subunit of linear ubiquitin chain assembly complex, results in an early postnatal lethality in mice due to severe skin inflammation. The inflammation was mainly triggered by TNF-α–induced apoptosis in RNF31 KO keratinocytes. Mechanistically, the deficiency of RNF31 not only impaired TNF-α–induced NF-B activation, but also significantly increased apoptosis. Consistently, deleting TNF receptor 1 could rescue the lethality of RNF31 epidermis-specific KO mice and also the skin inflammation. Collectively, our study provides an in vivo insight that linear ubiquitination is critical for maintaining the homeostasis of keratinocytes, which will shed light on designing therapeutic compounds to treat skin inflammation.

https://ift.tt/2LXvyUt

Integrin Activation Controls Regulatory T Cell-Mediated Peripheral Tolerance [IMMUNE REGULATION]

Maintenance of the regulatory T (Treg) cell pool is essential for peripheral tolerance and prevention of autoimmunity. Integrins, heterodimeric transmembrane proteins consisting of α and β subunits that mediate cell-to-cell and cell-to-extracellular matrix interactions, play an important role in facilitating Treg cell contact–mediated suppression. In this article, we show that integrin activation plays an essential, previously unappreciated role in maintaining murine Treg cell function. Treg cell–specific loss of talin, a β integrin–binding protein, or expression of talin(L325R), a mutant that selectively abrogates integrin activation, resulted in lethal systemic autoimmunity. This dysfunction could be attributed, in part, to a global dysregulation of the Treg cell transcriptome. Activation of integrin α₄β₁ led to increased suppressive capacity of the Treg cell pool, suggesting that modulating integrin activation on Treg cells may be a useful therapeutic strategy for autoimmune and inflammatory disorders. Taken together, these results reveal a critical role for integrin-mediated signals in controlling peripheral tolerance by virtue of maintaining Treg cell function.

https://ift.tt/2LWQQlf