Isolation and molecular characterization of the fungal endophytic microbiome from conventionally and organically grown avocado trees in South Florida

Abstract

Fungal endophytes are the most ubiquitous and highly diverse microorganisms that inhabit the interior of healthy plants. They are important in plant ecology and offer untapped potential to improve plant health and productivity in agroecosystems. The endophytic assemblage of avocado is poorly understood; therefore, surveys of fungal endophytes of Persea americana Mill. (Avocado) in South Florida organic and conventional orchards were conducted. A total of 17 endophytic fungal species were recovered from healthy avocado terminal branches. Endophytic fungal species were identified by rDNA sequencing of the internal transcribed spacer (ITS) region, using UNITE Species Hypotheses to reliably assign a taxon name, and determined as belonging to the genera Alternaria, Cladosporium, Colletotrichum, Corynespora, Diaporthe, Lasiodiplodia, Neofusicoccum, Neopestalotiopsis, Phyllosticta, and Strelitziana. Endophyte community assemblage differed between organic and conventional agroecosystems. This is the first report of Alternaria eichhorniae, Cladosporium tenuissimum, Corynespora cassiicola, Colletotrichum alatae, Diaporthe fraxini-angustifoliae, Lasiodiplodia gonubiensis, Neofusicoccum algeriense, Neofusicoccum andinum, Neopestalotiopsis foedans, Phyllosticta capitalensis, and Strelitziana africana as endophytes of avocado. Evaluation using pathogenicity tests on avocado leaves and terminal branches showed that endophytic fungal isolates did not cause disease symptoms.

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Fistulous-type vein of Galen malformation phantom model for endovascular training and research

Introduction

Vein of Galen malformation (VGM), a high-flow intracranial arteriovenous shunt, is among the most severe neurovascular diseases in childhood. In many cases untreated children die or survive only severely disabled. Endovascular embolization is the preferred treatment.

Objective

To develop a simple fistulous-type VGM phantom model for teaching and training of different endovascular treatment methods and to investigate new treatment options and devices.

Methods

An experimental in vitro pulsatile phantom model was developed imitating a high-flow fistulous-type VGM, which is typical, especially in the neonatal phase. Pressure measurements at different arterial sites were performed before and after closure of the VGM. Closure of the VGM was achieved by coiling using a combined microcatheter-based transvenous and transarterial approach called 'kissing microcatheter technique'.

Results

The behaviour of the phantom model in vitro under fluoroscopy and under angiographic runs was extremely similar to that in in vivo conditions in children. The results showed that intra-arterial pressures changed and increased statistically significantly at all measurement sites after embolization, as in human arteriovenous malformation. We also demonstrated different and complementary visualizations of hemodynamics and angioarchitecture by antegrade and retrograde microcatheter injections.

Conclusions

Our phantom model behaves like a typical fistulous-type VGM and can be used in vitro for teaching and training and for further research. It offers a new and better understanding of hemodynamics and angioarchitecture in the endovascular management of VGM.

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In vitro comparison of intracranial stent visibility using various concentrations of gadolinium contrast agent under 1.5 T and 3 T MR angiography

Background and purpose

MR angiography (MRA) is an increasingly used evaluation method following intracranial stenting. However, the various artifacts created by the stent limit this technique. The purpose of this study was to investigate the effects of various concentrations of gadolinium contrast agent on the visibility and signal characteristics of two stents using the a contrast enhanced MRA technique.

Material and method

Two intracranial stents (Enterprise and Helistent) were placed in polyvinyl chloride tubes as vascular phantoms. They were filled with six different doses of gadolinium contrast agent (1.0, 2.0, 4.0, 6.0, 8.0, and 10.0 mmol/L dimeglumine gadopentetate, respectively) and imaged using 3 T and 1.5 T MR systems. Relative in-stent signal (RIS) was calculated and artificial luminal narrowing (ALN) was obtained using pixel by pixel analysis.

Result

The Enterprise stent, performed in both 1.5 T and 3 T MR systems, showed mean RIS values much less than those for the Helistent for all different doses of gadolinium solution. Increased gadolinium concentration resulted in a gradual reduction in RIS values in the Enterprise group. Also, ALN in the Enterprise group showed no or little change with various gadolinium doses.

Conclusions

The Enterprise stent demonstrated good luminal visibility regardless of gadolinium concentration. The relative in-stent signals were more predictable in the Enterprise stent with various doses of gadolinium. Therefore, the Enterprise stent has been shown to provide better in-stent visibility compared with the Helistent using various gadolinium doses.

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SIRT1 Mediates Depression-Like Behaviors in the Nucleus Accumbens

Depression is a recurring and life-threatening illness that affects up to 120 million people worldwide. In the present study, we show that chronic social defeat stress, an ethologically validated model of depression in mice, increases SIRT1 levels in the nucleus accumbens (NAc), a key brain reward region. Increases in SIRT1, a well characterized class III histone deacetylase, after chronic social defeat suggest a role for this enzyme in mediating depression-like behaviors. When resveratrol, a pharmacological activator of SIRT1, was directly infused bilaterally into the NAc, we observed an increase in depression- and anxiety-like behaviors. Conversely, intra-NAc infusions of EX-527, a SIRT1 antagonist, reduced these behaviors; EX-527 also reduced acute stress responses in stress-naive mice. Next, we increased SIRT1 levels directly in NAc by use of viral-mediated gene transfer and observed an increase in depressive- and anxiety-like behaviors when mice were assessed in the open-field, elevated-plus-maze, and forced swim tests. Using a Cre-inducible viral vector system to overexpress SIRT1 selectively in dopamine D1 or D2 subpopulations of medium spiny neurons (MSNs) in the NAc, we found that SIRT1 promotes depressive-like behaviors only when overexpressed in D1 MSNs, with no effect seen in D2 MSNs. Conversely, selective ablation of SIRT1 in the NAc using viral-Cre in floxed Sirt1 mice resulted in decreased depression- and anxiety-like behaviors. Together, these results demonstrate that SIRT1 plays an essential role in the NAc in regulating mood-related behavioral abnormalities and identifies a novel signaling pathway for the development of innovative antidepressants to treat major depressive disorders.

SIGNIFICANCE STATEMENT In this study, we demonstrate a pivotal role for SIRT1 in anxiety- and depression-like behaviors in the nucleus accumbens (NAc), a key brain reward region. We show that stress stably induces SIRT1 expression in this brain region and that altering SIRT1 activity using a pharmacological or genetic approach regulates anxiety- and depression-like behaviors. These results suggest that SIRT1 plays an essential role in regulating mood-related behaviors and introduces a novel signaling pathway for the development of innovative antidepressants to treat depression and other stress-related disorders. A recent groundbreaking publication by the CONVERGE Consortium (2015) identified a reproducible association of the SIRT1 locus with major depression in humans. Therefore, our results are timely and have significant translational relevance.

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This Week in The Journal

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Specialized Networks for Social Cognition: A Defining Role for the Oxytocin Receptor

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Cell-Specific Cholinergic Modulation of Excitability of Layer 5B Principal Neurons in Mouse Auditory Cortex

The neuromodulator acetylcholine (ACh) is crucial for several cognitive functions, such as perception, attention, and learning and memory. Whereas, in most cases, the cellular circuits or the specific neurons via which ACh exerts its cognitive effects remain unknown, it is known that auditory cortex (AC) neurons projecting from layer 5B (L5B) to the inferior colliculus, corticocollicular neurons, are required for cholinergic-mediated relearning of sound localization after occlusion of one ear. Therefore, elucidation of the effects of ACh on the excitability of corticocollicular neurons will bridge the cell-specific and cognitive properties of ACh. Because AC L5B contains another class of neurons that project to the contralateral cortex, corticocallosal neurons, to identify the cell-specific mechanisms that enable corticocollicular neurons to participate in sound localization relearning, we investigated the effects of ACh release on both L5B corticocallosal and corticocollicular neurons. Using in vitro electrophysiology and optogenetics in mouse brain slices, we found that ACh generated nicotinic ACh receptor (nAChR)-mediated depolarizing potentials and muscarinic ACh receptor (mAChR)-mediated hyperpolarizing potentials in AC L5B corticocallosal neurons. In corticocollicular neurons, ACh release also generated nAChR-mediated depolarizing potentials. However, in contrast to the mAChR-mediated hyperpolarizing potentials in corticocallosal neurons, ACh generated prolonged mAChR-mediated depolarizing potentials in corticocollicular neurons. These prolonged depolarizing potentials generated persistent firing in corticocollicular neurons, whereas corticocallosal neurons lacking mAChR-mediated depolarizing potentials did not show persistent firing. We propose that ACh-mediated persistent firing in corticocollicular neurons may represent a critical mechanism required for learning-induced plasticity in AC.

SIGNIFICANCE STATEMENT Acetylcholine (ACh) is crucial for cognitive functions. Whereas in most cases the cellular circuits or the specific neurons via which ACh exerts its cognitive effects remain unknown, it is known that auditory cortex (AC) corticocollicular neurons projecting from layer 5B to the inferior colliculus are required for cholinergic-mediated relearning of sound localization after occlusion of one ear. Therefore, elucidation of the effects of ACh on the excitability of corticocollicular neurons will bridge the cell-specific and cognitive properties of ACh. Our results suggest that cell-specific ACh-mediated persistent firing in corticocollicular neurons may represent a critical mechanism required for learning-induced plasticity in AC. Moreover, our results provide synaptic mechanisms via which ACh may mediate its effects on AC receptive fields.

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Distributed Representation of "What" and "Where" Information in the Parahippocampal Region

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Medial Orbitofrontal Neurons Preferentially Signal Cues Predicting Changes in Reward during Unblocking

The orbitofrontal cortex (OFC) has been broadly implicated in the ability to use the current value of expected outcomes to guide behavior. Although value correlates have been prominently reported in lateral OFC, they are more often associated with more medial areas. Further, recent studies in primates have suggested a dissociation in which the lateral OFC is involved in credit assignment and representation of reward identity and more medial areas are critical to representing value. Previously, we used unblocking to test more specifically what information about outcomes is represented by OFC neurons in rats; consistent with the proposed dichotomy between the lateral and medial OFC, we found relatively little linear value coding in the lateral OFC (Lopatina et al., 2015). Here we have repeated this experiment, recording in the medial OFC, to test whether such value signals might be found there. Neurons were recorded in an unblocking task as rats learned about cues that signaled either more, less, or the same amount of reward. We found that medial OFC neurons acquired responses to these cues; however, these responses did not signal different reward values across cues. Surprisingly, we found that cells developed responses to cues predicting a change, particularly a decrease, in reward value. This is consistent with a special role for medial OFC in representing current value to support devaluation/revaluation sensitive changes in behavior.

SIGNIFICANCE STATEMENT This study uniquely examines encoding in rodent mOFC at the single-unit level in response to cues that predict more, less, or no change in reward in rats during training in a Pavlovian unblocking task, finding more cells responding to change-predictive cues and stronger activity in response to cues predictive of less reward.

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Silent Expectations: Dynamic Causal Modeling of Cortical Prediction and Attention to Sounds That Weren't

There is increasing evidence that human perception is realized by a hierarchy of neural processes in which predictions sent backward from higher levels result in prediction errors that are fed forward from lower levels, to update the current model of the environment. Moreover, the precision of prediction errors is thought to be modulated by attention. Much of this evidence comes from paradigms in which a stimulus differs from that predicted by the recent history of other stimuli (generating a so-called "mismatch response"). There is less evidence from situations where a prediction is not fulfilled by any sensory input (an "omission" response). This situation arguably provides a more direct measure of "top-down" predictions in the absence of confounding "bottom-up" input. We applied Dynamic Causal Modeling of evoked electromagnetic responses recorded by EEG and MEG to an auditory paradigm in which we factorially crossed the presence versus absence of "bottom-up" stimuli with the presence versus absence of "top-down" attention. Model comparison revealed that both mismatch and omission responses were mediated by increased forward and backward connections, differing primarily in the driving input. In both responses, modeling results suggested that the presence of attention selectively modulated backward "prediction" connections. Our results provide new model-driven evidence of the pure top-down prediction signal posited in theories of hierarchical perception, and highlight the role of attentional precision in strengthening this prediction.

SIGNIFICANCE STATEMENT Human auditory perception is thought to be realized by a network of neurons that maintain a model of and predict future stimuli. Much of the evidence for this comes from experiments where a stimulus unexpectedly differs from previous ones, which generates a well-known "mismatch response." But what happens when a stimulus is unexpectedly omitted altogether? By measuring the brain's electromagnetic activity, we show that it also generates an "omission response" that is contingent on the presence of attention. We model these responses computationally, revealing that mismatch and omission responses only differ in the location of inputs into the same underlying neuronal network. In both cases, we show that attention selectively strengthens the brain's prediction of the future.

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miR-155 Deletion in Mice Overcomes Neuron-Intrinsic and Neuron-Extrinsic Barriers to Spinal Cord Repair

Axon regeneration after spinal cord injury (SCI) fails due to neuron-intrinsic mechanisms and extracellular barriers including inflammation. microRNA (miR)-155–5p is a small, noncoding RNA that negatively regulates mRNA translation. In macrophages, miR-155-5p is induced by inflammatory stimuli and elicits a response that could be toxic after SCI. miR-155 may also independently alter expression of genes that regulate axon growth in neurons. Here, we hypothesized that miR-155 deletion would simultaneously improve axon growth and reduce neuroinflammation after SCI by acting on both neurons and macrophages. New data show that miR-155 deletion attenuates inflammatory signaling in macrophages, reduces macrophage-mediated neuron toxicity, and increases macrophage-elicited axon growth by ~40% relative to control conditions. In addition, miR-155 deletion increases spontaneous axon growth from neurons; adult miR-155 KO dorsal root ganglion (DRG) neurons extend 44% longer neurites than WT neurons. In vivo, miR-155 deletion augments conditioning lesion-induced intraneuronal expression of SPRR1A, a regeneration-associated gene; ~50% more injured KO DRG neurons expressed SPRR1A versus WT neurons. After dorsal column SCI, miR-155 KO mouse spinal cord has reduced neuroinflammation and increased peripheral conditioning-lesion-enhanced axon regeneration beyond the epicenter. Finally, in a model of spinal contusion injury, miR-155 deletion improves locomotor function at postinjury times corresponding with the arrival and maximal appearance of activated intraspinal macrophages. In miR-155 KO mice, improved locomotor function is associated with smaller contusion lesions and decreased accumulation of inflammatory macrophages. Collectively, these data indicate that miR-155 is a novel therapeutic target capable of simultaneously overcoming neuron-intrinsic and neuron-extrinsic barriers to repair after SCI.

SIGNIFICANCE STATEMENT Axon regeneration after spinal cord injury (SCI) fails due to neuron-intrinsic mechanisms and extracellular barriers, including inflammation. Here, new data show that deleting microRNA-155 (miR-155) affects both mechanisms and improves repair and functional recovery after SCI. Macrophages lacking miR-155 have altered inflammatory capacity, which enhances neuron survival and axon growth of cocultured neurons. In addition, independent of macrophages, adult miR-155 KO neurons show enhanced spontaneous axon growth. Using either spinal cord dorsal column crush or contusion injury models, miR-155 deletion improves indices of repair and recovery. Therefore, miR-155 has a dual role in regulating spinal cord repair and may be a novel therapeutic target for SCI and other CNS pathologies.

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Compartment-Dependent Degradation of Mutant Huntingtin Accounts for Its Preferential Accumulation in Neuronal Processes

In neurodegenerative diseases caused by misfolded proteins, including Huntington's disease (HD), the neuronal processes and terminals are particularly prone to the accumulation of misfolded proteins, leading to axonal and synaptic dysfunction. This compartment-dependent accumulation can result from either the altered transport of misfolded proteins or impaired protein degradation. Mutant huntingtin (mHtt), the HD protein, is known to affect intracellular transport and can be degraded by the proteasome and autophagy, but how mHtt accumulates in the neuronal processes, an early pathological event in the brains of HD patients, still remains unclear. Using an "optical pulse-chase" assay that can quantify protein degradation in specific subcellular regions, we found that neuronal mHtt is removed faster in the cell body than in neurites. Furthermore, mHtt is cleared more rapidly in astrocytes than in neurons. The ubiquitin-proteasome system plays a much bigger role than autophagy in degrading soluble mHtt via K48 ubiquitination in both the cytoplasm and processes of neurons and astrocytes. By injecting adenoviral vectors expressing mHtt into the mouse brain, we confirmed that mHtt is removed more slowly in neurites than in the cytoplasm of the cell body of neurons. Our findings provide evidence for the cell type- and compartment-dependent degradation of mHtt and explain why mHtt preferentially accumulates and aggregates in the neuropils of vulnerable neurons. In addition, our findings suggest that enhancing proteasomal activity could be an effective way to reduce the preferential accumulation of soluble mHtt in neuronal processes.

SIGNIFICANCE STATEMENT The clearance of misfolded proteins is key to preventing neurodegeneration in Huntington's disease, but how mutant huntingtin (mHtt) accumulates differentially in different cell types and subcellular regions remains unclear. We found mHtt is cleared slowly in neuronal processes compared with the cytoplasm and is cleared more efficiently in astrocytes than in neurons. Moreover, this compartment-dependent degradation of soluble mHtt is mediated primarily by the ubiquitin-proteasome system rather than autophagy. Our findings imply that enhancing proteasome activity could be an efficient way to clear soluble misfolded proteins in the neuronal processes.

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Investigating mitochondrial redox state using NADH and NADPH autofluorescence

Publication date: Available online 9 August 2016
Source:Free Radical Biology and Medicine
Author(s): Thomas S. Blacker, Michael R. Duchen
The redox states of the NAD and NADP pyridine nucleotide pools play critical roles in defining the activity of energy producing pathways, in driving oxidative stress and in maintaining antioxidant defences. Broadly speaking, NAD is primarily engaged in regulating energy-producing catabolic processes, whilst NADP may be involved in both antioxidant defence and free radical generation. Defects in the balance of these pathways are associated with numerous diseases, from diabetes and neurodegenerative disease to heart disease and cancer. As such, a method to assess the abundance and redox state of these separate pools in living tissues would provide invaluable insight into the underlying pathophysiology. Experimentally, the intrinsic fluorescence of the reduced forms of both redox cofactors, NADH and NADPH, has been used for this purpose since the mid-twentieth century. In this review, we outline the modern implementation of these techniques for studying mitochondrial redox state in complex tissue preparations. As the fluorescence spectra of NADH and NADPH are indistinguishable, interpreting the signals resulting from their combined fluorescence, often labelled NAD(P)H, can be complex. We therefore discuss recent studies using fluorescence lifetime imaging microscopy (FLIM) which offer the potential to discriminate between the two separate pools. This technique provides increased metabolic information from cellular autofluorescence in biomedical investigations, offering biochemical insights into the changes in time-resolved NAD(P)H fluorescence signals observed in diseased tissues.



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Low dose dietary nitrate improves endothelial dysfunction and plaque stability in the ApoE-/- mouse fed a high fat diet

Publication date: Available online 9 August 2016
Source:Free Radical Biology and Medicine
Author(s): JR Bakker, NP Bondonno, TA Gaspari, BK Kemp-Harper, AJ McCashney, JM Hodgson, KD Croft, NC Ward
BackgroundNitric oxide (NO) is an important vascular signalling molecule. NO is synthesised endogenously by endothelial nitric oxide synthase (eNOS). An alternate pathway is exogenous dietary nitrate, which can be converted to nitrite and then stored or further converted to NO and used immediately. Atherosclerosis is associated with endothelial dysfunction and subsequent lesion formation. This is thought to arise due to a reduction in the bioavailability and/or bioactivity of endogenous NO.AimTo determine if dietary nitrate can protect against endothelial dysfunction and lesion formation in the ApoE^-/- mouse fed a high fat diet (HFD).Methods & ResultsApoE^-/- fed a HFD were randomized to receive (i) high nitrate (10mmol/kg/day, n=12), (ii) moderate nitrate (1mmol/kg/day, n=8), (iii) low nitrate (0.1mmol/kg/day, n=8), or (iv) sodium chloride supplemented drinking water (control, n=10) for 10 weeks. A group of C57BL6 mice (n=6) received regular water and served as a healthy reference group. At 10 weeks, ACh-induced vessel relaxation was significantly impaired in ApoE^-/- mice versus C57BL6. Mice supplemented with low or moderate nitrate showed significant improvements in ACh-induced vessel relaxation compared to ApoE^-/- mice given the high nitrate or sodium chloride. Plaque collagen expression was increased and lipid deposition reduced following supplementation with low or moderate nitrate compared to sodium chloride, reflecting increased plaque stability with nitrate supplementation. Plasma nitrate and nitrite levels were significantly increased in all three groups fed the nitrate-supplemented water.ConclusionLow and moderate dose nitrate significantly improved endothelial function and atherosclerotic plaque composition in ApoE^-/- mice fed a HFD.

Graphical abstract

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Super-Resolution Imaging for Monitoring Cytoskeleton Dynamics

Analyst, 2016, Accepted Manuscript
DOI: 10.1039/C6AN00731G, Critical Review

Solaire Finkenstaedt-Quinn, Tian Autumn Qiu, Kayeong Shin, Christy Haynes
The cytoskeleton is a key cellular structure that is important in the control of cellular movement, structure, and sensing. To successfully image the individual cytoskeleton components high resolution and super-resolution...
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Increased Obesity Resistance and Insulin Sensitivity in Mice Lacking the Isocitrate Dehydrogenase 2 Gene

Publication date: Available online 9 August 2016
Source:Free Radical Biology and Medicine
Author(s): Su Jeong Lee, Sung Hwan Kim, Kwon Moo Park, Jin Hyup Lee, Jeen-Woo Park
Reactive oxygen species (ROS) are a byproduct of normal metabolism and play important roles in cell signaling and homeostasis. Mitochondria, the main organelles involved in intracellular ROS production, play central roles in modulating redox-dependent cellular processes such as metabolism and apoptosis. We recently reported an important role for mitochondrial NADP⁺-dependent isocitrate dehydrogenase (IDH2) in cellular redox regulation. Here, we show that mice with targeted disruption of IDH2 exhibit resistance to obesity, with lower body weight and reduced visceral fat, and increased insulin sensitivity accompanied by enhanced energy expenditure relative to controls. This function of IDH2 is linked to its capacity to suppress lipogenesis in visceral adipose tissue, partly via transcriptional repression of SREBP1, and to increase thermogenesis in adipocytes by transcriptional activation of UCP1 via activation of the p38 signaling axis. Our results highlight the importance of redox balance in the regulation of metabolism and demonstrate that IDH2 plays a major role in modulating both insulin sensitivity and fuel metabolism, thereby establishing this protein as a potential therapeutic target in the treatment of type 2 diabetes and obesity.

Graphical abstract

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DUX4-inducedconstitutive DNA damage and oxidative stress contribute to aberrant differentiation of myoblasts from FSHD patients

Publication date: Available online 9 August 2016
Source:Free Radical Biology and Medicine
Author(s): Petr Dmitriev, Yara Bou Saada, Carla Dib, Eugénie Ansseau, Ana Barat, Aline Hamade, Philippe Dessen, Thomas Robert, Vladimir Lazar, Ruy A.N. Louzada, Corinne Dupuy, Vlada Zakharova, Gilles Carnac, Marc Lipinski, Yegor S. Vassetzky
Facioscapulohumeral dystrophy (FSHD) is one of the three most common muscular dystrophies in the Western world, however, its etiology remains only partially understood. Here, we provide evidence of constitutive DNA damage in in vitro cultured myoblasts isolated from FSHD patients and demonstrate oxidative DNA damage implication in the differentiation of these cells into phenotypically-aberrant myotubes. Double homeobox 4 (DUX4), the major actor in FSHD pathology induced DNA damage accumulation when overexpressed in normal human myoblasts, and RNAi-mediated DUX4 inhibition reduced the level of DNA damage in FSHD myoblasts. Addition of tempol, a powerful antioxidant, to the culture medium of proliferating DUX4-transfected myoblasts and FSHD myoblasts reduced the level of DNA damage, suggesting that DNA alterations are mainly due to oxidative stress. Antioxidant treatment during the myogenic differentiation of FSHD myoblasts significantly reduced morphological defects in myotube formation. We propose that the induction of DNA damage is a novel function of the DUX4 protein affecting myogenic differentiation of FSHD myoblasts.

Graphical abstract

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Thin-layer voltammetry of soluble species on screen-printed electrodes: Proof of concept

Analyst, 2016, Accepted Manuscript
DOI: 10.1039/C6AN01374K, Paper

Santiago Botasini, Arturo Marti, Eduardo Mendez
Thin-layer diffusion conditions were accomplished on screen-printed electrodes by placing a controlled-weight onto the cast solution and allowing for its natural spreading. The restricted diffusive conditions were assessed by cyclic...
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The Face-Processing Network Is Resilient to Focal Resection of Human Visual Cortex

Human face perception requires a network of brain regions distributed throughout the occipital and temporal lobes with a right hemisphere advantage. Present theories consider this network as either a processing hierarchy beginning with the inferior occipital gyrus (occipital face area; IOG-faces/OFA) or a multiple-route network with nonhierarchical components. The former predicts that removing IOG-faces/OFA will detrimentally affect downstream stages, whereas the latter does not. We tested this prediction in a human patient (Patient S.P.) requiring removal of the right inferior occipital cortex, including IOG-faces/OFA. We acquired multiple fMRI measurements in Patient S.P. before and after a preplanned surgery and multiple measurements in typical controls, enabling both within-subject/across-session comparisons (Patient S.P. before resection vs Patient S.P. after resection) and between-subject/across-session comparisons (Patient S.P. vs controls). We found that the spatial topology and selectivity of downstream ipsilateral face-selective regions were stable 1 and 8 month(s) after surgery. Additionally, the reliability of distributed patterns of face selectivity in Patient S.P. before versus after resection was not different from across-session reliability in controls. Nevertheless, postoperatively, representations of visual space were typical in dorsal face-selective regions but atypical in ventral face-selective regions and V1 of the resected hemisphere. Diffusion weighted imaging in Patient S.P. and controls identifies white matter tracts connecting retinotopic areas to downstream face-selective regions, which may contribute to the stable and plastic features of the face network in Patient S.P. after surgery. Together, our results support a multiple-route network of face processing with nonhierarchical components and shed light on stable and plastic features of high-level visual cortex following focal brain damage.

SIGNIFICANCE STATEMENT Brain networks consist of interconnected functional regions commonly organized in processing hierarchies. Prevailing theories predict that damage to the input of the hierarchy will detrimentally affect later stages. We tested this prediction with multiple brain measurements in a rare human patient requiring surgical removal of the putative input to a network processing faces. Surprisingly, the spatial topology and selectivity of downstream face-selective regions are stable after surgery. Nevertheless, representations of visual space were typical in dorsal face-selective regions but atypical in ventral face-selective regions and V1. White matter connections from outside the face network may support these stable and plastic features. As processing hierarchies are ubiquitous in biological and nonbiological systems, our results have pervasive implications for understanding the construction of resilient networks.

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Synchronous Spike Patterns in Macaque Motor Cortex during an Instructed-Delay Reach-to-Grasp Task

The computational role of spike time synchronization at millisecond precision among neurons in the cerebral cortex is hotly debated. Studies performed on data of limited size provided experimental evidence that low-order correlations occur in relation to behavior. Advances in electrophysiological technology to record from hundreds of neurons simultaneously provide the opportunity to observe coordinated spiking activity of larger populations of cells. We recently published a method that combines data mining and statistical evaluation to search for significant patterns of synchronous spikes in massively parallel spike trains (Torre et al., 2013). The method solves the computational and multiple testing problems raised by the high dimensionality of the data. In the current study, we used our method on simultaneous recordings from two macaque monkeys engaged in an instructed-delay reach-to-grasp task to determine the emergence of spike synchronization in relation to behavior. We found a multitude of synchronous spike patterns aligned in both monkeys along a preferential mediolateral orientation in brain space. The occurrence of the patterns is highly specific to behavior, indicating that different behaviors are associated with the synchronization of different groups of neurons ("cell assemblies"). However, pooled patterns that overlap in neuronal composition exhibit no specificity, suggesting that exclusive cell assemblies become active during different behaviors, but can recruit partly identical neurons. These findings are consistent across multiple recording sessions analyzed across the two monkeys.

SIGNIFICANCE STATEMENT Neurons in the brain communicate via electrical impulses called spikes. How spikes are coordinated to process information is still largely unknown. Synchronous spikes are effective in triggering a spike emission in receiving neurons and have been shown to occur in relation to behavior in a number of studies on simultaneous recordings of few neurons. We recently published a method to extend this type of investigation to larger data. Here, we apply it to simultaneous recordings of hundreds of neurons from the motor cortex of macaque monkeys performing a motor task. Our analysis reveals groups of neurons selectively synchronizing their activity in relation to behavior, which sheds new light on the role of synchrony in information processing in the cerebral cortex.

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GABAB Receptors Tune Cortical Feedback to the Olfactory Bulb

Sensory perception emerges from the confluence of sensory inputs that encode the composition of external environment and top-down feedback that conveys information from higher brain centers. In olfaction, sensory input activity is initially processed in the olfactory bulb (OB), serving as the first central relay before being transferred to the olfactory cortex. In addition, the OB receives dense connectivity from feedback projections, so the OB has the capacity to implement a wide array of sensory neuronal computation. However, little is known about the impact and the regulation of this cortical feedback. Here, we describe a novel mechanism to gate glutamatergic feedback selectively from the anterior olfactory cortex (AOC) to the OB. Combining in vitro and in vivo electrophysiological recordings, optogenetics, and fiber-photometry-based calcium imaging applied to wild-type and conditional transgenic mice, we explore the functional consequences of circuit-specific GABA type-B receptor (GABA_BR) manipulation. We found that activation of presynaptic GABA_BRs specifically depresses synaptic transmission from the AOC to OB inhibitory interneurons, but spares direct excitation to principal neurons. As a consequence, feedforward inhibition of spontaneous and odor-evoked activity of principal neurons is diminished. We also show that tunable cortico-bulbar feedback is critical for generating beta, but not gamma, OB oscillations. Together, these results show that GABA_BRs on cortico-bulbar afferents gate excitatory transmission in a target-specific manner and thus shape how the OB integrates sensory inputs and top-down information.

SIGNIFICANCE STATEMENT The olfactory bulb (OB) receives top-down inputs from the olfactory cortex that produce direct excitation and feedforward inhibition onto mitral and tufted cells, the principal neurons. The functional role of this feedback and the mechanisms regulating the balance of feedback excitation and inhibition remain unknown. We found that GABA_B receptors are expressed in cortico-bulbar axons that synapse on granule cells and receptor activation reduces the feedforward inhibition of spontaneous and odor-driven mitral and tufted cells' firing activity. In contrast, direct excitatory inputs to these principal neurons remain unchanged. This study demonstrates that activation of GABA_B receptors biases the excitation/inhibition balance provided by cortical inputs to the OB, leading to profound effects on early stages of sensory information processing.

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3D Visual Response Properties of MSTd Emerge from an Efficient, Sparse Population Code

Neurons in the dorsal subregion of the medial superior temporal (MSTd) area of the macaque respond to large, complex patterns of retinal flow, implying a role in the analysis of self-motion. Some neurons are selective for the expanding radial motion that occurs as an observer moves through the environment ("heading"), and computational models can account for this finding. However, ample evidence suggests that MSTd neurons exhibit a continuum of visual response selectivity to large-field motion stimuli. Furthermore, the underlying computational principles by which these response properties are derived remain poorly understood. Here we describe a computational model of macaque MSTd based on the hypothesis that neurons in MSTd efficiently encode the continuum of large-field retinal flow patterns on the basis of inputs received from neurons in MT with receptive fields that resemble basis vectors recovered with non-negative matrix factorization. These assumptions are sufficient to quantitatively simulate neurophysiological response properties of MSTd cells, such as 3D translation and rotation selectivity, suggesting that these properties might simply be a byproduct of MSTd neurons performing dimensionality reduction on their inputs. At the population level, model MSTd accurately predicts eye velocity and heading using a sparse distributed code, consistent with the idea that biological MSTd might be well equipped to efficiently encode various self-motion variables. The present work aims to add some structure to the often contradictory findings about macaque MSTd, and offers a biologically plausible account of a wide range of visual response properties ranging from single-unit selectivity to population statistics.

SIGNIFICANCE STATEMENT Using a dimensionality reduction technique known as non-negative matrix factorization, we found that a variety of medial superior temporal (MSTd) neural response properties could be derived from MT-like input features. The responses that emerge from this technique, such as 3D translation and rotation selectivity, spiral tuning, and heading selectivity, can account for a number of empirical results. These findings (1) provide a further step toward a scientific understanding of the often nonintuitive response properties of MSTd neurons; (2) suggest that response properties, such as complex motion tuning and heading selectivity, might simply be a byproduct of MSTd neurons performing dimensionality reduction on their inputs; and (3) imply that motion perception in the cortex is consistent with ideas from the efficient-coding and free-energy principles.

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Acute Stress Suppresses Synaptic Inhibition and Increases Anxiety via Endocannabinoid Release in the Basolateral Amygdala

Stress and glucocorticoids stimulate the rapid mobilization of endocannabinoids in the basolateral amygdala (BLA). Cannabinoid receptors in the BLA contribute to anxiogenesis and fear-memory formation. We tested for rapid glucocorticoid-induced endocannabinoid regulation of synaptic inhibition in the rat BLA. Glucocorticoid application to amygdala slices elicited a rapid, nonreversible suppression of spontaneous, but not evoked, GABAergic synaptic currents in BLA principal neurons; the effect was also seen with a membrane-impermeant glucocorticoid, but not with intracellular glucocorticoid application, implicating a membrane-associated glucocorticoid receptor. The glucocorticoid suppression of GABA currents was not blocked by antagonists of nuclear corticosteroid receptors, or by inhibitors of gene transcription or protein synthesis, but was blocked by inhibiting postsynaptic G-protein activity, suggesting a postsynaptic nongenomic steroid signaling mechanism that stimulates the release of a retrograde messenger. The rapid glucocorticoid-induced suppression of inhibition was prevented by blocking CB1 receptors and 2-arachidonoylglycerol (2-AG) synthesis, and it was mimicked and occluded by CB1 receptor agonists, indicating it was mediated by the retrograde release of the endocannabinoid 2-AG. The rapid glucocorticoid effect in BLA neurons in vitro was occluded by prior in vivo acute stress-induced, or prior in vitro glucocorticoid-induced, release of endocannabinoid. Acute stress also caused an increase in anxiety-like behavior that was attenuated by blocking CB1 receptor activation and inhibiting 2-AG synthesis in the BLA. Together, these findings suggest that acute stress causes a long-lasting suppression of synaptic inhibition in BLA neurons via a membrane glucocorticoid receptor-induced release of 2-AG at GABA synapses, which contributes to stress-induced anxiogenesis.

SIGNIFICANCE STATEMENT We provide a cellular mechanism in the basolateral amygdala (BLA) for the rapid stress regulation of anxiogenesis in rats. We demonstrate a nongenomic glucocorticoid induction of long-lasting suppression of synaptic inhibition that is mediated by retrograde endocannabinoid release at GABA synapses. The rapid glucocorticoid-induced endocannabinoid suppression of synaptic inhibition is initiated by a membrane-associated glucocorticoid receptor in BLA principal neurons. We show that acute stress increases anxiety-like behavior via an endocannabinoid-dependent mechanism centered in the BLA. The stress-induced endocannabinoid modulation of synaptic transmission in the BLA contributes, therefore, to the stress regulation of anxiety, and may play a role in anxiety disorders of the amygdala.

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Tonotopic Optimization for Temporal Processing in the Cochlear Nucleus

In the auditory system, sounds are processed in parallel frequency-tuned circuits, beginning in the cochlea. Auditory nerve fibers reflect this tonotopy and encode temporal properties of acoustic stimuli by "locking" discharges to a particular stimulus phase. However, physiological constraints on phase-locking depend on stimulus frequency. Interestingly, low characteristic frequency (LCF) neurons in the cochlear nucleus improve phase-locking precision relative to their auditory nerve inputs. This is proposed to arise through synaptic integration, but the postsynaptic membrane's selectivity for varying levels of synaptic convergence is poorly understood. The chick cochlear nucleus, nucleus magnocellularis (NM), exhibits tonotopic distribution of both input and membrane properties. LCF neurons receive many small inputs and have low input thresholds, whereas high characteristic frequency (HCF) neurons receive few, large synapses and require larger currents to spike. NM therefore presents an opportunity to study how small membrane variations interact with a systematic topographic gradient of synaptic inputs. We investigated membrane input selectivity and observed that HCF neurons preferentially select faster input than their LCF counterparts, and that this preference is tolerant of changes to membrane voltage. We then used computational models to probe which properties are crucial to phase-locking. The model predicted that the optimal arrangement of synaptic and membrane properties for phase-locking is specific to stimulus frequency and that the tonotopic distribution of input number and membrane excitability in NM closely tracks a stimulus-defined optimum. These findings were then confirmed physiologically with dynamic-clamp simulations of inputs to NM neurons.

SIGNIFICANCE STATEMENT One way that neurons represent temporal information is by phase-locking, which is discharging in response to a particular phase of the stimulus waveform. In the auditory system, central neurons are optimized to retain or improve phase-locking precision compared with input from the auditory nerve. However, the difficulty of this computation varies systematically with stimulus frequency. We examined properties that contribute to temporal processing both physiologically and in a computational model. Neurons processing low-frequency input benefit from integration of many weak inputs, whereas those processing higher frequencies progressively lose precision by integration of multiple inputs. Here, we reveal general features of input-output optimization that apply to all neurons that process time varying input.

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Cognitive impairment among patients with multiple sclerosis: associations with employment and quality of life

Objectives

To explore the relationship between cognitive impairment and conventional measures of disability in multiple sclerosis (MS), quality of life (QOL) and employment status using the brief international cognitive assessment for multiple sclerosis (BICAMS) in the routine outpatient clinic.

Methods

62 patients with MS were assessed on the BICAMS test battery for cognitive impairment. Data were obtained on employment status and a number of questionnaires completed including fatigue severity score, multiple sclerosis neuropsychological questionnaire, hospital anxiety and depression scale, the functional assessment of multiple sclerosis (FAMS) as well as on the EuroQOL five dimension questionnaire (EQ-5D). Other assessments include the patient activation measure and unidimensional self-efficacy scale for multiple sclerosis.

Results

Cognitive assessment revealed 44 subjects (65%) had evidence of cognitive impairment on formal testing. In comparison with patients without evidence of cognitive impairment, cognitively impaired patients exhibited significantly higher rates of unemployment (p=0.009). The symbol digits modalities test was the most significant predictor of unemployment. Cognitive impairment was associated with lower QOL scores on the FAMS (p=0.001) and EQ-5D (p<0.001).

Conclusions

BICAMS provides a sensitive and easy to administer screening test for cognitive impairment within the outpatient setting. Cognitive impairment is common in our cohort of patients with MS attending outpatients and appears to be associated with increased rates of unemployment and lower measures of QOL.

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Prehospital Application of the Canadian Triage and Acuity Scale by Emergency Medical Services

Research Articles
Murdoch Leeies, Cheryl ffrench, Trevor Strome, Erin Weldon, Michael Bullard, Rob Grierson
Canadian Journal of Emergency Medicine,FirstView Article(s), 6 pages

Abstract


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Letter to the editor: Progressive neurology in a young woman with a known Currarino’s triad

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Boston Sci’s EMBLEM MRI Subcutaneous Implantable Defibrillator FDA Approved

Boston Scientific won FDA approval for its EMBLEM MRI Subcutaneous Implantable Defibrillator (S-ICD), as well as retroactive magnetic resonance (MR) conditional labeling for already implanted EMBLEM S-ICDs. The new regulatory decision will allow patients sporting these devices to continue to be protected from cardiac arrest even while inside an MRI machine.

The new system includes SMART Pass technology, which can also be added to existing devices via a software update, that improves the accuracy of shock delivery so it's only done when necessary. Additionally, the new AF Monitor feature detects atrial fibrillation events and reports those to the patient's cardiologist for closer inspection.

Flashbacks: Subcutaneous Implantable Cardiac Defibrillator FDA Approved…

Product page: EMBLEM S-ICD…

Source: Boston Scientific…

This post Boston Sci's EMBLEM MRI Subcutaneous Implantable Defibrillator FDA Approved appeared first on Medgadget.

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‘Paramedic’ ranked by Tinder as fifth most attractive job to have in Fla.

LOS ANGELES — Single male paramedic? Think about making a trip to Florida, where "Paramedic" ranked on the Tinder dating app as the fifth most attractive profession for a man to have.

Tinder started allowing users to list their job in their dating profiles, and then used that information to create rankings of the jobs most likely to receive a favorable "right swipe."

Paramedics broke the top 10 rankings for most attractive jobs in a national sample earlier this year, but the Palm Beach Post reports that Florida medics beat police officers, physicians and even CEOs to claim the number five spot.

While female paramedics didn't make the list, women with professions in the medical and health fields like nurses, pharmacy technicians and psychologists counted for a total of five spots in the top 15.

Check out the full list below.

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Toward Biomarker Development in Large Clinical Cohorts: An Integrated High-Throughput 96-Well-Plate-Based Sample Preparation Workflow for Versatile Downstream Proteomic Analyses

Analytical Chemistry

DOI: 10.1021/acs.analchem.6b01333

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Normalizing surface electromyographic measures of the masticatory muscles: Comparison of two different methods for clinical purpose

Publication date: Available online 10 August 2016
Source:Journal of Electromyography and Kinesiology
Author(s): Andrea Mapelli, Gianluca Martino Tartaglia, Stephen Thaddeus Connelly, Virgilio Ferruccio Ferrario, Claudia Maria De Felicio, Chiarella Sforza
PurposeTo compare a new normalization technique (wax pad, WAX) with the currently utilized cotton roll (COT) method in surface electromyography (sEMG) of the masticatory muscles.MethodssEMG of the masseter and anterior temporalis muscles of 23 subjects was recorded while performing two repetitions of 5s maximum voluntary clenches (MVC) on COT and WAX. For each task, the mean value of sEMG amplitude and its coefficient of variation were calculated, and the differences between the two repetitions computed. The standard error of measurement (SEM) was calculated. For each subject and muscle, the COT-to-WAX maximum activity increment was computed. Participant preference between tasks was also recorded.ResultsWAX MVC tasks had larger maximum muscular activity than COT MVC tasks (P<0.001), with COT-to-WAX maximum activity increments of 61% (temporalis) and 94% (masseter) (P=0.006). WAX MVC had better test-retest repeatability than COT. For both MVC modalities, the mean amplitude (P>0.391) and its coefficient of variation were unchanged (P>0.180). The WAX task was the more comfortable for 18/23 subjects (P=0.007).ConclusionWAX normalization ensures the same stability level of maximum muscular activity as COT normalization, but it is more repeatable, elicits larger maximum muscular contraction, and is felt to be more comfortable by subjects.



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Human upper airway epithelium produces nitric oxide in response to Staphylococcus epidermidis

Background

Nitric oxide (NO) is produced by sinonasal epithelial cells as part of the innate immune response against bacteria. We previously described bitter-taste-receptor-dependent and -independent NO responses to product(s) secreted by Pseudomonas aeruginosa and Staphylococcus aureus, respectively. We hypothesized that sinonasal epithelium would be able to detect the gram-positive, coagulase-negative bacteria Staphylococcus epidermidis and mount a similar NO response.

Methods

Sinonasal air-liquid interface cultures were treated with conditioned medium (CM) from lab strains and clinical isolates of coagulase-negative staphylococci and S aureus. NO production was quantified by fluorescence imaging. Bitter taste receptor signaling inhibitors were utilized to characterize the pathway responsible for NO production in response to S epidermidis CM.

Results

S epidermidis CM contains a low-molecular-weight, heat, and protease-stabile product that induces an NO synthase (NOS)–mediated NO production that is less robust than the response triggered by S aureus CM. The S epidermidis CM–stimulated NO response is not inhibited by antagonists of phospholipase C isoform β-2 nor the transient receptor potential melastatin isoform 5 ion channel, both critical to bitter taste signaling.

Conclusion

This study identifies an NO-mediated innate defense response in sinonasal epithelium elicited by S epidermidis product(s). The active bacterial product is likely a small, nonpeptide molecule that stimulates a pathway independent of bitter taste receptors. Although the NO response to S epidermidis is less vigorous compared with S aureus, the product(s) share similar characteristics. Together, the responses to staphylococci species may help explain the pathophysiology of upper respiratory infections.

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Winter-training for Swedish ambulance crews:

To be good, you must train! In Norway, i did one weekend with instructor in car. 7 Km. ice-trac. To get speed up in safe way, and training on emergency drills, more. ( Norway = legal with 220 spikes per wheel, emergency vehicle. Normal is 110 )ExEMTNor

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Smooth is fast...

If no room to give way, better/faster to turn off lights and sirene. Place vehicle so you are seen, in mirror, and by meeting traffic. Timing is "everything", think faar ahead. Never get "trapped". Komments after my exam: We don`t follov the line-markings, -good progress on the motor-way ( I did not use all of the lines/space in a roundabout, could had litle more speed on apex (= faster out ) Leveled out at 190 Km.h. as "transport speed" on "empty" motor-way (= well under "construction-speed" vehicle.) Here driver-training for 2 intensive weeks, pluss one weekend at ice-trac ( Police plow upp tracs on mountainlakes around contry for training ) In Norway we can only take test 3 times in life, -not tallented enough if you need more. ExEMTNor

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Self-reported wellbeing and body image after abdominoperineal excision for rectal cancer

Abstract

Purpose

Patients with low rectal cancer are often operated with an abdominoperineal excision (APE) rendering them a permanent stoma. The surgical procedure itself, the cancer diagnosis, and the permanent stoma might all affect quality of life. The aim of this study was to explore wellbeing and body image 3 years after APE in a population-based cohort of patients.

Methods

All patients with rectal cancer operated with an APE between 2007 and 2009 were identified using the Swedish ColoRectal Cancer Registry. A total of 545 patients answered a questionnaire 3 years after surgery. Two open-ended questions were analyzed with a mixed method design using both qualitative and quantitative content analysis. Main themes and sub-themes on wellbeing and body image were identified.

Results

Three main themes were identified: bodily limitations, mental suffering, and acceptance. Bodily limitations included other symptoms than stoma-related problems. A majority of patients expressed acceptance to their situation regardless of bodily limitations and mental suffering. However, 18 % did not describe any acceptance of their current situation.

Conclusions

Most patients expressed acceptance reflecting wellbeing 3 years after APE for rectal cancer. There is, however, a subset of patients (18 %) who describe bodily limitations and mental suffering without acceptance and who require further support. Many aspects of the portrayed bodily limitations and mental suffering could be prevented or treated.

Trial registration

NCT01296984.

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15-Lipoxygenase-1 Is Involved in the Effects of Atorvastatin on Endothelial Dysfunction

Statins exert pleiotropic effects on endothelial cells in addition to lowering cholesterol. 15-Lipoxygenase-1 (ALOX15) has been implicated in vascular inflammation and disease. The relationship between atorvastatin and ALOX15 was investigated using a rat carotid artery balloon-injury model. Hematoxylin and eosin (HE) staining showed that ALOX15 overexpression increased the thickness of the intima-media (IMT). Immunohistochemistry and western blotting showed that atorvastatin increased the expression of cellular adhesion molecules (CAMs) but decreased the expression of endothelial nitric oxide synthase (eNOS); these effects of atorvastatin were blocked by ALOX15 overexpression. In human umbilical venous endothelial cells (HUVECs), silencing of ALOX15 enhanced the effects of atorvastatin on endothelial function. Expression levels of CAMs and Akt/eNOS/NO under oxidized low-density lipoprotein (ox-LDL) stimulation were modulated by ALOX15 inhibitor and ALOX15 small interfering RNA (siRNA). Atorvastatin abolished the activation of nuclear factor-kappa B (NF-κB) induced by ox-LDL. Exposure to ox-LDL induced upregulation of ALOX15 in HUVECs, but this effect was partially abolished by atorvastatin or the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). These results demonstrate that regulation of ALOX15 expression might be involved in the effects of atorvastatin on endothelial dysfunction.

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Fractional carbon dioxide laser versus low-dose UVA-1 phototherapy for treatment of localized scleroderma: a clinical and immunohistochemical randomized controlled study

Abstract

Morphea is a rare fibrosing skin disorder that occurs as a result of abnormal homogenized collagen synthesis. Fractional ablative laser resurfacing has been used effectively in scar treatment via abnormal collagen degradation and induction of healthy collagen synthesis. Therefore, fractional ablative laser can provide an effective modality in treatment of morphea. The study aimed at evaluating the efficacy of fractional carbon dioxide laser as a new modality for the treatment of localized scleroderma and to compare its results with the well-established method of UVA-1 phototherapy. Seventeen patients with plaque and linear morphea were included in this parallel intra-individual comparative randomized controlled clinical trial. Each with two comparable morphea lesions that were randomly assigned to either 30 sessions of low-dose (30 J/cm²) UVA-1 phototherapy (340–400 nm) or 3 sessions of fractional CO₂ laser (10,600 nm-power 25 W). The response to therapy was then evaluated clinically and histopathologically via validated scoring systems. Immunohistochemical analysis of TGF-ß1 and MMP1 was done. Patient satisfaction was also assessed. Wilcoxon signed rank test for paired (matched) samples and Spearman rank correlation equation were used as indicated. Comparing the two groups, there was an obvious improvement with fractional CO₂ laser that was superior to that of low-dose UVA-1 phototherapy. Statistically, there was a significant difference in the clinical scores (p = 0.001), collagen homogenization scores (p = 0.012), and patient satisfaction scores (p = 0.001). In conclusion, fractional carbon dioxide laser is a promising treatment modality for cases of localized morphea, with proved efficacy of this treatment on clinical and histopathological levels.

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Erratum to: Picosecond pulsed infrared laser tuned to amide I band dissociates polyglutamine fibrils in cells

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Association between rheumatoid arthritis and systemic mastocytosis: a case report and literature review

Abstract

Classically, mast cells (MC) are considered as important actors of the innate immune response playing a pivotal role in IgE-mediated allergic and antiparasite responses. In the last two decades, many experimental evidences demonstrated that these hematopoietic-derived cells present in both connective and mucosal tissues are also key modulators of the adaptive immune response and could contribute to autoimmune disease notably in rheumatoid arthritis (RA). Recently, Bader-Meunier et al. reported a series of 31 patients suffering from inflammatory joint diseases associated with mastocytosis, suggesting that mastocytosis was associated with a higher prevalence in spondyloarthritis. We discuss here the possible link between chronic inflammatory arthritis and mastocytosis through the report of a clinical case describing a patient developing RA after a long history of mastocytosis. Of great interest, antihistamine treatment alone was sufficient to treat RA in this patient.

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Analysis of the influence of 111 In on 90 Y-bremsstrahlung SPECT based on Monte Carlo simulation

Abstract

Objective

⁹⁰Y-ibritumomab tiuxetan (Zevalin) which is used for the treatment of malignant lymphomas can be used for SPECT imaging based on bremsstrahlung from ⁹⁰Y beta particles. However, gamma rays emitted by ¹¹¹In, which is administered to evaluate the indication for the treatment, contaminate the ⁹⁰Y bremsstrahlung images. Our objective is to investigate the influence of ¹¹¹In on the ⁹⁰Y SPECT images using Monte Carlo simulation.

Methods

We used an in-house developed simulation code for the Monte Carlo simulation of electrons and photons (MCEP). Two hot spheres with diameters of 40 mm were put in an elliptical phantom. Both spheres ("sphere 1" and "sphere 2") were filled with ⁹⁰Y and ¹¹¹In mixed solutions. The activities of ⁹⁰Y in sphere 1 and sphere 2 were 241 and 394 kBq/mL, respectively, and the ones of ¹¹¹In were 8.14 and 13.3 kBq/mL, respectively. The background activity of ⁹⁰Y was 38.6 kBq/mL, whereas that of ¹¹¹In was 1.30 kBq/mL; moreover, the acquisition time was 30 min. Two energy windows were used: one is 90–190 keV included the ¹¹¹In photopeak; the other is 90–160 keV. To evaluate the quality of the SPECT images, the contrast recovery coefficient (CRC) and the constant noise ratio (CNR) of the SPECT images were derived.

Results

For the energy window between 90 and 160 keV, the ¹¹¹In count was 74 % of the total. In that case, the CRC values were 30.1 and 30.7 % for "sphere 1" and "sphere 2", respectively, whereas the CNR values were 6.8 and 12.1, respectively. For the energy window between 90 and 190 keV, the ¹¹¹In count reached 85 % of the total count. The CRC and CNR values were 38.6 and 40.0 % and 10.6 and 19.4, respectively.

Conclusions

Our simulation study revealed that the cross talk between ¹¹¹In and ⁹⁰Y in SPECT imaging is rather serious. Even for the energy window excluding the ¹¹¹In photopeak, the count ratio of ⁹⁰Y was less than 30 % of the total. However, the influence of ¹¹¹In on ⁹⁰Y-SPECT imaging cannot be ignored, and the count ratio because of ¹¹¹In is important to estimate the density of ⁹⁰Y.

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Mass Development of Diazotrophic Cyanobacteria ( Nostocales ) and Production of Neurotoxic Anatoxin-a in a Planktothrix ( Oscillatoriales ) Dominated Temperate Lake

Abstract

In spite of extensive studies on multispecies toxigenic cyanobacterial blooms, they are still difficult to eliminate, and factors regulating their succession and toxin production remain still to discover. A 4-year study revealed periodical mass development of diazotrophic Nostocales such as Dolichospermum spp. (previously Anabaena), Aphanizomenon gracile and expansive Cuspidothrix (previously Aphanizomenon) issatschenkoi in a lake affected by perennial blooms of Planktothrix agardhii (Oscillatoriales). Compared to Oscillatoriales, Nostocales reached the highest total biomass (up to 16 mg L⁻¹) and contributed nearly 33–85 % to the total biomass of filamentous cyanobacteria at higher water temperatures (average values 17.5–22.6 °C) and higher ratio (11.8–14.1) of dissolved inorganic nitrogen to dissolved inorganic phosphorus (DIN/DIP). Species structure of Nostocales changed considerably from year to year as indicated by the Jaccard similarity index (0.33–0.78). Concentrations of intracellular anatoxin-a (ANTX) ranged from 0.03 to 2.19 μg L⁻¹ of the lake water, whilst extracellular toxin reached up to 0.55 μg L⁻¹. The highest positive correlations were found between the intracellular ANTX and the biomass of Dolichospermum spp. (R ² = 0.73) and C. issatschenkoi (R ² = 0.43–0.65). Our study suggests that ANTX production by Dolichospermum depended mainly on water temperature, whereas that by C. issatschenkoi was related to water conductivity and DIN/DIP ratio. P-PO₄ concentrations also seemed to be important. The relatively short-term mass development of neurotoxic Nostocales is an additional threat to shallow, highly eutrophic water bodies continuously affected by Oscillatoriales blooms and may be controlled mainly by the DIN/DIP ratio. ANTX should be considered as a pollutant of freshwaters.

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Hydrated Oil Shale Ash Mitigates Greenhouse Gas Emissions from Horizontal Subsurface Flow Filters for Wastewater Treatment

Abstract

Previous pilot-scale studies have shown outstanding levels of efficiency in phosphorus removal by using hydrated oil shale ash (HOSA) sediments in horizontal subsurface flow (HSSF) filters with low greenhouse gas emissions. However, no long-term full-scale experiment has been conducted using this material. From September 2013 to December 2015, two HSSF filters with different hydraulic loading regimes (NH1 with a stable loading regime and NH2 with a fluctuating regime), used to treat municipal wastewater, were analysed to estimate greenhouse gas (GHG) fluxes and to develop a treatment system with minimised GHG emissions. The fluxes of CO₂, CH₄ and N₂O, as well as their emission factors were significantly lower when compared with studies where regular filter materials (sand, gravel, etc.) are in use. The fluctuating loading regime significantly increased CO₂ and N₂O fluxes (median values of −3.3 and 2.6 mg CO₂−C m⁻² h⁻¹, and 5.7 and 8.6 μg N₂O−N m⁻² h⁻¹ for NH1 and NH2 regimes, respectively), whereas no impact could be seen on CH₄ emissions (median 93.3 and 95.6 μg CH₄−C m⁻² h⁻¹, for NH1 and NH2, respectively). All GHG emissions were strongly affected by the chemical composition of the water entering into the system. The water purification efficiency of the system was satisfactory for most water quality parameters and excellent for phosphorus. Thus, the HOSA-filled filters have a good potential for municipal wastewater treatment with low GHG emission.

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Real-time assessment of Streptococcus mutans biofilm metabolism on resin composite

Publication date: Available online 8 August 2016
Source:Dental Materials
Author(s): Fernando Luis Esteban Florez, Rochelle Denise Hiers, Kristin Smart, Jens Kreth, Fengxia Qi, Justin Merritt, Sharukh Soli Khajotia
ObjectiveThe release of unpolymerized monomers and by-products of resin composites influences biofilm growth and confounds the measurement of metabolic activity. Current assays to measure biofilm viability have critical limitations and are typically not performed on relevant substrates. The objective of the present study was to determine the utility of firefly luciferase assay for quantification of the viability of intact biofilms on a resin composite substrate, and correlate the results with a standard method (viable colony counts).MethodsDisk-shaped specimens of a dental resin composite were fabricated, wet-polished, UV-sterilized, and stored in water. Biofilms of Streptococcus mutans (strain UA159 modified by insertion of constitutively expressed firefly luc gene) were grown (1:500 dilution; anaerobic conditions, 24h, 37°C) in two media concentrations (0.35x and 0.65x THY medium supplemented with 0.1% sucrose; n=15/group). An additional group of specimens with biofilms grown in 0.65x+sucrose media was treated with chlorhexidine gluconate solution to serve as the control group. Bioluminescence measurements of non-disrupted biofilms were obtained after addition of d-Luciferin substrate. The adherent biofilms were removed by sonication, and bioluminescence of sonicated bacteria was then measured. Viable colony counts were performed after plating sonicated bacteria on THY agar plates supplemented with spectinomycin. Bioluminescence values and cell counts were correlated using Spearman correlation tests (α=0.05).ResultsStrong positive correlations between viable colony counts and bioluminescence values, both before- and after-sonication, validated the utility of this assay.SignificanceA novel non-disruptive, real-time bioluminescence assay is presented for quantification of intact S. mutans biofilms grown on a resin composite, and potentially on antibacterial materials and other types of dental biomaterials.



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A novel experimental approach to investigate the effect of different agitation methods using sodium hypochlorite as an irrigant on the rate of bacterial biofilm removal from the wall of a simulated root canal model

Publication date: Available online 8 August 2016
Source:Dental Materials
Author(s): Saif alarab Mohmmed, Morgana E. Vianna, Matthew R. Penny, Stephen T. Hilton, Nicola Mordan, Jonathan C. Knowles
ObjectiveRoot canal irrigation is an important adjunct to control microbial infection. This study aimed primarily to develop a transparent root canal model to study in situ Enterococcus faecalis biofilm removal rate and remaining attached biofilm using passive or active irrigation solution for 90s. The change in available chlorine and pH of the outflow irrigant were assessed.MethodsA total of forty root canal models (n=10 per group) were manufactured using 3D printing. Each model consisted of two longitudinal halves of an 18mm length simulated root canal with size 30 and taper 0.06. E. faecalis biofilms were grown on the apical 3mm of the models for 10days in Brain Heart Infusion broth. Biofilms were stained using crystal violet for visualization. The model halves were reassembled, attached to an apparatus and observed under a fluorescence microscope. Following 60s of 9mL of 2.5% NaOCl irrigation using syringe and needle, the irrigant was either left stagnant in the canal or activated using gutta-percha, sonic and ultrasonic methods for 30s. Images were then captured every second using an external camera. The residual biofilm percentages were measured using image analysis software. The data were analyzed using Kruskal–Wallis test and generalized linear mixed model.ResultsThe highest level of biofilm removal was with ultrasonic agitation (90.13%) followed by sonic (88.72%), gutta-percha (80.59%), and passive irrigation group (control) (43.67%) respectively. All agitation groups reduced the available chlorine and pH of NaOCl more than that in the passive irrigation group.SignificanceThe 3D printing method provided a novel model to create a root canal simulation for studying and understanding a real-time biofilm removal under microscopy. Ultrasonic agitation of NaOCl left the least amount of residual biofilm in comparison to sonic and gutta-percha agitation methods.



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Incidental paranasal sinusitis on routine brain magnetic resonance scans: association with atherosclerosis

Background

Incidental paranasal sinusitis (IPS) is common on imaging for non-sinusitis disorders, usually without symptoms or obstructive features, and possibly arising from periodontitis (PD). PD associations with atherosclerosis have been widely reported. We test if IPS may also be associated with atherosclerosis.

Methods

IPS was scored retrospectively in a random sample of 180 magnetic resonance (MR) brain scans and compared with chart review for atherosclerosis (all subtypes), rhinosinusitis, and related factors (smoking, asthma, and relevant surgery). IPS was scored out of 30, from all sinuses, with maxillary sinuses weighted double volumetrically. Significant IPS (Sig IPS) was designated as 6 or more out of 30. Bivariate logistic regression was used to test for associations of Sig IPS to the clinical data, with multivariate analysis then testing for potential confounders.

Results

A total of 173 subjects were analyzed (7 exclusions). MR indications included suspected acute/prior stroke (22.0%). Sig IPS found in 20 (11.6%). Positive histories for atherosclerosis were cerebral, 57 (32.9%); coronary, 48 (27.7%); and peripheral arterial disease, 14 (8.1%). IPS ≥6 was strongly associated with cerebrovascular disease (odds ratio [OR] 6.0, p < 0.001), and less robustly to smoking (OR 2.9, p = 0.07) and rhinosinusitis (OR 2.4, p = 0.09). No associations with coronary or peripheral artery diseases were found. After controlling for smoking and rhinosinusitis, yielding significant subclinical sinusitis, the link of Sig IPS to cerebrovascular disease persisted (modified OR 5.2, p = 0.002).

Conclusion

Significant incidental sinusitis, which is mostly subclinical sinusitis, is associated with cerebrovascular disease but not other atheroscleroses. This suggests possible common causation of both by PD.

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Paranasal sinus opacification-to-pneumatization ratio applied as a rapid and validated clinician assessment

Background

The utility of clinician-applied instruments, particularly the Lund-Mackay score, in the assessment of paranasal sinus computed tomography (CT) in chronic rhinosinusitis (CRS) remains incompletely defined. The purpose of this study was to determine if a new approach to the evaluation of sinus CT could accurately predict the extent of opacification while remaining simple for clinician use.

Methods

Twenty-four sinus CT scans were measured for the percent of sinus opacification using three-dimensional (3D) volumetric analyses. The same scans were also evaluated using the Lund-Mackay score to measure opacification and the Assessment of Pneumatization of the Paranasal Sinuses (APPS) score to measure total sinus volume (TSV). Correlation analysis was performed for the Lund-Mackay to APPS score ratio as a predictor of percent opacification. Validation analysis was also performed to determine the optimal orientation for Lund-Mackay scoring, which has not previously been described.

Results

The Lund-Mackay to APPS score ratio was very strongly correlated with the percentage of sinus opacification measured by 3D volumetric analysis (r = 0.862, r² = 0.743, p < 0.001). Lund-Mackay scoring was not statistically different between axial-only, coronal-only, or triplanar groups for interrater (p = 0.379) and intrarater reliability (p = 0.312).

Conclusion

The Lund-Mackay score is validated for rater reliability in multiple orientations. Using the APPS score as a measure of TSV, the Lund-Mackay-to-APPS ratio very strongly correlates with the percentage of sinus opacification by 3D volumetric analysis. Further study will be required to determine if this ratio is predictive of symptom severity.

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Reversible and irreversible emergence of chiroptical signals in J-aggregates of achiral 4-sulfonatophenyl substituted porphyrins: Intrinsic chirality vs. chiral ordering in the solution

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC05709H, Communication

Oriol Arteaga, Zoubir El-Hachemi, Adolf Canillas, Joaquim Crusats, Meritxell Rovira, Josep M. Ribo
Mueller matrix polarimetry distinguishes the different origin of the reversible and irreversible chiroptical effects emerging in stirred solutions of J-aggregate nanoparticles: the reversible effect is due to an anisotropic ordering...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Quantitative analysis of mucosal oxygenation using ex vivo imaging of healthy and inflamed mammalian colon tissue

Abstract

Colonic inflammation is associated with decreased tissue oxygenation, significantly affecting gut homeostasis. However, the crosstalk between O₂ consumption and supply in the inflamed tissue are not fully understood. Using a murine model of colitis, we analysed O₂ in freshly prepared samples of healthy and inflamed colon tissue. We developed protocols for efficient ex vivo staining of mouse distal colon mucosa with a cell-penetrating O₂ sensitive probe Pt-Glc and high-resolution imaging of O₂ concentration in live tissue by confocal phosphorescence lifetime-imaging microscopy (PLIM). Microscopy analysis revealed that Pt-Glc stained mostly the top 50–60 μm layer of the mucosa, with high phosphorescence intensity in epithelial cells. Measured O₂ values in normal mouse tissue ranged between 5 and 35 μM (4–28 Torr), tending to decrease in the deeper tissue areas. Four-day treatment with dextran sulphate sodium (DSS) triggered colon inflammation, as evidenced by an increase in local IL6 and mKC mRNA levels, but did not affect the gross architecture of colonic epithelium. We further observed an increase in oxygenation, partial activation of hypoxia inducible factor (HIF) 1 signalling, and negative trends in pyruvate dehydrogenase activity and O₂ consumption rate in the colitis mucosa, suggesting a decrease in mitochondrial respiration, which is known to be regulated via HIF-1 signalling and pyruvate oxidation rate. These results along with efficient staining with Pt-Glc of rat and human colonic mucosa reveal high potential of PLIM platform as a powerful tool for the high-resolution analysis of the intestinal tissue oxygenation in patients with inflammatory bowel disease and other pathologies, affecting tissue respiration.

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Winter-training for Swedish ambulance crews:

To be good, you must train! In Norway, i did one weekend with instructor in car. 7 Km. ice-trac. To get speed up in safe way, and training on emergency drills, more. ExEMTNor

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Smooth is fast...

If no room to give way, better/faster to turn off lights and sirene. Place vehicle so you are seen, in mirror, and by meeting traffic. Timing is "everything", think faar ahead. Never get "trapped". Komments after my exam: We don`t follov the line-markings, -good progress on the motor-way ( I did not use all of the lines/space in a roundabout, could had litle more speed on apex (= faster out ) Leveled out at 190 Km.h. as "transport speed" on "empty" motor-way (= well under "construction-speed" vehicle.) Here driver-training for 2 intensive weeks, pluss one weekend at ice-trac ( Police plow upp tracs on mountainlakes around contry for training ) In Norway we can only take test 3 times in life, -not tallented enough if you need more. ExEMTNor

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