Photodegradation using TiO 2 -activated borosilicate tubes

Abstract

This study examines the photocatalytic activity of titanium dioxide (TiO₂) semiconductor supported on borosilicate tubes (cut-off 290 nm) towards removal of a mix of persistent organic pollutants (POPs) from water. For this purpose, two widely used analgesic and anti-inflammatory drugs (NSAIDs), ibuprofen (IBU) and mefenamic acid, along with MCPA sodium monohydrate, which is a common herbicide frequently used in the agricultural activities, were selected as a case study. Borosilicate tubes were coated with titanium oxide through two different approaches: sol-gel dip-coating and a hybrid nanoparticle dip-coating and plasma-enhanced chemical vapour deposition (PECVD) process. The photochemical reactor that hosts the titania-coated tubes was designed to permit continuous throughput of liquid feed stream. The photodegradation experiments were performed in laboratory conditions under artificial irradiation simulating solar light. The efficiency of direct photolysis and heterogeneous photocatalysis (TiO₂) was investigated, and the performance of each coating method was evaluated. Kinetic studies for each experiment were accomplished, the overall results showed poor efficiency and insufficient removal for NSAIDs through direct photolysis, whereas applying heterogeneous photacatalysis with TiO₂ coated on borosilicate tubes was found to accelerate their degradation rate with complete decomposition. Concomitantly, kinetic experimental results showed a critical difference of performance for the two coating methods used; in particular, the degradation rates of pollutants by the sol-gel-coated tubes were much faster than the degradation by the nanoparticle/PECVD-coated tubes. Using TiO₂ supported on borosilicate tubes appears to be a promising alternative to conventional TiO₂ suspension and avoid post-separation stages. The results achieved in this study can be used to optimise large-scale applications, and expanding the study to cover a wide range of pollutants will lead to achieve more representative results.

An Unusual Finding During Robotic-Assisted Laparoscopic Radical Prostatectomy

Schistosomiasis haematobiumperitoneal schistosomiasisrobotic-assisted laparoscopic radical prostatectomy

In the Literature

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Ecological risk assessment of potentially toxic elements (PTEs) in the soil-plant system after reclamation of dredged sediment

Abstract

The Shayinghe River is an important tributary of the Huaihe River in China. The concentrations of potential toxic elements (PTEs), such as As, Hg, Pb, Cu, Zn, Cr, and Cd in soils and dominant vegetation from mud-dumping areas reclaimed with dredged sediments, and areas without mud-dumping (non-mud-dumping areas) adjacent to the Shayinghe River were investigated. The potential ecological risk index (ERI) and transfer coefficient (TC) were calculated and evaluated. The results showed that the potential toxic element concentrations in all sampling areas decreased in the order of (Zn, Cr) > (Cu, Pb) > As>Cd > Hg. Additionally, the total concentrations of the PTEs significantly increased from mud-dumping to the non-mud-dumping areas. Ecological risk assessment of soils showed that all the elements did not exhibit apparent ecological risks (except for As). This element exhibited a moderate ecological risk, implying that the dredging of sediments could increase the potential ecological risk of individual PTEs. Additionally, the PTEs in some of dominant plants in mud-dumping areas did not increase, indicating no apparent accumulation. The principal component analysis (PCA) showed that the principal components of the PTEs in plants from dredged sediments were different from those in the agricultural soil, indicating the influence of dredging on PTEs. Finally, Cd, Zn, and Hg had higher transfer coefficients (up to 6), even if their concentrations were relatively low, suggesting potential ecological risks to the plants.

Research on the ecological efficiency of the Yangtze River Delta region in China from the perspective of sustainable development of the economy-energy-environment (3E) system

Abstract

Balancing the relationship between economic development, energy utilization, and environmental protection has become an important task in China's Strip Planning and Construction. This article takes the annual panel data from 2005 to 2015 as the research object firmly grasps the research basis of the Economy-Energy-Environment (3E) System, and focuses on building a new research framework from both internal and external perspectives of the eco-efficiency index to achieve the exploratory research on regional ecological efficiency changes and influencing factors. First of all, it uses super-efficient slacks-based measure (SBM) model which introduces undesired outputs to measure eco-efficiency at different levels. Then, it applies Malmquist index to calculate total factor productivity and structural efficiencies. Finally, it selects six indicators and uses the STIRPAT regression model to analyze external factors. The results indicate that (1) the overall ecological efficiency is effective and maintaining a good momentum of development. Among all the cities and provinces, Shanghai and Zhejiang provinces play the role of "stabilizers," while Jiangsu and Anhui provinces act as "accelerators." (2) All 41 prefecture-level cities can be divided into four different types, i.e., "high-high", "low-high", "low-low," and "high-low" cities, and there is an obvious phenomenon of spatial clustering; (3) pure technical efficiency and scale efficiency is the core driving force for the improvement of ecological efficiency. (4) Anhui and Jiangsu provinces show a U-shaped relationship, while Zhejiang province shows an inverted U-shaped relationship.

Graphical abstract

The structure of introduction-body paragraphs-conclusion carbon

Quality of life with talazoparib versus physician’s choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial

Abstract

Background

In the EMBRACA phase III trial, talazoparib (1 mg daily, orally) demonstrated a statistically significant improvement in PFS versus physician's choice of chemotherapy (PCT; capecitabine, eribulin, gemcitabine, or vinorelbine) in patients with HER2-negative advanced breast cancer carrying a germline BRCA1/2 mutation; we evaluated patient-reported outcomes (PROs).

Patients and methods

Patients were randomized 2 : 1 to receive talazoparib or PCT. PROs were assessed at day 1 (baseline), the start of each treatment cycle (every 3 weeks), and at the end of treatment, using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-30) and its breast cancer module, QLQ-BR23. Prespecified exploratory analyses included a longitudinal mixed-effect model comparing treatment arms and a time to definitive clinically meaningful deterioration (TTD) analysis carried out in the global health status/quality of life (GHS/QoL), and all functional and symptom scales from the EORTC QLQ-C30 and -BR23 questionnaires. Between-arm TTD comparisons were made using a stratified log-rank test and a Cox proportional hazards model.

Results

Baseline scores were similar between arms. Statistically significant estimated overall improvement from baseline in GHS/QoL was seen for talazoparib compared with statistically significant deterioration for PCT {3.0 [95% confidence interval (CI) 1.2, 4.8] versus −5.4 [95% CI −8.8, −2.0]; between arms, P < 0.0001}. A statistically significant greater delay was observed in TTD in GHS/QoL, favoring talazoparib over PCT [hazard ratio, 0.38 (95% CI 0.26, 0.55; median, 24.3 versus 6.3 months, respectively; P < 0.0001)]. A statistically significant overall change and a statistically significant delay in TTD, all favoring talazoparib, were also observed in multiple functions and symptoms.

Conclusion

Patients who received talazoparib had significant overall improvements and significant delay in TTD in multiple cancer-related and breast cancer-specific symptoms, functions, and GHS/QoL.

ClinicalTrials.gov

NCT01945775.

Multipurpose efficacy of the lyophilized cell-free supernatant of Salmonella bongori isolated from the freshwater fish, Devario aequipinnatus: toxicity against microbial pathogens and mosquito vectors

Abstract

Presently, the discovery of effective drugs and pesticides from eco-friendly biological sources is an important challenge in the field of life sciences. The present research was aimed for standardizing an innovative approach in the evaluation of the biological potentiality of the metabolites of fish-associated bacteria. We have identified 17 skin-associated bacteria from the freshwater fish, giant danio, Devario aquipinnatus. They were screened through biofilm forming and extracellular enzyme producing ability. The results of preliminary antibacterial evaluation of the bacterial supernatants underlined the importance of three potential strains (BH8, BH10 and BH11) for further applied research. Hence, such strains were subsequently subjected to a novel extraction procedure to overcome the difficulties found in polar solvents mixed with the supernatant. The lyophilized cell-free supernatant (LCFS) of 3 isolates were individually extracted by using methanol. During the testing of LCFS's methanolic extract (LCFS-ME) of 3 isolates, only the extract of BH11-strain exhibited potent inhibitory activity against the pathogenic bacteria and fungi. Furthermore, the larvicidal and mosquitocidal assays on the filariasis vector, Culex quinquefasciatus also showed its potent toxicity on both the adults and developmental instars of mosquito. Through molecular and phylogenetic analyses, the BH11 strain was identified as Salmonella bongori (KR350635). The present finding emphasized that the S. bongori could be an important novel source of effective antimicrobials and mosquitocidal agents.

Efficacy and safety of DFN-11 (sumatriptan injection, 3 mg) in adults with episodic migraine: an 8-week open-label extension study

DFN-11, a 3 mg sumatriptan subcutaneous (SC) autoinjector for acute treatment of migraine, has not been assessed previously in multiple attacks. The objective of this study was to evaluate the efficacy, tolera...

Efficacy and safety of DFN-11 (sumatriptan injection, 3 mg) in adults with episodic migraine: a multicenter, randomized, double-blind, placebo-controlled study

In a previous randomized, double-blind, proof-of-concept study in rapidly escalating migraine, a 3 mg dose of subcutaneous sumatriptan (DFN-11) was associated with fewer and shorter triptan sensations than a 6...

Complement C3 Inhibition Modulates Neurodegeneration in Chronic Traumatic Brain Injury

Ventral Hippocampal Inputs Preferentially Drive Corticocortical Neurons in the Infralimbic Prefrontal Cortex

Inputs from the ventral hippocampus (vHPC) to the prefrontal cortex (PFC) play a key role in working memory and emotional control. However, little is known about how excitatory inputs from the vHPC engage different populations of neurons in the PFC. Here we use optogenetics and whole-cell recordings to study the cell-type specificity of synaptic connections in acute slices from the mouse PFC. We first show that vHPC inputs target pyramidal neurons whose cell bodies are located in layer (L)2/3 and L5 of infralimbic (IL) PFC, but only in L5 of prelimbic (PL) PFC, and not L6 of either IL or PL. We then compare connections onto different classes of projection neurons located in these layers and subregions of PFC. We establish vHPC inputs similarly contact corticocortical (CC) and cortico-amygdala neurons in L2/3 of IL, but preferentially target CC neurons over cortico-pontine neurons in L5 of both IL and PL. Of all these neurons, we determine that vHPC inputs are most effective at driving action potential (AP) firing of CC neurons in L5 of IL. We also show this connection exhibits frequency-dependent facilitation, with repetitive activity enhancing AP firing of IL L5 CC neurons, even in the presence of feedforward inhibition. Our findings reveal how vHPC inputs engage defined populations of projection neurons in the PFC, allowing preferentially activation of the intratelencephalic network.

SIGNIFICANCE STATEMENT We examined the impact of connections from the ventral hippocampus (vHPC) onto different projection neurons in the mouse prefrontal cortex (PFC). We found vHPC inputs were strongest at corticocortical neurons in layer 5 of infralimbic PFC, where they robustly evoked action potential firing, including during repetitive activity with intact feedforward inhibition.

The Successor Representation: Its Computational Logic and Neural Substrates

Reinforcement learning is the process by which an agent learns to predict long-term future reward. We now understand a great deal about the brain's reinforcement learning algorithms, but we know considerably less about the representations of states and actions over which these algorithms operate. A useful starting point is asking what kinds of representations we would want the brain to have, given the constraints on its computational architecture. Following this logic leads to the idea of the successor representation, which encodes states of the environment in terms of their predictive relationships with other states. Recent behavioral and neural studies have provided evidence for the successor representation, and computational studies have explored ways to extend the original idea. This paper reviews progress on these fronts, organizing them within a broader framework for understanding how the brain negotiates tradeoffs between efficiency and flexibility for reinforcement learning.

Increased Prefrontal Activity with Aging Reflects Nonspecific Neural Responses Rather than Compensation

Elevated prefrontal cortex activity is often observed in healthy older adults despite declines in their memory and other cognitive functions. According to one view, this activity reflects a compensatory functional posterior-to-anterior shift, which contributes to maintenance of cognitive performance when posterior cortical function is impaired. Alternatively, the increased prefrontal activity may be less efficient or less specific because of structural and neurochemical changes accompanying aging. These accounts are difficult to distinguish on the basis of average activity levels within brain regions. Instead, we used a novel, model-based multivariate analysis technique applied to two independent fMRI datasets from an adult-lifespan human sample (N = 123 and N = 115; approximately half female). Standard analysis replicated the age-related increase in average prefrontal activation, but multivariate tests revealed that this activity did not carry additional information. The results contradict the hypothesis of a compensatory posterior-to-anterior shift. Instead, they suggest that the increased prefrontal activation reflects reduced efficiency or specificity rather than compensation.

SIGNIFICANCE STATEMENT Functional brain imaging studies have often shown increased activity in prefrontal brain regions in older adults. This has been proposed to reflect a compensatory shift to greater reliance on prefrontal cortex (PFC), helping to maintain cognitive function. Alternatively, activity may become less specific as people age. This is a key question in the neuroscience of aging. In this study, we used novel tests of how different brain regions contribute to long- and short-term memory. We found increased activity in PFC in older adults, but this activity carried less information about memory outcomes than activity in visual regions. These findings are relevant for understanding why cognitive abilities decline with age, suggesting that optimal function depends on successful brain maintenance rather than compensation.

Neuronal Correlates of Serial Decision-Making in the Supplementary Eye Field

Human behavior is influenced by serial decision-making: past decisions affect choices that set the context for selecting future options. A primate brain region that may be involved in linking decisions across time is the supplementary eye field (SEF), which, in addition to its well known visual responses and saccade-related activity, also signals the rules that govern flexible decisions and the outcomes of those decisions. Our hypotheses were that SEF neurons encode events during serial decision-making and link the sequential decisions with sustained activity. We recorded from neurons in the SEF of two rhesus monkeys (Macaca mulatta, one male, one female) that performed a serial decision-making task. The monkeys used saccades to select a rule that had to be applied later in the same trial to discriminate between visual stimuli. We found, first, that SEF neurons encoded the spatial parameters of saccades during rule selection but not during visual discrimination, suggesting a malleability to their movement-related tuning. Second, SEF activity linked the sequential decisions of rule selection and visual discrimination, but not continuously. Instead, rule-encoding activity appeared in a "just-in-time" manner before the visual discrimination. Third, SEF neurons encoded trial outcomes both prospectively, before decisions within a trial, and retrospectively, across multiple trials. The results thus identify neuronal correlates of rule selection and application in the SEF, including transient signals that link these sequential decisions. Its activity patterns suggest that the SEF participates in serial decision-making in a contextually dependent manner as part of a broader network.

SIGNIFICANCE STATEMENT Much research has gone into studying the neurobiological basis of single, isolated decisions. An important next step is to understand how the brain links multiple decisions to generate a coherent stream of thought and behavior. We studied neural activity related to serial decision-making in an area of frontal cortex known as the supplementary eye field (SEF). Neural recordings were conducted in monkeys that performed a serial decision-making task in which they selected and applied rules. We found that SEF neurons convey signals for serial decision-making, including transient encoding of one decision at the time it is needed for the next one and longer-term representations of trial outcomes, suggesting that the region plays a role in continuity of cognition and behavior.

Quantitative Association of Anatomical and Functional Classes of Olfactory Bulb Neurons

Juxtaglomerular cells (JGCs) of the olfactory bulb (OB) glomerular layer (GL) play a fundamental role in olfactory information processing. Their variability in morphology, physiology, and connectivity suggests distinct functions. The quantitative understanding of population-wise morphological and physiological properties and a comprehensive classification based on quantitative parameters, however, is still lacking, impeding the analysis of microcircuits. Here, we provide multivariate clustering of 95 in vitro sampled cells from the GL of the mouse (male or female C57BL/6) OB and perform detailed morphological and physiological characterization for the seven computed JGC types. Using a classifier based on a subselection of parameters, we identified the neuron types in paired recordings to characterize their functional connectivity. We found that 4 of the 7 clusters comply with prevailing concepts of GL cell types, whereas the other 3 represent own distinct entities. We have labeled these entities horizontal superficial tufted cell (hSTC), vertical superficial tufted cell, and microglomerular cell (MGC): The hSTC is a tufted cell with a lateral dendrite that much like mitral cells and tufted cells receives excitatory inputs from the external tufted cell but likewise serves as an excitatory element for glomerular interneurons. The vertical superficial tufted cell, on the other hand, represents a tufted cell type with vertically projecting basal dendrites. We further define the MGC, characterized by a small dendritic tree and plateau action potentials. In addition to olfactory nerve-driven and external tufted cell driven interneurons, these MGCs represent a third functionally distinct type, the hSTC-driven interneurons. The presented correlative analysis helps to bridge the gap between branching patterns and cellular functional properties, permitting the integration of results from in vivo recordings, advanced morphological tools, and connectomics.

SIGNIFICANCE STATEMENT The variance of neuron properties is a feature across mammalian cerebral circuits, contributing to signal processing and adding computational robustness to the networks. It is particularly noticeable in the glomerular layer of the olfactory bulb, the first site of olfactory information processing. We provide the first unbiased population-wise multivariate analysis to correlate morphological and physiological parameters of juxtaglomerular cells. We identify seven cell types, including four previously described neuron types, and identify further three distinct classes. The presented correlative analysis of morphological and physiological parameters gives an opportunity to predict morphological classes from physiological measurements or the functional properties of neurons from morphology and opens the way to integrate results from in vivo recordings, advanced morphological tools, and connectomics.

Modulating Regional Motor Cortical Excitability with Noninvasive Brain Stimulation Results in Neurochemical Changes in Bilateral Motor Cortices

Learning a novel motor skill is dependent both on regional changes within the primary motor cortex (M1) contralateral to the active hand and also on modulation between and within anatomically distant but functionally connected brain regions. Interregional changes are particularly important in functional recovery after stroke, when critical plastic changes underpinning behavioral improvements are observed in both ipsilesional and contralesional M1s. It is increasingly understood that reduction in GABA in the contralateral M1 is necessary to allow learning of a motor task. However, the physiological mechanisms underpinning plasticity within other brain regions, most importantly the ipsilateral M1, are not well understood. Here, we used concurrent two-voxel magnetic resonance spectroscopy to simultaneously quantify changes in neurochemicals within left and right M1s in healthy humans of both sexes in response to transcranial direct current stimulation (tDCS) applied to left M1. We demonstrated a decrease in GABA in both the stimulated (left) and nonstimulated (right) M1 after anodal tDCS, whereas a decrease in GABA was only observed in nonstimulated M1 after cathodal stimulation. This GABA decrease in the nonstimulated M1 during cathodal tDCS was negatively correlated with microstructure of M1:M1 callosal fibers, as quantified by diffusion MRI, suggesting that structural features of these fibers may mediate GABA decrease in the unstimulated region. We found no significant changes in glutamate. Together, these findings shed light on the interactions between the two major network nodes underpinning motor plasticity, offering a potential framework from which to optimize future interventions to improve motor function after stroke.

SIGNIFICANCE STATEMENT Learning of new motor skills depends on modulation both within and between brain regions. Here, we use a novel two-voxel magnetic resonance spectroscopy approach to quantify GABA and glutamate changes concurrently within the left and right primary motor cortex (M1) during three commonly used transcranial direct current stimulation montages: anodal, cathodal, and bilateral. We also examined how the neurochemical changes in the unstimulated hemisphere were related to white matter microstructure between the two M1s. Our results provide insights into the neurochemical changes underlying motor plasticity and may therefore assist in the development of further adjunct therapies.

Cerebellar Processing Common to Delay and Trace Eyelid Conditioning

Results from previous lesion studies have been interpreted as evidence that the cerebellar cortex plays different roles for delay and trace conditioning of eyelid responses. However, the cerebellar cortex is organized by parasagittal stripes of Purkinje cells (PCs) that converge onto common deep nucleus neurons and receive common or related climbing fiber inputs. Based on this organization, we hypothesized that cerebellar tasks involving the same response system, such as delay and trace eyelid conditioning, would engage the same PCs and that the relationships between PC activity and expression of behavioral responses would be similar for both tasks. To test these hypotheses, we used tetrode recordings from eyelid PCs in rabbits during expression of delay- and trace-conditioned eyelid responses. Previous recording studies during delay conditioning described a strong relationship between eyelid PC activity and the kinematics of conditioned eyelid responses. The present results replicate these findings for delay conditioning and show that the same relationship exists during trace eyelid conditioning. During transitions from delay to trace responding, the relationship between eyelid PCs and behavioral responses was relatively stable. We found that an inverse firing rate model tuned to predict PC activity during one training paradigm could then predict equally well the PC activity during the other training paradigm. These results provide strong evidence that cerebellar cortex processing is similar for delay and trace eyelid conditioning and that the parasagittal organization of the cerebellum, not the conditioning paradigm, dictate which neurons are engaged to produce adaptively timed conditioned responses.

SIGNIFICANCE STATEMENT A variety of evidence from eyelid conditioning and other cerebellar-dependent behaviors indicates that the cerebellar cortex is necessary for learning and proper timing of cerebellar learned responses. Debates exist about whether trace eyelid conditioning data show that fundamentally different mechanisms operate in the cerebellum during tasks when input from the forebrain is necessary for learning. We show here that learning-related changes in a specific population of Purkinje cells control the timing and amplitude of cerebellar responses the same way regardless of the inputs necessary to learn the task. Our results indicate the parasagittal organization of the cerebellar cortex, not the complexity of inputs to the cerebellum, determines which neurons are engaged in the learning and execution of cerebellar-mediated responses.

This Week in The Journal

Gating of Sensory Input at Subcortical and Cortical Levels during Grasping in Humans

Afferent input from the periphery to the cortex contributes to the control of grasping. How sensory input is gated along the ascending sensory pathway and its functional role during gross and fine grasping in humans remain largely unknown. To address this question, we assessed somatosensory-evoked potential components reflecting activation at subcortical and cortical levels and psychophysical tests at rest, during index finger abduction, precision, and power grip. We found that sensory gating at subcortical level and in the primary somatosensory cortex (S1), as well as intracortical inhibition in the S1, increased during power grip compared with the other tasks. To probe the functional relevance of gating in the S1, we examined somatosensory temporal discrimination threshold by measuring the shortest time interval to perceive a pair of electrical stimuli. Somatosensory temporal discrimination threshold increased during power grip, and higher threshold was associated with increased intracortical inhibition in the S1. These novel findings indicate that humans gate sensory input at subcortical level and in the S1 largely during gross compared with fine grasping. Inhibitory processes in the S1 may increase discrimination threshold to allow better performance during power grip.

SIGNIFICANCE STATEMENT Most of our daily life actions involve grasping. Here, we demonstrate that gating of afferent input increases at subcortical level and in the primary somatosensory cortex (S1) during gross compared with fine grasping in intact humans. The precise timing of sensory information is critical for human perception and behavior. Notably, we found that the ability to perceive a pair of electrical stimuli, as measured by the somatosensory temporal discrimination threshold, increased during power grip compared with the other tasks. We propose that reduced afferent input to the S1 during gross grasping behaviors diminishes temporal discrimination of sensory processes related, at least in part, to increased inhibitory processes within the S1.

Abnormal Low-Frequency Oscillations Reflect Trait-Like Pain Ratings in Chronic Pain Patients Revealed through a Machine Learning Approach

Measures of moment-to-moment fluctuations in brain activity of an individual at rest have been shown to be a sensitive and reliable metric for studying pathological brain mechanisms across various chronic pain patient populations. However, the relationship between pathological brain activity and clinical symptoms are not well defined. Therefore, we used regional BOLD signal variability/amplitude of low-frequency oscillations (LFOs) to identify functional brain abnormalities in the dynamic pain connectome in chronic pain patients that are related to chronic pain characteristics (i.e., pain intensity). Moreover, we examined whether there were sex-specific attributes of these functional brain abnormalities and whether functional brain abnormalities in patients is related to pain intensity characteristics on different time scales. We acquired resting-state functional MRI and quantified frequency-specific regional LFOs in chronic pain patients with ankylosing spondylitis. We found that patients exhibit frequency-specific aberrations in LFOs. Specifically, lower-frequency (slow-5) abnormalities were restricted to the ascending pain pathway (thalamus and S1), whereas higher-frequency abnormalities also included the default mode (i.e., posterior cingulate cortex; slow-3, slow-4) and salience (i.e., mid-cingulate cortex) networks (slow-4). Using a machine learning approach, we found that these abnormalities, in particular within higher frequencies (slow-3), can be used to make generalizable inferences about patients' average pain ratings (trait-like pain) but not current (i.e., state-like) pain levels. Furthermore, we identified sex differences in LFOs in patients that were not present in healthy controls. These novel findings reveal mechanistic brain abnormalities underlying the longer-lasting symptoms (trait pain intensity) in chronic pain.

SIGNIFICANCE STATEMENT Measures of moment-to-moment fluctuations in brain activity of an individual at rest have been shown to be a reliable metric for studying functional brain associated with chronic pain. The current results demonstrate that dysfunction in these intrinsic fluctuations/oscillations in the ascending pain pathway, default mode network, and salience network during resting state display sex differences and can be used to make inferences about trait-like pain intensity ratings in chronic pain patients. These results provide robust and generalizable implications for investigating brain mechanisms associated with longer-lasting/trait-like chronic pain symptoms.

Archaeal Unfoldase Counteracts Protein Misfolding Retinopathy in Mice

Deregulation of cellular proteostasis due to the failure of the ubiquitin proteasome system to dispose of misfolded aggregation-prone proteins is a hallmark of various neurodegenerative diseases in humans. Microorganisms have evolved to survive massive protein misfolding and aggregation triggered by heat shock using their protein-unfolding ATPases (unfoldases) from the Hsp100 family. Because the Hsp100 chaperones are absent in homoeothermic mammals, we hypothesized that the vulnerability of mammalian neurons to misfolded proteins could be mitigated by expressing a xenogeneic unfoldase. To test this idea, we expressed proteasome-activating nucleotidase (PAN), a protein-unfolding ATPase from thermophilic Archaea, which is homologous to the 19S eukaryotic proteasome and similar to the Hsp100 family chaperones in rod photoreceptors of mice. We found that PAN had no obvious effect in healthy rods; however, it effectively counteracted protein-misfolding retinopathy in G₁ knock-out mice. We conclude that archaeal PAN can rescue a protein-misfolding neurodegenerative disease, likely by recognizing misfolded mammalian proteins.

SIGNIFICANCE STATEMENT This study demonstrates successful therapeutic application of an archaeal molecular chaperone in an animal model of neurodegenerative disease. Introducing the archaeal protein-unfolding ATPase proteasome-activating nucleotidase (PAN) into the retinal photoreceptors of mice protected these neurons from the cytotoxic effect of misfolded proteins. We propose that xenogeneic protein-unfolding chaperones could be equally effective against other types of neurodegenerative diseases of protein-misfolding etiology.

Closed-Loop Slow-Wave tACS Improves Sleep-Dependent Long-Term Memory Generalization by Modulating Endogenous Oscillations

Benefits in long-term memory retention and generalization have been shown to be related to sleep-dependent processes, which correlate with neural oscillations as measured by changes in electric potential. The specificity and causal role of these oscillations, however, are still poorly understood. Here, we investigated the potential for augmenting endogenous slow-wave (SW) oscillations in humans with closed-loop transcranial alternating current stimulation (tACS) with an aim toward enhancing the consolidation of recent experiences into long-term memory. Sixteen (three female) participants were trained presleep on a target detection task identifying targets hidden in complex visual scenes. During post-training sleep, closed-loop SW detection and stimulation were used to deliver tACS matching the phase and frequency of the dominant oscillation in the range of 0.5–1.2 Hz. Changes in performance were assessed the following day using test images that were identical to the training ("repeated"), and images generated from training scenes but with novel viewpoints ("generalized"). Results showed that active SW tACS during sleep enhanced the postsleep versus presleep target detection accuracy for the generalized images compared with sham nights, while no significant change was found for repeated images. Using a frequency-agnostic clustering approach sensitive to stimulation-induced spectral power changes in scalp EEG, this behavioral enhancement significantly correlated with both a poststimulation increase and a subsequent decrease in measured spectral power within the SW band, which in turn showed increased coupling with spindle amplitude. These results suggest that augmenting endogenous SW oscillations can enhance consolidation by specifically improving generalization over recognition or cued recall.

SIGNIFICANCE STATEMENT This human study demonstrates the use of a closed-loop noninvasive brain stimulation method to enhance endogenous neural oscillations during sleep with the effect of improving consolidation of recent experiences into long-term memory. Here we show that transient slow oscillatory transcranial alternating current stimulation (tACS) triggered by endogenous slow oscillations and matching their frequency and phase can increase slow-wave power and coupling with spindles. Further, this increase correlates with overnight improvements in generalization of recent training to facilitate performance in a target detection task. We also provide novel evidence for a tACS-induced refractory period following the tACS-induced increase. Here slow-wave power is temporarily reduced relative to sham stimulation, which nonetheless maintains a positive relationship with behavioral improvements.

Large-Scale, High-Resolution Comparison of the Core Visual Object Recognition Behavior of Humans, Monkeys, and State-of-the-Art Deep Artificial Neural Networks

Primates, including humans, can typically recognize objects in visual images at a glance despite naturally occurring identity-preserving image transformations (e.g., changes in viewpoint). A primary neuroscience goal is to uncover neuron-level mechanistic models that quantitatively explain this behavior by predicting primate performance for each and every image. Here, we applied this stringent behavioral prediction test to the leading mechanistic models of primate vision (specifically, deep, convolutional, artificial neural networks; ANNs) by directly comparing their behavioral signatures against those of humans and rhesus macaque monkeys. Using high-throughput data collection systems for human and monkey psychophysics, we collected more than one million behavioral trials from 1472 anonymous humans and five male macaque monkeys for 2400 images over 276 binary object discrimination tasks. Consistent with previous work, we observed that state-of-the-art deep, feedforward convolutional ANNs trained for visual categorization (termed DCNN_IC models) accurately predicted primate patterns of object-level confusion. However, when we examined behavioral performance for individual images within each object discrimination task, we found that all tested DCNN_IC models were significantly nonpredictive of primate performance and that this prediction failure was not accounted for by simple image attributes nor rescued by simple model modifications. These results show that current DCNN_IC models cannot account for the image-level behavioral patterns of primates and that new ANN models are needed to more precisely capture the neural mechanisms underlying primate object vision. To this end, large-scale, high-resolution primate behavioral benchmarks such as those obtained here could serve as direct guides for discovering such models.

SIGNIFICANCE STATEMENT Recently, specific feedforward deep convolutional artificial neural networks (ANNs) models have dramatically advanced our quantitative understanding of the neural mechanisms underlying primate core object recognition. In this work, we tested the limits of those ANNs by systematically comparing the behavioral responses of these models with the behavioral responses of humans and monkeys at the resolution of individual images. Using these high-resolution metrics, we found that all tested ANN models significantly diverged from primate behavior. Going forward, these high-resolution, large-scale primate behavioral benchmarks could serve as direct guides for discovering better ANN models of the primate visual system.

Neuropathic Pain Creates an Enduring Prefrontal Cortex Dysfunction Corrected by the Type II Diabetic Drug Metformin But Not by Gabapentin

Chronic pain patients suffer from pain-related cognitive deficits, even when taking commonly prescribed analgesics. These deficits are likely related to pain-related maladaptive plasticity in the frontal cortex. We sought to model cognitive deficits in mice with neuropathic pain to examine maladaptive morphological plasticity in the mPFC and to assess the effects of several therapeutics. We used an attentional set-shifting task in mice with spared nerve injury (SNI) who received either a single intrathecal injection of an analgesic dose of clonidine, 7 d of 100 mg/kg gabapentin, or 7 d of 200 mg/kg metformin. Male SNI mice were significantly more impaired in the set-shifting task than females. This deficit correlated with a loss of parvalbumin (PV) and reductions in axon initial segment (AIS) length in layers 5/6 of the infralimbic (IL) cortex. Acute pain relief with clonidine had no effect on set-shifting performance, whereas pain relief via 7 day treatment with gabapentin worsened the impairment in both SNI and sham mice. Gabapentin reversed the PV loss in the IL but had no effect on AIS length. Treatment with the AMPK-activator metformin completely reversed the pain-related cognitive impairment and restored AIS length in the IL but had little effect on PV expression. Our findings reveal that neuropathic pain-related cognitive impairments in male mice are correlated to bilateral morphological changes in PV interneurons and layer 5/6 IL pyramidal neuron AIS. Pain relief with metformin can reverse some of the functional and anatomical changes.

SIGNIFICANCE STATEMENT Cognitive impairments are a comorbidity of neuropathic pain but are inadequately addressed by existing therapeutics. We used a neuropathic pain model in mice to demonstrate that male (but not female) mice show a robust pain-related deficit in attentional set-shifting, which is associated with structural plasticity in axon initial segments in the infralimbic cortex. These deficits were completely reversed by 7 day treatment with the antidiabetic drug metformin, suggesting that this drug can be repurposed for the treatment of neuropathic pain and its cognitive comorbidities. Our findings have implications for our understanding of how neuropathic pain causes structural plasticity in the brain, and they point to a marked sexual dimorphism in neuropathic pain mechanisms in mice.

Emergence of an Adaptive Command for Orienting Behavior in Premotor Brainstem Neurons of Barn Owls

The midbrain map of auditory space commands sound-orienting responses in barn owls. Owls precisely localize sounds in frontal space but underestimate the direction of peripheral sound sources. This bias for central locations was proposed to be adaptive to the decreased reliability in the periphery of sensory cues used for sound localization by the owl. Understanding the neural pathway supporting this biased behavior provides a means to address how adaptive motor commands are implemented by neurons. Here we find that the sensory input for sound direction is weighted by its reliability in premotor neurons of the midbrain tegmentum of owls (male and female), such that the mean population firing rate approximates the head-orienting behavior. We provide evidence that this coding may emerge through convergence of upstream projections from the midbrain map of auditory space. We further show that manipulating the sensory input yields changes predicted by the convergent network in both premotor neural responses and behavior. This work demonstrates how a topographic sensory representation can be linearly read out to adjust behavioral responses by the reliability of the sensory input.

SIGNIFICANCE STATEMENT This research shows how statistics of the sensory input can be integrated into a behavioral command by readout of a sensory representation. The firing rate of midbrain premotor neurons receiving sensory information from a topographic representation of auditory space is weighted by the reliability of sensory cues. We show that these premotor responses are consistent with a weighted convergence from the topographic sensory representation. This convergence was also tested behaviorally, where manipulation of stimulus properties led to bidirectional changes in sound localization errors. Thus a topographic representation of auditory space is translated into a premotor command for sound localization that is modulated by sensory reliability.

Correction: Sepers et al., "Endocannabinoid-Specific Impairment in Synaptic Plasticity in Striatum of Huntington's Disease Mouse Model"

Resolution of Atypical Lichen Myxedematosus After Sofosbuvir-Velpatasvir Treatment for Hepatitis C

This case report describes a patient with lichen myxedematosus that resolved after sofosbuvir-velpatasvir treatment for hepatitis C infection.

A Case of Pigmented Longitudinal Melanonychia

A man in his 40s presented to the dermatology clinic for evaluation of a dark brown longitudinal pigment band covering his left second toenail; the lesion appeared 12 months prior, had been growing, and was asymptomatic. What is your diagnosis?

Safety Risk of Dermatoscope Magnets in Patients With Cardiovascular Implanted Electronic Devices

This observational cross-sectional study assesses the magnets in 3 different dermatoscopes to determine their ability to disrupt the functionality of pacemakers, defibrillators, and other implanted devices in patients.

Aprepitant for the Treatment of Pruritus in Sézary Syndrome

This randomized clinical trial assesses whether treatment with the neurokinin 1 receptor antagonist aprepitant decreases pruritus vs placebo in patients with Sézary syndrome.

Self-reported Patient Motivations for Seeking Cosmetic Procedures

This multicenter observational study assesses the importance of self-reported factors that motivate patients to undergo minimally invasive cosmetic surgical procedures.

Interpretation of Melanocytic Lesions in the Digital Era vs Traditional Microscopy

This study of 87 pathologists compares the use of digital whole-slide imaging vs traditional microscopy in pathologists' ability to accurately interpret melanocytic lesions and reproduce correct diagnoses.

Correction to: Discussion of Shue et al. “Fat Injection: A Systemic Review of Injection Volumes by Facial Subunit”

Dino Elyassnia was left off the original version of this article. The author line is correct here.

Announcement: A New Section Entitled Technology Pearls

Publication date: September 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 3

Author(s):

Dermatology Calendar

Publication date: September 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 3

Author(s):

Daily oxymetazoline cream demonstrates high and sustained efficacy in patients with persistent erythema of rosacea through 52 weeks of treatment

Publication date: September 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 3

Author(s): Michael H. Gold, Mark Lebwohl, Brian S. Biesman, Deanne Mraz Robinson, Lei Luo, David R. Berk, Gurpreet Ahluwalia, Nancy Alvandi

Reply to: “Comment on ‘Prognostic value of sentinel lymph node biopsy according to Breslow thickness for cutaneous melanoma’”

Publication date: September 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 3

Author(s): Evan Stiegel, Alok Vij

Comment on “Prognostic value of sentinel lymph node biopsy according to Breslow thickness for cutaneous melanoma”

Publication date: September 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 3

Author(s): Elizabeth Greenwald, Tracey N. Liebman, David Polsky, Jennifer A. Stein

Reply to: “Serum vitamin D level and disease severity of alopecia areata: A meta-regression analysis”

Publication date: September 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 3

Author(s): Tsung-Yu Tsai, Yu-Chen Huang

Serum vitamin D level and disease severity of alopecia areata: A meta-regression analysis

Publication date: September 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 3

Author(s): Chun-An Yao

Thromboprophylaxis and thalidomide in the noncancer setting: Toward an algorithm that is based on patient risk factors and underlying disease?

Publication date: September 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 3

Author(s): François Chasset, Laurent Arnaud, Camille Francès

Thalidomide and thromboprophylaxis for dermatologic indications: An unmet need for more evidence

Publication date: September 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 3

Author(s): Anuradha Bishnoi, Vaneet Singh, Sanjeev Handa, Keshavamurthy Vinay

Response to “Vitamin D deficiency in patients with alopecia areata: A systematic review and meta-analysis” and an investigation of vitamin D in pediatric patients

Publication date: September 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 3

Author(s): Elana Putterman, Leslie Castelo-Soccio

Tacking sutures to shrink surgical defects near free margins

Publication date: September 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 3

Author(s): Stephanie Bayers, Kishwer S. Nehal, Rajiv I. Nijhawan

Dose escalation of doxepin for intractable pruritus

Publication date: September 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 3

Author(s): Kristen M. Beck, Eric J. Yang, John Koo

Ethical challenges with treating nonadherent patients in a group practice setting

Publication date: September 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 3

Author(s): Benjamin Freemyer, Benjamin Stoff

Effect of psoriatic arthritis on ixekizumab clinical outcomes in moderate-to-severe psoriasis patients: A post hoc analysis

Publication date: September 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 3

Author(s): Alice B. Gottlieb, Kim A. Papp, Charles A. Birbara, Catherine L. Shuler, Russel Burge, Janelle Erickson, Lisa Kerr, Philip J. Mease

Bioimpedance measurement as an assessment of margin positivity in Mohs surgical specimens of nonmelanoma skin cancer: Management implications

Publication date: September 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 3

Author(s): Ryan M. Svoboda, Manish J. Gharia, John Shell, William D. Gregory

Clinical, dermoscopic, and trichoscopic analysis of frontal fibrosing alopecia associated with acquired dermal macular hyperpigmentation: A cross sectional observational case-control study

Publication date: September 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 3

Author(s): Muthu Sendhil Kumaran, Muhammed Razmi T, Keshavamurthy Vinay, Davinder Parsad

An effective game-based learning intervention for improving melanoma recognition

Publication date: September 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 3

Author(s): Amit Sharma, Muneeb Ilyas, Nishita Maganty, Nan Zhang, Mark R. Pittelkow

Type I pityriasis rubra pilaris treated with tumor necrosis factor inhibitors, ustekinumab, or secukinumab: A review

Publication date: September 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 3

Author(s): Nolan J. Maloney, Lisa D. Hisaw, Scott Worswick

Skin cancer prevention messages on Facebook: Likes, shares, and comments

Publication date: September 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 3

Author(s): Adi Nosrati, Matthew A. Pimentel, Ashley Falzone, Roshini Hegde, Shilpa Goel, Mary-Margaret Chren, Rachel Eye, Eleni Linos, Sherry Pagoto, Barbara J. Walkosz

Inflammatory response and cytokine levels induced by intralesional photodynamic therapy and 630-nm laser in a case series of basal cell carcinoma

Publication date: September 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 3

Author(s): María Jesús Suárez-Valladares, Sara María Calleja-Antolín, Jose María García Ruíz de Morales, Manuel Angel Rodríguez Prieto, Jesús Vega-Gutierrez

A Pilot Study to Evaluate the Effects of Topically Applied Cosmetic Creams on Epidermal Responses

Application of exogenous products, such as creams, to the skin can result in subclinical changes in selected epidermal functions such as transepidermal water loss (TEWL), hydration, redness, and pH; these changes may lead to or contribute to irritation. Changes in skin surface inflammatory factors may provide further insight into this potential for irritation. The objective of this study was to evaluate the changes in epidermal properties and inflammatory mediators after 4 days of topical application of 2 different polymers formulated in cosmetic creams. Ten healthy volunteers (mean age ± SD: 20.0 ± 2.4 years) completed the study. TEWL, color, and pH were not significantly different after repeated application of these polymers. Hydration was significantly lower at sites treated with polymer A after 5 days. Significant increases in IL-1α, IL-1RA, and IL-1β were observed after cream application at sites treated with polymer A. This is the first study to apply noninvasive measurements to quantify subclinical changes in epidermal properties and inflammatory mediator expression before and after the application of a cosmetic product, which will allow for a more enhanced safety profile to be achieved.
Skin Pharmacol Physiol 2018;31:269–282

Epidermal Lamellar Granules

In the mid-1950s and 1960s, transmission electron microscopes became widely available, leading to many studies of the ultrastructure of various tissues including the epidermis. Most of these studies involved tissue fixation with formaldehyde and postfixation with osmium tetroxide. A few studies employed freeze-fracture electron microscopy. One set of these studies identified a small organelle variously called lamellar granules (LGs), lamellar bodies, membrane-coating granules, cementsomes, and Odland bodies. LGs are round to ovoid in shape, with a diameter of about 200 nm. They have a bounding membrane surrounding a stack of internal lipid lamellae. These small organelles are first seen in the spinous layer and accumulate with differentiation in the granular layer. In the uppermost granular cells, the bounding membrane of the LG fuses into the cell plasma membrane, and the internal contents are extruded into the intercellular space. The initially extruded contents of the LG then rearrange to form the intercellular lamellae of the stratum corneum. In this context, LGs serve as the precursor to the permeability barrier of the skin. Various studies have provided evidence that they are derived from the Golgi apparatus, specifically the trans-Golgi. Isolated LGs contain phosphoglycerides, sphingomyelin, and glucosylceramides. The most unusual lipid component is a linoleate-containing glucosylceramide comprising 30- to 34-carbon ω-hydroxy­acids. Isolated granules also contain acid hydrolases including glucocerebrosidase, sphingomyelinase, and phospholipase A. They also contain proteases and antimicrobial peptides. Defective LGs have been associated with a number of skin diseases including ichthyotic conditions and defective barrier function. Recently, studies employing cryo-transmission electron microscopy have called into question the validity of observations on LGs with more conventional electron microscopic techniques. These studies suggest a continuity of the membrane structure from the Golgi through the intercellular lamellae of the stratum corneum.
Skin Pharmacol Physiol 2018;31:262–268

Encapsulation of cinnamon essential oil in whey protein enhances the protective effect against single or combined sub-chronic toxicity of fumonisin B 1 and/or aflatoxin B 1 in rats

Abstract

Fumonisin B₁ (FB₁) and aflatoxin B₁ (AFB₁) are fungal metabolites that frequently co-occur in foodstuffs and are responsible for mycotoxicosis and several primary cancers. Cinnamon essential oil (CEO) has a spacious range of benefit effects but also has some limitations owing to its strong taste or its interaction with some drugs. This study aimed to use the cinnamon oil emulsion droplets (COED) for the protection against oxidative stress, cytotoxicity, and reproductive toxicity in male Sprague-Dawley rats sub-chronically exposed to FB₁ and/or AFB₁. The composition of CEO was identified using GC-MS then was encapsulated using whey protein as wall material. Male rats were divided into eight groups and treated orally for 8 weeks as follows: control group, AFB₁-trreated group (80 μg/kg b.w), FB₁-treated group (100 mg/kg b.w), FB₁ plus AFB₁-treated group, and the groups treated with COED plus FB₁ and/or AFB₁. Blood and samples of the kidney, liver, and testis were collected for different analysis and histopathological examination. The GC-MS analysis revealed that cinnamaldehyde, α-copaene, trans-cinnamaldehyde, caryophyllene, and delta-cadinene were the main compounds in COE. The average size of COED was 235 ± 1.4 nm and the zeta potential was − 6.24 ± 0.56. Treatment with FB₁ and/or AFB₁ induced significant disturbances in the serum biochemical analysis, oxidative stress parameters, DNA fragmentation, gene expression, and testosterone and severe pathological changes in the tested organs. Moreover, treatment with both mycotoxins induced synergistic toxic effects. COED did not induce toxic effects and could normalize the majority of the tested parameters and improve the histological picture in rats treated with FB₁ and/or AFB₁. It could be concluded that COED induce potential protective effects against the single or combined exposure to FB₁ and AFB₁.

A prospective diagnostic study on povidone–iodine retention in lesions suspected to be squamous cell carcinoma or keratoacanthoma

Australasian Journal of Dermatology, EarlyView.

Complete resolution and periodic recurrence of multiple postradiation atypical vascular lesions

Australasian Journal of Dermatology, EarlyView.

Subungual Bowen disease. Complete remission 14 years post‐photodynamic therapy (PDT)

Australasian Journal of Dermatology, EarlyView.

Rapamycin for refractory discoid lupus erythematosus

Dermatologic Therapy, EarlyView.

Manganese tolerance in Verbascum olympicum Boiss. affecting elemental uptake and distribution: changes in nicotinic acid levels under stress conditions

Abstract

A multielemental determination methodology in conjunction with an organic acid analysis that were supplemented with other stress parameters and an ultrastructural analysis used herein to study Verbascum olympicum Boiss. (Scrophulariaceae) under Mn stress. Uptake and accumulation characteristics of B, Cu, Fe, Mn, Mo, and Zn were evaluated in 8-week-old seedlings grown in Hoagland's nutrient solution and exposed to 5 (CK), 50, and 200 μM MnSO₄ for 7 days. Hydrogen peroxide levels were determined to evaluate oxidative stress, and changes in compatible substance levels (total phenolic contents, glutathione and glutathione disulfide levels) were determined to assess antioxidant defense mechanisms. The distribution of manganese on the root surface was characterized by scanning electron microscopy images and energy-dispersive X-ray spectroscopy analysis. The levels of nicotinic acid, which is involved in nicotinamide adenine dinucleotide biosynthesis, were determined in roots and leaves to assess tolerance mechanisms. V. olympicum exhibited the ability to cope with oxidative stress originating from excessive Mn, while increased Mn concentrations were observed in both roots and leaves. The translocation factor of B was the most affected among other studied elements under the experimental conditions. Total nicotinic acid levels exhibited a trend of reduction in the roots and leaves, which could be attributed to the appropriate metabolic progress associated with oxidative stress based on the nicotinamide adenine dinucleotide cycle that may reach glutathione in response to manganese stress during plant growth.