Mg–Fe layered double hydroxide assembled on biochar derived from rice husk ash: facile synthesis and application in efficient removal of heavy metals

Abstract

The pollution of toxic and persistent heavy metals commonly exist in water environment; such multi-component pollutants pose a serious threat to human beings and other organisms. Herein, to make full use of the advantages of both layered double hydroxide (LDH) and rice husk ash (RHA), a novel Mg–Fe-LDH-RHA functional material was synthesized by assembling LDH on the biochar derived from RHA and used as an adsorbent for removal of heavy metal ions including Pb²⁺, Cu²⁺, Co²⁺, Ni²⁺, Zn²⁺, and Cd²⁺. The adsorption kinetics and isotherms of heavy metal ions in a mono-component system, the adsorption capacities in mixed multi-metal ion system, and the regeneration of the adsorbent were studied in detail. The results showed that the synthesized Mg–Fe-LDH-RHA might efficiently remove the above six heavy metals in water under optimized experimental conditions. Interestingly, the removal performance toward Pb(II) showed high static distribution coefficients (K_d) of ~ 10⁷ mL/g and maximum capacity of ~ 682 mg/g. Besides, further characterizations of the adsorbent have been conducted, and the result suggested the formation of abundant functional groups including hydroxyl, carbonyl, and carboxyl groups. The removal mechanism of the metal ions might be related to ion-exchange, surface precipitation, complexation, and hydrogen binding during the interactions between the LDH-RHA material and pollutants. Such a facile and environmentally friendly approach, efficient removal performance suggests that the LDH-RHA material thus has potential for efficient removal of heavy metals in practical application.

A multi-criteria sustainability assessment framework: development and application in comparing two food waste management options using a UK region as a case study

Abstract

Preventing food wastage is a key element of sustainable resource management. But as food waste is still generated at high volumes, priority is placed on its proper management as a resource, maximising sustainability benefits. This study, by integrating a multi-criteria decision analysis with a sustainability assessment approach, develops a screening and decision support framework for comparing the sustainability performance of food waste management options. A structured process for selecting criteria based on the consideration of environmental, economic and social aspects related to region-specific food waste system planning, policy and management has been developed. Two food waste management options, namely the use of food waste disposal units, which grind food waste at the household's kitchen sink and discharge it to the sewer, and the anaerobic co-digestion of separately collected food waste with sewage sludge, were selected for comparison due to their potential to create synergies between local authorities, waste and water companies, with local circumstances determining which of the two options to adopt. A simplified process used for assessing and comparing the two food waste management options in the Anglian region in the UK, indicated that there are benefits in using the framework as a screening tool for identifying which option may be the most sustainable. To support decision-making, a detailed analysis that incorporates stakeholders' perspectives is required. An additional use of the framework can be in providing recommendations for optimising food waste management options in a specific region, maximising their sustainability performance.

Combustion performance and exhaust emissions fuelled with non-surfactant water-in-diesel emulsion fuel made from different water sources

Abstract

Non-surfactant water-in-diesel emulsion fuel (NWD) is an alternative fuel that has the potential to reduce major exhaust emissions while simultaneously improving the combustion performance of a diesel engine. NWD comprises of diesel fuel and water (about 5% in volume) without any additional surfactants. This emulsion fuel is produced through an in-line mixing system that is installed very close to the diesel engine. This study focuses mainly on the performance and emission of diesel engine fuelled with NWD made from different water sources. The engine used in this study is a direct injection diesel engine with loads varying from 1 to 4 kW. The result shows that NWD made from tap water helps the engine to reduce nitrogen oxide (NO_x) by 32%. Rainwater reduced it by 29% and seawater by 19%. In addition, all NWDs show significant improvements in engine performance as compared to diesel fuel, especially in the specific fuel consumption that indicates an average reduction of 6%. It is observed that all NWDs show compelling positive effects on engine performance, which is caused by the optimum water droplet size inside NWD.

Trace element contaminant uptake in phytocap vegetation and implications for koala habitat, Lismore, Australia

Abstract

Phytocapping is increasingly regarded as an economical and environmentally sustainable post-closure landfill management strategy. During 2013, a phytocap comprised of koala habitat trees was established on a historic landfill site in Lismore as part of an Australian trial program (A-ACAP). This case study was conducted to determine trace element contamination of the Lismore phytocap soil and foliage, and identify risks to grazing koalas. Foliage of Eucalyptus tereticornis, a key koala food tree, and Acacia melanoxylon, a reference native species, were assessed at the phytocap and an uncontaminated reference site. Concentrations of Ag, As, Hg and Pb were significantly higher in foliage from the phytocap compared to that from the reference site (p < 0.0001_{df 7, 52}). Mean trace element concentrations in phytocap E. tereticornis foliage were compliant with state and international standards for contaminants in food and animal feed (NSW State Government, 2010; WHO and FAO, 2015) and soil was compliant with national health-based investigation levels for contaminated sites (NEPC, 2011). However, contaminant distribution was not homogenous, and As and Pb concentrations exceeded guidelines in some soil and foliage samples. Based on available guidelines and weekly dietary intake calculations, risks to koala health posed by trace element contamination of phytocap foliage are currently low, though should be managed by continued monitoring as the vegetation matures.

Immunotherapy and Skin Side Effects

This Patient Page defines the cancer treatment immunotherapy and describes its potential side effects, particularly of the skin.

Good to Begin Well, Better to End Well

Sulfur Ointment Treatment of Cutaneous Myiasis Caused by the Tumbu Fly

This case report describes a patient treated with sulfur ointment for cutaneous myiasis caused by the tumbu fly.

Quality of Life and the Dermatologist

This Editorial discusses factors that affect quality of life in those with vascular malformations, and dermatologists' goal of improving these aspects for patients.

Carvedilol for Treatment of Red Vulva Syndrome

This case report describes 2 patients with red vulva syndrome treated with carvedilol.

Minoxidil for Endocrine Therapy–Induced Alopecia in Women With Breast Cancer

Thomas Hindson and Discovery of Ascorbic Acid to Treat Prickly Heat

Dr Thomas Hindson was born in northern England in 1934. After attending St John's College in Cambridge for medical school, he worked as a dermatologist at St Bartholomew's Hospital. In 1960, he enlisted as a serviceman in the Royal Army Medical Corps and was later commissioned to the Armed Services in 1963.

Vascular Malformations and Health-Related Quality of Life

This systematic review and meta-analysis uses validated health-related quality-of-life instruments to compare the health-related quality of life of patients with vascular malformations with that of the US general population.

Mogamilizumab Prior to HSCT and GVHD in Patients With CTCL

This case series describes the occurrence of graft-vs-host-disease (GVHD) in patients with cutaneous T-cell lymphomas (CTCLs) treated with the CC chemokine receptor 4 (CCR4) antibody mogalizumab prior to allogeneic hematopoietic stem cell transplantation (HSCT).

Endocrine Therapy–Induced Alopecia in Patients With Breast Cancer

This cohort study describes clinical features, quality of life, and response to minoxidil among female patients with breast cancer who have endocrine therapy–induced alopecia.

Recurrent Unilateral Periorbital Edema Associated With Subcutaneous Cysticercosis

This case report describes a patient with recurrent unilateral periorbital edema caused by subcutaneous cysticercosis.

Efficacy of Guselkumab Compared With Adalimumab and Placebo for Psoriasis in Specific Body Regions

This secondary analysis of 2 randomized clinical trials evaluates the effect of guselkumab vs adalimumab or placebo on psoriasis in specific difficult-to-treat body regions.

Knowledge Removes Discomfort—Reply

In Reply We thank Dr Nwabudike for replying to our publication on the Patient Health Questionnaire-2 (PHQ-2) in Dermatology. We address his inquiries in chronological order:

Interest and Uptake of MC1R Testing for Melanoma Risk in a Diverse Primary Care Population

This randomized clinical trial examines the prevalence of interest in and uptake of MC1R testing in the general population and examines patterns across demographic and skin cancer risk factors.

Endurance—Frostbite, Then and Now

The 2018 Olympics remind us of what it means to truly brave the odds.

Cost-effectiveness of Skin Cancer Referral and Consultation Using Teledermoscopy in Australia

This study uses a decision-analytic model to assess the cost-effectiveness of teledermoscopy as a referral mechanism for skin cancer diagnosis and management in Australia.

June 2018 Issue Highlights

Association of Nodal Metastasis With Vermilion Lip Location in Cutaneous SCC of the Lip

This cohort study of patients with cutaneous squamous cell carcinomas of the lip evaluates the risk differences for recurrence, metastasis, and death in tumors of the vermilion vs cutaneous lip locations.

Teaching Intuitive Visual Diagnosis of Melanoma

This diagnostic study compares the training efficacy of a novel web-based application to the publicly available Internet Curriculum For Melanoma Early Detection Skin Education Series to determine if intuitive visual diagnosis training is superior to a traditional rule-based algorithm in the diagnosis of melanomas.

Frontalis Myocutaneous Transposition Flap for Forehead Defect Reconstruction

This case series of 12 patients with large, deep forehead defects secondary to Mohs surgery assesses whether the frontalis myocutaneous transposition flap represents a good alternative for the reconstruction of forehead defects.

Association between Breslow Thickness and Dermoscopic Findings in Acral Melanoma

Dermoscopy is a useful tool for the diagnosis of acral melanomas (AM). However, little is known about the influence of tumor thickness on the dermoscopic findings of AM.

Symptom-based Interventions to Promote Quality Survivorship

Abstract

Survival alone is no longer an adequate outcome for persons with brain tumors; the quality of the survivorship experience should be viewed with equal importance. Symptom management is a significant component of quality survivorship care. Regardless of their histology, brain tumors and therapies used to treat them produce symptoms that affect an individual's ability to function in everyday life. Common symptoms include fatigue, cognitive impairment, distress, and sleep disturbance. Symptom-based interventions for persons with brain tumors focus on prevention, self-management and prescriptive interventions targeted to these problems. Unfortunately, little evidence exists to support many interventions, making it challenging for clinicians to provide concrete recommendations. Research is needed to provide evidence in support of symptom-based interventions while novel approaches to these challenging problems are developed.

Rational social and political polarization

Abstract

Public discussions of political and social issues are often characterized by deep and persistent polarization. In social psychology, it's standard to treat belief polarization as the product of epistemic irrationality. In contrast, we argue that the persistent disagreement that grounds political and social polarization can be produced by epistemically rational agents, when those agents have limited cognitive resources. Using an agent-based model of group deliberation, we show that groups of deliberating agents using coherence-based strategies for managing their limited resources tend to polarize into different subgroups. We argue that using that strategy is epistemically rational for limited agents. So even though group polarization looks like it must be the product of human irrationality, polarization can be the result of fully rational deliberation with natural human limitations.

Polycyclic aromatic hydrocarbons, phthalates, parabens and other environmental contaminants in dust and suspended particulates of Algiers, Algeria

Abstract

Chemicals such as polycyclic aromatic hydrocarbons (PAHs), phthalateesters, parabens, siloxanes and squalene, all of them classified as endocrine-disrupting chemicals (EDCs), have been reported to occur in all environmental compartments. The effects of EDCs on development, reproduction, growth, metabolism and obesity constitute a real public health issue. A list of EDCs (> 40 compounds) were characterised in total suspended particulates (outdoor soot: 92 samples) collected in July–September 2016 in an Algiers urban area; besides, settled indoor dusts (36 samples) were collected between November and December 2016 in schools, homes, manufacture and hospital of the same province. The analytical procedure consisted of ultrasonic bath extraction, column chromatography separation into fractions of different polarity and gas chromatographic-mass spectrometric processing. The total loads of phthalates ranging from 6.0 to 347 ng/m² (median, 26 ng/m²) were determined in indoor dust and 4.6 to 11.6 ng/m³ (median, 7.9 ng/m³) in outdoor soot; meanwhile, PAHs ranged from 12.1 to 108 ng/m² (median, 36 ng/m²) in indoor dust and ranged from 5.6 to 7.7 ng/m³ (median 5.7 ng/m³) in outdoor soot. Finally, illicit substances such as cocaine, cannabinol and Δ⁹-tetrahydrocannabinol were found to range from 0.5 to 11 pg/m³, 4.6 to 9.2 pg/m³ and 11 to 81 pg/m³, respectively, in outdoor soot.

Subthalamic Nucleus Neurons Differentially Encode Early and Late Aspects of Speech Production

Basal ganglia-thalamocortical loops mediate all motor behavior, yet little detail is known about the role of basal ganglia nuclei in speech production. Using intracranial recording during deep brain stimulation surgery in humans with Parkinson's disease, we tested the hypothesis that the firing rate of subthalamic nucleus neurons is modulated in sync with motor execution aspects of speech. Nearly half of 79 unit recordings exhibited firing-rate modulation during a syllable reading task across 12 subjects (male and female). Trial-to-trial timing of changes in subthalamic neuronal activity, relative to cue onset versus production onset, revealed that locking to cue presentation was associated more with units that decreased firing rate, whereas locking to speech onset was associated more with units that increased firing rate. These unique data indicate that subthalamic activity is dynamic during the production of speech, reflecting temporally-dependent inhibition and excitation of separate populations of subthalamic neurons.

SIGNIFICANCE STATEMENT The basal ganglia are widely assumed to participate in speech production, yet no prior studies have reported detailed examination of speech-related activity in basal ganglia nuclei. Using microelectrode recordings from the subthalamic nucleus during a single-syllable reading task, in awake humans undergoing deep brain stimulation implantation surgery, we show that the firing rate of subthalamic nucleus neurons is modulated in response to motor execution aspects of speech. These results are the first to establish a role for subthalamic nucleus neurons in encoding of aspects of speech production, and they lay the groundwork for launching a modern subfield to explore basal ganglia function in human speech.

A Central Extended Amygdala Circuit That Modulates Anxiety

Both the amygdala and the bed nucleus of the stria terminalis (BNST) have been implicated in maladaptive anxiety characteristics of anxiety disorders. However, the underlying circuit and cellular mechanisms have remained elusive. Here we show that mice with Erbb4 gene deficiency in somatostatin-expressing (SOM⁺) neurons exhibit heightened anxiety as measured in the elevated plus maze test and the open field test, two assays commonly used to assess anxiety-related behaviors in rodents. Using a combination of electrophysiological, molecular, genetic, and pharmacological techniques, we demonstrate that the abnormal anxiety in the mutant mice is caused by enhanced excitatory synaptic inputs onto SOM⁺ neurons in the central amygdala (CeA), and the resulting reduction in inhibition onto downstream SOM⁺ neurons in the BNST. Notably, our results indicate that an increase in dynorphin signaling in SOM⁺ CeA neurons mediates the paradoxical reduction in inhibition onto SOM⁺ BNST neurons, and that the consequent enhanced activity of SOM⁺ BNST neurons is both necessary for and sufficient to drive the elevated anxiety. Finally, we show that the elevated anxiety and the associated synaptic dysfunctions and increased dynorphin signaling in the CeA–BNST circuit of the Erbb4 mutant mice can be recapitulated by stress in wild-type mice. Together, our results unravel previously unknown circuit and cellular processes in the central extended amygdala that can cause maladaptive anxiety.

SIGNIFICANCE STATEMENT The central extended amygdala has been implicated in anxiety-related behaviors, but the underlying mechanisms are unclear. Here we found that somatostatin-expressing neurons in the central amygdala (CeA) controls anxiety through modulation of the stria terminalis, a process that is mediated by an increase in dynorphin signaling in the CeA. Our results reveal circuit and cellular dysfunctions that may account for maladaptive anxiety.

Specialized Subpopulations of Deep-Layer Pyramidal Neurons in the Neocortex: Bridging Cellular Properties to Functional Consequences

Neocortical pyramidal neurons with somata in layers 5 and 6 are among the most visually striking and enigmatic neurons in the brain. These deep-layer pyramidal neurons (DLPNs) integrate a plethora of cortical and extracortical synaptic inputs along their impressive dendritic arbors. The pattern of cortical output to both local and long-distance targets is sculpted by the unique physiological properties of specific DLPN subpopulations. Here we revisit two broad DLPN subpopulations: those that send their axons within the telencephalon (intratelencephalic neurons) and those that project to additional target areas outside the telencephalon (extratelencephalic neurons). While neuroscientists across many subdisciplines have characterized the intrinsic and synaptic physiological properties of DLPN subpopulations, our increasing ability to selectively target and manipulate these output neuron subtypes advances our understanding of their distinct functional contributions. This Viewpoints article summarizes our current knowledge about DLPNs and highlights recent work elucidating the functional differences between DLPN subpopulations.

Somatotopic Representation of Second Pain in the Primary Somatosensory Cortex of Humans and Rodents

There is now compelling evidence that selective stimulation of A nociceptors eliciting first pain evokes robust responses in the primary somatosensory cortex (S1). In contrast, whether the C-fiber nociceptive input eliciting second pain has an organized projection to S1 remains an open question. Here, we recorded the electrocortical responses elicited by nociceptive-specific laser stimulation of the four limbs in 202 humans (both males and females, using EEG) and 12 freely moving rats (all males, using ECoG). Topographical analysis and source modeling revealed in both species, a clear gross somatotopy of the unmyelinated C-fiber input within the S1 contralateral to the stimulated side. In the human EEG, S1 activity could be isolated as an early-latency negative deflection (C-N1 wave peaking at 710–730 ms) after hand stimulation, but not after foot stimulation because of the spatiotemporal overlap with the subsequent large-amplitude supramodal vertex waves (C-N2/P2). In contrast, because of the across-species difference in the representation of the body surface within S1, S1 activity could be isolated in rat ECoG as a C-N1 after both forepaw and hindpaw stimulation. Finally, we observed a functional dissociation between the generators of the somatosensory-specific lateralized waves (C-N1) and those of the supramodal vertex waves (C-N2/P2), indicating that C-fiber unmyelinated input is processed in functionally distinct somatosensory and multimodal cortical areas. These findings demonstrated that C-fiber input conveys information about the spatial location of noxious stimulation across the body surface, a prerequisite for deploying an appropriate defensive motor repertoire.

SIGNIFICANCE STATEMENT Unmyelinated C-fibers are the evolutionarily oldest peripheral afferents responding to noxious environmental stimuli. Whether C-fiber input conveys information about the spatial location of the noxious stimulation to the primary somatosensory cortex (S1) remains an open issue. In this study, C-fibers were activated by radiant heat stimuli delivered to different parts of the body in both humans and rodents while electrical brain activity was recorded. In both species, the C-fiber peripheral input projects to different parts of the contralateral S1, coherently with the representation of the body surface within this brain region. These findings demonstrate that C-fiber input conveys information about the spatial location of noxious stimulation across the body surface, a prerequisite for deploying an appropriate defensive motor repertoire.

Statistics of Natural Communication Signals Observed in the Wild Identify Important Yet Neglected Stimulus Regimes in Weakly Electric Fish

Sensory systems evolve in the ecological niches that each species is occupying. Accordingly, encoding of natural stimuli by sensory neurons is expected to be adapted to the statistics of these stimuli. For a direct quantification of sensory scenes, we tracked natural communication behavior of male and female weakly electric fish, Apteronotus rostratus, in their Neotropical rainforest habitat with high spatiotemporal resolution over several days. In the context of courtship, we observed large quantities of electrocommunication signals. Echo responses, acknowledgment signals, and their synchronizing role in spawning demonstrated the behavioral relevance of these signals. In both courtship and aggressive contexts, we observed robust behavioral responses in stimulus regimes that have so far been neglected in electrophysiological studies of this well characterized sensory system and that are well beyond the range of known best frequency and amplitude tuning of the electroreceptor afferents' firing rate modulation. Our results emphasize the importance of quantifying sensory scenes derived from freely behaving animals in their natural habitats for understanding the function and evolution of neural systems.

SIGNIFICANCE STATEMENT The processing mechanisms of sensory systems have evolved in the context of the natural lives of organisms. To understand the functioning of sensory systems therefore requires probing them in the stimulus regimes in which they evolved. We took advantage of the continuously generated electric fields of weakly electric fish to explore electrosensory stimulus statistics in their natural Neotropical habitat. Unexpectedly, many of the electrocommunication signals recorded during courtship, spawning, and aggression had much smaller amplitudes or higher frequencies than stimuli used so far in neurophysiological characterizations of the electrosensory system. Our results demonstrate that quantifying sensory scenes derived from freely behaving animals in their natural habitats is essential to avoid biases in the choice of stimuli used to probe brain function.

Polyamine Modulation of Anticonvulsant Drug Response: A Potential Mechanism Contributing to Pharmacoresistance in Chronic Epilepsy

Despite the development of numerous novel anticonvulsant drugs, ~30% of epilepsy patients remain refractory to antiepileptic drugs (AEDs). Many established and novel AEDs reduce hyperexcitability via voltage- and use-dependent inhibition of voltage-gated Na⁺ channels. For the widely used anticonvulsant carbamazepine (CBZ), use-dependent block of Na⁺ channels is significantly reduced both in experimental and human epilepsy. However, the molecular underpinnings of this potential cellular mechanism for pharmacoresistance have remained enigmatic.

Here, we describe the mechanism that leads to the emergence of CBZ-resistant Na⁺ channels. We focused on the endogenous polyamine system, which powerfully modulates Na⁺ channels in a use-dependent manner. We had shown previously that the intracellular polyamine spermine is reduced in chronic epilepsy, resulting in increased persistent Na⁺ currents. Because spermine and CBZ both bind use-dependently in spatial proximity within the Na⁺ channel pore, we hypothesized that spermine loss might also be related to diminished CBZ response. Using the pilocarpine model of refractory epilepsy in male rats and whole-cell patch-clamp recordings, we first replicated the reduction of use-dependent block by CBZ in chronically epileptic animals. We then substituted intracellular spermine via the patch pipette in different concentrations. Under these conditions, we found that exogenous spermine significantly rescues use-dependent block of Na⁺ channels by CBZ. These findings indicate that an unexpected modulatory mechanism, depletion of intracellular polyamines, leads both to increased persistent Na⁺ currents and to diminished CBZ sensitivity of Na⁺ channels. These findings could lead to novel strategies for overcoming pharmacoresistant epilepsy that target the polyamine system.

SIGNIFICANCE STATEMENT Pharmacoresistant epilepsy affects ~18 million people worldwide, and intense efforts have therefore been undertaken to uncover the underlying molecular and cellular mechanisms. One of the key known candidate mechanisms of pharmacoresistance has been a loss of use-dependent Na⁺ channel block by the anticonvulsant carbamazepine (CBZ), both in human and experimental epilepsies. Despite intense scrutiny, the molecular mechanisms underlying this phenomenon have not been elucidated. We now show that a loss of intracellular spermine in chronic epilepsy is a major causative factor leading to the development of CBZ-resistant Na⁺ currents. This finding can be exploited both for the screening of anticonvulsants in expression systems, and for novel strategies to overcome pharmacoresistance that target the polyamine system.

Neural Signatures of the Processing of Temporal Patterns in Sound

The ability to detect regularities in sound (i.e., recurring structure) is critical for effective perception, enabling, for example, change detection and prediction. Two seemingly unconnected lines of research concern the neural operations involved in processing regularities: one investigates how neural activity synchronizes with temporal regularities (e.g., frequency modulation; FM) in sounds, whereas the other focuses on increases in sustained activity during stimulation with repeating tone-frequency patterns. In three electroencephalography studies with male and female human participants, we investigated whether neural synchronization and sustained neural activity are dissociable, or whether they are functionally interdependent. Experiment I demonstrated that neural activity synchronizes with temporal regularity (FM) in sounds, and that sustained activity increases concomitantly. In Experiment II, phase coherence of FM in sounds was parametrically varied. Although neural synchronization was more sensitive to changes in FM coherence, such changes led to a systematic modulation of both neural synchronization and sustained activity, with magnitude increasing as coherence increased. In Experiment III, participants either performed a duration categorization task on the sounds, or a visual object tracking task to distract attention. Neural synchronization was observed regardless of task, whereas the sustained response was observed only when attention was on the auditory task, not under (visual) distraction. The results suggest that neural synchronization and sustained activity levels are functionally linked: both are sensitive to regularities in sounds. However, neural synchronization might reflect a more sensory-driven response to regularity, compared with sustained activity which may be influenced by attentional, contextual, or other experiential factors.

SIGNIFICANCE STATEMENT Optimal perception requires that the auditory system detects regularities in sounds. Synchronized neural activity and increases in sustained neural activity both appear to index the detection of a regularity, but the functional interrelation of these two neural signatures is unknown. In three electroencephalography experiments, we measured both signatures concomitantly while listeners were presented with sounds containing frequency modulations that differed in their regularity. We observed that both neural signatures are sensitive to temporal regularity in sounds, although they functionally decouple when a listener is distracted by a demanding visual task. Our data suggest that neural synchronization reflects a more automatic response to regularity compared with sustained activity, which may be influenced by attentional, contextual, or other experiential factors.

This Week in The Journal

miR126-5p Downregulation Facilitates Axon Degeneration and NMJ Disruption via a Non-Cell-Autonomous Mechanism in ALS

Axon degeneration and disruption of neuromuscular junctions (NMJs) are key events in amyotrophic lateral sclerosis (ALS) pathology. Although the disease's etiology is not fully understood, it is thought to involve a non–cell-autonomous mechanism and alterations in RNA metabolism. Here, we identified reduced levels of miR126-5p in presymptomatic ALS male mice models, and an increase in its targets: axon destabilizing Type 3 Semaphorins and their coreceptor Neuropilins. Using compartmentalized in vitro cocultures, we demonstrated that myocytes expressing diverse ALS-causing mutations promote axon degeneration and NMJ dysfunction, which were inhibited by applying Neuropilin1 blocking antibody. Finally, overexpressing miR126-5p is sufficient to transiently rescue axon degeneration and NMJ disruption both in vitro and in vivo. Thus, we demonstrate a novel mechanism underlying ALS pathology, in which alterations in miR126-5p facilitate a non–cell-autonomous mechanism of motor neuron degeneration in ALS.

SIGNIFICANCE STATEMENT Despite some progress, currently no effective treatment is available for amyotrophic lateral sclerosis (ALS). We suggest a novel regulatory role for miR126-5p in ALS and demonstrate, for the first time, a mechanism by which alterations in miR126-5p contribute to axon degeneration and NMJ disruption observed in ALS. We show that miR126-5p is altered in ALS models and that it can modulate Sema3 and NRP protein expression. Furthermore, NRP1 elevations in motor neurons and muscle secretion of Sema3A contribute to axon degeneration and NMJ disruption in ALS. Finally, overexpressing miR126-5p is sufficient to transiently rescue NMJ disruption and axon degeneration both in vitro and in vivo.

A Critical Neurodevelopmental Role for L-Type Voltage-Gated Calcium Channels in Neurite Extension and Radial Migration

Despite many association studies linking gene polymorphisms and mutations of L-type voltage-gated Ca²⁺ channels (VGCCs) in neurodevelopmental disorders such as autism and schizophrenia, the roles of specific L-type VGCC during brain development remain unclear. Calcium signaling has been shown to be essential for neurodevelopmental processes such as sculpting of neurites, functional wiring, and fine tuning of growing networks. To investigate this relationship, we performed submembraneous calcium imaging using a membrane-tethered genetically encoded calcium indicator (GECI) Lck-G-CaMP7. We successfully recorded spontaneous regenerative calcium transients (SRCaTs) in developing mouse excitatory cortical neurons prepared from both sexes before synapse formation. SRCaTs originated locally in immature neurites independently of somatic calcium rises and were significantly more elevated in the axons than in dendrites. SRCaTs were not blocked by tetrodoxin, a Na⁺ channel blocker, but were strongly inhibited by hyperpolarization, suggesting a voltage-dependent source. Pharmacological and genetic manipulations revealed the critical importance of the Ca_v1.2 (CACNA1C) pore-forming subunit of L-type VGCCs, which were indeed expressed in immature mouse brains. Consistently, knocking out Ca_v1.2 resulted in significant alterations of neurite outgrowth. Furthermore, expression of a gain-of-function Ca_v1.2 mutant found in Timothy syndrome, an autosomal dominant multisystem disorder exhibiting syndromic autism, resulted in impaired radial migration of layer 2/3 excitatory neurons, whereas postnatal abrogation of Ca_v1.2 enhancement could rescue cortical malformation. Together, these lines of evidence suggest a critical role for spontaneous opening of L-type VGCCs in neural development and corticogenesis and indicate that L-type VGCCs might constitute a perinatal therapeutic target for neuropsychiatric calciochannelopathies.

SIGNIFICANCE STATEMENT Despite many association studies linking gene polymorphisms and mutations of L-type voltage-gated Ca²⁺ channels (VGCCs) in neurodevelopmental disorders such as autism and schizophrenia, the roles of specific L-type VGCCs during brain development remain unclear. We here combined the latest Ca²⁺ indicator technology, quantitative pharmacology, and in utero electroporation and found a hitherto unsuspected role for L-type VGCCs in determining the Ca²⁺ signaling landscape of mouse immature neurons. We found that malfunctional L-type VGCCs in immature neurons before birth might cause errors in neuritic growth and cortical migration. Interestingly, the retarded corticogenesis phenotype was rescued by postnatal correction of L-type VGCC signal aberration. These findings suggest that L-type VGCCs might constitute a perinatal therapeutic target for neurodevelopment-associated psychiatric disorders.

The Frequency Response of Outer Hair Cell Voltage-Dependent Motility Is Limited by Kinetics of Prestin

The voltage-dependent protein SLC26a5 (prestin) underlies outer hair cell electromotility (eM), which is responsible for cochlear amplification in mammals. The electrical signature of eM is a bell-shaped nonlinear capacitance (NLC), deriving from prestin sensor-charge (Q_p) movements, which peaks at the membrane voltage, V_h, where charge is distributed equally on either side of the membrane. Voltage dependencies of NLC and eM differ depending on interrogation frequency and intracellular chloride, revealing slow intermediate conformational transitions between anion binding and voltage-driven Q_p movements. Consequently, NLC exhibits low-pass characteristics, substantially below prevailing estimates of eM frequency response. Here we study in guinea pig and mouse of either sex synchronous prestin electrical (NLC, Q_p) and mechanical (eM) activity across frequencies under voltage clamp (whole cell and microchamber). We find that eM and Q_p magnitude and phase correspond, indicating tight piezoelectric coupling. Electromechanical measures (both NLC and eM) show dual-Lorentzian, low-pass behavior, with a limiting (₂) time constant at V_h of 32.6 and 24.8 μs, respectively. As expected for voltage-dependent kinetics, voltage excitation away from V_h has a faster, flatter frequency response, with our fastest measured ₂ for eM of 18.2 μs. Previous observations of ultrafast eM ( 2 μs) were obtained at offsets far removed from V_h. We hypothesize that trade-offs in eM gain-bandwith arising from voltage excitation at membrane potentials offset from V_h influence the effectiveness of cochlear amplification across frequencies.

SIGNIFICANCE STATEMENT Of two types of hair cells within the organ of Corti, inner hair cells and outer hair cells, the latter evolved to boost sensitivity to sounds. Damage results in hearing loss of 40–60 dB, revealing amplification gains of 100–1000x that arise from voltage-dependent mechanical responses [electromotility (eM)]. eM, driven by the membrane protein prestin, may work beyond 70 kHz. However, this speed exceeds, by over an order of magnitude, kinetics of typical voltage-dependent membrane proteins. We find eM is actually low pass in nature, indicating that prestin bears kinetics typical of other membrane proteins. These observations highlight potential difficulties in providing sufficient amplification beyond a cutoff frequency near 20 kHz. Nevertheless, observed trade-offs in eM gain-bandwith may sustain cochlear amplification across frequency.

Prostaglandin Transporter OATP2A1/SLCO2A1 Is Essential for Body Temperature Regulation during Fever

Prostaglandin E₂ (PGE₂) in the hypothalamus is a principal mediator of the febrile response. However, the role of organic anion transporting polypeptide 2A1 (OATP2A1/SLCO2A1), a prostaglandin transporter, in facilitating this response is unknown. Here, we investigated the effect of Slco2a1 deficiency on the body core temperature (Tc) and on the PGE₂ concentration in hypothalamus interstitial fluid (C_isf) and CSF (C_csf) of lipopolysaccharide (LPS; 100 μg/kg, i.p.)-treated mice of both sexes. Slco2a1^–/– mice did not develop a febrile response. C_csf was increased in Slco2a1^+/+ and Slco2a1^–/– mice, and C_csf of Slco2a1^–/– mice was well maintained at 5 h after LPS injection (1160 pg/ml) compared with Slco2a1^+/+ mice (316 pg/ml). A microdialysis study revealed that C_isf peaked at 2 h after LPS injection in Slco2a1^+/+ mice (841 pg/ml), whereas the increase in C_isf was negligible in Slco2a1^–/– mice. The PGE₂ plasma concentration in Slco2a1^–/– mice (201 pg/ml) was significantly higher than that in Slco2a1^+/+ mice (54 pg/ml) at 1 h after LPS injection, whereas the two groups showed similar PGE₂ concentrations in the hypothalamus. Strong Oatp2a1 immunoreactivity was observed in F4/80-positive microglia and perivascular cells and in brain capillary endothelial cells. The changes in Tc and C_isf seen in LPS-injected Slco2a1^+/+ mice were partially attenuated in monocyte-/macrophage-specific Slco2a1^–/– (Slco2a1^Fl/Fl/LysM^Cre/+) mice. Thus, OATP2A1 facilitates the LPS-induced febrile response by maintaining a high level of C_isf, possibly by regulating PGE₂ secretion from F4/80-positive glial cells and/or facilitating PGE₂ transport across the blood–brain barrier. These findings suggest that OATP2A1 is a useful therapeutic target for neuroinflammation.

SIGNIFICANCE STATEMENT Fever is a physiological response caused by pyrogen-induced release of prostaglandin E₂ (PGE₂) in the hypothalamus, which plays a central role in regulating the set-point of body temperature. However, it is unclear whether the prostaglandin transporter OATP2A1/SLCO2A1 is involved in this response. We show here that LPS-induced fever is associated with increased PGE₂ concentration in hypothalamus interstitial fluid (C_isf), but not in CSF (C_csf), by means of a microdialysis study in global Slco2a1-knock-out mice and monocyte-/macrophage-specific Slco2a1-knock-out mice. The results suggest that OATP2A1 serves as a regulator of C_isf in F4/80-positive glial cells. OATP2A1 was detected immunohistochemically in brain capillary endothelial cells and, therefore, may also play a role in PGE₂ transport across the blood–brain barrier.

Identification of a Rhythmic Firing Pattern in the Enteric Nervous System That Generates Rhythmic Electrical Activity in Smooth Muscle

The enteric nervous system (ENS) contains millions of neurons essential for organization of motor behavior of the intestine. It is well established that the large intestine requires ENS activity to drive propulsive motor behaviors. However, the firing pattern of the ENS underlying propagating neurogenic contractions of the large intestine remains unknown. To identify this, we used high-resolution neuronal imaging with electrophysiology from neighboring smooth muscle. Myoelectric activity underlying propagating neurogenic contractions along murine large intestine [also referred to as colonic migrating motor complexes, (CMMCs)] consisted of prolonged bursts of rhythmic depolarizations at a frequency of ~2 Hz. Temporal coordination of this activity in the smooth muscle over large spatial fields (~7 mm, longitudinally) was dependent on the ENS. During quiescent periods between neurogenic contractions, recordings from large populations of enteric neurons, in mice of either sex, revealed ongoing activity. The onset of neurogenic contractions was characterized by the emergence of temporally synchronized activity across large populations of excitatory and inhibitory neurons. This neuronal firing pattern was rhythmic and temporally synchronized across large numbers of ganglia at ~2 Hz. ENS activation preceded smooth muscle depolarization, indicating rhythmic depolarizations in smooth muscle were controlled by firing of enteric neurons. The cyclical emergence of temporally coordinated firing of large populations of enteric neurons represents a unique neural motor pattern outside the CNS. This is the first direct observation of rhythmic firing in the ENS underlying rhythmic electrical depolarizations in smooth muscle. The pattern of neuronal activity we identified underlies the generation of CMMCs.

SIGNIFICANCE STATEMENT How the enteric nervous system (ENS) generates neurogenic contractions of smooth muscle in the gastrointestinal (GI) tract has been a long-standing mystery in vertebrates. It is well known that myogenic pacemaker cells exist in the GI tract [called interstitial cells of Cajal (ICCs)] that generate rhythmic myogenic contractions. However, the mechanisms underlying the generation of rhythmic neurogenic contractions of smooth muscle in the GI tract remains unknown. We developed a high-resolution neuronal imaging method with electrophysiology to address this issue. This technique revealed a novel pattern of rhythmic coordinated neuronal firing in the ENS that has never been identified. Rhythmic neuronal firing in the ENS was found to generate rhythmic neurogenic depolarizations in smooth muscle that underlie contraction of the GI tract.

Neurotrophin Responsiveness of Sympathetic Neurons Is Regulated by Rapid Mobilization of the p75 Receptor to the Cell Surface through TrkA Activation of Arf6

The p75 neurotrophin receptor (p75NTR) plays an integral role in patterning the sympathetic nervous system during development. Initially, p75NTR is expressed at low levels as sympathetic axons project toward their targets, which enables neurotrophin-3 (NT3) to activate TrkA receptors and promote growth. Upon reaching nerve growth factor (NGF) producing tissues, p75NTR is upregulated, resulting in formation of TrkA-p75 complexes, which are high-affinity binding sites selective for NGF, thereby blunting NT3 signaling. The level of p75NTR expressed on the neuron surface is instrumental in regulating trophic factor response; however, the mechanisms by which p75NTR expression is regulated are poorly understood. Here, we demonstrate a rapid, translation independent increase in surface expression of p75NTR in response to NGF in rat sympathetic neurons. p75NTR was mobilized to the neuron surface from GGA3-postitive vesicles through activation of the GTPase Arf6, which was stimulated by NGF, but not NT3 binding to TrkA. Arf6 activation required PI3 kinase activity and was prevented by an inhibitor of the cytohesin family of Arf6 guanine nucleotide exchange factors. Overexpression of a constitutively active Arf6 mutant (Q67L) was sufficient to significantly increase surface expression of p75NTR even in the absence of NGF. Functionally, expression of active Arf6 markedly attenuated the ability of NT3 to promote neuronal survival and neurite outgrowth, whereas the NGF response was unaltered. These data suggest that NGF activation of Arf6 through TrkA is critical for the increase in p75NTR surface expression that enables the switch in neurotrophin responsiveness during development in the sympathetic nervous system.

SIGNIFICANCE STATEMENT p75NTR is instrumental in the regulation of neuronal survival and apoptosis during development and is also implicated as a contributor to aberrant neurodegeneration in numerous conditions. Therefore, a better understanding of the mechanisms that mediate p75NTR surface availability may provide insight into how and why neurodegenerative processes manifest and reveal new therapeutic targets. Results from this study indicate a novel mechanism by which p75NTR can be rapidly shuttled to the cell surface from existing intracellular pools and explores a unique pathway by which NGF regulates the sympathetic innervation of target tissues, which has profound consequences for the function of these organs.

Suppression of AMPA Receptor Exocytosis Contributes to Hippocampal LTD

The decrease in number of AMPA-type glutamate receptor (AMPAR) at excitatory synapses causes LTD, a cellular basis of learning and memory. The number of postsynaptic AMPARs is regulated by the balance of exocytosis and endocytosis, and enhanced endocytosis of AMPAR has been suggested to underlie the LTD expression. However, it remains unclear how endocytosis and exocytosis of AMPAR change during LTD. In this study, we addressed this question by analyzing exocytosis and endocytosis of AMPAR by imaging super-ecliptic pHlorin (SEP)-tagged AMPAR around postsynaptic structure formed directly on the glass surface in the hippocampal culture prepared from rat embryos of both sexes. Contrary to a prevailing view on the LTD expression by endocytosis enhancement, the LTD induction by NMDA application only transiently enhanced endocytosis of SEP-tagged GluA1 subunits of AMPAR, which was counteracted by simultaneous augmentation of exocytosis. As a result, soon after the start of the LTD induction (~1 min), the surface AMPAR did not markedly decrease. Thereafter, the surface GluA1-SEP gradually decreased (2–5 min) and kept at a low level until the end of observation (>30 min). Surprisingly, this gradual and sustained decrease of surface AMPAR was accompanied not by the enhanced endocytic events of GluA1, but by the suppression of exocytosis. Together, our data highlight an unprecedented mechanism for the LTD expression by attenuation of exocytosis of AMPAR, but not by enhanced endocytosis, together with a reduction of postsynaptic AMPAR scaffolding protein PSD95.

SIGNIFICANCE STATEMENT It has been generally assumed that LTD is expressed by enhancement of AMPAR endocytosis. Previous studies reported that endocytosis-related protein was involved in LTD and that significant amount of cell-surface AMPAR moved into intracellular compartments during LTD. Here, we report changes of cell-surface amount of AMPAR, and where and when individual exocytosis and endocytosis occurred during LTD. Cell-surface AMPAR gradually decreased in synchrony with suppression of exocytosis but not with enhancement of endocytosis. These results suggest that the decrease of cell-surface AMPAR amount during LTD was caused not by enhancement of endocytosis but rather by suppression of exocytosis, which revises current understanding of the expression mechanism of LTD.

Expectations Do Not Alter Early Sensory Processing during Perceptual Decision-Making

Two factors play important roles in shaping perception: the allocation of selective attention to behaviorally relevant sensory features, and prior expectations about regularities in the environment. Signal detection theory proposes distinct roles of attention and expectation on decision-making such that attention modulates early sensory processing, whereas expectation influences the selection and execution of motor responses. Challenging this classic framework, recent studies suggest that expectations about sensory regularities enhance the encoding and accumulation of sensory evidence during decision-making. However, it is possible, that these findings reflect well documented attentional modulations in visual cortex. Here, we tested this framework in a group of male and female human participants by examining how expectations about stimulus features (orientation and color) and expectations about motor responses impacted electroencephalography (EEG) markers of early sensory processing and the accumulation of sensory evidence during decision-making (the early visual negative potential and the centro-parietal positive potential, respectively). We first demonstrate that these markers are sensitive to changes in the amount of sensory evidence in the display. Then we show, counter to recent findings, that neither marker is modulated by either feature or motor expectations, despite a robust effect of expectations on behavior. Instead, violating expectations about likely sensory features and motor responses impacts posterior alpha and frontal theta oscillations, signals thought to index overall processing time and cognitive conflict. These findings are inconsistent with recent theoretical accounts and suggest instead that expectations primarily influence decisions by modulating post-perceptual stages of information processing.

SIGNIFICANCE STATEMENT Expectations about likely features or motor responses play an important role in shaping behavior. Classic theoretical frameworks posit that expectations modulate decision-making by biasing late stages of decision-making including the selection and execution of motor responses. In contrast, recent accounts suggest that expectations also modulate decisions by improving the quality of early sensory processing. However, these effects could instead reflect the influence of selective attention. Here we examine the effect of expectations about sensory features and motor responses on a set of electroencephalography (EEG) markers that index early sensory processing and later post-perceptual processing. Counter to recent empirical results, expectations have little effect on early sensory processing but instead modulate EEG markers of time-on-task and cognitive conflict.

Problematic End Points in a Keratinocyte Carcinoma Chemoprevention Trial—Reply

In Reply We appreciate the close scrutiny of our published work and the opportunity to elaborate on the end points we used for analysis of the trial data. The VAKCC Trial primary end point was the rate of occurrence of keratinocyte carcinoma (KC) over the course of the 4-year trial. In the process of creating and executing this trial, however, the study team explicitly discussed that there were other important outcomes. In particular, while we did not have evidence to guide our estimation of the timing and duration of the effect of our intervention, if any, on the occurrence of KC, basal cell carcinoma, or squamous cell carcinoma (SCC), we realized that a short-term effect on risk (eg, during the first year) could be of considerable clinical importance even if the effect did not persist for the entire duration of the trial. We further recognized that even if there was a substantial effect in the first year, it could be lost in the 4-year results unless specifically examined. Hence, when analysis plans were discussed prior to unblinding the data, it was explicitly stated by the study chair, and summarized in the form of email guidance to the study statistician, that outcomes at 1 year were important to calculate and report. With the focus on completing the report, we chose not to officially amend the statistical analysis plan. This was an administrative decision that did not prevent appropriate analysis and should not prevent appropriate scientific interpretation. The final analyses, as reported, revealed a clinically and statistically significant 75% reduction in SCC risk in the first year. It is appropriate for this finding to influence the clinical care of those at high risk of face and ear SCC.

An Elderly Woman With Painful Buttock and Vulvar Ulcers

A woman in her 80s presented with somnolence, fatigue, lower urinary tract symptoms, and progressively worsening vulvar and buttock pain. What is your diagnosis?

Association of RARβ Expression With Lichen Sclerosus–Associated Vulvar Squamous Cell Carcinoma

This case-control study examines the association of retinoic acid receptor β tumor-suppressor gene with the onset and progression of lichen sclerosus–associated vulvar squamous cell carcinoma.

Problematic End Points in a Keratinocyte Carcinoma Chemoprevention Trial

To the Editor Treatment with topical fluorouracil, 5%, compared with placebo reduced risk of surgically treated squamous cell carcinoma (SCC) and Mohs surgery for keratinocyte carcinoma (KC) for 1 year, according to a randomized clinical trial (RCT) report. However, because neither of these outcomes was prespecified, these findings should be interpreted very cautiously and should not sway clinical practice.

Efficacy and Safety of Ozenoxacin for Treatment of Patients With Impetigo

This randomized clinical trial evaluates the efficacy, safety, and tolerability of ozenoxacin cream vs placebo in children and adults with impetigo.

Contributions by MC1R Variants to Melanoma Risk in Males and Females

This case-control study evaluates the association of melanocortin-1-receptor (MC1R) with melanoma risk in males vs females, adjusting for risk factors such as age, pigmentation, phenotype, signs of skin damage, and sun exposure.

An Evaluation of the Relationship among Urine, Air, and Hand Measures of Exposure to Bisphenol A (BPA) in US Manufacturing Workers

Abstract

Background

Exposure to bisphenol A (BPA) can be assessed using external and internal exposure measures. We examined the relationship between two measures of external BPA exposure (air and hand-wipe samples) and one of internal exposure (total BPA in urine) for a group of US manufacturing workers.

Methods

During 2013–2014, we recruited 78 workers from six US companies that made BPA or made products with BPA. We quantified BPA in seven urine samples, two full-shift air samples and in pre- and end-shift hand-wipe samples collected from workers over 2 consecutive days. We examined correlations between creatinine-corrected urinary concentrations of total BPA (total BPA_CR) and BPA levels in air and hand wipes using Pearson's correlation coefficient. We also applied mixed-effects regression models to examine the relationship between total BPA_CR with BPA in air (urine~air model) and with BPA in end-shift hand wipes (urine~hand model), separately and together (urine~air+hand model), after adjusting for covariates.

Results

End-shift total BPA_CR strongly correlated with BPA in air (r_p = 0.79, P < 0.0001) and nearly as strongly with BPA in end-shift hand wipes (r_p = 0.75, P < 0.0001). In mixed-effect models, BPA air concentration and end-shift hand-wipe BPA level were significantly and positively associated with end-shift total BPA_CR (P < 0.0001 each). We found a significant effect of the Day 1 BPA air concentration on Day 2 total BPA_CR (P = 0.0104). When BPA air concentration and end-shift hand-wipe BPA level were in the same model, the air concentration (P < 0.0001) was more significant than the hand-wipe level (P = 0.0106).

Conclusion

BPA levels in air and end-shift hand wipes strongly correlated with total BPA_CR, suggesting that both inhalation and dermal contract were likely exposure routes; however, inhalation, on average, appeared to be a more dominant exposure route than dermal contact for these manufacturing workers.

Carbonaceous Monolithic Multi-Channel Denuders as Vapour–Particle Partitioning Tools for the Occupational Sampling of Semi-Volatile Organic Compounds

Abstract

Denuders are gas–particle partitioning tools and can be used in combination with filters and adsorbers for phase-separated collection of hazardous semi-volatile organic compound (SVOC) aerosols. Here, we investigated the suitability of carbonaceous monolithic multi-channel denuders for this approach. Particle transmission efficiency through the denuders was investigated using particles of polystyrene latex (PSL) and droplets of n-hexadecane and diethylene glycol. The time-dependent vapour collection efficiency was analysed for n-hexadecane and diethylene glycol vapours and also compared to calculated predictions. Our measurements showed an averaged transmission efficiency of 97 ± 4.4% for PSL particles with diameters of 0.51, 0.99, 1.93, and 3.00 µm. Measurements with one denuder and 1.08, 1.98, and 2.97 µm particles consisting of n-hexadecane or diethylene glycol resulted in an averaged transmission efficiency of 99 ± 6.5%. Regarding the vapour collection efficiency at a flow rate of 5 l min⁻¹, n-hexadecane vapour could be adsorbed to a similar extent (91 ± 1.4% for one denuder, 98 ± 0.3% for two denuders) as diethylene glycol vapour (93 ± 1.8% for one denuder, 97 ± 0.9% for two denuders). The comparison between experimental and theoretical vapour collection efficiencies revealed differences around 2.8% for n-hexadecane and around 12.3% for diethylene glycol. The results show that the tested denuders can be used as vapour collection tools for SVOCs, and can be integrated in currently used personal air samplers for separated vapour and particle collection.

Pemetrexed anaphylaxis – an unusual suspect

Publication date: Available online 13 June 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Leonor Carneiro-Leão, Vladyslava Barzylovych, Josefina Cernadas

Efectividad de la fototerapia ultravioleta B de banda estrecha con un esquema bisemanal en el tratamiento de la micosis fungoide estadio temprano en una cohorte de 18 pacientes argentinos

Publication date: Available online 13 June 2018
Source:Actas Dermo-Sifiliográficas
Author(s): D.A. De Luca, E.A. Zambrano, R.L. Galimberti, P.A. Enz

Association between Breslow Thickness and Dermoscopic Findings in Acral Melanoma

Publication date: Available online 13 June 2018
Source:Journal of the American Academy of Dermatology
Author(s): Je-Ho Mun, Gwanghyun Jo, Claudia C. Darmawan, Jin Park, Jung Min Bae, HyunJu Jin, Woo-Il Kim, Hoon-Soo Kim, Hyun-Chang Ko, Byung-Soo Kim, Moon-Bum Kim
BackgroundDermoscopy is a useful tool for the diagnosis of acral melanomas (AM). However, little is known about the influence of tumor thickness on the dermoscopic findings of AM.ObjectiveTo investigate the impact of Breslow thickness (BT) on the dermoscopic patterns of AM.MethodsData on cases of AM on the glabrous skin were collected from four university hospitals. We investigated the frequency of each dermoscopic feature of AM according to the BT. Statistical analysis was performed to investigate the association between the specific dermoscopic patterns and BT.ResultsMultivariable analysis revealed that red (odds ratio [OR] 16.482, 95% confidence interval [CI] 3.605-99.016), blue (OR 7.092; 95% CI 1.707-37.435), and white colors (OR 5.048, 95% CI 1.152-22.897) were more common in AM with BT >2 mm. Regarding patterns, atypical vascular patterns (OR 34.589, 95% CI 6.458-305.852), blue-white veil (OR 9.605, 95% CI 1.971-72.062), and ulcers (OR 5.084, 95% CI 1.145-24.152) were more frequently detected in cases with BT >2 mm.LimitationsA retrospective study design and small sample sizeConclusionThis study showed an association between dermoscopic patterns and tumor thickness among patients with AM. Dermoscopy can be a useful adjuvant tool in predicting BT in AM.

Noninvasive Assessment of Hemodynamic Stress Distribution after Indirect Revascularization for Pediatric Moyamoya Vasculopathy [PEDIATRICS]

BACKGROUND AND PURPOSE:

Indirect revascularization surgery is an effective treatment in children with Moyamoya vasculopathy. In the present study, we hypothesized that DSC-PWI may reliably assess the evolution of CBF-related parameters after revascularization surgery, monitoring the outcome of surgical pediatric patients with Moyamoya vasculopathy. Thus, we aimed to evaluate differences in DSC-PWI parameters, including the hemodynamic stress distribution, in surgical and nonsurgical children with Moyamoya vasculopathy and to correlate them with long-term postoperative outcome.

MATERIALS AND METHODS:

Pre- and postoperative DSC parameters of 28 patients (16 females; mean age, 5.5 ± 4.8 years) treated with indirect revascularization were compared with those obtained at 2 time points in 10 nonsurgical patients (6 females; mean age, 6.9 ± 4.7 years). We calculated 4 normalized CBF-related parameters and their percentage variance: mean normalized CBF of the MCA territory, mean normalized CBF of the proximal MCA territory, mean normalized CBF of cortical the MCA territory, and hemodynamic stress distribution. The relationship between perfusion parameters and postoperative outcomes (poor, fair, good, excellent) was explored using 1-way analysis of covariance (P < .05).

RESULTS:

A significant decrease of the mean normalized CBF of the proximal MCA territory and hemodynamic stress distribution and an increase of the mean normalized CBF of the cortical MCA territory were observed after revascularization surgery (P < .001). No variations were observed in nonsurgical children. Postoperative hemodynamic stress distribution and its percentage change were significantly different in outcome groups (P < .001).

CONCLUSIONS:

DSC-PWI indices show postoperative hemodynamic changes that correlate with clinical outcome after revascularization surgery in children with Moyamoya disease.

Targeting the Clot in Acute Stroke [letter]

Surpass Streamline Flow-Diverter Embolization Device for Treatment of Iatrogenic and Traumatic Internal Carotid Artery Injuries [INTERVENTIONAL]

SUMMARY:

Iatrogenic and traumatic cerebral internal carotid artery injuries are uncommon but potentially lethal complications. Direct surgical repair of ICA injuries may be difficult in an acute setting. However, endovascular treatment with a flow-diverter embolization device is a feasible alternative technique that we experienced. In this clinical report, we describe demographic data, radiographic images, lesion characteristics, endovascular procedure notes, postprocedural hospital course, and follow-up digital subtraction angiography of 5 patients. At least 6-month follow-up was available in all patients without occurrence of rebleeding and other complications.

Consensus Needed for Noncontrast CT Markers in Intracerebral Hemorrhage [letter]

Clinical Outcomes of Endovascular Treatment within 24 Hours in Patients with Mild Ischemic Stroke and Perfusion Imaging Selection [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Endovascular thrombectomy has been accepted as the standard of care for patients with acute ischemic stroke. Our aim was to investigate the clinical outcomes of patients with mild ischemic stroke with acute proximal large-vessel occlusion after endovascular treatment within 24 hours of symptom onset.

MATERIALS AND METHODS:

Between January 2014 and August 2017, ninety-three Chinese patients with mild ischemic stroke (NIHSS scores, 0–8) and large-vessel occlusion with endovascular treatment were retrospectively enrolled from 7 comprehensive stroke centers. They were divided into 2 groups: ≤6 hours and 6–24 hours from symptom onset to groin puncture. We analyzed their modified Rankin Scale scores at 90 days, symptomatic intracranial hemorrhage at 48 hours, and mortality during 90 days. Multivariable linear regression analysis was used to identify predictors for NIHSS shift after discharge.

RESULTS:

Twenty-nine patients received endovascular treatment within 6–24 hours after symptom onset and had an imaging mismatch based on perfusion CT or diffusion-weighted MR imaging. There were no substantial differences between the 2 groups in 90-day functional independence (P = .54) and the risks of the combination of symptomatic intracranial hemorrhage and death (P = .72). Two significant indicators of NIHSS shift were 48-hour symptomatic intracranial hemorrhage (unstandardized β = 7.28; 95% CI, 3.48–11.1; P < .001) and baseline systolic blood pressure (unstandardized β = 0.08; 95% CI, 0.03–0.14; P = .005).

CONCLUSIONS:

Patients with mild ischemic stroke and large-vessel occlusion in the anterior circulation, an imaging mismatch, and endovascular treatment within 6–24 hours of initial symptoms showed no heterogeneity in the efficacy and safety outcome compared with those treated ≤6 hours from symptom onset.

Increasing the Accuracy of Optic Nerve Measurement Using 3D Volumetry [letter]

Cavitary Plaques in Otospongiosis: CT Findings and Clinical Implications [HEAD & NECK]

BACKGROUND AND PURPOSE:

Cavitary plaques have been reported as a manifestation of otospongiosis. They have been related to third window manifestations, complications during cochlear implantation, and sensorineural hearing loss. However, their etiology and clinical implications are not entirely understood. Our purpose was to determine the prevalence, imaging findings, and clinical implications of cavitary plaques in otospongiosis.

MATERIALS AND METHODS:

We identified patients with otospongiosis at a tertiary care academic medical center from January 2012 to April 2017. Cross-sectional CT images and clinical records of 47 patients (89 temporal bones) were evaluated for the presence, location, and imaging features of cavitary and noncavitary otospongiotic plaques, as well as clinical symptoms and complications in those who underwent cochlear implantation.

RESULTS:

Noncavitary otospongiotic plaques were present in 86 (97%) temporal bones and cavitary plaques in 30 (35%). Cavitary plaques predominated with increasing age (mean age, 59 years; P = .058), mostly involving the anteroinferior wall of the internal auditory canal (P = .003), and their presence was not associated with a higher grade of otospongiosis by imaging (P = .664) or with a specific type of hearing loss (P = .365). No patients with cavitary plaques had third window manifestations, and those with a history of cochlear implantation (n = 6) did not have complications during the procedure.

CONCLUSIONS:

Cavitary plaques occurred in one-third of patients with otospongiosis. Typically, they occurred in the anteroinferior wall of the internal auditory canal. There was no correlation with the degree of otospongiosis, type of hearing loss, or surgical complications. Cavitary plaques tended to present in older patients.

REPLY: [reply]

CSF Pressure Change in Relation to Opening Pressure and CSF Volume Removed [SPINE]

BACKGROUND AND PURPOSE:

Idiopathic intracranial hypertension is a complex neurologic disorder resulting from increased intracranial pressure. Our aim was to determine whether a correlation exists between the CSF pressure-volume relationship, specifically the craniospinal elastance and pressure-volume index, in patients with idiopathic intracranial hypertension and whether opening pressure affects this relationship.

MATERIALS AND METHODS:

Lumbar punctures performed for suspected idiopathic intracranial hypertension from 2006 to 2017 were identified. Opening and closing pressures, CSF volume removed, and clinical diagnosis of idiopathic intracranial hypertension were obtained from the medical records. The craniospinal elastance (pressure change per milliliter of CSF removed) and pressure-volume index were calculated, and the Pearson correlation coefficients between both the craniospinal elastance and pressure-volume index and opening pressure were determined. Linear regression models of craniospinal elastance and the pressure-volume index and interaction terms with opening pressure were assessed for covariate influence on this association.

RESULTS:

One hundred sixteen patients were included in the final analysis. The mean craniospinal elastance according to opening pressure group was 0.52 ± 0.18 for <20 cm H₂O, 0.57 ± 0.20 for 20–29 cm H₂O, 0.91 ± 0.28 for 30–39 cm H₂O, and 1.20 ± 0.25 for ≥40 cm H₂O. There was a positive linear association between opening pressure and craniospinal elastance with a 0.28 cm H₂O/mL increase in craniospinal elastance (standard error = 0.03, P < .001) for every 10 cm H₂O increase in opening pressure. Of the covariables analyzed, only age older than 50 years and total volume of CSF removed affected this association.

CONCLUSIONS:

As opening pressure increases, the craniospinal elastance increases in a linear fashion while the pressure-volume index decreases. Further studies are needed to determine whether these changes relate to the underlying pathophysiology of idiopathic intracranial hypertension or simply represent established CSF volume pressure dynamics.

[other]

Multicentric Experience in Distal-to-Proximal Revascularization of Tandem Occlusion Stroke Related to Internal Carotid Artery Dissection [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Internal carotid dissection is a frequent cause of ischemic stroke in young adults. It may cause tandem occlusions in which cervical carotid obstruction is associated with intracranial proximal vessel occlusion. To date, no consensus has emerged concerning endovascular treatment strategy. Our aim was to evaluate our endovascular "distal-to-proximal" strategy in the treatment of this stroke subtype in the first large multicentric cohort.

MATERIALS AND METHODS:

Prospectively managed stroke data bases from 2 separate centers were retrospectively studied between 2009 and 2014 for records of tandem occlusions related to internal carotid dissection. Atheromatous tandem occlusions were excluded. The first step in the revascularization procedure was intracranial thrombectomy. Then, cervical carotid stent placement was performed depending on the functionality of the circle of Willis and the persistence of residual cervical ICA occlusion, severe stenosis, or thrombus apposition. Efficiency, complications, and radiologic and clinical outcomes were recorded.

RESULTS:

Thirty-four patients presenting with tandem occlusion stroke secondary to internal carotid dissection were treated during the study period. The mean age was 52.5 years, the mean initial NIHSS score was 17.29 ± 6.23, and the mean delay between onset and groin puncture was 3.58 ± 1.1 hours. Recanalization TICI 2b/3 was obtained in 21 cases (62%). Fifteen patients underwent cervical carotid stent placement. There was no recurrence of ipsilateral stroke in the nonstented subgroup. Twenty-one patients (67.65%) had a favorable clinical outcome after 3 months.

CONCLUSIONS:

Endovascular treatment of internal carotid dissection–related tandem occlusion stroke using the distal-to-proximal recanalization strategy appears to be feasible, with low complication rates and considerable rates of successful recanalization.

What Have We Learned from Perfusion MRI in Multiple Sclerosis? [ADULT BRAIN]

SUMMARY:

Using MR imaging, perfusion can be assessed either by dynamic susceptibility contrast MR imaging or arterial spin-labeling. Alterations of cerebral perfusion have repeatedly been described in multiple sclerosis compared with healthy controls. Acute lesions exhibit relative hyperperfusion in comparison with normal-appearing white matter, a finding mostly attributed to inflammation in this stage of lesion development. In contrast, normal-appearing white and gray matter of patients with MS has been mostly found to be hypoperfused compared with controls, and correlations with cognitive impairment as well as fatigue in multiple sclerosis have been described. Mitochondrial failure, axonal degeneration, and vascular dysfunction have been hypothesized to underlie the perfusion MR imaging findings. Clinically, perfusion MR imaging could allow earlier detection of the acute focal inflammatory changes underlying relapses and new lesions, and could constitute a marker for cognitive dysfunction in MS. Nevertheless, the clinical relevance and pathogenesis of the brain perfusion changes in MS remain to be clarified.

Anatomic and Angiographic Analyses of Ophthalmic Artery Collaterals in Moyamoya Disease [EXTRACRANIAL VASCULAR]

BACKGROUND AND PURPOSE:

Moyamoya disease is a progressive neurovascular pathology defined by steno-occlusive disease of the distal internal carotid artery and associated with the development of compensatory vascular collaterals. The etiology and exact anatomy of vascular collaterals have not been extensively studied. The aim of this study was to describe the anatomy of collaterals developed between the ophthalmic artery and the anterior cerebral artery in a Moyamoya population.

MATERIALS AND METHODS:

All patients treated for Moyamoya disease from 2004 to 2016 in 4 neurosurgical centers with available cerebral digital subtraction angiography were included. Sixty-three cases were evaluated, and only 38 met the inclusion criteria. Two patients had a unilateral cervical internal carotid occlusion that limited analysis of ophthalmic artery collaterals to one hemisphere. This study is consequently based on the analysis of 74 cerebral hemispheres.

RESULTS:

Thirty-eight patients fulfilled the inclusion criteria. The most frequently encountered anastomosis between the ophthalmic artery and cerebral artery was a branch of the anterior ethmoidal artery (31.1%, 23 hemispheres). In case of proximal stenosis of the anterior cerebral artery, a collateral from the posterior ethmoidal artery could be visualized (16 hemispheres, 21.6%). One case (1.4%) of anastomosis between the lacrimal artery and the middle meningeal artery that permitted the vascularization of a middle cerebral artery territory was also noted.

CONCLUSIONS:

Collaterals from the ophthalmic artery are frequent in Moyamoya disease. Their development depends on the perfusion needs of the anterior cerebral artery territories. Three other systems of compensation could be present (callosal circle, leptomeningeal anastomosis, and duro-pial anastomoses).

Who's Contributing Most to American Neuroscience Journals: American or Foreign Authors? [research-article]

BACKGROUND AND PURPOSE:

With globalization, the contributions of authors from abroad to the American published literature has increased. We sought to determine the changes with time in the proportional contributions of American and non-American authors in the American neurosciences literature. We hypothesized the following: 1) During the past 21 years, manuscript contributions of American institutions have proportionally decreased in neuroradiology, more than in neurosurgery or neurology; 2) contributions of Asian institutions have affected neuroradiology more than neurosurgery and neurology; and 3) American articles garner more citations.

MATERIALS AND METHODS:

We reviewed the May issues of 2 of the highest impact American-based neurology, neurosurgery, and neuroradiology journals published from 1997 to 2017. We counted the number of articles published by nation based on the institution of origin. We looked at trends across time and compared neurology, neurosurgery, and neuroradiology journals. We also gathered data on the number of citations of each article by nationality.

RESULTS:

We reviewed 3025 articles. There was a significantly lower ratio of American to non-American authorship in neuroradiology versus neurology/neurosurgery journals (odds ratio = 0.70; 95% confidence interval, 0.60–0.82). There was a significantly decreasing trend in American authorship across the 21 years in neuroradiology. Of the countries outside the United States, Japan contributed most for neuroradiology and neurosurgery journals, and the UK, for neurology. American-authored articles were cited, on average, 1.25 times more frequently than non-American-authored articles.

CONCLUSIONS:

Non-American contributions have impacted neuroradiology more than other clinical neuroscience fields with Asian authorship showing the greatest impact. That impact is growing, and the causes are manifold. Nonetheless American-authored articles are cited more.

Characteristic MR Imaging Findings of the Neonatal Brain in RASopathies [PEDIATRICS]

BACKGROUND AND PURPOSE:

Neuroimaging features in neonates with RASopathies are rarely reported, and to date, there are no neuroimaging studies conducted in this population. Our aim was to investigate the occurrence of supratentorial and posterior fossa abnormalities on brain MRIs of neonates with a RASopathy.

MATERIALS AND METHODS:

An observational case-control study of neonates with a confirmed RASopathy was conducted. The presence of an intraventricular and/or parenchymal hemorrhage and punctate white matter lesions and assessments of the splenium of the corpus callosum, gyrification of the cortical gray matter, and enlargement of the extracerebral space were noted. The vermis height, transverse cerebellar diameter, cranial base angle, tentorial angle, and infratentorial angle were measured.

RESULTS:

We reviewed 48 brain MR studies performed at 3 academic centers in 3 countries between 2009 and 2017. Sixteen of these infants had a genetically confirmed RASopathy (group 1), and 32 healthy infants were enrolled as the control group (group 2). An increased rate of white matter lesions, extracerebral space enlargement, simplification of the cortical gyrification, and white matter abnormalities were seen in group 1 (P < .001, for each). The vermis height of patients was significantly lower, and tentorial and infratentorial angles were significantly higher in group 1 (P = .01, P < .001, and P = .001, respectively).

CONCLUSIONS:

Neonates with a RASopathy had characteristic structural and acquired abnormalities in the cortical gray matter, white matter, corpus callosum, cerebellum, and posterior fossa. This study provides novel neuroimaging findings on supratentorial and posterior fossa abnormalities in neonates with a RASopathy.

Multisite Concordance of DSC-MRI Analysis for Brain Tumors: Results of a National Cancer Institute Quantitative Imaging Network Collaborative Project [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Standard assessment criteria for brain tumors that only include anatomic imaging continue to be insufficient. While numerous studies have demonstrated the value of DSC-MR imaging perfusion metrics for this purpose, they have not been incorporated due to a lack of confidence in the consistency of DSC-MR imaging metrics across sites and platforms. This study addresses this limitation with a comparison of multisite/multiplatform analyses of shared DSC-MR imaging datasets of patients with brain tumors.

MATERIALS AND METHODS:

DSC-MR imaging data were collected after a preload and during a bolus injection of gadolinium contrast agent using a gradient recalled-echo–EPI sequence (TE/TR = 30/1200 ms; flip angle = 72°). Forty-nine low-grade (n = 13) and high-grade (n = 36) glioma datasets were uploaded to The Cancer Imaging Archive. Datasets included a predetermined arterial input function, enhancing tumor ROIs, and ROIs necessary to create normalized relative CBV and CBF maps. Seven sites computed 20 different perfusion metrics. Pair-wise agreement among sites was assessed with the Lin concordance correlation coefficient. Distinction of low- from high-grade tumors was evaluated with the Wilcoxon rank sum test followed by receiver operating characteristic analysis to identify the optimal thresholds based on sensitivity and specificity.

RESULTS:

For normalized relative CBV and normalized CBF, 93% and 94% of entries showed good or excellent cross-site agreement (0.8 ≤ Lin concordance correlation coefficient ≤ 1.0). All metrics could distinguish low- from high-grade tumors. Optimum thresholds were determined for pooled data (normalized relative CBV = 1.4, sensitivity/specificity = 90%:77%; normalized CBF = 1.58, sensitivity/specificity = 86%:77%).

CONCLUSIONS:

By means of DSC-MR imaging data obtained after a preload of contrast agent, substantial consistency resulted across sites for brain tumor perfusion metrics with a common threshold discoverable for distinguishing low- from high-grade tumors.

Postnatal Brain Growth Assessed by Sequential Cranial Ultrasonography in Infants Born <30 Weeks' Gestational Age [PEDIATRICS]

BACKGROUND AND PURPOSE:

Brain growth in the early postnatal period following preterm birth has not been well described. This study of infants born at <30 weeks' gestational age and without major brain injury aimed to accomplish the following: 1) assess the reproducibility of linear measures made from cranial ultrasonography, 2) evaluate brain growth using sequential cranial ultrasonography linear measures from birth to term-equivalent age, and 3) explore perinatal predictors of postnatal brain growth.

MATERIALS AND METHODS:

Participants comprised 144 infants born at <30 weeks' gestational age at a single center between January 2011 and December 2013. Infants with major brain injury seen on cranial ultrasonography or congenital or chromosomal abnormalities were excluded. Brain tissue and fluid spaces were measured from cranial ultrasonography performed as part of routine clinical care. Brain growth was assessed in 3 time intervals: <7, 7–27, and >27 days' postnatal age. Data were analyzed using intraclass correlation coefficients and mixed-effects regression.

RESULTS:

A total of 429 scans were assessed for 144 infants. Several linear measures showed excellent reproducibility. All measures of brain tissue increased with postnatal age, except for the biparietal diameter, which decreased within the first postnatal week and increased thereafter. Gestational age of ≥28 weeks at birth was associated with slower growth of the biparietal diameter and ventricular width compared with gestational age of <28 weeks. Postnatal corticosteroid administration was associated with slower growth of the corpus callosum length, transcerebellar diameter, and vermis height. Sepsis and necrotizing enterocolitis were associated with slower growth of the transcerebellar diameter.

CONCLUSIONS:

Postnatal brain growth in infants born at <30 weeks' gestational age can be evaluated using sequential linear measures made from routine cranial ultrasonography and is associated with perinatal predictors of long-term development.

Edge Contrast of the FLAIR Hyperintense Region Predicts Survival in Patients with High-Grade Gliomas following Treatment with Bevacizumab [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Treatment with bevacizumab is standard of care for recurrent high-grade gliomas; however, monitoring response to treatment following bevacizumab remains a challenge. The purpose of this study was to determine whether quantifying the sharpness of the fluid-attenuated inversion recovery hyperintense border using a measure derived from texture analysis—edge contrast—improves the evaluation of response to bevacizumab in patients with high-grade gliomas.

MATERIALS AND METHODS:

MRIs were evaluated in 33 patients with high-grade gliomas before and after the initiation of bevacizumab. Volumes of interest within the FLAIR hyperintense region were segmented. Edge contrast magnitude for each VOI was extracted using gradients of the 3D FLAIR images. Cox proportional hazards models were generated to determine the relationship between edge contrast and progression-free survival/overall survival using age and the extent of surgical resection as covariates.

RESULTS:

After bevacizumab, lower edge contrast of the FLAIR hyperintense region was associated with poorer progression-free survival (P = .009) and overall survival (P = .022) among patients with high-grade gliomas. Kaplan-Meier curves revealed that edge contrast cutoff significantly stratified patients for both progression-free survival (log-rank ² = 8.3, P = .003) and overall survival (log-rank ² = 5.5, P = .019).

CONCLUSIONS:

Texture analysis using edge contrast of the FLAIR hyperintense region may be an important predictive indicator in patients with high-grade gliomas following treatment with bevacizumab. Specifically, low FLAIR edge contrast may partially reflect areas of early tumor infiltration. This study adds to a growing body of literature proposing that quantifying features may be important for determining outcomes in patients with high-grade gliomas.

Multisociety Consensus Quality Improvement Revised Consensus Statement for Endovascular Therapy of Acute Ischemic Stroke [research-article]

Postcontrast T1 Mapping for Differential Diagnosis of Recurrence and Radionecrosis after Gamma Knife Radiosurgery for Brain Metastasis [ADULT BRAIN]

BACKGROUND AND PURPOSE:

The differential diagnosis of radionecrosis and tumor recurrence in brain metastases is challenging. We investigated the diagnostic efficiency of postcontrast T1 mapping in solving this problem.

MATERIALS AND METHODS:

Between March 2016 and June 2017, fifty-six patients with brain metastases who underwent contrast-enhanced cerebral T1 mapping were recruited for this prospective study. The findings revealed new enhancement after gamma knife radiosurgery. The subjects were assigned to radionecrosis and recurrence groups based on follow-up (median, 11.5 months) and histopathologic results. T1 values of lesions 5 (T1_5min) and 60 (T1_60min) minutes after administration of contrast agent and their difference (T1_differ) were compared between the 2 groups with the 2-tailed Mann-Whitney U test. Receiver operating characteristic curves were used to determine the optimum cutoff values for differential diagnosis.

RESULTS:

There were significant differences between the 2 groups in T1_5min, T1_60min, and T1_differ values (P = .012, P = .004, and P < .001, respectively). Relative to T1_5min and T1_60min, T1_differ exhibited greater sensitivity and specificity (P < .001, respectively) in identifying radionecrosis. The optimum T1_differ value for differential diagnosis was 71.1 ms (area under the curve = 0.97; 95% CI, 0.93–1.00), with sensitivity and specificity of 81.5% and 96.5%, respectively.

CONCLUSIONS:

Postcontrast T1 mapping is optimal for the differential diagnosis of radionecrosis and tumor recurrence. Among T1 parameters, T1_differ is the most powerful parameter for differential diagnosis. Advantages in terms of quantitative analysis and high resolution portend the wide use of postcontrast T1 mapping in the future.

Skin Paddles Improve Muscle Flap Salvage Rates After Microvascular Compromise in Lower Extremity Reconstruction

Purpose Free tissue transfer after lower extremity trauma is associated with notoriously high complication rates. Theoretically, the inclusion of a cutaneous paddle on muscle free flaps may improve clinical flap monitoring. The effect of skin paddle presence on muscle free flap salvage outcomes after take-back was examined. Methods Retrospective query of our institutional free-flap registry (1979–2016) identified 362 muscle-based flaps performed for soft tissue coverage after below-knee trauma. Primary outcome measures were perioperative complications, specifically take-back indications, timing, and flap salvage rates. Univariate and multivariate regression analyses were performed where appropriate. Results The most common flaps were latissimus dorsi (166; 45.9%), rectus abdominis (123; 34%), and gracilis (42; 11.6%) with 90 flaps (24.9%) including skin paddles. Take-backs for vascular compromise occurred in 44 flaps (12.2%), of which 39% contained a skin paddle while 61% did not. Overall salvage rate was 20.5%, with 31.8% partial failures and 47.7% total flap losses. Muscle flaps with skin paddles were more likely to return to the operating room within 48 hours postoperatively than those without (57.1% vs 18.2%, P = 0.036). After take-back, significantly more muscle flaps with skin paddles were salvaged compared with muscle flaps without paddles (35.7% vs 4.5%, P = 0.024). Similarly, more muscle-only flaps after take-back failed compared with their counterparts with skin paddles (95.5% vs 65.3%, P = 0.024). Conclusions Muscle flaps with a cutaneous paddle were associated with earlier return to the operating room and more successful flap salvage after take-back compared with muscle-only flaps. These findings suggest that skin paddle presence may improve clinical flap monitoring and promote recognition and treatment of microvascular compromise in lower extremity reconstruction.

A Cyst Compressing the Ulnar Nerve Motor Branch: Ultrasonographic Diagnosis of a Tricking Neuropathy

No abstract available

Correction of Tuberous Nipple Areolar Complex Deformity in Gynecomastia: The Deformity That Can Get Forgotten

The desired end point of surgical reduction of gynecomastia is a masculine breast appearance and symmetry. This article concentrates on the tuberous deformity of the nipple areolar complex (NAC) that can present in gynecomastia and is sometimes overlooked at surgical correction. This deformity can be corrected at primary surgery if it is recognized preoperatively. If missed, or not adequately corrected, the postoperative result of primary reduction may be deemed incomplete by the patient and they will request revision. The deformity involves overprojection of the NAC in an anteroposterior direction, yet the base diameter may be close to normal. Correction involves reduction of the herniated breast bud, excision of excess areolar tissue, and careful radial scoring to flatten the NAC to a normal level of projection. For the NAC to have a masculine appearance, the areolae need to be symmetrical, of normal male size, and slightly oval in a transverse direction. The projection of both areola and nipple needs to be low, but present: not flattened. This article presents an operative technique to address primary or residual tuberous NAC deformity in the treatment of gynecomastia.

Computed Tomographic Angiography Used for Localization of the Cutaneous Perforators and Selection of Anterolateral Thigh Flap “Bail-Out” Branches

Background The purpose of this study was to evaluate the territory supplied by the lateral circumflex femoral artery for the consistency of a proximal perforator that could be used as an alternative pedicle for the anterolateral thigh flap if a tedious intramuscular course is encountered during elevation of the perforator used to develop the initial surgical plan. It is hypothesized that a consistent "bail-out" perforator supplying the proximal thigh would facilitate a simpler anterolateral thigh flap harvest, with minimal modification to flap design. Methods Computed tomographic images of 9 fresh cadavers were imported using Materialize's Interactive Medical Imaging Control System software to create surface-rendered 3-dimensional reconstructions of 15 lower limbs. Perforators emerging proximally and laterally to a 3-cm radius circle drawn at the midpoint of the anterior superior iliac spine and superolateral patella were considered potential bail-out perforators and evaluated for their number emerging diameter, length, course, and location relative to the anterior superior iliac spine. Results An average of 2.9 ± 1.8 perforators per limb were identified. Mean pedicle length was 111 ± 20 mm, measured from the origin in the lateral circumflex femoral artery to where the perforators emerged through the deep fascia directly overlying the thigh muscles. Average diameter at origin in the lateral circumflex femoral artery was 2.8 ± 0.8 mm, and that at emergence through the deep fascia was 1.1 ± 0.3 mm. Vessel course was predominantly musculocutaneous (90%). Conclusions A significant bail-out perforator routinely supplies the proximal anterolateral thigh and may be used as an alternative vascular pedicle for an anterolateral thigh flap if a tedious intramuscular course is encountered during elevation of a perforator identified within the conventional landmarks (3-cm radius circle at the midpoint of the anterior superior iliac spine and superolateral patella).

The Use of Expanded Polytetrafluoroethylene in Short Nose Elongation: Fourteen Years of Clinical Experience

Background Short nose elongation is a relatively common rhinoplasty procedure, especially in Asia. The selection of the adequate graft material is challenging. Previous reports have described the application of expanded polytetrafluoroethylene (ePTFE) for dorsal augmentation rhinoplasty, but studies using ePTFE for nose elongation are lacking. We propose ePTFE as an alternative treatment for short noses, describe the technique, and discuss outcomes, patient selection, and complications based on our 14-year experience. Methods From February 2003 to December 2016, 206 patients with varying degrees of short noses were included in this retrospective study. All patients underwent nose elongation surgery using an ePTFE implant. Nasal lengths before and after surgery were measured using a 3-dimensional simulation technology. Outcomes and complications including possible underlying reasons were analyzed. Patient satisfaction was evaluated using a self-assessment survey. Results Nasal elongation was successfully achieved using ePTFE. Mean increase in nasal length was 4.36 ± 0.85 mm. The mean follow-up period was 13.3 months, ranging from 6 months to 8 years. Follow-up examinations demonstrated stable results. The overall complication rate was 6.8%. Complications included infection, implant extrusion, migration, deviation, visibility, and/or prominence, tissue reaction, and reddening of the nasal skin. Most patients (93.6%) rated their outcome as improved and much improved. Conclusions Nasal elongation using ePTFE implantation is a feasible therapeutic approach for patients with short noses. Reliable outcomes and the absence of donor site morbidity contribute to the high patient acceptance. Meticulous surgical technique and careful patient selection are prerequisites for successful results.

Three-Dimensional Analysis of Mandibular Angle Classification and Aesthetic Evaluation of the Lower Face in Chinese Female Adults

Background Reduction gonioplasty is very popular in East Asia. However, there has been little quantitative criteria for mandibular angle classification or aesthetics. The aim of this study was to investigate the quantitative differences of mandibular angle types and determine the morphologic features of mandibular angle in attractive women. Methods We created a database of skull computed tomography and standardized frontal and lateral photographs of 96 Chinese female adults. Mandibular angle was classified into 3 groups, namely, extraversion, introversion, and healthy group, based on the position of gonion. We used a 5-point Likert scale to quantify attractiveness based on photographs. Those who scored 4 or higher were defined as attractive women. Three types of computed tomography measurements of the mandible were taken, including 4 distances, 4 angles, and 3 proportions. Discriminant analysis was applied to establish a mathematic model for mandibular angle aesthetics evaluation. Results Significant differences were observed between the different types of mandibular angle in lower facial width (Gol-Gor), mandibular angle (Co-Go-Me), and gonion divergence angle (Gol-Me-Gor) (P

Massive Localized Lymphedema: Analysis of Intraoperative Care

Massive localized lymphedema (MLL) is rare, but as the prevalence of obesity in adults rises, it can be foreseen that cases will increase in prevalence. These patients are unable to ambulate and have uncontrollable rash and skin breakdown. Operative management for MLL is offered when nonsurgical measures are ineffective. The surgery can be difficult with ambiguous tissue planes saturated with lymphatic fluid, ill-defined margins, large arteries and dilated veins, and extensive intraoperative fluid and blood loss. We performed a retrospective chart review and analysis with a focus on the intraoperative findings and management in order to provide improved awareness and recommendations for preoperative care. We reviewed the charts of 15 patients with MLL undergoing a total of 17 surgical resections at our institution. Patients were morbidly obese with an average body mass index of 63 kg/m2 and 5.5 other medical comorbidities. Average operative time was 4.5 hours. Operative time showed a moderate correlation with increased blood loss. Operative transfusion averaged approximately 1 U per case, with 12% (2/17) of cases needing additional transfusions following surgery. An increase in operative time correlated with an increase in crystalloid infusion. In conclusion, we recommend close communication between the surgery and anesthesia teams regarding the extent of the resection and potential for fluid resuscitation and transfusions. Preoperative laboratory tests are recommended, as well as type and cross-match prior to the operation to obtain a baseline for intraoperative and postoperative monitoring. Recommendations for intraoperative management include strict input and output monitoring and aggressive fluid resuscitation with appropriate arterial and venous access.

Periumbilical Perforator-Sparing Abdominoplasty in Patients With Abdominal Scars

Abdominoplasty is one of the most common cosmetic surgical procedures. Patients who undergo abdominoplasties with abdominal scars are at an increased risk for skin necrosis and wound breakdown. To prevent further disruption of vascularity, the dissection and mobilization is often limited resulting in a suboptimal esthetic result. The periumbilical perforator-sparing technique allows for vascular preservation and adequate mobilization to produce excellent esthetic results in patients with abdominal scars.

Microvascular Replantation Following Facial Dog Bites in Children: Systematic Review and Management Algorithm

Background Pediatric dog bite injuries account for 1% of emergency department visits per year and represent an underrecognized and underreported public health problem. Reconstructive surgery is frequently utilized, and in the most extreme injuries, microvascular replantation may be considered. We sought to systematically review the available literature on microvascular replantation after facial dog bite injuries in children, with particular attention to perioperative morbidity and long-term follow-up. Methods We reviewed a case of microvascular replantation after a facial dog bite injury in a child from our own institution and conducted a systematic literature search to identify other similar reports. Clinical variables were collected from the reported cases, and descriptive statistics were calculated. A management algorithm was developed from the reviewed published experience. Results We report the youngest child to date in the literature to undergo replantation after a facial dog bite injury. Nineteen other cases were found involving children aged 18 months to 17 years, with follow-up ranging from 2 weeks to 28 years. Anastomosis techniques varied considerably and included both an artery and vein in only 9 (47%) of 19 cases. Venous congestion was nearly universal, and multimodal techniques were used until native venous outflow was reestablished. Blood transfusion was common, but intensive care unit utilization was not frequently reported. Long-term outcomes were excellent, with growth of the replanted part and recovery of function; however, minor revision procedures were common. Conclusions Microvascular replantation following facial dog bite amputation injuries in the pediatric population is the ultimate step in the reconstructive ladder. Strong consideration should be given to microvascular exploration with involvement of large or whole segments of the lip, nose, or ear; however, parents should be counseled extensively regarding the known morbidity of replantation surgery. With meticulous surgical technique and careful postoperative care, replantation after facial dog bite amputation injuries may successfully achieve dramatic and lasting results for pediatric patients.