Τετάρτη 15 Νοεμβρίου 2017
Pan-Asian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer; A JSMO - ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS
Abstract
The most recent version of the European Society for Medical Oncology (ESMO) consensus guidelines for the treatment of patients with metastatic colorectal cancer (mCRC) was published in 2016, identifying both a more strategic approach to the administration of the available systemic therapy choices, and a greater emphasis on the use of ablative techniques, including surgery. At the 2016 ESMO Asia Meeting, in December 2016, it was decided by both ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting, endorsed by both ESMO and JSMO, immediately after the JSMO 2017 Annual Meeting. The aim was to adapt the ESMO consensus guidelines to take into account the ethnic differences relating to the toxicity as well as other aspects of certain systemic treatments in patients of Asian ethnicity. These guidelines represent the consensus opinions reached by experts in the treatment of patients with mCRC identified by the Presidents of the oncological societies of Japan (JSMO), China (CSCO), Korea (KACO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.An overview of methods to mitigate artifacts in optical coherence tomography imaging of the skin
Abstract
Background
Optical coherence tomography (OCT) of skin delivers three-dimensional images of tissue microstructures. Although OCT imaging offers a promising high-resolution modality, OCT images suffer from some artifacts that lead to misinterpretation of tissue structures. Therefore, an overview of methods to mitigate artifacts in OCT imaging of the skin is of paramount importance. Speckle, intensity decay, and blurring are three major artifacts in OCT images. Speckle is due to the low coherent light source used in the configuration of OCT. Intensity decay is a deterioration of light with respect to depth, and blurring is the consequence of deficiencies of optical components.
Method
Two speckle reduction methods (one based on artificial neural network and one based on spatial compounding), an attenuation compensation algorithm (based on Beer-Lambert law) and a deblurring procedure (using deconvolution), are described. Moreover, optical properties extraction algorithm based on extended Huygens-Fresnel (EHF) principle to obtain some additional information from OCT images are discussed.
Results
In this short overview, we summarize some of the image enhancement algorithms for OCT images which address the abovementioned artifacts. The results showed a significant improvement in the visibility of the clinically relevant features in the images. The quality improvement was evaluated using several numerical assessment measures.
Conclusion
Clinical dermatologists benefit from using these image enhancement algorithms to improve OCT diagnosis and essentially function as a noninvasive optical biopsy.
Patch testing in Israeli children with suspected allergic contact dermatitis: A retrospective study and literature review
Abstract
Background/objectives
Childhood allergic contact dermatitis is recognized as a significant clinical problem. The objective was to evaluate the rate of positive patch tests in Israeli children with clinically suspected allergic contact dermatitis, identify possible sex and age differences, compare results with those in Israeli adults, and review pediatric studies in the literature.
Methods
The study sample included 343 children and adolescents (197 female, 146 male; 1-18 years of age, mean age 11.8 years) with clinically suspected allergic contact dermatitis who underwent patch testing with a standard pediatric series of 23 allergens at a tertiary medical center from 1999 to 2012. Data on clinical characteristics and test results were collected retrospectively from the medical files.
Results
Ninety-eight subjects (28.6%) (75 girls [38.1%], 23 boys [15.8%]) had at least one positive reaction. The most frequent reactions were to nickel sulfate, followed by potassium dichromate and cobalt chloride. Nickel sulfate sensitivity was more common in girls, especially those younger than 3 years and older than 12 years. The prevalence of contact sensitization was similar in subjects with and without atopic dermatitis (50% and 51%, respectively).
Conclusion
Nickel is the most common allergen in Israeli children, especially girls. Patch testing should be performed in children with clinically suspected allergic contact dermatitis regardless of atopic background.
Ethnic differences in stratum corneum functions between Chinese and Thai infants residing in Bangkok, Thailand
Abstract
Background/Objectives
Ethnic and racial differences in infant skin have not been well characterized. The purpose of this study was to establish whether there are ethnic differences and similarities in the stratum corneum (SC) functions of Thai and Chinese infants.
Methods
Healthy infants 6 to 24 months of age (N = 60; 30 Thai, 30 Chinese) who resided in Bangkok, Thailand, were enrolled. Transepidermal water loss (TEWL) and SC hydration (capacitance) on the thigh, buttock, and upper arm were measured. Ceramide content was determined in the SC on the upper arm.
Results
SC hydration was not remarkably different between the two ethnicities at any site measured, but TEWL was significantly higher in Chinese infants than in Thai infants at all sites. Hydration of the SC was not significantly correlated with age in either ethnicity. TEWL had significant but weak correlations with age on the thigh and upper arm in Thai infants. Ceramide content was significantly higher in Chinese SC than in Thai SC. No relationship between ceramide content and TEWL or hydration was observed in either ethnicity.
Conclusion
The significant differences in TEWL and ceramide contents between Chinese and Thai infant skin could prove useful in designing skin care and diapering products that are best suited for each ethnicity.
Comparative Transcriptomics of Seasonal Phenotypic Flexibility in Two North American Songbirds
Synopsis
Phenotypic flexibility allows organisms to reversibly alter their phenotypes to match the changing demands of seasonal environments. Because phenotypic flexibility is mediated, at least in part, by changes in gene regulation, comparative transcriptomic studies can provide insights into the mechanistic underpinnings of seasonal phenotypic flexibility, and the extent to which regulatory responses to changing seasons are conserved across species. To begin to address these questions, we sampled individuals of two resident North American songbird species, American goldfinch (Spinus tristis) and black-capped chickadee (Poecile atricapillus) in summer and winter to measure seasonal variation in pectoralis transcriptomic profiles and to identify conserved and species-specific elements of these seasonal profiles. We found that very few genes exhibited divergent responses to changes in season between species, and instead, a core set of over 1200 genes responded to season concordantly in both species. Moreover, several key metabolic pathways, regulatory networks, and gene functional classes were commonly recruited to induce seasonal phenotypic shifts in these species. The seasonal transcriptomic responses mirror winter increases in pectoralis mass and cellular metabolic intensity documented in previous studies of both species, suggesting that these seasonal phenotypic responses are due in part to changes in gene expression. Despite growing evidence of muscle nonshivering thermogenesis (NST) in young precocial birds, we did not find strong evidence of upregulation of genes putatively involved in NST during winter in either species, suggesting that seasonal modification of muscular NST is not a prominent contributor to winter increases in thermogenic capacity for adult passerine birds. Together, these results provide the first comprehensive overview of potential common regulatory mechanisms underlying seasonally flexible phenotypes in wild, free-ranging birds.Thermal Acclimation Ability Varies in Temperate and Tropical Aquatic Insects from Different Elevations
Synopsis
It has long been recognized that populations and species occupying different environments vary in their thermal tolerance traits. However, far less attention has been given to the impact of different environments on the capacity for plastic adjustments in thermal sensitivity, i.e., acclimation ability. One hypothesis is that environments characterized by greater thermal variability and seasonality should favor the evolution of increased acclimation ability compared with environments that are aseasonal or thermally stable. Additionally, organisms under selection for high heat tolerance may experience a trade-off and lose acclimation ability. Few studies have tested these non-mutually exclusive hypotheses at both broad latitudinal and local elevation scales in phylogenetically paired taxa. Here, we measure short-term acclimation ability of the critical thermal maximum (CTMAX) in closely related temperate and tropical mayflies (Ephemeroptera) and stoneflies (Plecoptera) from mountain streams at different elevations. We found that stream temperature was a good predictor of acclimation ability in mayflies, but not in stoneflies. Specifically, tropical mayflies showed reduced acclimation ability compared with their temperate counterparts. High elevation tropical mayflies had greater acclimation ability than low elevation mayflies, which reflected the wider temperature variation experienced in high elevation streams. In contrast, temperate and tropical stoneflies exhibited similar acclimation responses. We found no evidence for a trade-off between heat tolerance and acclimation ability in either taxonomic order. The acclimation response in stoneflies may reflect their temperate origin or foraging mode. In combination with previous studies showing tropical taxa have narrower thermal breadths, these results demonstrate that many lower elevation tropical aquatic insects are more vulnerable to climate warming than their temperate relatives.Understanding Evolutionary Impacts of Seasonality: An Introduction to the Symposium
Synopsis
Seasonality is a critically important aspect of environmental variability, and strongly shapes all aspects of life for organisms living in highly seasonal environments. Seasonality has played a key role in generating biodiversity, and has driven the evolution of extreme physiological adaptations and behaviors such as migration and hibernation. Fluctuating selection pressures on survival and fecundity between summer and winter provide a complex selective landscape, which can be met by a combination of three outcomes of adaptive evolution: genetic polymorphism, phenotypic plasticity, and bet-hedging. Here, we have identified four important research questions with the goal of advancing our understanding of evolutionary impacts of seasonality. First, we ask how characteristics of environments and species will determine which adaptive response occurs. Relevant characteristics include costs and limits of plasticity, predictability, and reliability of cues, and grain of environmental variation relative to generation time. A second important question is how phenological shifts will amplify or ameliorate selection on physiological hardiness. Shifts in phenology can preserve the thermal niche despite shifts in climate, but may fail to completely conserve the niche or may even expose life stages to conditions that cause mortality. Considering distinct environmental sensitivities of life history stages will be key to refining models that forecast susceptibility to climate change. Third, we must identify critical physiological phenotypes that underlie seasonal adaptation and work toward understanding the genetic architectures of these responses. These architectures are key for predicting evolutionary responses. Pleiotropic genes that regulate multiple responses to changing seasons may facilitate coordination among functionally related traits, or conversely may constrain the expression of optimal phenotypes. Finally, we must advance our understanding of how changes in seasonal fluctuations are impacting ecological interaction networks. We should move beyond simple dyadic interactions, such as predator prey dynamics, and understand how these interactions scale up to affect ecological interaction networks. As global climate change alters many aspects of seasonal variability, including extreme events and changes in mean conditions, organisms must respond appropriately or go extinct. The outcome of adaptation to seasonality will determine responses to climate change.Life History Adaptations to Seasonality
Synopsis
Seasonality creates a template for many natural processes and evolutionary adaptations. Organisms are often faced with an annual cycle consisting of a productive (favorable) and unproductive period. This yearly cycle along with other seasonal variations in abiotic factors and associated biotic interactions form strong selection pressures shaping the scheduling of annual activities and the developmental stages and modes of life through the year. Annual decisions impact trade-offs that involve both current and future reproductive value (RV), and life history theory provides the foundation to understand these linkages between phenology and an organism's full life. Annual routine models further allow for multiple annual decisions to be optimized and predicted with respect to lifetime consequences. Studies of life history adaptations to seasonality are concerned with questions such as: within the productive season, should growth come first, followed by reproduction, or the other way around? What is the best time to diapause or migrate, and how will this timing impact other life history traits? Should energy reserves be built, to transfer resources from 1 year to the next, and allow for the spatial and temporal freedom of capital breeding? If offspring value is low during parts of the productive season, what is then the best alternative to reproduction: accumulate stores, grow, or wait in safety? To help answer these and other questions, I provide an overview of key theoretical concepts and some of the main life schedules, annual routines, and trade-offs involved. Adaptations to the unproductive period include diapause (dormancy), embryonic resting stages (eggs, seeds), energy reserves, and seasonal migrations. Adaptations to the productive window include rapid growth, high reproductive effort, capital breeding, and reproduction entrained to the annual cycle and with precise timing. Distinct annual routines, large body size, energy storage capacities, and parental care are also adaptations to seasonality. Phenotypic plasticity and state-dependence are important parts of these traits and are adaptations in their own. I give particular attention to timing of breeding and the associated birth-time dependent contributions to fitness. Seasonality in offspring value impacts the scheduling of growth, storage, and reproduction and may create parent–offspring conflicts over breeding timing. A combined offspring and parent value perspective should be adopted more broadly, also because of the management implications. I further argue for strategic but careful use of latitudinal (and altitudinal) gradients, and more attention to the role of seasonally varying predation risk as a selective force.Genetic Decoupling of Thermal Hardiness across Metamorphosis in Drosophila melanogaster
Synopsis
As organisms age the environment fluctuates, exerting differential selection across ontogeny. In particular, highly seasonal environments expose life stages to often drastically different thermal environments. This developmental variation is particularly striking in organisms with complex life cycles, wherein life history stages also exhibit distinct morphologies, physiologies, and behaviors. Genes acting pleiotropically on thermal responses may produce genetic correlations across ontogeny, constraining the independent evolution of each life stage to their respective thermal environments. To investigate whether developmental genetic correlations constrain the evolution thermal hardiness of the fly Drosophila melanogaster, we applied quantitative genetic analyses to cold hardiness measured in both larvae and adults from isogenic lines of the Drosophila Genetic Reference Panel (DGRP), using survival at stressful low temperatures as the phenotypic metric. Using full genome resequencing data for the DGRP, we also implemented genome-wide association (GWA) analysis using Bayesian Sparse Linear Mixed Models (BSLMMs) to estimate associations between naturally segregating variation and cold hardiness for both larvae and adults. Quantitative genetic analyses revealed no significant genetic correlation for cold hardiness between life stages, suggesting complete genetic decoupling of thermal hardiness across the metamorphic boundary. Both quantitative genetic and GWA analyses suggested that polygenic variation underlies cold hardiness in both stages, and that associated loci largely affected one stage or the other, but not both. However, reciprocal enrichment tests and correlations between BSLMM parameters for each life stage support some shared physiological mechanisms that may reflect common cellular thermal response pathways. Overall, these results suggest no developmental genetic constraints on cold hardiness across metamorphosis in D. melanogaster, an important consideration in evolutionary models of responses to changing climates. Genetic correlations for environmental sensitivity across ontogeny remains largely unexplored in other organisms, thus assessing the generality of genetic decoupling will require further quantitative or population genetic analysis in additional species.To Everything There Is a Season: Summer-to-Winter Food Webs and the Functional Traits of Keystone Species
Synopsis
From a trophic perspective, a seasonal increase in air temperature and photoperiod propagates as bottom-up pulse of primary production by plants, secondary production by herbivores, and tertiary production by carnivores. However, food web seasonality reflects not only abiotic variation in temperature and photoperiod, but also the composition of the biotic community and their functional responses to this variation. Some plants and animals—here referred to as seasonal specialists—decouple from food webs in winter through migration or various forms of metabolic arrest (e.g., senescence, diapause, and hibernation), whereas some plants and resident animals—here referred to as seasonal generalists—remain present and trophically coupled in winter. The co-occurrence of species with divergent responses to winter introduces seasonal variation in interaction strengths, resulting in summer-to-winter differences in trophic organization. Autumn cooling and shortening day length arrests primary productivity and cues seasonal herbivores to decouple, leaving generalist carnivores to concentrate their predation on the few generalist herbivores that remain resident, active, and vulnerable to predation in winter, which themselves feed on the few generalist plant structures available in winter. Thus, what was a bottom-up pulse, spread among many species in summer, including highly productive seasonal specialists, reverses into strong top-down regulation in winter that is top-heavy, and concentrated among a small number of generalist herbivores and their winter foods. Intermediate-sized, generalist herbivores that remain active and vulnerable to predation in winter are likely to be keystone species in seasonal food webs because they provide the essential ecosystem service of turning summer primary productivity into winter food for carnivores. Empirical examination of terrestrial mammals and their seasonal trophic status in the boreal forest and across an arctic-to-tropics seasonality gradient indicates seasonal specialization is more common among herbivores, small body sizes, and in regions with intermediate seasonality, than among carnivores, large body size, and regions where summers are very short or very long. Better understanding of food webs in seasonal environments, including their vulnerability and resilience to climate change, requires a multi-season perspective.A Complex Lens for a Complex Eye
Synopsis
A key innovation for high resolution eyes is a sophisticated lens that precisely focuses light onto photoreceptors. The eyes of holometabolous larvae range from very simple eyes that merely detect light to eyes that are capable of high spatial resolution. Particularly interesting are the bifocal lenses of Thermonectus marmoratus larvae, which differentially focus light on spectrally-distinct retinas. While functional aspects of insect lenses have been relatively well studied, little work has explored their molecular makeup, especially in regard to more complex eye types. To investigate this question, we took a transcriptomic and proteomic approach to identify the major proteins contributing to the principal bifocal lenses of T. marmoratus larvae. Mass spectrometry revealed 10 major lens proteins. Six of these share sequence homology with cuticular proteins, a large class of proteins that are also major components of corneal lenses from adult compound eyes of Drosophila melanogaster and Anopheles gambiae. Two proteins were identified as house-keeping genes and the final two lack any sequence homologies to known genes. Overall the composition seems to follow a pattern of co-opting transparent and optically dense proteins, similar to what has been described for other animal lenses. To identify cells responsible for the secretion of specific lens proteins, we performed in situ hybridization studies and found some expression differences between distal and proximal corneagenous cells. Since the distal cells likely give rise to the periphery and the proximal cells to the center of the lens, our findings highlight a possible mechanism for establishing structural differences that are in line with the bifocal nature of these lenses. A better understanding of lens composition provides insights into the evolution of proper focusing, which is an important step in the transition between low-resolution and high-resolution eyes.Canalization of Seasonal Phenology in the Presence of Developmental Variation: Seed Dormancy Cycling in an Annual Weed
Synopsis
Variation in the developmental timing in one life stage may ramify within and across generations to disrupt optimal phenology of other life stages. By focusing on a common mechanism of developmental arrest in plants—seed dormancy—we investigated how variation in flowering time influenced seed germination behavior and identified potential processes that can lead to canalized germination behavior despite variation in reproductive timing. We quantified effects of reproductive timing on dormancy cycling by experimentally manipulating the temperature during seed maturation and the seasonal timing of seed dispersal/burial, and by assessing temperature-dependent germination of un-earthed seeds over a seasonal cycle. We found that reproductive timing, via both seed-maturation temperature and the timing of dispersal, strongly influenced germination behavior in the weeks immediately following seed burial. However, buried seeds subsequently canalized their germination behavior, after losing primary dormancy and experiencing natural temperature and moisture conditions in the field. After the complete loss of primary dormancy, germination behavior was similar across seed-maturation and dispersal treatments, even when secondary dormancy was induced. Maternal effects themselves may contribute to the canalization of germination: first, by inducing stronger dormancy in autumn-matured seeds, and second by modifying the responses of those seeds to their ambient environment. Genotypes differed in dormancy cycling, with functional alleles of known dormancy genes necessary for the suppression of germination at warm temperatures in autumn through spring across multiple years. Loss of function of dormancy genes abolished almost all dormancy cycling. In summary, effects of reproductive phenology on dormancy cycling of buried seeds were apparent only as long as seeds retained primary dormancy, and a combination of genetically imposed seed dormancy, maternally induced seed dormancy, and secondary dormancy can mitigate variation in germination behavior imposed by variation in reproductive phenology.Low-Resolution Vision—at the Hub of Eye Evolution
Synopsis
Simple roles for photoreception are likely to have preceded more demanding ones such as vision. The driving force behind this evolution is the improvement and elaboration of animal behaviors using photoreceptor input. Because the basic role for all senses aimed at the external world is to guide behavior, we argue here that understanding this "behavioral drive" is essential for unraveling the evolutionary past of the senses. Photoreception serves many different types of behavior, from simple shadow responses to visual communication. Based on minimum performance requirements for different types of tasks, photoreceptors have been argued to have evolved from non-directional receptors, via directional receptors, to low-resolution vision, and finally to high-resolution vision. Through this sequence, the performance requirements on the photoreceptors have gradually changed from broad to narrow angular sensitivity, from slow to fast response, and from low to high contrast sensitivity during the evolution from simple to more advanced and demanding behaviors. New behaviors would only evolve if their sensory performance requirements to some degree overlap with the requirements of already existing behaviors. This need for sensory "performance continuity" must have determined the order by which behaviors have evolved and thus been an important factor guiding animal evolution. Naturally, new behaviors are most likely to evolve from already existing behaviors with similar neural processing needs and similar motor responses, pointing to "neural continuity" as another guiding factor in sensory evolution. Here we use these principles to derive an evolutionary tree for behaviors driven by photoreceptor input.Intracellular Recordings of Spectral Sensitivities in Stomatopods: a Comparison across Species
Synopsis
Stomatopods (mantis shrimps) possess one of the most complex eyes in the world with photoreceptors detecting up to 12 different colors. It is not yet understood why stomatopods have almost four times the number of spectral photoreceptors compared with most other animals. It has, however, been suggested that these seemingly redundant photoreceptors could encode color through a new mechanism. Here we compare the spectral sensitivities across five species of stomatopods within the superfamily Gonodactyloidea using intracellular electrophysiological recordings. The results show that the spectral sensitivities across species of stomatopods are remarkably similar apart from some variation in the long-wavelength receptors. We relate these results to spectral sensitivity estimates previously obtained using microspectrophotometry and discuss the variation in the spectral sensitivity maxima (λmax) of the long-wavelength receptors in regard to the previous findings that stomatopods are able to tune their spectral sensitivities according to their respective light environment. We further discuss the similarities of the spectral sensitivities across species of stomatopods in regard to how color information might be processed by their visual systems.Sensory Biology of Starfish—With Emphasis on Recent Discoveries in their Visual Ecology
Synopsis
Asteroidea, starfish, constitutes a major part of the macrobenthos in most marine environments. Being members of the echinoderms, they have a nervous system with no well-defined central nervous system. Accordingly, starfish are assumed to pick up rather limited information from the surroundings, and it is also often assumed that most of their behaviors are guided by olfaction. Here, the sensory biology of starfish is reviewed in order to evaluate these assumptions. There is a vast amount of behavioral data dealing with mechanoreception, chemoreception, and combinations of the two (chemosensory-mediated rheotaxis), but the receptors have not yet been identified and almost nothing is known about the physiology behind these senses. What can be concluded from the available data is that starfish possess a sense of touch, some are able to sense gravity and many display positive rheotaxis, moving up currents. A number of starfish species use olfaction during foraging and prey localization. Interestingly, eyes are also present in most starfish, and recent studies have documented that in Linckia laevigata and Acanthaster planci vision plays a major role in seeking out their feeding grounds. The physiology and structure of the eyes filter out small moving objects while optimizing the contrast between the large stationary objects (e.g., coral boulders in the habitat) and the surrounding water. These new results demonstrate the importance of controlling the visual environment when conducting experiments on starfish behavior.A Novel Display System Reveals Anisotropic Polarization Perception in the Motion Vision of the Butterfly Papilio xuthus
Synopsis
While the linear polarization of light is virtually invisible to humans, many invertebrates' eyes can detect it. How this information is processed in the nervous system, and what behavioral function it serves, are in many cases unclear. One reason for this is the technical difficulty involved in presenting images or video containing polarization contrast, particularly if intensity and/or color contrast is also required. In this primarily methods-focused article, we present a novel technique based on projecting video through a synchronously rotating linear polarizer. This approach allows the intensity, angle of polarization, degree of linear polarization, and potentially also color of individual pixels to be controlled independently. We characterize the performance of our system, and then use it to investigate the relationship between polarization and motion vision in the swallowtail butterfly Papilio xuthus. Although this animal has photoreceptors sensitive to four different polarization angles, we find that its motion vision cannot distinguish between diagonally-polarized and unpolarized light. Furthermore, it responds more strongly to vertically-polarized moving objects than horizontally-polarized ones. This implies that Papilio's polarization-based motion detection employs either an unbalanced two-channel (dipolatic) opponent architecture, or possibly a single-channel (monopolatic) scheme without opponent mechanisms.The Preoptic Area and the RFamide-Related Peptide Neuronal System Gate Seasonal Changes in Chemosensory Processing
Synopsis
Males of many species rely on chemosensory information for social communication. In male Syrian hamsters (Mesocricetus auratus), as in many species, female chemosignals potently stimulate sexual behavior and a concurrent, rapid increase in circulating luteinizing hormone (LH) and testosterone (T). However, under winter-like, short-day (SD) photoperiods, when Syrian hamsters are reproductively quiescent, these same female chemosignals fail to elicit behavioral or hormonal responses, even after T replacement. It is currently unknown where in the brain chemosensory processing is gated in a seasonally dependent manner such that reproductive responses are only displayed during the appropriate breeding season. The goal of the present study was to determine where this gating occurred by identifying neural loci that respond differentially to female chemosignals across photoperiods, independent of circulating T concentrations. Adult male Syrian hamsters were housed under either long-day (LD) (reproductively active) or SD (reproductively inactive) photoperiods with half of the SD animals receiving T replacement. Animals were exposed to either female hamster vaginal secretions (FHVSs) diluted in mineral oil or to vehicle, and the activational state of chemosensory processing centers and elements of the neuroendocrine reproductive axis were examined. Components of the chemosensory pathway upstream of hypothalamic centers increased expression of FOS, an indirect marker of neuronal activation, similarly across photoperiods. In contrast, the preoptic area (POA) of the hypothalamus responded to FHVS only in LD animals, consistent with its role in promoting expression of male sexual behavior. Within the neuroendocrine axis, the RF-amide related peptide (RFRP), but not the kisspeptin neuronal system responded to FHVS only in LD animals. Neither response within the POA or the RFRP neuronal system was rescued by T replacement in SD animals, mirroring photoperiodic regulation of reproductive responses. Considering the POA and the RFRP neuronal system promote reproductive behavior and function in male Syrian hamsters, differential activation of these systems represents a potential means by which photoperiod limits expression of reproduction to the appropriate environmental context.Moving in Dim Light: Behavioral and Visual Adaptations in Nocturnal Ants
Synopsis
Visual navigation is a benchmark information processing task that can be used to identify the consequence of being active in dim-light environments. Visual navigational information that animals use during the day includes celestial cues such as the sun or the pattern of polarized skylight and terrestrial cues such as the entire panorama, canopy pattern, or significant salient features in the landscape. At night, some of these navigational cues are either unavailable or are significantly dimmer or less conspicuous than during the day. Even under these circumstances, animals navigate between locations of importance. Ants are a tractable system for studying navigation during day and night because the fine scale movement of individual animals can be recorded in high spatial and temporal detail. Ant species range from being strictly diurnal, crepuscular, and nocturnal. In addition, a number of species have the ability to change from a day- to a night-active lifestyle owing to environmental demands. Ants also offer an opportunity to identify the evolution of sensory structures for discrete temporal niches not only between species but also within a single species. Their unique caste system with an exclusive pedestrian mode of locomotion in workers and an exclusive life on the wing in males allows us to disentangle sensory adaptations that cater for different lifestyles. In this article, we review the visual navigational abilities of nocturnal ants and identify the optical and physiological adaptations they have evolved for being efficient visual navigators in dim-light.Crustacean Larvae—Vision in the Plankton
Synopsis
We review the visual systems of crustacean larvae, concentrating on the compound eyes of decapod and stomatopod larvae as well as the functional and behavioral aspects of their vision. Larval compound eyes of these macrurans are all built on fundamentally the same optical plan, the transparent apposition eye, which is eminently suitable for modification into the abundantly diverse optical systems of the adults. Many of these eyes contain a layer of reflective structures overlying the retina that produces a counterilluminating eyeshine, so they are unique in being camouflaged both by their transparency and by their reflection of light spectrally similar to background light to conceal the opaque retina. Besides the pair of compound eyes, at least some crustacean larvae have a non-imaging photoreceptor system based on a naupliar eye and possibly other frontal eyes. Larval compound-eye photoreceptors send axons to a large and well-developed optic lobe consisting of a series of neuropils that are similar to those of adult crustaceans and insects, implying sophisticated analysis of visual stimuli. The visual system fosters a number of advanced and flexible behaviors that permit crustacean larvae to survive extended periods in the plankton and allows them to reach acceptable adult habitats, within which to metamorphose.Thermal Performance Curves Reveal Variation in the Seasonal Niche of a Short-Lived Annual
Synopsis
An organism's environment can vary over spatial and temporal scales. Seasonal variation is an important but overlooked source of environmental variation that often shapes the ranges of organisms. The seasonal niche is a description of the spatiotemporal range of an organism resulting from spatial variation in seasonal conditions. In this study, I describe the seasonal niche of a short-lived annual plant, and variation within the species in seasonal niche breadth. I construct a seasonal species distribution model (SDM) for the species, and using thermal performance curves (TPCs), construct mechanistic SDMs (MSDMs) for individual genotypes. I quantify the correlation between the suitability scores generated in the SDM and the predicted dry weight generated by the MSDMs for each genotype, to estimate variation in seasonal niche breadth among genotypes. Thus, the parameters of TPCs reflect generalist/specialist strategies. I detected significant relationships between thermal performance breadth and maximum predicted fitness and significant correlations between optimal growth temperature and thermal performance breadth. There were large positive correlations between predictions of the SDM and MSDMs based on growth within individual genotypes. The variation in these correlations suggests variation in the degree of specialization. Genotypes with the broadest TPCs had the largest correlations between their MSDMs and the SDM, suggesting that they were generalists. The results show that correlative and MSDMs make similar predictions over the seasonal range, and that ecological specialization can vary dramatically within species.Resolving the Trade-off Between Visual Sensitivity and Spatial Acuity—Lessons from Hawkmoths
Synopsis
The visual systems of many animals, particularly those active during the day, are optimized for high spatial acuity. However, at night, when photons are sparse and the visual signal competes with increased noise levels, fine spatial resolution cannot be sustained and is traded-off for the greater sensitivity required to see in dim light. High spatial acuity demands detectors and successive visual processing units whose receptive fields each cover only a small area of visual space, in order to reassemble a finely sampled and well resolved image. However, the smaller the sampled area, the fewer the photons that can be collected, and thus the worse the visual sensitivity becomes—leading to the classical trade-off between sensitivity and resolution. Nocturnal animals usually resolve this trade-off in favour of sensitivity, and thus have lower spatial acuity than their diurnal counterparts. Here we review results highlighting how hawkmoths, a highly visual group of insects with species active at different light intensities, resolve the trade-off between sensitivity and spatial resolution. We compare adaptations both in the optics and retina, as well as at higher levels of neural processing in a nocturnal and a diurnal hawkmoth species, and also give a perspective on the behavioral consequences. We broaden the scope of our review by drawing comparisons with the adaptive strategies used by other nocturnal and diurnal insects.Defining the Degree of Seasonality and its Significance for Future Research
Synopsis
Seasonality describes cyclic and largely predictable fluctuations in the environment. Such variations in day length, temperature, rainfall, and resource availability are ubiquitous and can exert strong selection pressure on organisms to adapt to seasonal environments. However, seasonal variations exhibit large scale geographical divergences caused by a whole suite of factors such as solar radiation, ocean currents, extent of continents, and topography. Realizing these contributions in driving patterns of overall seasonality may help advance our understanding of the kinds of evolutionary adaptations we should expect at a global scale. Here, we introduce a new concept and provide the data describing the overall degree of seasonality, based on its two major components—amplitude and predictability. Using global terrestrial datasets on temperature, precipitation and primary productivity, we show that these important seasonal factors exhibit strong differences in their spatial patterns with notable asymmetries between the southern and the northern hemisphere. Furthermore, our analysis reveals that seasonality is highly diverse across latitudes as well as longitudinal gradients. This indicates that using a direct measure of seasonality and its components, amplitude and predictability, may yield a better understanding of how organisms are adapted to seasonal environments and provide support for predictions on the consequences of rapid environmental change.Insect Development, Thermal Plasticity and Fitness Implications in Changing, Seasonal Environments
Synopsis
Historical data show that recent climate change has caused advances in seasonal timing (phenology) in many animals and plants, particularly in temperate and higher latitude regions. The population and fitness consequences of these phenological shifts for insects and other ectotherms have been heterogeneous: warming can increase development rates and the number of generations per year (increasing fitness), but can also lead to seasonal mismatches between animals and their resources and increase exposure to environmental variability (decreasing fitness). Insect populations exhibit local adaptation in their developmental responses to temperature, including lower developmental thresholds and the thermal requirements to complete development, but climate change can potentially disrupt seasonal timing of juvenile and adult stages and alter population fitness. We investigate these issues using a global dataset describing how insect developmental responds to temperature via two traits: lower temperature thresholds for development (T0) and the cumulative degree-days required to complete development (G). As suggested by previous analyses, T0 decreases and G increases with increasing (absolute) latitude; however, these traits and the relationship between G and latitude varies significantly among taxonomic orders. The mean number of generations per year (a metric of fitness) increases with both decreasing T0 and G, but the effects of these traits on fitness vary strongly with latitude, with stronger selection on both traits at higher (absolute) latitudes. We then use the traits to predict developmental timing and temperatures for multiple generations within seasons and across years (1970–2010). Seasonality drives developmental temperatures to peak mid-season and for generation lengths to decline across seasons, particularly in temperate regions. We predict that climate warming has advanced phenology and increased the number of generations, particularly at high latitudes. The magnitude of increases in developmental temperature varies little across latitude. Increases in the number of seasonal generations have been greatest for populations experiencing the greatest phenological advancements and warming. Shifts in developmental rate and timing due to climate change will have complex implications for selection and fitness in seasonal environments.Evaluation of some chronical diseases in etiopathogenesis of demodicosis
Publication date: December 2017
Source:Dermatologica Sinica, Volume 35, Issue 4
Author(s): Zeynep Tas Cengiz, Hatice Uce Ozkol, Yunus Emre Beyhan, Murat Ozturk, Hasan Yilmaz
BackgroundThe aim of this study is to assess the effect of chronic diseases on the etiopathogenesis of demodicosis through the determination of Demodex sp. positivity in the face and eyelashes of the people with the chronic disease.MethodsThis study is conducted on the patients who were referred to the Laboratory of Parasitology from the Yuzuncu Yil University, Faculty of Medicine, Outpatient Clinic of Dermatology. The samples were taken from the patients with standard skin surface biopsy. Furthermore, eyelashes of the patients were examined for Demodex sp.ResultWhen the patient groups are considered, demodicosis was found in the ratio of 18.5% of the patients with diabetes mellitus (p < 0.05), in 27% of those with hypertension (p < 0.01), in 25% of those with cancer (p < 0.01), in 32.5% of those with chronic renal failure (p < 0.01), in 23.7% of those with hypothyroidism (p < 0.05) and in 22.2% of the patients with hepatitis B (p < 0.05). Demodex sp. positivity was determined in the eyelashes of eight patients (p > 0.05).ConclusionIt is concluded that, in such patients the presence of this parasite should be taken into consideration in case of dermatoses occurring on the face, and these patients could be under the risk of occurring blepharitis as well.
Lichen planus pigmentosus-inversus: A peculiar variant of lichen planus
Publication date: December 2017
Source:Dermatologica Sinica, Volume 35, Issue 4
Author(s): Duru Tabanlıoğlu-Onan, Pınar İncel-Uysal, Ayşe Öktem, Derya Yayla, Esra Özhamam, Ferda Artüz
Lichen planus pigmentosus-inversus (LPP-inversus) which is an uncommon variant of lichen planus, is characterized by well bordered hyperpigmented macules and patches involving intertriginous areas. Since it was first defined, very few cases have been reported worldwide. Herein we report eight new patients with characteristic features of LPP-inversus. The hyperpigmented lesions of our patients were mostly located on axilla and the inguinal region. Two patients also had lesions that were clinically consistent with classic lichen planus. Three patients had lesions with unilateral distribution. In all of the cases a skin biopsy was performed to confirm the clinical diagnosis of LPP-inversus. LPP-inversus is a disease with unique clinical and histopathological features that we should bear in mind in the differential diagnosis of hyperpigmented flexural lesions. The etiopathogenesis and the treatment strategy of this rare entity need to be clarified.
Fluorescence in situ hybridization for diagnosis of malignant melanoma using RREB1, MYB, Cep6, and CCND1 probes in Japanese patients
Publication date: December 2017
Source:Dermatologica Sinica, Volume 35, Issue 4
Author(s): Jun Aoi, Satoshi Fukushima, Masatoshi Jinnin, Hironobu Ihn
Penile traumatic neuroma—A case report and literature review
Publication date: December 2017
Source:Dermatologica Sinica, Volume 35, Issue 4
Author(s): Cheng-Han Liu, Hsing-Jou Su, Julia Yu-Yun Lee, Chao-Chun Yang
A case of scar sarcoid on cosmetic tattoos successfully treated with intralesional corticosteroid injections
Publication date: December 2017
Source:Dermatologica Sinica, Volume 35, Issue 4
Author(s): Eiko Nagamoto, Akihiko Fujisawa, Masatoshi Jinnin, Yuichiro Yoshino
Unilateral granulomatous rosacea – The immunocompromised district as a possible cause
Publication date: December 2017
Source:Dermatologica Sinica, Volume 35, Issue 4
Author(s): Ming-Ying Wu, Chien-Yio Lin, Tseng-tong Kuo, Chien-Hsun Chen
Palmoplantar pustulosis with severe psoriatic nail dystrophy in a patient receiving etanercept for treatment of ankylosing spondylitis
Publication date: December 2017
Source:Dermatologica Sinica, Volume 35, Issue 4
Author(s): Sheng-Pei Wang, Chien-Sheng Wu, Po-Hsuan Lu
Copyright transfer statement
Publication date: December 2017
Source:Dermatologica Sinica, Volume 35, Issue 4
Serration pattern analysis for differentiating epidermolysis bullosa acquisita from other pemphigoid diseases
Direct immunofluorescence microscopy (DIF) of a skin biopsy specimen is the reference standard for the diagnosis of pemphigoid diseases (PD). Serration pattern analysis enables differentiation of epidermolysis bullosa acquisita (EBA) from other PD using DIF microscopy alone. However, practice gaps need to be addressed for implication of this technique in daily routine diagnostics.
The helsinki face transplantation: surgical aspects and one-year outcome
Since 2005, at least 38 facial transplantations have been performed worldwide. We herein describe the surgical technique and one year clinical outcome in Finland's first face transplant case.
Clinical and Imaging Characteristics of Arteriopathy Subtypes in Children with Arterial Ischemic Stroke: Results of the VIPS Study [PEDIATRICS]
BACKGROUND AND PURPOSE:
Childhood arteriopathies are rare but heterogenous, and difficult to diagnose and classify, especially by nonexperts. We quantified clinical and imaging characteristics associated with childhood arteriopathy subtypes to facilitate their diagnosis and classification in research and clinical settings.
MATERIALS AND METHODS:The Vascular Effects of Infection in Pediatric Stroke (VIPS) study prospectively enrolled 355 children with arterial ischemic stroke (2010–2014). A central team of experts reviewed all data to diagnose childhood arteriopathy and classify subtypes, including arterial dissection and focal cerebral arteriopathy–inflammatory type, which includes transient cerebral arteriopathy, Moyamoya disease, and diffuse/multifocal vasculitis. Only children whose stroke etiology could be conclusively diagnosed were included in these analyses. We constructed logistic regression models to identify characteristics associated with each arteriopathy subtype.
RESULTS:Among 127 children with definite arteriopathy, the arteriopathy subtype could not be classified in 18 (14%). Moyamoya disease (n = 34) occurred mostly in children younger than 8 years of age; focal cerebral arteriopathy–inflammatory type (n = 25), in children 8–15 years of age; and dissection (n = 26), at all ages. Vertigo at stroke presentation was common in dissection. Dissection affected the cervical arteries, while Moyamoya disease involved the supraclinoid internal carotid arteries. A banded appearance of the M1 segment of the middle cerebral artery was pathognomonic of focal cerebral arteriopathy–inflammatory type but was present in <25% of patients with focal cerebral arteriopathy–inflammatory type; a small lenticulostriate distribution infarct was a more common predictor of focal cerebral arteriopathy–inflammatory type, present in 76%. It remained difficult to distinguish focal cerebral arteriopathy–inflammatory type from intracranial dissection of the anterior circulation. We observed only secondary forms of diffuse/multifocal vasculitis, mostly due to meningitis.
CONCLUSIONS:Childhood arteriopathy subtypes have some typical features that aid diagnosis. Better imaging methods, including vessel wall imaging, are needed for improved classification of focal cerebral arteriopathy of childhood.
Patient Outcomes and Cerebral Infarction after Ruptured Anterior Communicating Artery Aneurysm Treatment [INTERVENTIONAL]
BACKGROUND AND PURPOSE:
Anterior communicating artery aneurysm rupture and treatment is associated with high rates of dependency, which are more severe after clipping compared with coiling. To determine whether ischemic injury might account for these differences, we characterized cerebral infarction burden, infarction patterns, and patient outcomes after surgical or endovascular treatment of ruptured anterior communicating artery aneurysms.
MATERIALS AND METHODS:We performed a retrospective cohort study of consecutive patients with ruptured anterior communicating artery aneurysms. Patient data and neuroimaging studies were reviewed. A propensity score for outcome measures was calculated to account for the nonrandom assignment to treatment. Primary outcome was the frequency of frontal lobe and striatum ischemic injury. Secondary outcomes were patient mortality and clinical outcome at discharge and at 3 months.
RESULTS:Coiled patients were older (median, 55 versus 50 years; P = .03), presented with a worse clinical status (60% with Hunt and Hess Score >2 versus 34% in clipped patients; P = .02), had a higher modified Fisher grade (P = .01), and were more likely to present with intraventricular hemorrhage (78% versus 56%; P = .03). Ischemic frontal lobe infarction (OR, 2.9; 95% CI, 1.1–8.4; P = .03) and recurrent artery of Heubner infarction (OR, 20.9; 95% CI, 3.5–403.7; P < .001) were more common in clipped patients. Clipped patients were more likely to be functionally dependent at discharge (OR, 3.2; P = .05) compared with coiled patients. Mortality and clinical outcome at 3 months were similar between coiled and clipped patients.
CONCLUSIONS:Frontal lobe and recurrent artery of Heubner infarctions are more common after surgical clipping of ruptured anterior communicating artery aneurysms, and are associated with poorer clinical outcomes at discharge.
Real-Time Motor Cortex Mapping for the Safe Resection of Glioma: An Intraoperative Resting-State fMRI Study [FUNCTIONAL]
BACKGROUND AND PURPOSE:
Resting-state functional MR imaging has been used for motor mapping in presurgical planning but never used intraoperatively. This study aimed to investigate the feasibility of applying intraoperative resting-state functional MR imaging for the safe resection of gliomas using real-time motor cortex mapping during an operation.
MATERIALS AND METHODS:Using interventional MR imaging, we conducted preoperative and intraoperative resting-state intrinsic functional connectivity analyses of the motor cortex in 30 patients with brain tumors. Factors that may influence intraoperative imaging quality, including anesthesia type (general or awake anesthesia) and tumor cavity (filled with normal saline or not), were studied to investigate image quality. Additionally, direct cortical stimulation was used to validate the accuracy of intraoperative resting-state fMRI in mapping the motor cortex.
RESULTS:Preoperative and intraoperative resting-state fMRI scans were acquired for all patients. Fourteen patients who successfully completed both sufficient intraoperative resting-state fMRI and direct cortical stimulation were used for further analysis of sensitivity and specificity. Compared with those subjected to direct cortical stimulation, the sensitivity and specificity of intraoperative resting-state fMRI in localizing the motor area were 61.7% and 93.7%, respectively. The image quality of intraoperative resting-state fMRI was better when the tumor cavity was filled with normal saline (P = .049). However, no significant difference between the anesthesia types was observed (P = .102).
CONCLUSIONS:This study demonstrates the feasibility of using intraoperative resting-state fMRI for real-time localization of functional areas during a neurologic operation. The findings suggest that using intraoperative resting-state fMRI can avoid the risk of intraoperative seizures due to direct cortical stimulation and may provide neurosurgeons with valuable information to facilitate the safe resection of gliomas.
Transient Focal Neurologic Symptoms Correspond to Regional Cerebral Hypoperfusion by MRI: A Stroke Mimic in Children [PEDIATRICS]
SUMMARY:
Children who present with acute transient focal neurologic symptoms raise concern for stroke or transient ischemic attack. We present a series of 16 children who presented with transient focal neurologic symptoms that raised concern for acute stroke but who had no evidence of infarction and had unilateral, potentially reversible imaging features on vascular and perfusion-sensitive brain MR imaging. Patients were examined with routine brain MR imaging, MRA, perfusion-sensitive sequences, and DWI. Fourteen (88%) children had lateralized MRA evidence of arterial tree pruning without occlusion, all had negative DWI findings, and all showed evidence of hemispheric hypoperfusion by susceptibility-weighted imaging or arterial spin-labeling perfusion imaging at presentation. These findings normalized following resolution of symptoms in all children who had follow-up imaging (6/16, 38%). The use of MR imaging with perfusion-sensitive sequences, DWI, and MRA can help to rapidly distinguish children with conditions mimicking stroke from those with acute stroke.
Differences in Morphologic and Hemodynamic Characteristics for "PHASES-Based" Intracranial Aneurysm Locations [INTERVENTIONAL]
BACKGROUND AND PURPOSE:
Several recent prospective studies have found that unruptured intracranial aneurysms at various anatomic locations have different propensities for future rupture. This study aims to uncover the lack of understanding regarding rupture-prone characteristics, such as morphology and hemodynamic factors, associated with different intracranial aneurysm location.
MATERIALS AND METHODS:We investigated the characteristics of 311 unruptured aneurysms at our center. Based on the PHASES study, we separated and compared morphologic and hemodynamic characteristics among 3 aneurysm location groups: 1) internal carotid artery; 2) middle cerebral artery; and 3) anterior communicating, posterior communicating, and posterior circulation arteries.
RESULTS:A mixed model statistical analysis showed that size ratio, low wall shear stress area, and pressure loss coefficient were different between the intracranial aneurysm location groups. In addition, a pair-wise comparison showed that ICA aneurysms had lower size ratios, lower wall shear stress areas, and lower pressure loss coefficients compared with MCA aneurysms and compared with the group of anterior communicating, posterior communicating, and posterior circulation aneurysms. There were no statistical differences between MCA aneurysms and the group of anterior communicating, posterior communicating, and posterior circulation aneurysms for morphologic or hemodynamic characteristics.
CONCLUSIONS:ICA aneurysms may be subjected to less rupture-prone morphologic and hemodynamic characteristics compared with other locations, which could explain the decreased rupture propensity of intracranial aneurysms at this location.
Flow Diversion with Low-Profile Braided Stents for the Treatment of Very Small or Uncoilable Intracranial Aneurysms at or Distal to the Circle of Willis [INTERVENTIONAL]
BACKGROUND AND PURPOSE:
The endovascular treatment of aneurysms located at or distal to the circle of Willis and not amenable to coiling remains a challenge. We report our experience with flow-diversion treatment using low-profile braided stents as a stent monotherapy procedure for treating distally located very small or uncoilable aneurysms.
MATERIALS AND METHODS:We retrospectively reviewed our data bases to identify patients with aneurysms located at or distal to the circle of Willis who were treated with stent monotherapy using low-profile braided stents. The immediate and follow-up angiographic findings and clinical status of the patients were assessed.
RESULTS:Twenty aneurysms in 19 patients were included in the study. The mean size of the aneurysms was 4.7 ± 2.4 mm. Patients were treated via telescopic implantation of 2 stents for 11 aneurysms; single-stent placement was used for the remaining aneurysms. The technical success rate was 95%. We observed a technical complication in 1 case (5.3%) and a late ischemic event in another (5.3%). The final angiographies during a mean follow-up of 14.7 months showed complete aneurysm occlusion in 73.7%. The complete occlusion rate of the aneurysms treated with telescopic stent placement was 81.8%. The modified Rankin scale scores of all patients at the last follow-up were between 0 and 2.
CONCLUSIONS:Flow diversion with low-profile braided stents as a stent monotherapy procedure for very small or uncoilable intracranial aneurysms located at or beyond the circle of Willis is a promising, relatively safe, and durable endovascular procedure.
The Diagnostic Accuracy of Contrast-Enhanced CT of the Neck for the Investigation of Sialolithiasis [HEAD & NECK]
BACKGROUND AND PURPOSE:
Sialolithiasis is a common benign pathology affecting the salivary glands but it is unclear if contrast-enhanced CT, which is commonly used for investigation of head and neck pathology, can identify calculi as accurately as noncontrast CT. The aim of this study was to assess the diagnostic accuracy of contrast-enhanced CT of the neck in the diagnosis of sialolithiasis compared with noncontrast CT of the neck used as the criterion standard.
MATERIALS AND METHODS:This was a retrospective, case-control study of 92 consecutive cases in 90 patients who underwent both noncontrast CT of the neck and contrast-enhanced CT of the neck in 2 tertiary referral centers from January 2011 to December 2015 for investigation of sialolithiasis. Axial 3-mm-section images were assessed by a fellowship-trained diagnostic neuroradiologist and diagnostic neuroradiology fellow in consensus. Blinded assessment of the contrast-enhanced CT of the neck was performed first, followed by noncontrast CT of the neck after a 2-week interval. The presence or absence of a stone and stone location and size were documented. Statistical analysis was undertaken to assess the agreement between CT protocols and calculate the sensitivity and specificity of contrast-enhanced CT of the neck.
RESULTS:Fifty calculi were identified on noncontrast CT of the neck in 31 cases; and 48 calculi, in 31 cases on contrast-enhanced CT of the neck. No calculi were identified in the remaining 61 cases. The sensitivity and specificity of contrast-enhanced CT of the neck in the detection of sialolithiasis was 96% (95% CI, 86.3%–99.5%) and 100% (95% CI, 94.1%–100%), respectively. The positive predictive value of contrast-enhanced CT of the neck was 100% (95% CI, 92.6%–100%), and the negative predictive value was 96.8% (95% CI, 89%–99.6%). The accuracy of contrast-enhanced CT of the neck in diagnosing the presence or absence of salivary calculi was 98%.
CONCLUSIONS:Contrast-enhanced CT of the neck is accurate in the detection of sialolithiasis, with no difference in diagnostic accuracy compared with noncontrast CT of the neck.
Does the Addition of a "Black Bone" Sequence to a Fast Multisequence Trauma MR Protocol Allow MRI to Replace CT after Traumatic Brain Injury in Children? [PEDIATRICS]
BACKGROUND AND PURPOSE:
Head CT is the current neuroimaging tool of choice in acute evaluation of pediatric head trauma. The potential cancer risks of CT-related ionizing radiation should limit its use in children. We evaluated the role of MR imaging, including a "black bone" sequence, compared with CT in detecting skull fractures and intracranial hemorrhages in children with acute head trauma.
MATERIALS AND METHODS:We performed a retrospective evaluation of 2D head CT and brain MR imaging studies including the black bone sequence of children with head trauma. Two experienced pediatric neuroradiologists in consensus created the standard of reference. Another pediatric neuroradiologist blinded to the diagnosis evaluated brain MR images and head CT images in 2 separate sessions. The presence of skull fractures and intracranial posttraumatic hemorrhages was evaluated. We calculated the sensitivity and specificity of CT and MR imaging with the black bone sequence in the diagnosis of skull fractures and intracranial hemorrhages.
RESULTS:Twenty-eight children (24 boys; mean age, 4.89 years; range, 0–15.5 years) with head trauma were included. MR imaging with the black bone sequence revealed lower sensitivity (66.7% versus 100%) and specificity (87.5% versus 100%) in identifying skull fractures. Four of 6 incorrectly interpreted black bone MR imaging studies showed cranial sutures being misinterpreted as skull fractures and vice versa.
CONCLUSIONS:Our preliminary results show that brain MR imaging complemented by a black bone sequence is a promising nonionizing alternative to head CT for the assessment of skull fractures in children. However, accuracy in the detection of linear fractures in young children and fractures of aerated bone remains limited.
T1-Weighted Dynamic Contrast-Enhanced MR Perfusion Imaging Characterizes Tumor Response to Radiation Therapy in Chordoma [SPINE]
BACKGROUND AND PURPOSE:
Chordomas notoriously demonstrate a paucity of changes following radiation therapy on conventional MR imaging. We hypothesized that dynamic contrast-enhanced MR perfusion imaging parameters of chordomas would change significantly following radiation therapy.
MATERIALS AND METHODS:Eleven patients with pathology-proved chordoma who completed dynamic contrast-enhanced MR perfusion imaging pre- and postradiation therapy were enrolled. Quantitative tumor measurements were obtained by 2 attending neuroradiologists. ROIs were used to calculate vascular permeability and plasma volume and generate dynamic contrast-enhancement curves. Quantitative analysis was performed to determine mean and maximum plasma volume and vascular permeability values, while semiquantitative analysis on averaged concentration curves was used to determine the area under the curve. A Mann-Whitney U test at a significance level of P < .05 was used to assess differences of the above parameters between pre- and postradiation therapy.
RESULTS:Plasma volume mean (pretreatment mean = 0.82; posttreatment mean = 0.42), plasma volume maximum (pretreatment mean = 3.56; posttreatment mean = 2.27), and vascular permeability mean (pretreatment mean = 0.046; posttreatment mean = 0.028) in the ROIs significantly decreased after radiation therapy (P < .05); this change thereby demonstrated the potential for assessing tumor response. Area under the curve values also demonstrated significant differences (P < .05).
CONCLUSIONS:Plasma volume and vascular permeability decreased after radiation therapy, suggesting that these dynamic contrast-enhanced MR perfusion parameters may be useful for monitoring chordoma growth and response to radiation therapy. Additionally, the characteristic dynamic MR signal intensity–time curve of chordoma may provide a radiographic means of distinguishing chordoma from other spinal lesions.
Nose and lips graft variants: a subunit anatomical study
Background. In the field of Vascularized Composite tissue Allotransplantation (VCA), the surgical design of facial subunit grafts is an evolving concept. The purpose of the present paper is to study the possibilities to divide the historical nose and lips face transplant into several morphological and functional subunit grafts, depending on their respective supply. Methods. Our study was conducted in 20 adult cadavers. The facial artery and its branches were dissected bilaterally in 16 fresh and 4 embalmed heads. Nasolabial perfusion was assessed by selective injection of methylene blue and eosin (n=2) or indian ink (n=2) in superior labial artery (SLA) and distal facial artery (DFA). Dynamic perfusion through the DFA was illustrated by fluoroscopy (n=3). Three nose-upper lip grafts were harvested and injected with barium sulfate for micro-Angio CT analysis. Finally, three isolated nasal and bilabial grafts were procured and their vascular patency assessed by fluoroscopy. Results. DFA can perfuse the entire nose, septum and upper lip, without any contribution of SLA. A dense anastomotic network indeed exists between the respective distal rami of both vessels. Furthermore, the exclusion of SLA from the harvested nasal subunit allowed safe bilabial subunit procurement, from the same specimen. Conclusions. Our results demonstrate the feasibility of harvesting nasal and labial subunits, in an isolated or a combined manner. These results can find applications in subunit autologous replantation, allotransplantation, allogenic face partial retransplantation, and in the emerging field of vascularized composite tissue engineering. Financial Disclosure Statement: The authors have no conflict of interest to disclose. This work was financially supported by a Fondation Saint-Luc Grant, FSR-UCL (Fonds Spécial de la Recherche) and Fonds Dr. Gaëtan Lagneaux. The content of the work is solely the responsibility of the authors. None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript. Acknowledgments: We would like to thank Mrs. Pascale Segers and Mr Walter Hudders for manuscript editing, Mrs. Michelle Cougnon and Mr Eric Legrand for administrative support, Mr. Bernard Caelen and Mrs. Maïté Van de Woestijne for assistance in cadaver procurement, Prof. Anne Bol for Micro-CT acquisition support. Conflict of interest: none. Authorships: JD Designed study, performed part of experimental manipulations, reviewed and interpreted all data, wrote article, gave approval for publication. LM Performed part of experimental manipulations, participated to data collection and analysis, gave approval for publication AG Performed part of experimental manipulations, participated to data collection and analysis, revised article, gave approval for publication MV Performed radiographic acquisition and reconstruction, reviewed and interpreted data, gave approval for publication. PG Supported experiments, reviewed and interpreted data, revised article, gave approval for publication. CB Supported experiments, reviewed and interpreted data, revised article, gave approval for publication. BL Supported experiments and designed study, reviewed data, revised article extensively, gave final approval for publication. Corresponding author: Benoît Lengelé, MD, PhD, FRCS, UCL/IREC/MORF,, Avenue E. Mounier 51, Bte B1.52.04, B-1200 Brussels (BELGIUM) Tel: +3227645251, Fax: + 3227645225, E-mail : benoit.lengele@uclouvain.be ©2017American Society of Plastic Surgeons
Endoscopic Carpal Tunnel Release with and without Sedation
Background: This study evaluates outcomes and complications with endoscopic carpal tunnel release (eCTR) performed with local anesthesia (LOCAL) only versus local anesthesia with sedation (SEDATION). We hypothesize that patient outcomes and satisfaction will be equivalent in both groups irrespective of anesthesia type. Methods: One hundred fifty-four consecutive patients undergoing eCTR with either LOCAL or SEDATION protocols were prospectively enrolled in a study of satisfaction and outcomes. The patients were surveyed preoperatively and at 2-weeks and 3-months postoperatively to evaluate satisfaction, symptoms, complications, and disability using the QuickDASH survey, the Levine-Katz carpal tunnel survey, and a customized LIKERT scale. Results: The hypothesis was upheld. Both groups of patients reported high levels of satisfaction (96% in LOCAL and 93% in SEDATION groups at 3 weeks). Disability, pain, and symptom scores did not differ significantly between groups at either postoperative time point. Following surgery, patients in the SEDATION group recalled more mean preoperative anxiety (4/10 versus 2.03/10 at 3 months). If they were to undergo the surgery again, patients in the SEDATION group were likely to desire either sedation (68%) or general anesthesia (29%) while patients in the LOCAL group were likely to wish for similar local-only anesthesia (78%). There were no reoperations or epinephrine-related complications in either group. Conclusions: Patients undergoing eCTR experience similar levels of satisfaction and outcomes with LOCAL and SEDATION protocols. The findings of this study confirm that both methods of anesthesia provide excellent results and allow for surgeons and patients to choose freely between the two anesthetic techniques. Financial Disclosure Statement: The authors have nothing to disclose. No funding was received for this research. Presented at: American Society for Surgery of the Hand annual meeting 2016 in Austin, TX, USA Author contributions: Tulipan: Data gathering, data analysis, manuscript preparation Kim: Data gathering, data analysis, manuscript preparation Ilyas: Data gathering, data analysis, manuscript preparation Matzon: Data gathering, data analysis, manuscript preparation This study was approved by the institutional review board at Thomas Jefferson University *CORRESPONDING AUTHOR: Jacob Tulipan, MD, 1025 Walnut St, Suite 516 College, Philadelphia, PA, United States. (215) 955-1500, (215) 503-0530, Jacob.tulipan@gmail.com ©2017American Society of Plastic Surgeons
Cleft-Related Orthognathic Surgery Based On Maxillary Vertical Lengthening Of the Anterior Facial Height
Background: The conventional approach during orthognathic surgery for cleft-related deformities has largely focused on restoration of maxilla retrusion, using the maxillary advancement as a standard treatment objective. However, we thought the maxillary vertical shortening and deficient incisor show could be the additional key elements of cleft-related deformities. Although slight vertical lengthening can be obtained with only maxillary advancement, it would not be enough to obtain satisfactory aesthetical results in terms of the anterior facial height. We hypothesized that vertical deficiency as well as anteroposterior maxillary retrusion exists in cleft-related deformities. Therefore, orthognathic surgery including intentional vertical lengthening and advancement would be better than the conventional simple advancement. Methods: A new approach was used to treat consecutive patients with dentofacial deformities between December 2007 and December 2016. The inclusion criterion was patients with cleft-related deformities. Results: Forty-one patients with cleft-related dentofacial deformities were included. The distance from the nasion to the incisor tip was 76.70 mm, angle of the lines connecting the sella, nasion, and point A was 74.03∘, and the incisor show was 1.02 mm. Corresponding measurements in forty patients without clefts were 81.57 mm, 80.08∘, and 3.38 mm, respectively. Postoperatively, the average vertical lengthening achieved was 0.88 mm in simple maxillary advancement group and 7.65 mm in intentional vertical lengthening accompanied by the maxillary advancement group. Conclusions: Our results suggest that simultaneous maxillary vertical lengthening with horizontal advancement is a viable approach to orthognathic surgery for cleft-related deformities given the long-term stability of outcomes demonstrated in this study. Financial Disclosure Statement: None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript. Acknowledgment: This article was presented at 2016 EACMFS in London, England. Corresponding author: Jong Woo Choi, M.D., Ph.D., MMM, Associate Professor, Department of Plastic and Reconstructive Surgery, University of Ulsan College of Medicine, Asan Medical Center, 388-1 PungNap-2Dong, SongPa-Gu, Seoul 138-736, Korea, Phone: 82-2-3010-3604; Fax: 82-2-476-7471, E-mail: pschoi@amc.seoul.kr ©2017American Society of Plastic Surgeons
Reconstruction of Microtias with Constricted Ear Features: A 22-Year Experience
Background: The surgical correction of 'microtias with constricted ear features' has remained a challenge due to the variable shape and large volume of the remnant cartilage and skin involved. In order to clarify how this remnant cartilage and skin should be treated, we have reviewed and analyzed cases operated at our Center. Methods: A total of 167 cases of Microtia with Constricted Ear Features, operated from 1992 to 2014, were included in the study. They were reviewed through medical records and photographs, analysis of surgical methods, and postoperative outcomes. Results: A total of 141 cases (84 percent) were followed for 2 months to 13 years (an average of 28 months). The average score given to the aesthetic outcomes, rated on a four-point Likert scale (i.e., 1=poor, 2=fair, 3=good, 4=excellent), was 3.1. For framework construction, we used remnant cartilage saving methods (n=37) or remnant cartilage replacement methods (n=104). The average (median) scores for the aesthetic outcome for these methods were 2.56 (3) and 3.36 (4), respectively. The difference in these scores was statistically significant (P
Gender Confirmation Surgery Using the Pedicle Transverse Colon Flap for Vaginal Reconstruction: A Clinical Outcome and Sexual Function Evaluation Study
Introduction: Vaginal reconstruction and vaginoplasty are indicated in vaginal agenesis, following pelvic tumor resection, trauma and for gender confirmation surgery. Different surgical options have been described when using these techniques. Herein, we present the clinical outcomes and sexual function evaluation using the pedicle transverse colon flap (TCF) for gender confirmation surgery in transgender women. Methods: This is a retrospective chart review of all transgender women who underwent gender confirmation surgery using the pedicle TCF. Demographics, etiology, procedure specifics and surgical outcomes were recorded and analyzed. Sexual function was measured using the Female Sexual Function Index (FSFI) and the female genital self-image scale (FGSIS) one year after surgery. Results: 15 patients underwent gender confirmation surgery using the pedicle transverse colon flap. Average age was 20, (range: 18-32 years), average OR time was 10.1 hours; (8-12.5 hrs.). The average length and width of the flaps was 15 cm and 2.8 cm respectively. During a 12-year follow-up, two complications were reported: one patient had pain due to narrowing at the introitus vaginalis, which required intervention and one patient had excessive amount of secretions in the first month which subsided at the third month after surgery. The mean FSFI score was 28.6 (range 24-31). All patients achieved a normal sexual function as indicated by a FSFI score of 25 or more. For the FGSIS, the mean total score was 20.0 ± 4.5 (range: 7- 28). Conclusion: The pedicle transverse colon flap is another valuable alternative method for vaginoplasty with promising results and minor complications. Financial Disclosure:None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript. Corresponding Author: Oscar J. Manrique M.D., Senior Associated Consultant, Assistant Professor of Surgery, Division of Plastic and Reconstructive Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, Tel: +1-507-284-3214; Fax: +1-507-284-5994, Email: manrique.oscar@mayo.edu ©2017American Society of Plastic Surgeons
“State of the Art Techniques in Treating Peripheral Nerve Injury”
Background – Peripheral nerve injuries remain a major clinical concern as they often lead to chronic disability and significant health care expenditures. Despite advancements in microsurgical techniques to enhance nerve repair, biologic approaches are needed to augment nerve regeneration and improve functional outcomes after injury. Methods – Presented herein is a review of the current literature on state of the art techniques to enhance functional recovery for patients with nerve injury. Four categories are considered: (1) electroceuticals; (2) nerve guidance conduits; (3) fat grafting, and; (4) optogenetics. Significant study results are highlighted, focusing on histological and functional outcome measures. Results – This review documents the current state of the literature. Advancements in neuronal stimulation, tissue engineering, and cell-based therapies demonstrate promise with regards to augmenting nerve regeneration and appropriate rehabilitation. Conclusions – The future of treating peripheral nerve injury will include multimodality utilization of electroconductive conduits, fat grafting, neuronal stimulation, and optogenetics. Further clinical investigation is needed to confirm the efficacy of these technologies on peripheral nerve recovery in humans, and how best to implement this treatment for a diverse population of nerve-injured patients. Financial Disclosure Statement: The authors have no financial disclosures to report. Corresponding author: Stephen W.P. Kemp, Ph.D, Director, Neuromuscular Lab, Assistant Research Professor, University of Michigan, Section of Plastic Surgery, Department of Biomedical Engineering, 1150 W Medical Center Drive, MSRB II, A570, Ann Arbor, MI, 48109-5456, P: (734) 615-2598; F: (734) 615-3292, swpkemp@med.umich.edu ©2017American Society of Plastic Surgeons
DIEP Flap Breast Reconstruction in Patients with Breast Ptosis: 2-Stage Reconstruction Using 3-Dimensional Surface Imaging and a Printed Mold
Background: Autologous breast reconstruction can be performed for breasts with ptosis to a certain extent, but if patients desire to correct ptosis, mastopexy of the contralateral breast is indicated. However, accurate prediction of post-mastopexy breast shape is difficult to make, and symmetrical breast reconstruction requires certain experience. We have previously reported the use of three-dimensional (3D) imaging and printing technologies in deep inferior epigastric artery perforator (DIEP) flap breast reconstruction. In the present study, these technologies were applied to the reconstruction of breasts with ptosis. Methods: Eight breast cancer patients with ptotic breasts underwent two-stage unilateral DIEP flap breast reconstruction. In the initial surgery, tissue expander (TE) placement and contralateral mastopexy are performed simultaneously. Four to six months later, 3D bilateral breast imaging is performed after confirming that the shape of the contralateral breast (post-mastopexy) is somewhat stabilized, and a 3D-printed breast mold is created based on the mirror image of the shape of the contralateral breast acquired using analytical software. Then, DIEP flap surgery is performed, where the breast mold is used to determine the required flap volume and to shape the breast mound. Results: All flaps were engrafted without any major perioperative complications during both the initial and DIEP flap surgeries. Objective assessment of cosmetic outcome revealed that good breast symmetry was achieved in all cases. Conclusions: The method described here may allow even inexperienced surgeons to achieve reconstruction of symmetrical, non-ptotic breasts with ease and in a short time. While the requirement of two surgeries is a potential disadvantage, our method will be particularly useful in cases involving TEs, i.e., delayed reconstruction or immediate reconstruction involving significant skin resection.Evaluation of sequential SPECT and CT for targeted radionuclide therapy dosimetry
Abstract
Purpose
In targeted radionuclide therapy (TRT), a prior knowledge of the absorbed dose biodistribution is essential for pre-therapy treatment planning. Previously, we showed that non-rigid organ-by-organ registration in sequential quantitative SPECT images improved dose estimation. This study aims to investigate if sequential CT can further improve TRT dosimetric accuracy.
Methods
We simulated SPECT/CT acquisitions at 1, 12, 24, 72 and 144 h In-111 Zevalin post-injection using an analytical MEGP projector, modeling attenuation, scatter and collimator-detector response. We later recruited a patient injected with 222 MBq In-111 DTPAOC imaged at 3 SPECT/CT sessions for clinical evaluations. Four registration schemes were evaluated: whole-body-based registration performed on sequential (1) SPECT (WB-SPECT) or (2) CT (WB-CT) images; organ-based registration applied on organs individually segmented from sequential (3) SPECT (O-SPECT) or (4) CT (O-CT) images. Voxel-by-voxel integration was performed followed by Y-90 voxel-S-kernel convolution. Organ-absorbed doses, iso-dose curves, dose–volume histograms (DVHs) were generated for targeted organs for analysis.
Results:
In simulation study, organ-absorbed dose errors were (− 8.66 ± 2.83)%, (− 2.51 ± 3.69)%, (− 9.23 ± 3.28)%, (− 7.17 ± 2.53)% for liver, (− 14.81 ± 4.91)%, (− 3.60 ± 4.37)%, (− 18.13 ± 4.44)%, (− 11.34 ± 4.22)% for spleen, for O-SPECT, O-CT, WB-SPECT and WB-CT registrations, respectively. For all organs, O-CT showed superior results. Results of iso-dose contour, DVHs were in accordance with the organ-absorbed doses. In clinical studies, the results were also consistent which showed O-CT method deviated the most from the result with no registration.
Conclusions:
We conclude that if both sequential SPECT/CT scans are available, CT organ-based registration method can more effectively improve the 3D dose estimation. Sequential low-dose CT scans might be considered to be included in the standard TRT protocol.
Predictors and Patterns of Psychiatric Treatment Dropout During Pregnancy Among Low-Income Women
Abstract
Objective This study compared psychiatric treatment discontinuation rates among pregnant women using psychotropic medications, outpatient psychotherapy, or both before conception. Methods Using data from Pennsylvania Medicaid Fee-For-Service and Managed Care Organization claims and Medicaid enrollment, 3030 women were identified who gave birth between 2007 and 2009, had ≥ 1 claim for psychiatric treatment during the 120 days prior to pregnancy, and were enrolled in Medicaid until they delivered. Kaplan–Meier and Cox regression analyses were used to estimate psychiatric treatment dropout rate during pregnancy and examine relationships between treatment dropout and age, race/ethnicity, and pre-pregnancy psychiatric diagnosis and treatment pattern. Results After the first trimester, the probability of discontinuing psychotropic medications was 83 versus 37.8% for cessation of psychotherapy among combined treatment users. Two or more psychotherapy sessions in the 4 months prior to pregnancy were associated with decreased psychotherapy dropout during pregnancy. Psychotherapy during pregnancy was associated with prenatal psychotropic medication adherence. Conclusions To retain women in treatment during pregnancy, when discontinuation from care is common, innovative models of care should consider type of pre-pregnancy mental healthcare and individual characteristics.
Diagnostic Accuracy of Pediatric Teledermatology Using Parent-Submitted Photographs
This randomized clinical trial assesses whether smartphone photographs of pediatric skin conditions taken by parents are of sufficient quality to permit accurate diagnosis.
Underuse of Sentinel Lymph Node Biopsy for Squamous Cell Carcinoma
This study examines the underuse of the sentinel lymph node biopsy in the management of high-risk squamous cell carcinoma.
Vegetating Darier Disease Treated With Botulinum Toxin
This case report describes a patient with vegetating Darier disease treated with botulinum toxin.
Treatment for Livedoid Vasculopathy
This systematic review uses the MEDLINE and EMBASE databases to identify the available therapies for livedoid vasculopathy and their clinical outcomes.
Hyperpigmented Cutaneous Plaques With Ulceration on the Legs
A woman in her 80s had a well-demarcated, oval ulcer with a violaceous, dusky border and central yellow fibrin mixed with granulation tissue and numerous violaceous to dull red, indurated plaques on the legs. What is your diagnosis?
Hospice care, cancer-directed therapy, and Medicare expenditures among older patients dying with malignant brain tumors
Abstract
Background
End-of-life care for older adults with malignant brain tumors is poorly understood. The purpose of this study is to quantify end-of-life utilization of hospice care, cancer-directed therapy, and associated Medicare expenditures among older adults with malignant brain tumors. Methods
This retrospective cohort study included deceased Medicare beneficiaries age ≥65 with primary (PMBT) or secondary (SMBT) malignant brain tumor receiving care within a Southeastern cancer community network including academic and community hospitals from 2012-2015. Utilization of hospice and cancer-directed therapy and total Medicare expenditures in the last 30 days of life were calculated using generalized linear and mixed effect models, respectively. Results
Late (1-3 days prior to death) or no hospice care was received by 24% of PMBT (n=383) and 32% of SMBT (n=940) patients. SMBT patients received late hospice care more frequently than PMBT patients (10% vs. 5%, p=0.002). Cancer-directed therapy was administered to 18% of patients with PMBT versus 25% with SMBT (p=0.003). Non-white race, male sex, and receipt of any hospital-based care in the final 30 days of life were associated with increased risk of late or no hospice care. The average decrease in Medicare expenditures associated with hospice utilization for patients with PMBT was $-12,138 (95% CI $-18,065 to $-6210) and with SMBT was $-1,508 (95% CI $-3,613 to $598). Conclusions
Receiving late or no hospice care was common among older patients with malignant brain tumors and was significantly associated with increased total Medicare expenditures for patients with PMBT.Desmoplastic Nodular Medulloblastoma in Young Children: A Management Dilemma
Abstract
Background
Children with desmoplastic nodular medulloblastoma (DNMB) have excellent survival, leading multiple groups globally to attempt reduction of treatment-related morbidity. In 2013, the Children's Oncology Group began a clinical trial (ACNS1221) eliminating both radiation therapy (RT) and intraventricular methotrexate for children under 3 years of age with localized DNMB, aiming to build upon the excellent outcomes of the German (HIT) trials. ACNS1221 has recently closed due to increased incidence of recurrences noted at the 2-year interim analysis, raising important questions regarding optimal therapy for DNMB. Methods
A review of major clinical trials that included children with DNMB was performed through July 2017. Results
One hundred and eighty eight DNMB patients enrolled on 11 prospective clinical trials were identified. The use of marrow-ablative chemotherapy and autologous hematopoietic cell rescue (AuHCR), or treatment with intraventricular methotrexate has been associated with excellent outcomes. RT was usually required for patients with evidence of disease at the end of therapy. Conclusions
The minimal intensity and duration of chemotherapy required to maximally cure children with DNMB without need of RT, remains unknown. Further trials are required to better identify a subset of DNMB patients who can be cured without marrow-ablative chemotherapy or intraventricular methotrexate.Lysosome biogenesis regulated by the amino-acid transporter SLC15A4 is critical for functional integrity of mast cells
Abstract
Mast cells possess specialized lysosomes, so-called secretory granules, which play a key role not only in allergic responses but also in various immune disorders. The molecular mechanisms that control secretory-granule formation are not fully understood. Solute carrier family member 15A4 (SLC15A4) is a lysosome-resident amino-acid/oligopeptide transporter that is preferentially expressed in hematopoietic-lineage cells. Here we demonstrated that SLC15A4 is required for mast-cell secretory granule homeostasis, and limits mast-cell functions and inflammatory responses by controlling the mTORC1–TFEB signaling axis. In mouse Slc15a4−/− mast cells, diminished mTORC1 activity increased the expression and nuclear translocation of TFEB, which caused secretory granules to degranulate more potently. This alteration of TFEB function in mast cells strongly affected the FcεRI-mediated responses and IL-33–triggered inflammatory responses both in vitro and in vivo. Our results reveal a close relationship between SLC15A4 and secretory-granule biogenesis that is critical for the functional integrity of mast cells.Cord blood platelet gel alone or in combination with photobiomodulation therapy for the treatment of oral ulcerations in patients with epidermolysis bullosa: a pilot clinical comparative study
Epidermolysis bullosa (EB) is a rare group of genetically heterogeneous diseases, characterized by deficiencies in the synthesis of proteins involved in the adhesion of the connective tissue to the epithelium; the oral cavity is frequently involved but, although oral bullae, ulcers, and erosions are common, there are few published data about possible treatment (1).
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Sensorimotor Processing in the Basal Ganglia Leads to Transient Beta Oscillations during Behavior
Brief epochs of beta oscillations have been implicated in sensorimotor control in the basal ganglia of task-performing healthy animals. However, which neural processes underlie their generation and how they are affected by sensorimotor processing remains unclear. To determine the mechanisms underlying transient beta oscillations in the LFP, we combined computational modeling of the subthalamo-pallidal network for the generation of beta oscillations with realistic stimulation patterns derived from single-unit data recorded from different basal ganglia subregions in rats performing a cued choice task. In the recordings, we found distinct firing patterns in the striatum, globus pallidus, and subthalamic nucleus related to sensory and motor events during the behavioral task. Using these firing patterns to generate realistic inputs to our network model led to transient beta oscillations with the same time course as the rat LFP data. In addition, our model can account for further nonintuitive aspects of beta modulation, including beta phase resets after sensory cues and correlations with reaction time. Overall, our model can explain how the combination of temporally regulated sensory responses of the subthalamic nucleus, ramping activity of the subthalamic nucleus, and movement-related activity of the globus pallidus leads to transient beta oscillations during behavior.
SIGNIFICANCE STATEMENT Transient beta oscillations emerge in the normal functioning cortico-basal ganglia loop during behavior. Here, we used a unique approach connecting a computational model closely with experimental data. In this way, we achieved a simulation environment for our model that mimics natural input patterns in awake, behaving animals. We demonstrate that a computational model for beta oscillations in Parkinson's disease (PD) can also account for complex patterns of transient beta oscillations in healthy animals. Therefore, we propose that transient beta oscillations in healthy animals share the same mechanism with pathological beta oscillations in PD. This important result connects functional and pathological roles of beta oscillations in the basal ganglia.
Distinctive Modulation of Dopamine Release in the Nucleus Accumbens Shell Mediated by Dopamine and Acetylcholine Receptors
Nucleus accumbens (NAc) shell shows unique dopamine (DA) signals in vivo and plays a unique role in DA-dependent behaviors such as reward-motivated learning and the response to drugs of abuse. A disynaptic mechanism for DA release was reported and shown to require synchronized firing of cholinergic interneurons (CINs) and activation of nicotinic acetylcholine (ACh) receptors (nAChRs) in DA neuron (DAN) axons. The properties of this disynaptic mechanism of DA transmission are not well understood in the NAc shell. In this study, in vitro fast-scan cyclic voltammetry was used to examine the modulation of DA transmission evoked by CINs firing in the shell of mice and compared with other striatal regions. We found that DA signals in the shell displayed significant degree of summation in response to train stimulation of CINs, contrary to core and dorsal striatum. The summation was amplified by a D2-like receptor antagonist and experiments with mice with targeted deletion of D2 receptors to DANs or CINs revealed that D2 receptors in CINs mediate a fast inhibition observed within 100 ms of the first pulse, whereas D2 autoreceptors in DAN terminals are engaged in a slower inhibition that peaks at ~500 ms. ACh also contributes to the use-dependent inhibition of DA release through muscarinic receptors only in the shell, where higher activity of acetylcholinesterase minimizes nAChR desensitization and promotes summation. These findings show that DA signals are modulated differentially by endogenous DA and ACh in the shell, which may underlie the unique features of shell DA signals in vivo.
SIGNIFICANCE STATEMENT The present study reports that dopamine (DA) release evoked by activation of cholinergic interneurons displays a high degree of summation in the shell and shows unique modulation by endogenous DA and acetylcholine. Desensitization of nicotinic receptors, which is a prevailing mechanism for use-dependent inhibition in the nucleus accumbens core and dorsal striatum, is also minimal in the shell in part due to elevated acetylcholinesterase activity. This distinctive modulation of DA transmission in the shell may have functional implications in the acquisition of reward-motivated behaviors and reward seeking.
The Gain-of-Function Integrin {beta}3 Pro33 Variant Alters the Serotonin System in the Mouse Brain
Engagement of integrins by the extracellular matrix initiates signaling cascades that drive a variety of cellular functions, including neuronal migration and axonal pathfinding in the brain. Multiple lines of evidence link the ITGB3 gene encoding the integrin β3 subunit with the serotonin (5-HT) system, likely via its modulation of the 5-HT transporter (SERT). The ITGB3 coding polymorphism Leu33Pro (rs5918, PlA2) produces hyperactive αvβ3 receptors that influence whole-blood 5-HT levels and may influence the risk for autism spectrum disorder (ASD). Using a phenome-wide scan of psychiatric diagnoses, we found significant, male-specific associations between the Pro33 allele and attention-deficit hyperactivity disorder and ASDs. Here, we used knock-in (KI) mice expressing an Itgb3 variant that phenocopies the human Pro33 variant to elucidate the consequences of constitutively enhanced αvβ3 signaling to the 5-HT system in the brain. KI mice displayed deficits in multiple behaviors, including anxiety, repetitive, and social behaviors. Anatomical studies revealed a significant decrease in 5-HT synapses in the midbrain, accompanied by decreases in SERT activity and reduced localization of SERTs to integrin adhesion complexes in synapses of KI mice. Inhibition of focal adhesion kinase (FAK) rescued SERT function in synapses of KI mice, demonstrating that constitutive active FAK signaling downstream of the Pro32Pro33 integrin αvβ3 suppresses SERT activity. Our studies identify a complex regulation of 5-HT homeostasis and behaviors by integrin αvβ3, revealing an important role for integrins in modulating risk for neuropsychiatric disorders.
SIGNIFICANCE STATEMENT The integrin β3 Leu33Pro coding polymorphism has been associated with autism spectrum disorders (ASDs) within a subgroup of patients with elevated blood 5-HT levels, linking integrin β3, 5-HT, and ASD risk. We capitalized on these interactions to demonstrate that the Pro33 coding variation in the murine integrin β3 recapitulates the sex-dependent neurochemical and behavioral attributes of ASD. Using state-of-the-art techniques, we show that presynaptic 5-HT function is altered in these mice, and that the localization of 5-HT transporters to specific compartments within the synapse, disrupted by the integrin β3 Pro33 mutation, is critical for appropriate reuptake of 5-HT. Our studies provide fundamental insight into the genetic network regulating 5-HT neurotransmission in the CNS that is also associated with ASD risk.
Correlated Disruption of Resting-State fMRI, LFP, and Spike Connectivity between Area 3b and S2 following Spinal Cord Injury in Monkeys
This study aims to understand how functional connectivity (FC) between areas 3b and S2 alters following input deprivation and the neuronal basis of disrupted FC of resting-state fMRI signals. We combined submillimeter fMRI with microelectrode recordings to localize the deafferented digit regions in areas 3b and S2 by mapping tactile stimulus-evoked fMRI activations before and after cervical dorsal column lesion in each male monkey. An average afferent disruption of 97% significantly reduced fMRI, local field potential (LFP), and spike responses to stimuli in both areas. Analysis of resting-state fMRI signal correlation, LFP coherence, and spike cross-correlation revealed significantly reduced functional connectivity between deafferented areas 3b and S2. The degrees of reductions in stimulus responsiveness and FC after deafferentation differed across fMRI, LFP, and spiking signals. The reduction of FC was much weaker than that of stimulus-evoked responses. Whereas the largest stimulus-evoked signal drop (~80%) was observed in LFP signals, the greatest FC reduction was detected in the spiking activity (~30%). fMRI signals showed mild reductions in stimulus responsiveness (~25%) and FC (~20%). The overall deafferentation-induced changes were quite similar in areas 3b and S2 across signals. Here we demonstrated that FC strength between areas 3b and S2 was much weakened by dorsal column lesion, and stimulus response reduction and FC disruption in fMRI covary with those of LFP and spiking signals in deafferented areas 3b and S2. These findings have important implications for fMRI studies aiming to probe FC alterations in pathological conditions involving deafferentation in humans.
SIGNIFICANCE STATEMENT By directly comparing fMRI, local field potential, and spike signals in both tactile stimulation and resting states before and after severe disruption of dorsal column afferent, we demonstrated that reduction in fMRI responses to stimuli is accompanied by weakened resting-state fMRI functional connectivity (FC) in input-deprived and reorganized digit regions in area 3b of the S1 and S2. Concurrent reductions in local field potential and spike FC validated the use of resting-state fMRI signals for probing neural intrinsic FC alterations in pathological deafferented cortex, and indicated that disrupted FC between mesoscale functionally highly related regions may contribute to the behavioral impairments.
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Publication date: Available online 25 July 2018 Source: Journal of Photochemistry and Photobiology B: Biology Author(s): Marco Ballestr...
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Editorial AJR Reviewers: Heartfelt Thanks From the Editors and Staff Thomas H. Berquist 1 Share + Affiliation: Citation: American Journal...
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Publication date: Available online 28 September 2017 Source: Actas Dermo-Sifiliográficas Author(s): F.J. Navarro-Triviño
