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OBJECTIVE: Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD), is a severe pediatric disorder of uncertain etiology resulting in hypothalamic dysfunction and frequent sudden death. Frequent co-occurrence of neuroblastic tumors have fueled suspicion of an autoimmune paraneoplastic neurological syndrome (PNS); however, specific anti-neural autoantibodies, a hallmark of PNS, have not been identified. Our objective is to determine if an autoimmune paraneoplastic etiology underlies ROHHAD. METHODS: Immunoglobulin G (IgG) from pediatric ROHHAD patients (n = 9), non-inflammatory individuals (n = 100) and relevant pediatric controls (n = 25) was screened using a programmable phage display of the human peptidome (PhIP-Seq). Putative ROHHAD-specific autoantibodies were orthogonally validated using radioactive ligand binding and cell-based assays. Expression of autoantibody targets in ROHHAD tumor and healthy brain tissue was assessed with immunohistochemistry and mass spectrometry, respectively. RESULTS: Autoantibodies to ZSCAN1 were detected in ROHHAD patients by PhIP-Seq and orthogonally validated in 7/9 ROHHAD patients and 0/125 controls using radioactive ligand binding and cell-based assays. Expression of ZSCAN1 in ROHHAD tumor and healthy human brain tissue was confirmed. INTERPRETATION: Our results support the notion that tumor-associated ROHHAD syndrome is a pediatric PNS, potentially initiated by an immune response to peripheral neuroblastic tumor. ZSCAN1 autoantibodies may aid in earlier, accurate diagnosis of ROHHAD syndrome, thus providing a means toward early detection and treatment. This work warrants follow-up studies to test sensitivity and specificity of a novel diagnostic test. Last, given the absence of the ZSCAN1 gene in rodents, our study highlights the value of human-based approaches for detecting novel PNS subtypes. ANN NEUROL 2022;92:279-291.
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Enfermedades del Sistema Nervioso Autónomo , Enfermedades del Sistema Endocrino , Enfermedades Hipotalámicas , Síndromes Paraneoplásicos del Sistema Nervioso , Autoanticuerpos , Niño , Humanos , Enfermedades Hipotalámicas/genética , Hipoventilación/genética , Ligandos , Síndromes Paraneoplásicos del Sistema Nervioso/diagnóstico , SíndromeRESUMEN
Coral reefs are declining globally as climate change and local water quality press environmental conditions beyond the physiological tolerances of holobionts-the collective of the host and its microbial symbionts. To assess the relationship between symbiont composition and holobiont stress tolerance, community diversity metrics were quantified for dinoflagellate endosymbionts (Family: Symbiodiniaceae) from eight Acropora millepora genets that thrived under or responded poorly to various stressors. These eight selected genets represent the upper and lower tails of the response distribution of 40 coral genets that were exposed to four stress treatments (and control conditions) in a 10-day experiment. Specifically, four 'best performer' coral genets were analyzed at the end of the experiment because they survived high temperature, high pCO2 , bacterial exposure, or combined stressors, whereas four 'worst performer' genets were characterized because they experienced substantial mortality under these stressors. At the end of the experiment, seven of eight coral genets mainly hosted Cladocopium symbionts, whereas the eighth genet was dominated by both Cladocopium and Durusdinium symbionts. Symbiodiniaceae alpha and beta diversity were higher in worst performing genets than in best performing genets. Symbiont communities in worst performers also differed more after stress exposure relative to their controls (based on normalized proportional differences in beta diversity), than did best performers. A generalized joint attribute model estimated the influence of host genet and treatment on Symbiodiniaceae community composition and identified strong associations among particular symbionts and host genet performance, as well as weaker associations with treatment. Although dominant symbiont physiology and function contribute to host performance, these findings emphasize the importance of symbiont community diversity and stochasticity as components of host performance. Our findings also suggest that symbiont community diversity metrics may function as indicators of resilience and have potential applications in diverse disciplines from climate change adaptation to agriculture and medicine.
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Viewing other people with distinctive accuracy-the degree to which personality impressions correspond with targets' unique characteristics-often predicts positive interpersonal experiences, including liking and relationship satisfaction. Does this hold in the context of first dates, or might distinctive accuracy have negative links with romantic interest in such evaluative settings? We examined this question using two speed-dating samples (Sample 1: N = 172, N = 2,407 dyads; Sample 2: N = 397, N = 1,849 dyads). Not surprisingly, positive impressions of potential dating partners were strongly associated with greater romantic interest. In contrast, distinctively accurate impressions were associated with significantly less romantic interest. This association was even stronger for potential partners whose personalities were less romantically appealing, specifically, those lower in extraversion. In sum, on a first date, distinctive accuracy tends to be paired with lower romantic interest. The potential implications of distinctive accuracy for romantic interest and of romantic interest for distinctive accuracy are discussed.
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Conducta de Elección , Personalidad , Conducta Sexual/psicología , Parejas Sexuales/psicología , Extraversión Psicológica , Femenino , Humanos , Relaciones Interpersonales , Masculino , Satisfacción Personal , Adulto JovenRESUMEN
BackgroundA congenital diaphragmatic hernia (DH) can result in severe lung hypoplasia that increases the risk of morbidity and mortality after birth; however, little is known about the cardiorespiratory transition at birth.MethodsUsing phase-contrast X-ray imaging and angiography, we examined the cardiorespiratory transition at birth in rabbit kittens with DHs. Surgery was performed on pregnant New Zealand white rabbits (n=18) at 25 days' gestation to induce a left-sided DH. Kittens were delivered at 30 days' gestation, intubated, and ventilated to achieve a tidal volume (Vt) of 8 ml/kg in control and 4 ml/kg in DH kittens while they were imaged.ResultsFunctional residual capacity (FRC) recruitment and Vt in the hypoplastic left lung were markedly reduced, resulting in a disproportionate distribution of FRC into the right lung. Following lung aeration, relative pulmonary blood flow (PBF) increased equally in both lungs, and the increase in pulmonary venous return was similar in both control and DH kittens.ConclusionThese findings indicate that nonuniform lung hypoplasia caused by DH alters the distribution of ventilation away from hypoplastic and into normally grown lung regions. During transition, the increase in PBF and pulmonary venous return, which is vital for maintaining cardiac output, is not affected by lung hypoplasia.
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Hernias Diafragmáticas Congénitas/fisiopatología , Pulmón/irrigación sanguínea , Ventilación Pulmonar , Animales , Animales Recién Nacidos , Femenino , Hernias Diafragmáticas Congénitas/diagnóstico por imagen , Hernias Diafragmáticas Congénitas/patología , Embarazo , Conejos , Flujo Sanguíneo Regional , Volumen de Ventilación PulmonarRESUMEN
An observational approach is recommended in newly diagnosed children with immune thrombocytopenia (ITP) at low risk of bleeding; however, there is no standard definition of risk. A standardized clinical assessment and management plan (SCAMP® ), a modifiable practice guideline, was implemented and revised (SCAMP-1 and SCAMP-2) and applied to 71 newly diagnosed patients with ITP. The Buchanan and Adix bleeding score guided treatment and was modified by stratifying by low- and high-risk grade 3 bleeding in SCAMP-2. Observation rates increased from 40% to 74% from SCAMP-1 to SCAMP-2 (P < 0.05) with no bleeding complications. We propose a modified bleeding score that increased observation rates in low-risk patients with ITP.
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Hemorragia/complicaciones , Planificación de Atención al Paciente , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/terapia , Adolescente , Niño , Preescolar , Manejo de la Enfermedad , Femenino , Humanos , Lactante , Masculino , Resultado del TratamientoRESUMEN
The orbitofrontal cortex (OFC) integrates information about the environment to guide decision-making. Glutamatergic synaptic transmission mediated through N-methyl-d-aspartate receptors is required for optimal functioning of the OFC. Additionally, abnormal dopamine signaling in this region has been implicated in impulsive behavior and poor cognitive flexibility. Yet, despite the high prevalence of psychostimulants prescribed for attention deficit/hyperactivity disorder, there is little information on how dopamine modulates synaptic transmission in the juvenile or the adult OFC. Using whole-cell patch-clamp recordings in OFC pyramidal neurons, we demonstrated that while dopamine or selective D2-like receptor (D2R) agonists suppress excitatory synaptic transmission of juvenile or adult lateral OFC neurons; in juvenile lateral OFC neurons, higher concentrations of dopamine can target dopamine receptors that couple to a phospholipase C (PLC) signaling pathway to enhance excitatory synaptic transmission. Interfering with the formation of a putative D1R-D2R interaction blocked the potentiation of excitatory synaptic transmission. Furthermore, targeting the putative D1R-D2R complex with a biased agonist, SKF83959, not only enhanced excitatory synaptic transmission in a PLC-dependent manner, but also improved the performance of juvenile rats on a reversal-learning task. Our results demonstrate that dopamine signaling in the lateral OFC differs between juveniles and adults, through potential crosstalk between dopamine receptor subtypes.
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Corteza Prefrontal/crecimiento & desarrollo , Corteza Prefrontal/metabolismo , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Aprendizaje Inverso/fisiología , Animales , Catéteres de Permanencia , Cognición/efectos de los fármacos , Cognición/fisiología , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Potenciales Postsinápticos Excitadores/fisiología , Función Ejecutiva/efectos de los fármacos , Función Ejecutiva/fisiología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Neurotransmisores , Técnicas de Placa-Clamp , Corteza Prefrontal/efectos de los fármacos , Células Piramidales/efectos de los fármacos , Células Piramidales/fisiología , Ratas Wistar , Receptores de Dopamina D1/agonistas , Receptores de Dopamina D1/antagonistas & inhibidores , Receptores de Dopamina D2/agonistas , Receptores de N-Metil-D-Aspartato/agonistas , Aprendizaje Inverso/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiología , Técnicas de Cultivo de TejidosRESUMEN
BACKGROUND: Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare neuroimmune disease with peak onset at 18 months, associated with neural crest tumors in 50% of patients. In part due to its rarity, misdiagnosis at onset is common, can delay treatment, and may contribute to adverse outcomes. Patient-reported registries may overcome some of these challenges in rare disease research. In this context, the OMSLife Foundation collaborated with the National Organization of Rare Diseases to create a patient-reported registry in OMAS. METHODS: Retrospective analysis was performed of data entered by parents of patients with OMAS into nine online surveys assessing demographics, symptoms at onset, triggers, time of diagnosis, treatment, and additional therapies. RESULTS: A total of 194 patients were enrolled. There was a female predominance (54%) and high rate of parental autoimmunity (31%). Age at onset peaked between 12 and 18 months overall. The age of onset was older in female patients (median [interquartile range]: females 22 [15 to 31] vs males 18 [14 to 23], P = 0.0223, P = 0.0223). Symptoms at onset most commonly included ataxia (84%) and were typically severe. Initial misdiagnosis occurred in nearly 50% and tumor discovery was delayed in 18 patients, but overall median time to correct diagnosis was 25 days. Most patients (56%) received combination immunomodulatory therapies, and nearly all underwent supportive therapies. CONCLUSIONS: Patient- and parent-powered research is feasible in OMAS and created the second largest published cohort of pediatric patients with OMAS. Results were similar to other large cohorts and also validated findings from prior case reports and smaller case series.
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Síndrome de Opsoclonía-Mioclonía , Sistema de Registros , Humanos , Masculino , Femenino , Síndrome de Opsoclonía-Mioclonía/diagnóstico , Síndrome de Opsoclonía-Mioclonía/terapia , Estudios Retrospectivos , Lactante , Preescolar , Niño , Adolescente , Medición de Resultados Informados por el Paciente , Edad de Inicio , Adulto Joven , AdultoRESUMEN
Amplicon sequencing is an effective and increasingly applied method for studying viral communities in the environment. Here, we present vAMPirus, a user-friendly, comprehensive, and versatile DNA and RNA virus amplicon sequence analysis program, designed to support investigators in exploring virus amplicon sequencing data and running informed, reproducible analyses. vAMPirus intakes raw virus amplicon libraries and, by default, performs nucleotide- and amino acid-based analyses to produce results such as sequence abundance information, taxonomic classifications, phylogenies and community diversity metrics. The vAMPirus analytical framework leverages 16 different opensource tools and provides optional approaches that can increase the ratio of biological signal-to-noise and thereby reveal patterns that would have otherwise been masked. Here, we validate the vAMPirus analytical framework and illustrate its implementation as a general virus amplicon sequencing workflow by recapitulating findings from two previously published double-stranded DNA virus datasets. As a case study, we also apply the program to explore the diversity and distribution of a coral reef-associated RNA virus. vAMPirus is streamlined within Nextflow, offering straightforward scalability, standardization and communication of virus lineage-specific analyses. The vAMPirus framework is designed to be adaptable; community-driven analytical standards will continue to be incorporated as the field advances. vAMPirus supports researchers in revealing patterns of virus diversity and population dynamics in nature, while promoting study reproducibility and comparability.
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Programas Informáticos , Biología Computacional/métodos , Virus ADN/genética , Virus ADN/clasificación , Virus/genética , Virus/clasificación , Virus/aislamiento & purificación , Virus ARN/genética , Virus ARN/clasificación , Virus ARN/aislamiento & purificación , FilogeniaRESUMEN
BACKGROUND: Cancer patients often experience treatment-related symptoms which, if uncontrolled, may require emergency department admission. We developed models identifying breast or genitourinary cancer patients at the risk of attending emergency department (ED) within 30-days and demonstrated the development, validation, and proactive approach to in-production monitoring of an artificial intelligence-based predictive model during a 3-month simulated deployment at a cancer hospital in the United States. METHODS: We used routinely-collected electronic health record data to develop our predictive models. We evaluated models including a variational autoencoder k-nearest neighbors algorithm (VAE-kNN) and model behaviors with a sample containing 84,138 observations from 28,369 patients. We assessed the model during a 77-day production period exposure to live data using a proactively monitoring process with predefined metrics. RESULTS: Performance of the VAE-kNN algorithm is exceptional (Area under the receiver-operating characteristics, AUC = 0.80) and remains stable across demographic and disease groups over the production period (AUC 0.74-0.82). We can detect issues in data feeds using our monitoring process to create immediate insights into future model performance. CONCLUSIONS: Our algorithm demonstrates exceptional performance at predicting risk of 30-day ED visits. We confirm that model outputs are equitable and stable over time using a proactive monitoring approach.
Patients with cancer often need to visit the hospital emergency department (ED), for example due to treatment side effects. Predicting these visits might help us to better manage the treatment of patients who are at risk. Here, we develop a computer-based tool to identify patients with cancer who are at risk of an unplanned ED visit within 30 days. We use health record data from over 28,000 patients who had visited a single cancer hospital in the US to create and test the model. The model performed well and was consistent across different demographic and disease groups. We monitor model behavior over time and show that it is stable. The approach we take to monitoring model performance may be a particularly useful contribution toward implementing similar predictive models in the clinic and checking that they are performing as intended.
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Filamentous viruses are hypothesized to play a role in stony coral tissue loss disease (SCTLD) through infection of the endosymbiotic dinoflagellates (Family Symbiodiniaceae) of corals. To evaluate this hypothesis, it is critical to understand the global distribution of filamentous virus infections across the genetic diversity of Symbiodiniaceae hosts. Using transmission electron microscopy, we demonstrate that filamentous virus-like particles (VLPs) are present in over 60% of Symbiodiniaceae cells (genus Cladocopium) within Pacific corals (Acropora hyacinthus, Porites c.f. lobata); these VLPs are more prevalent in Symbiodiniaceae of in situ colonies experiencing heat stress. Symbiodiniaceae expelled from A. hyacinthus also contain filamentous VLPs, and these cells are more degraded than their in hospite counterparts. Similar to VLPs reported from SCTLD-affected Caribbean reefs, VLPs range from ~150 to 1500 nm in length and 16-37 nm in diameter and appear to constitute various stages in a replication cycle. Finally, we demonstrate that SCTLD-affected corals containing filamentous VLPs are dominated by diverse Symbiodiniaceae lineages from the genera Breviolum, Cladocopium, and Durusdinium. Although this study cannot definitively confirm or refute the role of filamentous VLPs in SCTLD, it demonstrates that filamentous VLPs are not solely observed in SCTLD-affected corals or reef regions, nor are they solely associated with corals dominated by members of a particular Symbiodiniaceae genus. We hypothesize that filamentous viruses are a widespread, common group that infects Symbiodiniaceae. Genomic characterization of these viruses and empirical tests of the impacts of filamentous virus infection on Symbiodiniaceae and coral colonies should be prioritized.
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Antozoos , Dinoflagelados , Animales , Antozoos/genética , Dinoflagelados/genética , Arrecifes de Coral , Simbiosis , Océanos y MaresRESUMEN
Viruses can affect coral health by infecting their symbiotic dinoflagellate partners (Symbiodiniaceae). Yet, viral dynamics in coral colonies exposed to environmental stress have not been studied at the reef scale, particularly within individual viral lineages. We sequenced the viral major capsid protein (mcp) gene of positive-sense single-stranded RNA viruses known to infect symbiotic dinoflagellates ('dinoRNAVs') to analyze their dynamics in the reef-building coral, Porites lobata. We repeatedly sampled 54 colonies harboring Cladocopium C15 dinoflagellates, across three environmentally distinct reef zones (fringing reef, back reef, and forereef) around the island of Moorea, French Polynesia over a 3-year period and spanning a reef-wide thermal stress event. By the end of the sampling period, 28% (5/18) of corals in the fringing reef experienced partial mortality versus 78% (14/18) of corals in the forereef. Over 90% (50/54) of colonies had detectable dinoRNAV infections. Reef zone influenced the composition and richness of viral mcp amino acid types ('aminotypes'), with the fringing reef containing the highest aminotype richness. The reef-wide thermal stress event significantly increased aminotype dispersion, and this pattern was strongest in the colonies that experienced partial mortality. These findings demonstrate that dinoRNAV infections respond to environmental fluctuations experienced in situ on reefs. Further, viral productivity will likely increase as ocean temperatures continue to rise, potentially impacting the foundational symbiosis underpinning coral reef ecosystems.
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Within microeukaryotes, genetic variation and functional variation sometimes accumulate more quickly than morphological differences. To understand the evolutionary history and ecology of such lineages, it is key to examine diversity at multiple levels of organization. In the dinoflagellate family Symbiodiniaceae, which can form endosymbioses with cnidarians (e.g., corals, octocorals, sea anemones, jellyfish), other marine invertebrates (e.g., sponges, molluscs, flatworms), and protists (e.g., foraminifera), molecular data have been used extensively over the past three decades to describe phenotypes and to make evolutionary and ecological inferences. Despite advances in Symbiodiniaceae genomics, a lack of consensus among researchers with respect to interpreting genetic data has slowed progress in the field and acted as a barrier to reconciling observations. Here, we identify key challenges regarding the assessment and interpretation of Symbiodiniaceae genetic diversity across three levels: species, populations, and communities. We summarize areas of agreement and highlight techniques and approaches that are broadly accepted. In areas where debate remains, we identify unresolved issues and discuss technologies and approaches that can help to fill knowledge gaps related to genetic and phenotypic diversity. We also discuss ways to stimulate progress, in particular by fostering a more inclusive and collaborative research community. We hope that this perspective will inspire and accelerate coral reef science by serving as a resource to those designing experiments, publishing research, and applying for funding related to Symbiodiniaceae and their symbiotic partnerships.
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Arrecifes de Coral , Dinoflagelados , Variación Genética , Dinoflagelados/clasificación , Dinoflagelados/genética , Filogenia , Consenso , Antozoos , SimbiosisRESUMEN
Does how people generally engage with their online social networks relate to offline initial social interactions? Using a large-scale study of first impressions (N = 806, Ndyad = 4,565), we examined how different indicators of social media use relate to the positivity of dyadic in-person first impressions, from the perspective of the participants and their interaction partners. Many forms of social media use (e.g., Instagram, Snapchat, passive) were associated with liking and being liked by others more, although some forms of use (e.g., Facebook, active) were not associated with liking others or being liked by others. Furthermore, most associations held controlling for extraversion and narcissism. Thus, while some social media use may be generally beneficial for offline social interactions, some may be unrelated, highlighting the idea that how, rather than how much, people use social media can play a role in their offline social interactions.
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Medios de Comunicación Sociales , Emociones , Humanos , Narcisismo , Red SocialRESUMEN
Climate change-driven ocean warming is increasing the frequency and severity of bleaching events, in which corals appear whitened after losing their dinoflagellate endosymbionts (family Symbiodiniaceae). Viral infections of Symbiodiniaceae may contribute to some bleaching signs, but little empirical evidence exists to support this hypothesis. We present the first temporal analysis of a lineage of Symbiodiniaceae-infecting positive-sense single-stranded RNA viruses ("dinoRNAVs") in coral colonies, which were exposed to a 5-day heat treatment (+2.1 °C). A total of 124 dinoRNAV major capsid protein gene "aminotypes" (unique amino acid sequences) were detected from five colonies of two closely related Pocillopora-Cladocopium (coral-symbiont) combinations in the experiment; most dinoRNAV aminotypes were shared between the two coral-symbiont combinations (64%) and among multiple colonies (82%). Throughout the experiment, seventeen dinoRNAV aminotypes were found only in heat-treated fragments, and 22 aminotypes were detected at higher relative abundances in heat-treated fragments. DinoRNAVs in fragments of some colonies exhibited higher alpha diversity and dispersion under heat stress. Together, these findings provide the first empirical evidence that exposure to high temperatures triggers some dinoRNAVs to switch from a persistent to a productive infection mode within heat-stressed corals. Over extended time frames, we hypothesize that cumulative dinoRNAV production in the Pocillopora-Cladocopium system could affect colony symbiotic status, for example, by decreasing Symbiodiniaceae densities within corals. This study sets the stage for reef-scale investigations of dinoRNAV dynamics during bleaching events.
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Antozoos , Dinoflagelados , Virosis , Animales , Arrecifes de Coral , Dinoflagelados/genética , SimbiosisRESUMEN
A core component of social anxiety is the constant concern about what others think of the self. Could such metaperceptions-beliefs about how others view the self-play a role in relationship initiation attempts? In the present research, we examined whether metaperceptions may contribute to why people higher in social anxiety experience difficulties in initial interactions. In 2 first-impressions contexts, a platonic getting-acquainted context (Study 1: N = 544; 2,878 dyads) and a speed dating context (Study 2: N = 376; 4,797 dyads), we explored the roles of 2 components of metaperceptions: meta-positivity (i.e., believing interaction partners' perceptions of the self are in line with the socially desirable personality profile) and distinctive meta-accuracy (i.e., accurately recognizing interaction partners' unique perception of the self, controlling for meta-positivity). Results revealed that people higher in social anxiety were liked less by interaction partners across both contexts, a link that was partially accounted for by lower distinctive meta-accuracy displayed by those higher in social anxiety. Further, lower meta-positivity displayed by people higher in social anxiety also contributed to the links between greater social anxiety and being liked less in the platonic setting and liking others less in both contexts. In sum, metaperceptions may play an important role in shaping initial interactions, potentially helping to explain why people with greater social anxiety encounter difficulties forming new relationships. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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Relaciones Interpersonales , Percepción Social , Ansiedad , Actitud , Humanos , PersonalidadRESUMEN
BACKGROUND: The microbiomes of foundation (habitat-forming) species such as corals and sponges underpin the biodiversity, productivity, and stability of ecosystems. Consumers shape communities of foundation species through trophic interactions, but the role of consumers in dispersing the microbiomes of such species is rarely examined. For example, stony corals rely on a nutritional symbiosis with single-celled endosymbiotic dinoflagellates (family Symbiodiniaceae) to construct reefs. Most corals acquire Symbiodiniaceae from the environment, but the processes that make Symbiodiniaceae available for uptake are not resolved. Here, we provide the first comprehensive, reef-scale demonstration that predation by diverse coral-eating (corallivorous) fish species promotes the dispersal of Symbiodiniaceae, based on symbiont cell densities and community compositions from the feces of four obligate corallivores, three facultative corallivores, two grazer/detritivores as well as samples of reef sediment and water. RESULTS: Obligate corallivore feces are environmental hotspots of Symbiodiniaceae cells: live symbiont cell concentrations in such feces are 5-7 orders of magnitude higher than sediment and water environmental reservoirs. Symbiodiniaceae community compositions in the feces of obligate corallivores are similar to those in two locally abundant coral genera (Pocillopora and Porites), but differ from Symbiodiniaceae communities in the feces of facultative corallivores and grazer/detritivores as well as sediment and water. Combining our data on live Symbiodiniaceae cell densities in feces with in situ observations of fish, we estimate that some obligate corallivorous fish species release over 100 million Symbiodiniaceae cells per 100 m2 of reef per day. Released corallivore feces came in direct contact with coral colonies in the fore reef zone following 91% of observed egestion events, providing a potential mechanism for the transfer of live Symbiodiniaceae cells among coral colonies. CONCLUSIONS: Taken together, our findings show that fish predation on corals may support the maintenance of coral cover on reefs in an unexpected way: through the dispersal of beneficial coral symbionts in corallivore feces. Few studies examine the processes that make symbionts available to foundation species, or how environmental reservoirs of such symbionts are replenished. This work sets the stage for parallel studies of consumer-mediated microbiome dispersal and assembly in other sessile, habitat-forming species.
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BACKGROUND AND OBJECTIVES: Opsoclonus-myoclonus syndrome (OMS) is a rare autoimmune disorder associated with neuroblastoma in children, although idiopathic and postinfectious etiologies are present in children and adults. Small cohort studies in homogenous populations have revealed elevated rates of autoimmunity in family members of patients with OMS, although no differentiation between paraneoplastic and nonparaneoplastic forms has been performed. The objective of this study was to investigate the prevalence of autoimmune disease in first-degree relatives of pediatric patients with paraneoplastic and nonparaneoplastic OMS. METHODS: A single-center cohort study of consecutively evaluated children with OMS was performed. Parents of patients were prospectively administered surveys on familial autoimmune disease. Rates of autoimmune disease in first-degree relatives of pediatric patients with OMS were compared using Fisher exact t test and χ2 analysis: (1) between those with and without a paraneoplastic cause and (2) between healthy and disease (pediatric multiple sclerosis [MS]) controls from the United States Pediatric MS Network. RESULTS: Thirty-five patients (18 paraneoplastic, median age at onset 19.0 months; 17 idiopathic, median age at onset 25.0 months) and 68 first-degree relatives (median age 41.9 years) were enrolled. One patient developed systemic lupus erythematosus 7 years after OMS onset. Paraneoplastic OMS was associated with a 50% rate of autoimmune disease in a first-degree relative compared with 29% in idiopathic OMS (p = 0.31). The rate of first-degree relative autoimmune disease per OMS case (14/35, 40%) was higher than healthy controls (86/709, 12%; p < 0.001) and children with pediatric MS (101/495, 20%; p = 0.007). DISCUSSION: In a cohort of pediatric patients with OMS, there were elevated rates of first-degree relative autoimmune disease, with no difference in rates observed between paraneoplastic and idiopathic etiologies, suggesting an autoimmune genetic contribution to the development of OMS in children.
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Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/genética , Síndrome de Opsoclonía-Mioclonía/epidemiología , Síndrome de Opsoclonía-Mioclonía/genética , Adulto , Preescolar , Estudios de Cohortes , Familia , Femenino , Predisposición Genética a la Enfermedad , Humanos , Lactante , Masculino , Persona de Mediana Edad , PrevalenciaRESUMEN
We have developed an analyser-based phase contrast X-ray imaging technique to measure the mean length scale of pores or particles that cannot be resolved directly by the system. By combining attenuation, phase and ultra-small angle X-ray scattering information, the technique was capable of measuring differences in airway dimension between lungs of healthy mice and those with mild and severe emphysema. Our measurements of airway dimensions from 2D images showed a 1:1 relationship to the actual airway dimensions measured using micro-CT. Using 80 images, the sensitivity and specificity were measured to be 0.80 and 0.89, respectively, with the area under the ROC curve close to ideal at 0.96. Reducing the number of images to 11 slightly decreased the sensitivity to 0.75 and the ROC curve area to 0.90, whilst the specificity remained high at 0.89.
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PURPOSE: Despite the widespread practice of gradually adapting all new soft contact lens wearers (neophytes), there is little evidence-based research underpinning such practice. This work determined if a gradual adaptation period is necessary for neophytes when fitted with modern hydrogel or silicone-hydrogel daily disposable contact lenses. METHOD: At four sites, neophytes (19-32 years) were randomly assigned to an adaptation schedule: fast (10â¯h wear from the first day) or gradual (4â¯h on the first day, increasing their wear-time by 2â¯h on each subsequent day until they had reached 10â¯h) with hydrogel (nâ¯=â¯24 fast; nâ¯=â¯21 gradual) or silicone-hydrogel (nâ¯=â¯10 fast; nâ¯=â¯10 gradual) contact lenses. Masked investigators graded ocular surface physiology and non-invasive tear breakup time (NIBUT). A range of subjective scores (using 0-100 visual analogue scales) were recorded at the initial visit and after 10â¯h of lens wear, 4-6 days and 12-14 days after initial fitting. Subjective scores were also repeated after 7 days. RESULTS: There was no difference (pâ¯>â¯0.05) in ocular surface physiology between the fast and gradual adaptation groups at any time point in either lens type. NIBUT was similar at all time points for both adaptation groups in both lens types with the exception that the gradual adaptation silicone-hydrogel wearers had a slightly longer NIBUT (pâ¯=â¯0.007) than the fast adaptation group at 12-14 days. Subjective scores were also similar across the visits and lens types with the exception of 'lens awareness' and 'ease of lens removal' which were better (pâ¯<â¯0.05) in the fast compared with the gradual adaptation hydrogel lens group at day 7. Additionally, 'end-of-day discomfort' was better (pâ¯=â¯0.02) in the fast compared with the gradual adaptation hydrogel lens group at 12-14 days. CONCLUSION: There appears to be no benefit in daily disposable soft contact lens adaptation for neophytes with modern contact lens materials.
Asunto(s)
Adaptación Ocular/fisiología , Lentes de Contacto de Uso Prolongado , Córnea/fisiopatología , Satisfacción del Paciente , Errores de Refracción/terapia , Lágrimas/metabolismo , Adulto , Córnea/metabolismo , Equipos Desechables , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Prospectivos , Errores de Refracción/metabolismo , Errores de Refracción/fisiopatología , Método Simple Ciego , Adulto JovenRESUMEN
Newborns with lung hypoplasia (LH) commonly have limited respiratory function and often require ventilatory assistance after birth. We aimed to characterize the cardiorespiratory transition and respiratory function in newborn lambs with LH. LH was induced by draining fetal lung liquid in utero [110-133 days (d), term = 147d, n = 6]. At ~133d gestation, LH and Control lambs (n = 6) were instrumented and ventilated for 3 h to monitor blood-gas status, oxygenation, ventilator requirements, and hemodynamics during the transition from fetal to newborn life. Lambs with LH had significantly reduced relative wet and dry lung weights indicating hypoplastic lungs compared with Control lambs. LH lambs experienced persistent hypercapnia and acidosis during the ventilation period, had lower lung compliance, and had higher alveolar-arterial differences in oxygen and oxygenation index compared with Control lambs. As a result, LH lambs required greater respiratory support and more supplemental oxygen. Following delivery, LH lambs experienced periods of significantly lower pulmonary artery blood flow and higher carotid artery blood flow in association with the lower oxygenation levels. The detrimental effects of LH can be attributed to a reduction in lung size and poorer gas exchange capabilities. This study has provided greater understanding of the effect of LH itself on the physiology underpinning the transition from fetal to newborn life. Advances in this area is the key to identifying improved or novel management strategies for babies with LH starting in the delivery room, to favorably alter the fetal-to-newborn transition toward improved outcomes and reduced lifelong morbidity.NEW & NOTEWORTHY Current clinical management of newborns with lung hypoplasia (LH) is largely based on expert opinion rather than scientific evidence. We have generated physiological evidence for detrimental effects of LH on hemodynamics and respiratory function in newborn lambs, which mimics the morbidity observed in LH newborns clinically. The unfavorable consequences of LH can be attributed to a reduction in lung size and poorer gas exchange capabilities.