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BACKGROUND: Autism and attention deficit hyperactivity disorder (ADHD) are heterogeneous neurodevelopmental conditions with complex underlying neurobiology that is still poorly understood. Despite overlapping presentation and sex-biased prevalence, autism and ADHD are rarely studied together, and sex differences are often overlooked. Population modelling, often referred to as normative modelling, provides a unified framework for studying age-specific and sex-specific divergences in brain development. METHODS: Here we used population modelling and a large, multi-site neuroimaging dataset (N = 4255 after quality control) to characterise cortical anatomy associated with autism and ADHD, benchmarked against models of average brain development based on a sample of over 75,000 individuals. We also examined sex and age differences, relationship with autistic traits, and explored the co-occurrence of autism and ADHD (autism+ADHD). RESULTS: We observed robust neuroanatomical signatures of both autism and ADHD. Overall, autistic individuals showed greater cortical thickness and volume, that was localised to the superior temporal cortex, whereas individuals with ADHD showed more global increases in cortical thickness, but lower cortical volume and surface area across much of the cortex. The autism+ADHD group displayed a unique pattern of widespread increases in cortical thickness, and certain decreases in surface area. We also found evidence that sex modulates the neuroanatomy of autism but not ADHD, and an age-by-diagnosis interaction for ADHD only. CONCLUSIONS: These results indicate distinct cortical differences in autism and ADHD that are differentially impacted by age, sex, and potentially unique patterns related to their co-occurrence.
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OBJECTIVE: An expert commission has proposed the term "profound" autism for children on the spectrum who are minimally verbal or nonverbal and have intellectual disability (ID), behavioral challenges, and co-occurring conditions. It is unknown whether parents' rating of "severe" autism aligns with the definition of "profound" autism. Using the National Survey of Children's Health, we sought to (1) estimate the prevalence of parent-reported severe autism, (2) identify child characteristics that are associated with severe autism, (3) compare health care utilization, and (4) compare caregiver stress and resilience between families of children with severe versus mild/moderate autism. METHODS: Parent responses on the 2018 to 2019 NSCH were used to compare school-age children with parent-reported severe autism and those with mild/moderate autism. Descriptive statistics, χ2 tests, and logistic regression were used for statistical analysis. RESULTS: Among parents of 1,368 US children with autism, 10.1% characterized their child's autism as severe, a prevalence of 1 in 333. Parents of children with severe autism were more likely to report ID (45% vs 12.1%, p < 0.001), language delay (88% vs 58.7%, p < 0.001), and difficulties in dressing and bathing (67% vs 19.2%, p < 0.001). Children with severe autism had more behavioral problems and co-occurring conditions but were no more likely to see specialists or receive autism-specific behavioral therapy. Their caregivers reported more stress and less resilience. CONCLUSION: The characteristics of "profound" autism and parent-reported "severe" autism significantly overlap, allowing the use of the NSCH for studies of this vulnerable population. Children with profound/severe autism could benefit from more behavioral therapy, specialty care, and family support.
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This study investigates the paleobiological significance of pyritic stromatolites from the 3.48 billion-year-old Dresser Formation, Pilbara Craton. By combining paleoenvironmental analyses with observations from well-preserved stromatolites in newly obtained drill cores, the research reveals stratiform and columnar to domal pyritic structures with wavy to wrinkly laminations and crest thickening, hosted within facies variably influenced by syn-depositional hydrothermal activity. The columnar and domal stromatolites occur in strata with clearly distinguishable primary depositional textures. Mineralogical variability and fine-scale interference textures between the microbialites and the enclosing sediment highlight interplays between microbial and depositional processes. The stromatolites consist of organomineralization - nanoporous pyrite and microspherulitic barite - hosting significant thermally mature organic matter (OM). This includes filamentous organic microstructures encased within nanoporous pyrite, resembling the extracellular polymeric substance (EPS) of microbes. These findings imply biogenicity and support the activity of microbial life in a volcano-sedimentary environment with hydrothermal activity and evaporative cycles. Coupled changes in stromatolite morphology and host facies suggest growth in diverse niches, from dynamic, hydrothermally influenced shallow-water environments to restricted brine pools strongly enriched in SO 4 2 - $$ {\mathrm{SO}}_4^{2-} $$ from seawater and hydrothermal activity. These observations, along with S stable isotope data indicating influence by S metabolisms, and accumulations of biologically significant metals and metalloids (Ni and As) within the microbialites, help constrain microbial processes. Columnar to domal stromatolites in dynamic, hydrothermally influenced shallow water deposits likely formed by microbial communities dominated by phototrophs. Stratiform pyritic structures within barite-rich strata may reflect the prevalence of chemotrophs near hydrothermal venting, where hydrothermal activity and microbial processes influenced barite precipitation. Rapid pyrite precipitation, a putative taphonomic process for preserving microbial remnants, is attributed to microbial sulfate reduction and reduced S sourced from hydrothermal activity. In conclusion, this research underscores the biogenicity of the Dresser stromatolites and advances our understanding of microbial ecosystems in Earth's early history.
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Ecossistema , Sedimentos Geológicos , Sedimentos Geológicos/microbiologia , Sedimentos Geológicos/química , Sulfetos/química , Sulfetos/metabolismo , Fósseis , Ferro/metabolismo , Ferro/químicaRESUMO
Language and social symptoms improve with age in some autistic toddlers, but not in others, and such outcome differences are not clearly predictable from clinical scores alone. Here we aim to identify early-age brain alterations in autism that are prognostic of future language ability. Leveraging 372 longitudinal structural MRI scans from 166 autistic toddlers and 109 typical toddlers and controlling for brain size, we find that, compared to typical toddlers, autistic toddlers show differentially larger or thicker temporal and fusiform regions; smaller or thinner inferior frontal lobe and midline structures; larger callosal subregion volume; and smaller cerebellum. Most differences are replicated in an independent cohort of 75 toddlers. These brain alterations improve accuracy for predicting language outcome at 6-month follow-up beyond intake clinical and demographic variables. Temporal, fusiform, and inferior frontal alterations are related to autism symptom severity and cognitive impairments at early intake ages. Among autistic toddlers, brain alterations in social, language and face processing areas enhance the prediction of the child's future language ability.
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Transtorno Autístico , Encéfalo , Imageamento por Ressonância Magnética , Humanos , Masculino , Feminino , Pré-Escolar , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Transtorno Autístico/patologia , Transtorno Autístico/diagnóstico por imagem , Lactente , Idioma , Desenvolvimento da LinguagemRESUMO
BACKGROUND: Social affective and communication symptoms are central to autism spectrum disorder (ASD), yet their severity differs across toddlers: Some toddlers with ASD display improving abilities across early ages and develop good social and language skills, while others with "profound" autism have persistently low social, language and cognitive skills and require lifelong care. The biological origins of these opposite ASD social severity subtypes and developmental trajectories are not known. METHODS: Because ASD involves early brain overgrowth and excess neurons, we measured size and growth in 4910 embryonic-stage brain cortical organoids (BCOs) from a total of 10 toddlers with ASD and 6 controls (averaging 196 individual BCOs measured/subject). In a 2021 batch, we measured BCOs from 10 ASD and 5 controls. In a 2022 batch, we tested replicability of BCO size and growth effects by generating and measuring an independent batch of BCOs from 6 ASD and 4 control subjects. BCO size was analyzed within the context of our large, one-of-a-kind social symptom, social attention, social brain and social and language psychometric normative datasets ranging from N = 266 to N = 1902 toddlers. BCO growth rates were examined by measuring size changes between 1- and 2-months of organoid development. Neurogenesis markers at 2-months were examined at the cellular level. At the molecular level, we measured activity and expression of Ndel1; Ndel1 is a prime target for cell cycle-activated kinases; known to regulate cell cycle, proliferation, neurogenesis, and growth; and known to be involved in neuropsychiatric conditions. RESULTS: At the BCO level, analyses showed BCO size was significantly enlarged by 39% and 41% in ASD in the 2021 and 2022 batches. The larger the embryonic BCO size, the more severe the ASD social symptoms. Correlations between BCO size and social symptoms were r = 0.719 in the 2021 batch and r = 0. 873 in the replication 2022 batch. ASD BCOs grew at an accelerated rate nearly 3 times faster than controls. At the cell level, the two largest ASD BCOs had accelerated neurogenesis. At the molecular level, Ndel1 activity was highly correlated with the growth rate and size of BCOs. Two BCO subtypes were found in ASD toddlers: Those in one subtype had very enlarged BCO size with accelerated rate of growth and neurogenesis; a profound autism clinical phenotype displaying severe social symptoms, reduced social attention, reduced cognitive, very low language and social IQ; and substantially altered growth in specific cortical social, language and sensory regions. Those in a second subtype had milder BCO enlargement and milder social, attention, cognitive, language and cortical differences. LIMITATIONS: Larger samples of ASD toddler-derived BCO and clinical phenotypes may reveal additional ASD embryonic subtypes. CONCLUSIONS: By embryogenesis, the biological bases of two subtypes of ASD social and brain development-profound autism and mild autism-are already present and measurable and involve dysregulated cell proliferation and accelerated neurogenesis and growth. The larger the embryonic BCO size in ASD, the more severe the toddler's social symptoms and the more reduced the social attention, language ability, and IQ, and the more atypical the growth of social and language brain regions.
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Transtorno do Espectro Autista , Organoides , Humanos , Transtorno do Espectro Autista/patologia , Transtorno do Espectro Autista/fisiopatologia , Organoides/patologia , Masculino , Feminino , Pré-Escolar , Córtex Cerebral/patologia , Comportamento Social , Tamanho do Órgão , Lactente , Índice de Gravidade de Doença , Encéfalo/patologiaRESUMO
ABSTRACT: Liver disease has not been well described in patients with Fanconi anemia (FA). Improvements in outcomes of transplant mean that more individuals with FA are reaching adulthood and new features of the FA phenotype are being discovered. We performed a retrospective review of liver function in a cohort of 97 patients with FA followed-up for at least 10 years at a single center. We identified a high frequency of transaminitis (n = 31, 32%) without elevation of bilirubin and with no evidence of structural hepatic abnormality in patients with FA. Transaminitis was persistent in many cases, sometimes lasting more than a decade without clinical manifestation, although 2 patients with prolonged transaminitis are deceased from liver failure, indicating important long-term clinical consequences. Transaminitis was found in patients who had and had not received transplant but was more frequent in recipients of transplant. Exposure to total body irradiation increased risk (odds ratio, 15.5 [95% confidence interval, 2.44-304.54]; P = .01), whereas treatment with androgens did not. Review of limited numbers of liver biopsies and autopsy material showed a cholestatic pattern of liver injury, with progressive fibrosis, in the majority of patients. Occurrence in cases without transplant as well as cases with transplant argues against a potential diagnosis of atypical liver graft-versus-host disease. Limited data regarding therapy suggest no benefit from treatment with steroids or other immune suppressive medications or ursodeoxycholic acid. Our data show that liver disease is common in patients with FA, and because most children with FA now reach adulthood, end-stage liver disease in young adulthood means systematic testing of potential therapies is urgently needed.
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Anemia de Fanconi , Hepatopatias , Criança , Humanos , Adulto Jovem , Adulto , Anemia de Fanconi/complicações , Anemia de Fanconi/terapia , Androgênios/efeitos adversos , FenótipoRESUMO
Disparities exist in pediatric liver transplant (LT). We characterized barriers and facilitators to providing transplant and social care within pediatric LT clinics. This was a multicenter qualitative study. We oversampled caregivers reporting household financial strain, material economic hardship, or demonstrating poor health literacy. We also enrolled transplant team members. We conducted semistructured interviews with participants. Caregiver interviews focused on challenges addressing transplant and household needs. Transplant provider interviews focused on barriers and facilitators to providing social care within transplant teams. Interviews were recorded, transcribed, and coded according to the Capability, Opportunity, Motivation-Behavior model. We interviewed 27 caregivers and 27 transplant team members. Fifty-two percent of caregivers reported a household income <$60,000, and 62% reported financial resource strain. Caregivers reported experiencing (1) high financial burdens after LT, (2) added caregiving labor that compounds the financial burden, (3) dependency on their social network's generosity for financial and logistical support, and (4) additional support being limited to the perioperative period. Transplant providers reported (1) relying on the pretransplant psychosocial assessment for identifying social risks, (2) discomfort initiating social risk discussions in the post-transplant period, (3) reliance on social workers to address new social risks, and (4) social workers feeling overburdened by quantity and quality of the social work referrals. We identified barriers to providing effective social care in pediatric LT, primarily a lack of comfort in assessing and addressing new social risks in the post-transplant period. Addressing these barriers should enhance social care delivery and improve outcomes for these children.
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Cuidadores , Transplante de Fígado , Pesquisa Qualitativa , Humanos , Transplante de Fígado/psicologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/estatística & dados numéricos , Transplante de Fígado/economia , Cuidadores/psicologia , Cuidadores/estatística & dados numéricos , Cuidadores/economia , Masculino , Feminino , Criança , Pré-Escolar , Adulto , Adolescente , Apoio Social , Lactente , Efeitos Psicossociais da Doença , Entrevistas como Assunto , Atitude do Pessoal de Saúde , Pessoa de Meia-Idade , Disparidades em Assistência à Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/economia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/economia , Acessibilidade aos Serviços de Saúde/organização & administração , Adulto JovemRESUMO
BACKGROUND: The social determinants of health contribute to adverse post-liver transplant outcomes. Identifying unmet social risks may enable transplant teams to improve long-term outcomes for at-risk children. However, providers may feel uncomfortable asking about household-level social risks in the posttransplant period because they might make their patients/families uncomfortable. METHODS: We conducted a mixed-methods analysis of caregiver participants (ie, parents/guardians of pediatric liver transplant recipients) in the Social and Contextual Impact on Children Undergoing Liver Transplantation study to assess their perceptions of provider-based social risk screening. Participants (N = 109) completed a 20-min social determinants of health questionnaire that included questions on the acceptability of being asked intimate social risk questions. A subset of participants (N = 37) engaged in an in-depth qualitative interview to share their perceptions of social risk screening. RESULTS: Of 109 participants across 9 US transplant centers, 60% reported financial strain and 30% reported at least 1 material economic hardship (eg, food insecurity, housing instability). Overall, 65% of respondents reported it very or somewhat appropriate and 25% reported being neutral to being screened for social risks in a liver transplant setting. In qualitative analyses, participants reported trust in the providers and a clear understanding of the intention of the screening as prerequisites for liver transplant teams to perform social risk screening. CONCLUSIONS: Only a small minority of caregivers found social risk screening unacceptable. Pediatric liver transplant programs should implement routine social risk screening and prioritize the patient and family voices when establishing a screening program to ensure successful implementation.
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Cuidadores , Transplante de Fígado , Humanos , Criança , Transplante de Fígado/efeitos adversos , Habitação , Pobreza , Determinantes Sociais da SaúdeRESUMO
OBJECTIVE: To compare long-term outcomes of pediatric liver transplant (LT) recipients off immunosuppression (IS) with matched controls on IS using data from the Society of Pediatric Liver Transplant (SPLIT) registry. STUDY DESIGN: This was a retrospective case-control study. SPLIT participants <18 years of age, ≥4 years after isolated LT, and off IS for ≥1 year (cases) were age- and sex-matched 1:2 to patients with the same primary diagnosis and post-LT follow-up duration (controls). Primary outcomes included retransplantation, allograft rejection, IS comorbidities, and prevalence of SPLIT-derived composite ideal outcome (c-IO) achieved at the end of the follow-up period. Differences were compared using multiple linear regression for continuous outcomes and logistic regression for dichotomous data. RESULTS: The study cohort was composed of 33 cases (42.4% male, 60.6% biliary atresia, median age at LT of 0.7 [P25, P75, 0.5, 1.6] years, median IS withdrawal time of 9 [P25, P75, 6, 12] years after LT) and 66 age- and sex-matched controls. No cases required retransplantation. Cases and controls had similar growth parameters, laboratory values, calculated glomerular filtration rates, rates of post-transplant lymphoproliferative disease, graft rejection, and attainment of c-IO. CONCLUSIONS: No differences in allograft rejection rates, IS complications, or c-IO prevalence were seen between SPLIT patients off IS and age- and sex-matched controls remaining on IS. Discontinuation of IS most commonly occurred in the context of rigorously designed IS withdrawal trials. The available sample size was small, affecting generalizability to the broader pediatric LT population.
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Transplante de Fígado , Criança , Humanos , Masculino , Feminino , Estudos de Casos e Controles , Estudos Retrospectivos , Terapia de Imunossupressão , Rejeição de Enxerto/epidemiologia , Sistema de RegistrosRESUMO
Background: Autism and attention deficit hyperactivity disorder (ADHD) are heterogeneous neurodevelopmental conditions with complex underlying neurobiology. Despite overlapping presentation and sex-biased prevalence, autism and ADHD are rarely studied together, and sex differences are often overlooked. Normative modelling provides a unified framework for studying age-specific and sex-specific divergences in neurodivergent brain development. Methods: Here we use normative modelling and a large, multi-site neuroimaging dataset to characterise cortical anatomy associated with autism and ADHD, benchmarked against models of typical brain development based on a sample of over 75,000 individuals. We also examined sex and age differences, relationship with autistic traits, and explored the co-occurrence of autism and ADHD (autism+ADHD). Results: We observed robust neuroanatomical signatures of both autism and ADHD. Overall, autistic individuals showed greater cortical thickness and volume localised to the superior temporal cortex, whereas individuals with ADHD showed more global effects of cortical thickness increases but lower cortical volume and surface area across much of the cortex. The autism+ADHD group displayed a unique pattern of widespread increases in cortical thickness, and certain decreases in surface area. We also found evidence that sex modulates the neuroanatomy of autism but not ADHD, and an age-by-diagnosis interaction for ADHD only. Conclusions: These results indicate distinct cortical differences in autism and ADHD that are differentially impacted by age, sex, and potentially unique patterns related to their co-occurrence.
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Importance: Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions. Objective: To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients. Design, Setting, and Participants: This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody levels at enrollment between January 1, 2002, and February 28, 2023. Eligibility for live vaccine was determined by individual US pediatric solid organ transplant center protocols. Exposures: Exposure was defined as receipt of a posttransplant live vaccine. Transplant recipients received 1 to 3 doses of MMR vaccine and/or 1 to 3 doses of VZV vaccine. Main Outcome and Measure: Safety data were collected following each vaccination, and antibody levels were obtained at 0 to 3 months and 1 year following vaccination. Comparisons were performed using Mann-Whitney U test, and factors associated with development of postvaccination protective antibodies were explored using univariate analysis. Results: The cohort included 281 children (270 [96%] liver, 9 [3%] kidney, 2 [1%] liver-kidney recipients) from 18 centers. The median time from transplant to enrollment was 6.3 years (IQR, 3.4-11.1 years). The median age at first posttransplant vaccine was 8.9 years (IQR, 4.7-13.8 years). A total of 202 of 275 (73%) children were receiving low-level monotherapy immunosuppression at the time of vaccination. The majority of children developed protective antibodies following vaccination (107 of 149 [72%] varicella, 130 of 152 [86%] measles, 100 of 120 [83%] mumps, and 124 of 125 [99%] rubella). One year post vaccination, the majority of children who initially mounted protective antibodies maintained this protection (34 of 44 [77%] varicella, 45 of 49 [92%] measles, 35 of 42 [83%] mumps, 51 of 54 [94%] rubella). Five children developed clinical varicella, all of which resolved within 1 week. There were no cases of measles or rubella and no episodes of graft rejection within 1 month of vaccination. There was no association between antibody response and immunosuppression level at the time of vaccination. Conclusions and Relevance: The findings suggest that live vaccinations may be safe and immunogenic after solid organ transplant in select pediatric recipients and can offer protection against circulating measles, mumps, and varicella.
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Varicela , Sarampo , Caxumba , Rubéola (Sarampo Alemão) , Vacinas Virais , Criança , Humanos , Pré-Escolar , Adolescente , Varicela/prevenção & controle , Vacina contra Varicela/efeitos adversos , Vacinas Combinadas , Transplantados , Estudos de Coortes , Rubéola (Sarampo Alemão)/prevenção & controle , Sarampo/prevenção & controle , Vacinas Atenuadas/efeitos adversosRESUMO
Histamine is a biogenic amine that regulates multiple physiological functions in diverse organisms, specifically playing a central role in the mammalian immune response. The common bed bug, Cimex lectularius L. (Hemiptera: Cimicidae), excretes histamine in large amounts in its feces as a component of its aggregation pheromone, which contaminates homes. The potential health risks associated with the presence of indoor histamine are unclear, but to predict future exposure risks, it is critical that we understand if other arthropods excrete histamine in any discernible phylogenetic pattern. In the present study, we evaluated histamine excretion by various arthropods; specifically those commonly found in large numbers indoors, other hematophagous species, and other species in the order Hemiptera. To evaluate arthropods for histamine excretion, rearing containers for each arthropod were swabbed and/or the harborage substrates were collected. Samples were then analyzed for the presence of histamine using gas chromatography-mass spectrometry. For those arthropods where histamine was present above the method detection limit, total histamine excretion was quantified over a period of 2 wk. Our results indicate that histamine excretion is limited to hematophagous hemipterans (bed bugs, bat bugs, tropical bed bugs, and kissing bugs), suggesting that indoor histamine contamination in the United States can be primarily linked to bed bugs.
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Artrópodes , Percevejos-de-Cama , Animais , Histamina , Filogenia , Percevejos-de-Cama/fisiologia , Comportamento Alimentar , MamíferosRESUMO
Terrestrial hot springs harbor diverse microbial communities whose compositions are shaped by the wide-ranging physico-chemistries of individual springs. The effect of enormous physico-chemical differences on bacterial and archaeal distributions and population structures is little understood. We therefore analysed the prevalence and relative abundance of bacteria and archaea in the sediments (n = 76) of hot spring features, in the Taupo Volcanic Zone (New Zealand), spanning large differences in major anion water chemistry, pH (2.0-7.5), and temperature (17.5-92.9 °C). Community composition, based on 16S rRNA amplicon sequence variants (ASVs) was strongly influenced by both temperature and pH. However, certain lineages characterized diverse hot springs. At the domain level, bacteria and archaea shared broadly equivalent community abundances across physico-chemically diverse springs, despite slightly lower bacteria-to-archaea ratios and microbial 16S rRNA gene concentrations at higher temperatures. Communities were almost exclusively dominated by Proteobacteria, Euryarchaeota or Crenarchaeota. Eight archaeal and bacterial ASVs from Thermoplasmatales, Desulfurellaceae, Mesoaciditogaceae and Acidithiobacillaceae were unusually prevalent (present in 57.9-84.2% of samples) and abundant (1.7-12.0% sample relative abundance), and together comprised 44% of overall community abundance. Metagenomic analyses generated multiple populations associated with dominant ASVs, and showed characteristic traits of each lineage for sulfur, nitrogen and hydrogen metabolism. Differences in metabolic gene composition and genome-specific metabolism delineated populations from relatives. Genome coverage calculations showed that populations associated with each lineage were distributed across a physicochemically broad range of hot springs. Results imply that certain bacterial and archaeal lineages harbor different population structures and metabolic potentials for colonizing diverse hot spring environments.
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The western yellowjacket, Vespula pensylvanica (Saussure), is an important seasonal pest of recreational and outdoor venues in the western United States. Its propensity to scavenge food increases the likelihood of stinging incidences. Control measures are limited to intensive trapping and treating subterranean nests. The only toxicant registered for baiting in the US is esfenvalerate, which is ineffective. The objective of this study was to determine the potential of the isoxazoline fluralaner as a bait toxicant. With microsatellite genotyping, a minimum of 27 different colonies were shown to forage at a single monitoring site. Some colonies disappeared after baiting, and new colonies were detected. The implications for baiting and monitoring are discussed. Minced chicken and hydrogel baits containing 0.022% and 0.045% fluralaner significantly reduced foraging yellowjackets. Several bait applications covering large areas will be necessary to provide long-term control.
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OBJECTIVE: To evaluate whether the nature and severity of non-A-E severe acute hepatitis in children noted by the World Health Organization from late 2021 through early 2022 was indeed increased in 2021-2022 compared with prior years. STUDY DESIGN: We performed a single-center, retrospective study to track the etiology and outcomes of children with non-A-E severe acute hepatitis in 2021-2022 compared with the prior 3-year periods (2018-2019, 2019-2020, and 2020-2021). We queried electronic medical records of children ≤16 years of age with alanine or aspartate aminotransferase levels of >500 IU. Data were analyzed for the periods of October 1, 2021, to May 1, 2022, and compared with the same time periods in 2018-2021. RESULTS: Of 107 children meeting entry criteria, 82 cases occurred from October to May of 2018-2022. The average annual case number was 16.3 in 2018-2021 compared with a 2-fold increase (to 33) in 2021-2022 (P = .0054). Analyses of etiologies showed that this increase was associated with a higher number of children who tested positive for viruses (n = 16) when compared with the average of 3.7 for 2018-2021 (P = .018). Adenovirus (26.1%) and severe acute respiratory syndrome coronavirus-2 (10.3%) were the most frequently detected viruses in 2021-2022. Despite evidence of acute liver failure in 37.8% of children in the entire cohort and in 47% of those with viral infection, the overall survival rate was high at 91.4% and 88.9%, respectively. CONCLUSIONS: The number of children with severe acute hepatitis in our center increased from 2021 to May 2022, with a greater frequency of cases associated with adenovirus, yet transplant-free survival remains high.
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Infecções por Adenoviridae , COVID-19 , Hepatite , Humanos , Criança , Adenoviridae , Estudos Retrospectivos , Incidência , Infecções por Adenoviridae/epidemiologiaRESUMO
Liver transplantation risks transferring a genetic defect in metabolic pathways, including the urea cycle. We present a case of pediatric liver transplantation complicated by metabolic crisis and early allograft dysfunction (EAD) in a previously healthy unrelated deceased donor. Allograft function improved with supportive care, and retransplantation was avoided. Because hyperammonemia suggested an enzymatic defect in the allograft, genetic testing from donor-derived deoxyribonucleic acid revealed a heterozygous mutation in the ASL gene, which encodes the urea cycle enzyme argininosuccinate lyase. Homozygous ASL mutations precipitate metabolic crises during fasting or postoperative states, whereas heterozygous carriers retain sufficient enzyme activity and are asymptomatic. In the described case, postoperative ischemia/reperfusion injury created a metabolic demand that exceeded the enzymatic capacity of the allograft. To our knowledge, this is the first report of an acquired argininosuccinate lyase deficiency by liver transplantation and underscores the importance of considering occult metabolic variants in the allograft during EAD.
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Acidúria Argininossuccínica , Humanos , Criança , Mutação , Acidúria Argininossuccínica/genética , Fígado , Aloenxertos , UreiaRESUMO
Due to their mutualistic relationship with plant pests, the Argentine ant is considered a major pest in subtropical fruit orchards and vineyards. Besides insecticide sprays, liquid baiting has been demonstrated as an effective method to suppress the Argentine ant populations. To improve the economic feasibility of liquid baiting, hydrogel materials have been recently tested as a carrier for liquid baits containing various insecticidal active ingredients. Here, we tested boric acid as a toxicant in the aqueous sugar bait delivered in a biodegradable calcium alginate hydrogel. Laboratory tests demonstrated that boric acid (1%) liquid bait incorporated in the calcium alginate hydrogel effectively killed Argentine ant workers. Potassium sorbate (0.25%) added to the liquid bait as a preservative did not impact the efficacy of boric acid even though it significantly reduced the degree of swelling of the hydrogel beads in the bait solution. Testing with 2-month-old bait suggested that long-term storage might impact bait efficacy even with potassium sorbate preservative.
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Formigas , Inseticidas , Animais , Controle de Insetos/métodos , Hidrogéis , Ácido Sórbico , AlginatosRESUMO
Identifying prognostic early brain alterations is crucial for autism spectrum disorder (ASD). Leveraging structural MRI data from 166 ASD and 109 typical developing (TD) toddlers and controlling for brain size, we found that, compared to TD, ASD toddlers showed larger or thicker lateral temporal regions; smaller or thinner frontal lobe and midline structures; larger callosal subregion volume; and smaller cerebellum. Most of these differences were replicated in an independent cohort of 38 ASD and 37 TD toddlers. Moreover, the identified brain alterations were related to ASD symptom severity and cognitive impairments at intake, and, remarkably, they improved the accuracy for predicting later language outcome beyond intake clinical and demographic variables. In summary, brain regions involved in language, social, and face processing were altered in ASD toddlers. These early-age brain alterations may be the result of dysregulation in multiple neural processes and stages and are promising prognostic biomarkers for future language ability.
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BACKGROUND: Controversies in management of biliary atresia (BA) after hepatoportoenterostomy (HPE) lead to variable treatment protocols. We implemented standardized medical management after HPE, customizing the use of antibiotics and corticosteroids based on patient-specific factors. METHODS: In this retrospective analysis, 20 consecutive infants underwent HPE for BA and were compared to a historical cohort. Analysis of successful biliary drainage 3 months after HPE (defined as serum total bilirubin <2â¯mg/dL) was the primary endpoint; survival with native liver at 2 years was the secondary endpoint. RESULTS: Sixteen of 20 (80%) infants had successful bile drainage, compared to 8 of 20 (40%) infants in the historical cohort (Pâ¯=â¯0.0225). Sixteen of 20 patients in the new protocol have reached 2 years of age or required liver transplantation. Among the sixteen, 11 (68.8%) are alive with native livers versus 10 of 20 (50%) in the historical cohort (Pâ¯=â¯0.0970). CONCLUSION: This preliminary report suggests the potential benefit of tailored use of postoperative antibiotics and corticosteroids in improving biliary drainage after HPE. LEVEL OF EVIDENCE: III.
Assuntos
Atresia Biliar , Lactente , Humanos , Atresia Biliar/complicações , Estudos Retrospectivos , Bile , Portoenterostomia Hepática/métodos , Drenagem , Corticosteroides , Resultado do TratamentoRESUMO
Infants with critical CHD have abnormal neurobehavior assessed by the Neonatal ICU Network Neurobehavioral Scales. This retrospective cohort study hypothesized associations between abnormal infant neurobehavior in the first month of life and later neurodevelopmental outcomes at 1-2 years of age. Associations between abnormal infant attention (orienting to and tracking stimuli) on the Neonatal ICU Network Neurobehavioral Scales and later motor, cognitive, and language neurodevelopmental outcomes on the Bayley Scales of Infant Development-III at follow-up were examined with descriptive statistics and univariable and multivariable regression. Multiple imputation was used to account for missing outcome data. 189 infants with critical CHD were included, and 69% had abnormal neurobehavioral attention scores. 58 (31%) returned as toddlers for neurodevelopmental follow-up, of which 23% had motor delay. Abnormal infant attention had high sensitivity (92%, 95% CI 60-100%) but low specificity (36%, 95% CI 23-52%) for later motor delay. Higher infant attention scores were associated with higher later motor scores in univariable analysis (coefficient 3.49, 95% CI 0.52,6.46, p = 0.025), but not in multivariable analyses. Neither cognitive nor language scores were associated with infant attention scores. Lower birth weight and male sex were significantly associated with lower motor scores in multivariable analysis (p = 0.048, 0.007). Although impaired infant attention is interdependent with other clinical and demographic risk factors, it may be a sensitive clinical marker of risk for later motor delay. In children with critical CHD, impaired infant attention may be capturing early signs of abnormal visual-motor neurodevelopment.