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Lithium-ion batteries (LiBs) are used globally as a key component of clean and sustainable energy infrastructure, and emerging LiB technologies have incorporated a class of per- and polyfluoroalkyl substances (PFAS) known as bis-perfluoroalkyl sulfonimides (bis-FASIs). PFAS are recognized internationally as recalcitrant contaminants, a subset of which are known to be mobile and toxic, but little is known about environmental impacts of bis-FASIs released during LiB manufacture, use, and disposal. Here we demonstrate that environmental concentrations proximal to manufacturers, ecotoxicity, and treatability of bis-FASIs are comparable to PFAS such as perfluorooctanoic acid that are now prohibited and highly regulated worldwide, and we confirm the clean energy sector as an unrecognized and potentially growing source of international PFAS release. Results underscore that environmental impacts of clean energy infrastructure merit scrutiny to ensure that reduced CO2 emissions are not achieved at the expense of increasing global releases of persistent organic pollutants.
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OBJECTIVE: To improve knowledge of neonatal hypoxic-ischemic encephalopathy, a prospective, nationwide, population-based cohort of affected children is being set up between September 2015 and March 2017. METHODS: During this period, 794 cases are collected, with information on pregnancy, delivery, neonatal stay and outcome at the end of hospitalization. Clinical and parental questionnaire follow-up is planned until the child is 4 years old. RESULTS: This article presents the clinical presentation of the newborns included, the analysis of factors associated with short-term outcome at hospital discharge and the organizational factors associated with treatment with therapeutic hypothermia. CONCLUSION: These data illustrate the value of a prospective cohort to analyze the management of anoxo-ischemic encephalopathy in France.
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Hipotermia Inducida , Hipoxia-Isquemia Encefálica , Humanos , Hipotermia Inducida/métodos , Francia/epidemiología , Hipoxia-Isquemia Encefálica/terapia , Recién Nacido , Femenino , Estudios Prospectivos , Embarazo , Masculino , Estudios de Cohortes , Encuestas y Cuestionarios , LactanteRESUMEN
OBJECTIVE: To determine the risk on brain lesions according to gestational age (GA) in neonates with neonatal encephalopathy. DESIGN: Secondary analysis of the prospective national French population-based cohort, Long-Term Outcome of NeonataL EncePhALopathy. SETTING: French neonatal intensive care units. PATIENTS: Neonates with moderate or severe neonatal encephalopathy (NE) born at ≥34 weeks' GA (wGA) between September 2015 and March 2017. MAIN OUTCOME MEASURES: The results of MRI performed within the first 12 days were classified in seven injured brain regions: basal ganglia and thalami, white matter (WM), cortex, posterior limb internal capsule, corpus callosum, brainstem and cerebellum. A given infant could have several brain structures affected. Risk of brain lesion according to GA was estimated by crude and adjusted ORs (aOR). RESULTS: MRI was available for 626 (78.8%) of the 794 included infants with NE. WM lesions predominated in preterm compared with term infants. Compared with 39-40 wGA neonates, those born at 34-35 wGA and 37-38 wGA had greater risk of WM lesions after adjusting for perinatal factors (aOR 4.0, 95% CI (1.5 to 10.7) and ORa 2.0, 95% CI (1.1 to 3.5), respectively). CONCLUSION: WM is the main brain structure affected in late-preterm and early-term infants with NE, with fewer WM lesions as GA increases. This finding could help clinicians to estimate prognosis and improve the understanding of the pathophysiology of NE. TRIAL REGISTRATION NUMBER: NCT02676063, ClinicalTrials.gov.
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Edad Gestacional , Imagen por Resonancia Magnética , Femenino , Humanos , Recién Nacido , Masculino , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encefalopatías/diagnóstico por imagen , Encefalopatías/etiología , Francia/epidemiología , Recien Nacido Prematuro , Unidades de Cuidado Intensivo Neonatal , Estudios Prospectivos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patologíaRESUMEN
OBJECTIVES: To assess in newborns with neonatal encephalopathy (NE), presumptively related to a peripartum hypoxic-ischemic event, the frequency of dysglycemia and its association with neonatal adverse outcomes. STUDY DESIGN: We conducted a secondary analysis of LyTONEPAL (Long-Term Outcome of Neonatal hypoxic EncePhALopathy in the era of neuroprotective treatment with hypothermia), a population-based cohort study including 545 patients with moderate-to-severe NE. Newborns were categorized by the glycemia values assessed by routine clinical care during the first 3 days of life: normoglycemic (all glycemia measurements ranged from 2.2 to 8.3 mmol/L), hyperglycemic (at least 1 measurement >8.3 mmol/L), hypoglycemic (at least 1 measurement <2.2 mmol/L), or with glycemic lability (measurements included at least 1 episode of hypoglycemia and 1 episode of hyperglycemia). The primary adverse outcome was a composite outcome defined by death and/or brain lesions on magnetic resonance imaging, regardless of severity or location. RESULTS: In total, 199 newborns were categorized as normoglycemic (36.5%), 74 hypoglycemic (13.6%), 213 hyperglycemic (39.1%), and 59 (10.8%) with glycemic lability, based on the 2593 glycemia measurements collected. The primary adverse outcome was observed in 77 (45.8%) normoglycemic newborns, 37 (59.7%) with hypoglycemia, 137 (67.5%) with hyperglycemia, and 40 (70.2%) with glycemic lability (P < .01). With the normoglycemic group as the reference, the aORs and 95% 95% CIs for the adverse outcome were significantly greater for the group with hyperglycemia (aOR 1.81; 95% CI 1.06-3.11). CONCLUSIONS: Dysglycemia affects nearly two-thirds of newborns with NE and is independently associated with a greater risk of mortality and/or brain lesions on magnetic resonance imaging. TRIAL REGISTRATION: NCT02676063.
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Hiperglucemia , Hipoglucemia , Hipotermia Inducida , Hipotermia , Hipoxia-Isquemia Encefálica , Enfermedades del Recién Nacido , Humanos , Recién Nacido , Estudios de Cohortes , Hipoglucemia/terapia , Hipoglucemiantes , Hipotermia Inducida/métodos , Hipoxia-Isquemia Encefálica/terapia , Enfermedades del Recién Nacido/terapiaRESUMEN
In nature, microorganisms often reside in symbiotic co-existence providing nutrition, stability, and protection for each partner by applying "division of labor." This principle may also be used for the overproduction of targeted compounds in bioprocesses. It requires the engineering of a synthetic co-culture with distributed tasks for each partner. Thereby, the competition on precursors, redox cofactors, and energy-which occurs in a single host-is prevented. Current applications often focus on unidirectional interactions, that is, the product of partner A is used for the completion of biosynthesis by partner B. Here, we present a synthetically engineered Escherichia coli co-culture of two engineered mutant strains marked by the essential interaction of the partners which is achieved by implemented auxotrophies. The tryptophan auxotrophic strain E. coli ANT-3, only requiring small amounts of the aromatic amino acid, provides the auxotrophic anthranilate for the tryptophan producer E. coli TRP-3. The latter produces a surplus of tryptophan which is used to showcase the suitability of the co-culture to access related products in future applications. Co-culture characterization revealed that the microbial consortium is remarkably functionally stable for a broad range of inoculation ratios. The range of robust and functional interaction may even be extended by proper glucose feeding which was shown in a two-compartment bioreactor setting with filtrate exchange. This system even enables the use of the co-culture in a parallel two-level temperature setting which opens the door to access temperature sensitive products via heterologous production in E. coli in a continuous manner.
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Initiation of therapeutic hypothermia (TH) within 6 h of life is a major concern for treating neonatal hypoxic ischemic encephalopathy (HIE). We aimed to determine clinical and healthcare organizational factors associated with delayed TH in a French population-based cohort of neonates with moderate/severe HIE. Time to reach a rectal temperature of 34 °C defines optimal and delayed (within and over 6 h, respectively) TH. Clinical and healthcare organizational factors associated with delayed TH were analysed among neonates born in cooling centres (CCs) and non-cooling centres (non-CCs). Among 629 neonates eligible for TH, 574 received treatment (91.3%). TH was delayed in 29.8% neonates and in 20.3% and 36.2% of those born in CCs and non-CCs, respectively. Neonates with moderate HIE were more exposed to delayed TH in both CCs and non-CCs. After adjustment for HIE severity, maternal and neonatal characteristics and circumstances of birth were not associated with increased risk of delayed TH. However, this risk was 2 to 5 times higher in maternities with < 1999 annual births, when the delay between birth and call for transfer (adjusted odds ratio [aOR] 2.47, 95% confidence interval [CI] [1.03 to 5.96]) or between call for transfer and admission (aOR 6.06, 95%CI [2.60 to 14.12]) was > 3 h and when an undesirable event occurred during transfer (aOR 2.66, 95%CI [1.11 to 6.37]. Conclusion: Increasing early identification of neonates who could benefit from TH and access to TH in non-CCs before transfer are modifiable factors that could improve care of neonates with HIE. Trial registration: The trial was registered at ClinicalTrials.gov (NCT02676063). What is Known: ⢠International recommendations are to initiate therapeutic hypothermia before 6 h of life in neonates with moderate or severe hypoxic ischemic encephalopathy. What is New: â¢In this French population-based cohort of infants with hypoxic ischemic encephalopathy, nearly one-third of neonates eligible for treatment did not have access to hypothermia in the therapeutic window of 6 h of life. . ⢠Among infants born in non-cooling centres, healthcare organizational factors involved in delayed care were the small size of maternities (1999 annual births), a time interval of more than 3 h between birth and call for transfer and between call for transfer and admission in neonatology, and the occurrence of an undesirable event during transfer.
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Hipotermia Inducida , Hipoxia-Isquemia Encefálica , Recién Nacido , Lactante , Humanos , Hipoxia-Isquemia Encefálica/terapia , Hipoxia-Isquemia Encefálica/complicaciones , Hipotermia Inducida/efectos adversos , Unidades de Cuidado Intensivo Neonatal , Medición de Riesgo , Atención a la SaludRESUMEN
Context: Developing brain imaging is a critical subject for infants born preterm. Impaired brain growth is correlated with poor neurological outcomes, regardless of overt brain lesions, such as hemorrhage or leukomalacia. As magnetic resonance imaging (MRI) remains a research tool for assessing regional brain volumes, two-dimensional metrics (2D metrics) provide a reliable estimation of brain structures. In neonatal intensive care, cerebral ultrasound (cUS) is routinely performed to assess brain integrity. This prospective work has compared US and MRI accuracy for the measurement of 2D brain metrics and identification of overt injuries. Methods: MRI and cUS were performed at term equivalent age (TEA) in infants born before 32 weeks of gestation (GW). Demographical data and results of serial cUS (Neonatal Intensive Care Unit [NICU]-US) performed during hospitalization were gathered from medical charts. Blinded, experienced senior doctors reviewed the scans for both standard analysis and standardized, 2D measurements. The correlation of 2D metrics and inter-/intraobserver agreements were evaluated using Pearson's coefficient, Bland-Altman plots, and intraclass coefficient (ICC), respectively. Results: In total, 102 infants born preterm were included. The performance of "TEA-cUS and NICU-cUS" when compared to "TEA-MRI and NICU-cUS" was identical for the detection of high-grade hemorrhages and close for low-grade ones. However, TEA-MRI only detected nodular lesions of the white matter (WM). No infant presented a cerebellar infarct on imaging. Intra- and inter-observer agreements were excellent for all 2D metrics except for the corpus callosum width (CCW) and anteroposterior vermis diameter. MRI and cUS showed good to excellent correlation for brain and bones biparietal diameters, corpus callosum length (CCL), transcerebellar diameters (TCDs), and lateral ventricle diameters. Measures of CCW and vermis dimensions were poorly correlated. Conclusion and perspective: The cUS is a reliable tool to assess selected 2D measurements in the developing brain. Repetition of these metrics by serial cUS during NICU stay would allow the completion of growth charts for several brain structures. Further studies will assess whether these charts are relevant markers of neurological outcome.
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Pediatric morbidity from meningitis remains considerable. Preventing complications is a major challenge to improve neurological outcome. Seizures may reveal the meningitis itself or some complications of this disease. Amplitude-integrated electroencephalography (aEEG) is gaining interest for the management of patients with acute neurological distress, beyond the neonatal age. This study aimed at evaluating the predictive value of aEEG monitoring during the acute phase in meningitis among a population of infants hospitalized in the pediatric intensive care unit (PICU), and at assessing the practicability of the technique. AEEG records of 25 infants younger than one year of age hospitalized for meningitis were retrospectively analyzed and correlated to clinical data and outcome. Recording was initiated, on average, within the first six hours for n = 18 (72%) patients, and overall quality was considered as good. Occurrence of seizure, of status epilepticus, and the background pattern were significantly associated with unfavorable neurological outcomes. AEEG may help in the management and prognostic assessment of pediatric meningitis. It is an easily achievable, reliable technique, and allows detection of subclinical seizures with minimal training. However, it is important to consider the limitations of aEEG, and combinate it with conventional EEG for the best accuracy.
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BACKGROUND: Brain magnetic resonance imaging (MRI) is a key tool for the prognostication of encephalic newborns in the context of hypoxic-ischemic events. The purpose of this study was to finely characterize brain injuries in this context. METHODS: We provided a complete, descriptive analysis of the brain MRIs of infants included in the French national, multicentric cohort LyTONEPAL. RESULTS: Among 794 eligible infants, 520 (65.5%) with MRI before 12 days of life, grade II or III encephalopathy and gestational age ≥36 weeks were included. Half of the population had a brain injury (52.4%); MRIs were acquired before 6 days of life among 247 (47.5%) newborns. The basal ganglia (BGT), white matter (WM) and cortex were the three predominant sites of injuries, affecting 33.8% (n = 171), 33.5% (n = 166) and 25.6% (n = 128) of participants, respectively. The thalamus and the periventricular WM were the predominant sublocations. The BGT, posterior limb internal capsule, brainstem and cortical injuries appeared more frequently in the early MRI group than in the late MRI group. CONCLUSION: This study described an overview of brain injuries in hypoxic-ischemic neonatal encephalopathy. The basal ganglia with the thalamus and the WM with periventricular sublocation injuries were predominant. Comprehensive identification of brain injuries in the context of HIE may provide insight into the mechanism and time of occurrence.
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Preterm birth disrupts the in utero environment, preventing the brain from fully developing, thereby causing later cognitive and behavioral disorders. Such cerebral alteration occurs beneath an anatomical scale, and is therefore undetectable by conventional imagery. Prematurity impairs the microstructure and thus the histological process responsible for the maturation, including the myelination. Cerebral MRI diffusion tensor imaging sequences, based on water's motion into the brain, allows a representation of this maturation process. Similarly, the brain's connections become disorganized. The connectome gathers structural and anatomical white matter fibers, as well as functional networks referring to remote brain regions connected one over another. Structural and functional connectivity is illustrated by tractography and functional MRI, respectively. Their organizations consist of core nodes connected by edges. This basic distribution is already established in the fetal brain. It evolves greatly over time but is compromised by prematurity. Finally, cerebral plasticity is nurtured by a lifetime experience at microstructural and macrostructural scales. A preterm birth causes a negative and early disruption, though it can be partly mitigated by positive stimuli based on developmental neonatal care.
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BACKGROUND: Hypothermia is widely used for infants with hypoxic-ischemic neonatal encephalopathy but its impact remains poorly described at a population level. We aimed to describe brain imaging in infants born at ≥36 weeks' gestation, with moderate/severe encephalopathy treated with hypothermia. METHODS: Descriptive analysis of brain MRI and discharge neurological examination for infants included in the French national multicentric prospective observational cohort LyTONEPAL. RESULTS: Among 575 eligible infants, 479 (83.3%) with MRI before 12 days of life were included. MRI was normal for 48.2% (95% CI 43.7-52.8). Among infants with brain injuries, 62.5% (95% CI 56.2-68.5) had damage to more than one structure, 19.8% (95% CI 15.0-25.3) showed a pattern-associating injuries of basal ganglia/thalami (BGT), white matter (WM) and cortex. Overall, 68.4% (95% CI 62.0-74.3) of infants with normal MRI survived with a normal neurological examination. The rate of death was 15.4% (95% CI 12.3-19.0), predominantly for infants with the combined BGT, cortex, and/or WM injuries. CONCLUSIONS: Among infants with neonatal encephalopathy treated with hypothermia, two-thirds of those with normal MRI survived with a normal neurological examination at discharge. When present, brain injuries often involved more than one structure. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (NCT02676063). IMPACT: In this multicentric cohort of infants with neonatal encephalopathy (LYTONEPAL) two-thirds survived with normal MRI and neurological examination at discharge. In total, 10% of newborns showed a pattern associating injuries of the basal ganglia-thalami, white matter, and cortex, which was correlated with a high risk of death at discharge. The evolution of MRI techniques and sequences in the era of hypothermia calls for a revisiting of imaging protocol in neonatal encephalopathy, especially for the timing. The neurological examination did not give evidence of brain injuries, thus questioning the reproducibility of the clinical exam or the neonatal brain functionality.
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Lesiones Traumáticas del Encéfalo , Lesiones Encefálicas , Hipotermia Inducida , Hipotermia , Hipoxia-Isquemia Encefálica , Enfermedades del Recién Nacido , Lesiones Encefálicas/terapia , Lesiones Traumáticas del Encéfalo/terapia , Humanos , Hipotermia/terapia , Hipotermia Inducida/métodos , Hipoxia-Isquemia Encefálica/complicaciones , Hipoxia-Isquemia Encefálica/diagnóstico por imagen , Hipoxia-Isquemia Encefálica/terapia , Lactante , Recién Nacido , Enfermedades del Recién Nacido/diagnóstico , Imagen por Resonancia Magnética/métodos , Reproducibilidad de los ResultadosRESUMEN
Objective: Assessment of intellectual abilities in individuals with autism spectrum disorder (ASD) is a core component of a comprehensive diagnostic evaluation. However, relatively limited information is available regarding the validity of one of the most commonly-used measures of intelligence, the Wechsler Intelligence Scale for Children - 5th Edition (WISC-V) in ASD.Method: We investigated the factor structure and measurement invariance of the WISC-V in a sample of 349 children aged 6-16 diagnosed with ASD using single- and multi-group confirmatory factor analysis. The comparison group was the WISC-V standardization sample.Results: A four-index bifactor solution best fit the ASD group data. Measurement invariance analyses indicated support for configural and metric, but not scalar, invariance of the published 5-index structure, suggesting systematic differences in performance among some subscales in ASD. The 7-subtest FSIQ scale had partial scalar invariance after relaxing equality constraints on the Coding and Digit Span subtest intercepts, suggesting sources other than theorized IQ ability contribute to lower scores on these subtests within ASD. The Cognitive Proficiency Index (CPI) failed to demonstrate appropriate fit in baseline models. The General Ability Index (GAI) had full configural, metric, and scalar invariance.Conclusions: Statistical bias on the WISC-V within ASD in processing speed and working memory subtests creates significant limitations for the use of FSIQ and especially CPI index scores in ASD populations. The GAI showed strong measurement properties and should be considered as the preferred indicator of overall intellectual functioning when assessing children with ASD using the WISC-V.
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Trastorno del Espectro Autista , Adolescente , Niño , Cognición , Análisis Factorial , Humanos , Memoria a Corto Plazo , Escalas de WechslerRESUMEN
A pandemic linked to the new coronavirus strain (SARS-CoV-2) has been raging for several months. Pediatric populations are less impacted than adults, and critical respiratory diseases seem rare (1, 2). We report the case of an infant, who presented with life-threatening apneas at home requiring basic life support. SARS-CoV-2 was subsequently identified in the patient's nasopharyngeal aspirate. He did not present with bronchiolitis or hypoxic failure as described in severe forms of COVID-19. The outcome was favorable in a few hours. The occurrence of apneas is not uncommon during viral respiratory infections in early infancy; however, there are very few descriptions related to a documented SARS-CoV-2 respiratory tract infection. In light of this clinical case, it seems necessary to quickly bring up a potential COVID-19 contamination in infants admitted for life-threatening apnea, in order to properly report and isolate these patients to avoid further nosocomial dissemination of SARS-CoV-2.
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Disfunción Cognitiva/psicología , Infecciones por Coronavirus/psicología , Síndrome de Liberación de Citoquinas/psicología , Hipoxia/psicología , Inflamación/psicología , Trastornos Mentales/psicología , Neumonía Viral/psicología , Trastornos de Ansiedad/inmunología , Trastornos de Ansiedad/psicología , Betacoronavirus , Trastornos de la Coagulación Sanguínea/inmunología , Trastornos de la Coagulación Sanguínea/psicología , COVID-19 , Disfunción Cognitiva/inmunología , Infecciones por Coronavirus/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Humanos , Hipoxia/inmunología , Inflamación/inmunología , Trastornos Mentales/inmunología , Trastornos del Humor/inmunología , Trastornos del Humor/psicología , Pandemias , Neumonía Viral/inmunología , Síndrome de Dificultad Respiratoria/inmunología , Síndrome de Dificultad Respiratoria/psicología , SARS-CoV-2 , Trastornos por Estrés Postraumático/inmunología , Trastornos por Estrés Postraumático/psicología , Accidente Cerebrovascular/inmunología , Accidente Cerebrovascular/psicologíaRESUMEN
LAY ABSTRACT: Women who try to hide or "camouflage" their autistic traits are likely to report that they feel distressed, think of suicide, and/or struggle to function in everyday life. We asked 58 women with autistic traits to complete questionnaires about camouflaging and mental health. Most of these women did not have a formal diagnosis of autism, yet a majority reported that they camouflaged autistic traits, and a large majority reported significant mental health challenges. Some researchers have suggested that women with autistic traits are more likely than autistic men to experience mental health challenges because women may try more to "fit in" socially by camouflaging their autistic traits. Analyses showed that camouflaging was associated with feeling distressed (depressed, anxious, and/or stressed). For women who reported above-average levels of camouflaging, camouflaging was also associated with having thoughts about suicide and struggling to function in everyday life. Trying to camouflage autistic traits was associated with mental health challenges, regardless of whether those traits were very mild or more severe. The findings of this study may influence how mental health professionals evaluate and treat women with autistic traits.
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Trastorno del Espectro Autista , Trastorno Autístico , Suicidio , Femenino , Humanos , Masculino , Salud Mental , Encuestas y CuestionariosRESUMEN
Background: Functional neuroimaging research in autism spectrum disorder has reported patterns of decreased long-range, within-network, and interhemispheric connectivity. Research has also reported increased corticostriatal connectivity and between-network connectivity for default and attentional networks. Past studies have excluded individuals with autism and low verbal and cognitive performance (LVCP), so connectivity in individuals more significantly affected with autism has not yet been studied. This represents a critical gap in our understanding of brain function across the autism spectrum. Methods: Using behavioral support procedures adapted from Nordahl, et al. (J Neurodev Disord 8:20-20, 2016), we completed non-sedated structural and functional MRI scans of 56 children ages 7-17, including LVCP children (n = 17, mean IQ = 54), children with autism and higher performance (HVCP, n = 20, mean IQ = 106), and neurotypical children (NT, n = 19, mean IQ = 111). Preparation included detailed intake questionnaires, video modeling, behavioral and anxiety reduction techniques, active noise-canceling headphones, and in-scan presentation of the Inscapes movie paradigm from Vanderwal et al. (Neuroimage 122:222-32, 2015). A high temporal resolution multiband echoplanar fMRI protocol analyzed motion-free time series data, extracted from concatenated volumes to mitigate the influence of motion artifact. All participants had > 200 volumes of motion-free fMRI scanning. Analyses were corrected for multiple comparisons. Results: LVCP showed decreased within-network connectivity in default, salience, auditory, and frontoparietal networks (LVCP < HVCP) and decreased interhemispheric connectivity (LVCP < HVCP=NT). Between-network connectivity was higher for LVCP than NT between default and dorsal attention and frontoparietal networks. Lower IQ was associated with decreased connectivity within the default network and increased connectivity between default and dorsal attention networks. Conclusions: This study demonstrates that with moderate levels of support, including readily available techniques, information about brain similarities and differences in LVCP individuals can be further studied. This initial study suggested decreased network segmentation and integration in LVCP individuals. Further imaging studies of LVCP individuals with larger samples will add to understanding of origins and effects of autism on brain function and behavior.
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Trastorno Autístico/diagnóstico por imagen , Cognición , Desarrollo del Lenguaje , Adolescente , Trastorno Autístico/fisiopatología , Estudios de Casos y Controles , Niño , Femenino , Humanos , Inteligencia , Imagen por Resonancia Magnética , MasculinoRESUMEN
Human prion diseases are associated with a range of clinical presentations, and they are classified by both clinicopathological syndrome and etiology, with subclassification according to molecular criteria. Here, we describe updated procedures that are currently used within the MRC Prion Unit at UCL to determine a molecular diagnosis of human prion disease. Sequencing of the PRNP open reading frame to establish the presence of pathogenic mutations is described, together with detailed methods for immunoblot or immunohistochemical determination of the presence of abnormal prion protein in the brain or peripheral tissues.
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Secuenciación de Nucleótidos de Alto Rendimiento , Inmunohistoquímica/métodos , Mutación , Enfermedades por Prión/diagnóstico , Proteínas Priónicas/genética , Coloración y Etiquetado/métodos , Antiinfecciosos Locales/química , Secuencia de Bases , Encéfalo/metabolismo , Encéfalo/patología , Química Encefálica , Electroforesis en Gel de Poliacrilamida/métodos , Formiatos/química , Expresión Génica , Humanos , Immunoblotting/métodos , Microtomía/métodos , Sistemas de Lectura Abierta , Enfermedades por Prión/genética , Enfermedades por Prión/metabolismo , Enfermedades por Prión/patología , Proteínas Priónicas/metabolismo , Adhesión del Tejido/métodosRESUMEN
BACKGROUND: Depending on the initial pathology, hypovolemia, intra-abdominal hypertension, and sepsis are often encountered in neonatal digestive surgery. Accurate newborn monitoring during and after surgery is essential to adapt resuscitation protocols. Near infrared spectroscopy (NIRS) is non-invasive and can detect hypoperfusion which indicates a low circulatory blood flow, regardless of the cause. OBJECTIVE: Evaluating changes in cerebral and renal regional oxygen saturation during neonatal digestive surgeries, conducted according to normal practices, with commonly used monitoring parameters. Analyzing retrospectively the inter-relationships between NIRS values and mean arterial pressure (MAP) values as well as pre-ductal SpO2. METHODS: Prospective, descriptive, monocentric study. All neonates referred for surgery were included. NIRS allows the measurement of cerebral and renal oxygenation fluctuations, as well as calculating difference in intraoperative and postoperative values. RESULTS: Nineteen patients were included. Cerebral regional oxygen saturation (C rSO2) values were stable while renal regional oxygen saturation (R rSO2) values tended to decrease with time during surgery. Indeed, 72% of rSO2 decline episodes occurred after the first 30 min of surgery, without any significant statistical differences for the next 90 min of surgery. After surgery, the lowest average C and R rSO2 values were evidenced during the first 6 h, with 60% of C rSO2 and R rSO2 anomalies occurring in that time frame. There was no significant statistical difference observed in the following 18 h. There was a significant correlation between R rSO2 and SpO2 values (p < 0.01), but not with C rSO2 values. There was no correlation with the MAP either for the C rSO2 values or R rSO2 ones. CONCLUSION: NIRS is a promising non-invasive bedside tool to monitor cerebral and tissue perfusion, analyzing tissue microcirculation. NIRS has its interest to guide neonatal digestive surgeries (bowel manipulation, viscera reduction) and may represent an early warning for identifying patients requiring resuscitation during or after these surgeries.
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An extraction method using acidified methanol based on the quick polar pesticide (QuPPe) method using suppressed ion chromatography coupled to mass spectrometry was developed and validated for the direct analysis of polar pesticides, without the need for derivatization or ion pairing, in cereals and grapes. The method was robust, and results for glyphosate, aminomethyl phosphonic acid (AMPA), N-acetyl-AMPA, glufosinate, 3-methylphosphinicopropionic acid (3-MPPA), N-acetyl glufosinate, ethephon, chlorate, perchlorate, fosetyl aluminum, and phosphonic acid at three concentration levels (typically 0.01, 0.05, and 0.1 mg/kg) were compliant with SANTE/11945/2015 guideline method performance criteria. Cereal-based infant food proved to be a more challenging matrix and validated only for glyphosate, chlorate, and perchlorate at 0.005, 0.01, and 0.05 mg/kg. The developed method enables the multiresidue analysis of 12 ionic pesticides and relevant metabolites in a single analysis. Until now, the analysis of these compounds required several different single-residue methods using different chromatographic conditions. This multiresidue approach offers the possibility of more cost-effective and more efficient monitoring of polar ionic pesticides and contaminants that are of concern to food regulation bodies and consumers.
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Cromatografía Liquida/métodos , Contaminación de Alimentos/análisis , Residuos de Plaguicidas/química , Espectrometría de Masas en Tándem/métodos , Grano Comestible/química , Residuos de Plaguicidas/aislamiento & purificación , Plaguicidas/químicaRESUMEN
Mathematics achievement in autism spectrum disorder (ASD) has been understudied. However, the ability to solve applied math problems is associated with academic achievement, everyday problem-solving abilities, and vocational outcomes. The paucity of research on math achievement in ASD may be partly explained by the widely-held belief that most individuals with ASD are mathematically gifted, despite emerging evidence to the contrary. The purpose of the study was twofold: to assess the relative proportions of youth with ASD who demonstrate giftedness versus disability on applied math problems, and to examine which cognitive (i.e., perceptual reasoning, verbal ability, working memory) and clinical (i.e., test anxiety) characteristics best predict achievement on applied math problems in ASD relative to typically developing peers. Twenty-seven high-functioning adolescents with ASD and 27 age- and Full Scale IQ-matched typically developing controls were assessed on standardized measures of math problem solving, perceptual reasoning, verbal ability, and test anxiety. Results indicated that 22% of the ASD sample evidenced a mathematics learning disability, while only 4% exhibited mathematical giftedness. The parsimonious linear regression model revealed that the strongest predictor of math problem solving was perceptual reasoning, followed by verbal ability and test anxiety, then diagnosis of ASD. These results inform our theories of math ability in ASD and highlight possible targets of intervention for students with ASD struggling with mathematics.