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Research on COVID-19 vaccine hesitancy has been sparse among Latino/a immigrants, a population at high risk for infection. This exploratory study examines rates of vaccine acceptance and its association with psychological antecedents of vaccination among Latino/a immigrants. A cross-sectional telephone survey on perceptions of COVID-19 was administered between October 2020 to February 2021 in South Florida to 200 adult Latino/a immigrants. Descriptive statistics, bivariate analysis, and logistic regression were employed to determine the influence of independent variables on vaccine acceptance. Most participants indicated a willingness to get vaccinated. Participants with higher confidence (aOR = 10.2, 95% CI: 4.8-21.8) and collective responsibility scores were (aOR = 3.1, 95%CI:1.3-6.9) more likely to report vaccine acceptance than those with lower scores. No other psychological antecedents or demographic variables were significantly associated with vaccine acceptance. Study results provide insights into motivating factors for vaccination that can inform culturally tailored education campaigns to increase vaccine acceptability in this population.
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Vacunas contra la COVID-19 , COVID-19 , Emigrantes e Inmigrantes , Hispánicos o Latinos , Vacunación , Adulto , Humanos , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , Estudios Transversales , Responsabilidad Social , Confianza , Aceptación de la Atención de SaludRESUMEN
Placental assessment, although currently underused, can inform our understanding of the etiology and timing of Neonatal Encephalopathy (NE). We review our current understanding of the links between placental dysfunction and NE and how this information may inform clinical decisions, now and in the future, emphasizing the four major placental lesions associated with NE. In addition, we discuss maternal and fetal factors that are hypothesized to contribute to specific placental pathologies, especially innate or acquired thrombophilias. We outline the importance of assessing placenta across trimesters and after delivery. As this field continues to evolve, currently available placental histopathological examination methods may need to be combined with advanced prenatal molecular and imaging assessments of placenta and be applied in well-designed studies in large representative populations to better define the links between placental dysfunction and NE.
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Encefalopatías , Enfermedades del Recién Nacido , Enfermedades Placentarias , Encefalopatías/etiología , Encefalopatías/patología , Femenino , Humanos , Recién Nacido , Placenta/patología , Enfermedades Placentarias/patología , Embarazo , Embarazo de Alto RiesgoRESUMEN
Bisphenol A (BPA) is a ubiquitous environmental chemical that has been linked to behavioral differences in children and shown to impact critical neurodevelopmental processes in animal models. Though data is emerging, we still have an incomplete picture of how BPA disrupts neurodevelopment; in particular, how its impacts may vary across different genetic backgrounds. Given the genetic tractability of Drosophila melanogaster, they present a valuable model to address this question. Fruit flies are increasingly being used for assessment of neurotoxicants because of their relatively simple brain structure and variety of measurable behaviors. Here we investigated the neurodevelopmental impacts of BPA across two genetic strains of Drosophila-w1118 (control) and the Fragile X Syndrome (FXS) model-by examining both behavioral and neuronal phenotypes. We show that BPA induces hyperactivity in larvae, increases repetitive grooming behavior in adults, reduces courtship behavior, impairs axon guidance in the mushroom body, and disrupts neural stem cell development in the w1118 genetic strain. Remarkably, for every behavioral and neuronal phenotype examined, the impact of BPA in FXS flies was either insignificant or contrasted with the phenotypes observed in the w1118 strain. This data indicates that the neurodevelopmental impacts of BPA can vary widely depending on genetic background and suggests BPA may elicit a gene-environment interaction with Drosophila fragile X mental retardation 1 (dFmr1)-the ortholog of human FMR1, which causes Fragile X Syndrome and is associated with autism spectrum disorder.
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Compuestos de Bencidrilo/toxicidad , Drosophila melanogaster/efectos de los fármacos , Sistema Nervioso/efectos de los fármacos , Fenoles/toxicidad , Animales , Cortejo , Modelos Animales de Enfermedad , Drosophila melanogaster/genética , Drosophila melanogaster/crecimiento & desarrollo , Femenino , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/veterinaria , Aseo Animal/efectos de los fármacos , Larva/efectos de los fármacos , Larva/fisiología , Locomoción/efectos de los fármacos , Masculino , Sistema Nervioso/crecimiento & desarrolloRESUMEN
An external load on a particle packing is distributed internally through a heterogeneous network of particle contacts. This contact force distribution determines the stability of the particle packing and the resulting structure. Here, we investigate the homogeneity of the contact force distribution in packings of highly nonconvex particles both in two-dimensional (2D) and three-dimensional (3D) packings. A recently developed discrete element method is used to model packings of nonconvex particles of varying sphericity. Our results establish that in 3D packings the distribution of the contact forces in the normal direction becomes increasingly heterogeneous with decreasing particle sphericity. However, in 2D packings the contact force distribution is independent of particle sphericity, indicating that results obtained in 2D packings cannot be extrapolated readily to 3D packings. Radial distribution functions show that the crystallinity in 3D packings decreases with decreasing particle sphericity. We link the decreasing homogeneity of the contact force distributions to the decreasing crystallinity of 3D packings. These findings are complementary to the previously observed link between the heterogeneity of the contact force distribution and a decreasing packing crystallinity due to an increasing polydispersity of spherical particles.
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We report charge transfer and built-in electric fields across the epitaxial SrNb_{x}Ti_{1-x}O_{3-δ}/Si(001) interface. Electrical transport measurements indicate the formation of a hole gas in the Si and the presence of built-in fields. Hard x-ray photoelectron measurements reveal pronounced asymmetries in core-level spectra that arise from these built-in fields. Theoretical analysis of core-level spectra enables built-in fields and the resulting band bending to be spatially mapped across the heterojunction. The demonstration of tunable charge transfer, built-in fields, and the spatial mapping of the latter, lays the groundwork for the development of electrically coupled, functional heterojunctions.
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A diagnostic blood test for stroke is desirable but will likely require multiple proteins rather than a single "troponin." Validating large protein panels requires large patient numbers. Mass spectrometry (MS) is a cost-effective tool for this task. We compared differences in the abundance of 147 protein markers to distinguish 20 acute cerebrovascular syndrome (ACVS) patients who presented to the Emergency Department of one urban hospital within < 24 h from onset) and from 20 control patients who were enrolled via an outpatient neurology clinic. We targeted proteins from the stroke literature plus cardiovascular markers previously studied in our lab. One hundred forty-one proteins were quantified using MS, 8 were quantified using antibody protein enrichment with MS, and 32 were measured using ELISA, with some proteins measured by multiple techniques. Thirty proteins (4 by ELISA and 26 by the MS techniques) were differentially abundant between mimic and stroke after adjusting for age in robust regression analyses (FDR < 0.20). A logistic regression model using the first two principal components of the proteins significantly improved discrimination between strokes and controls compared to a model based on age alone (p < 0.001, cross-validated AUC 0.93 vs. 0.78). Significant proteins included markers of inflammation (47%), coagulation (40%), atrial fibrillation (7%), neurovascular unit injury (3%), and other (3%). These results suggest the potential value of plasma proteins as biomarkers for ACVS diagnosis and the role of plasma-based MS in this area.
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Proteínas Sanguíneas/metabolismo , Isquemia Encefálica/complicaciones , Proteómica/métodos , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Isquemia Encefálica/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Proyectos Piloto , Análisis de Componente Principal , Curva ROC , Accidente Cerebrovascular/diagnóstico por imagenRESUMEN
Fetus in fetu (FIF) is an extremely rare condition (1/500,000 live births) in which a fetiform structure is incorporated into the body of its twin. FIF can be a diagnostic dilemma due to its similarity to a teratoma, but identification of FIF is important for subsequent medical and surgical management. We compare two cases of fetal masses diagnosed on prenatal imaging that were later identified as FIF through further radiological, surgical, and pathologic evaluation. We use these cases to illustrate key pre- and postnatal features of FIF and highlight the benefits of prenatal detection and follow-up for postnatal management.
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Feto/anomalías , Embarazo Gemelar , Adulto , Femenino , Feto/diagnóstico por imagen , Humanos , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Embarazo , Diagnóstico Prenatal , Ultrasonografía PrenatalRESUMEN
Long-term potentiation (LTP) of excitatory synaptic transmission has long been considered a cellular correlate for learning and memory. Early LTP (less than 1 h) had initially been explained either by presynaptic increases in glutamate release or by direct modification of postsynaptic AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor function. Compelling models have more recently proposed that synaptic potentiation can occur by the recruitment of additional postsynaptic AMPA receptors (AMPARs), sourced either from an intracellular reserve pool by exocytosis or from nearby extra-synaptic receptors pre-existing on the neuronal surface. However, the exact mechanism through which synapses can rapidly recruit new AMPARs during early LTP remains unknown. In particular, direct evidence for a pivotal role of AMPAR surface diffusion as a trafficking mechanism in synaptic plasticity is still lacking. Here, using AMPAR immobilization approaches, we show that interfering with AMPAR surface diffusion markedly impairs synaptic potentiation of Schaffer collaterals and commissural inputs to the CA1 area of the mouse hippocampus in cultured slices, acute slices and in vivo. Our data also identify distinct contributions of various AMPAR trafficking routes to the temporal profile of synaptic potentiation. In addition, AMPAR immobilization in vivo in the dorsal hippocampus inhibited fear conditioning, indicating that AMPAR diffusion is important for the early phase of contextual learning. Therefore, our results provide a direct demonstration that the recruitment of new receptors to synapses by surface diffusion is a critical mechanism for the expression of LTP and hippocampal learning. Since AMPAR surface diffusion is dictated by weak Brownian forces that are readily perturbed by protein-protein interactions, we anticipate that this fundamental trafficking mechanism will be a key target for modulating synaptic potentiation and learning.
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Condicionamiento Clásico/fisiología , Difusión , Hipocampo/fisiología , Potenciación a Largo Plazo/fisiología , Receptores AMPA/metabolismo , Animales , Avidina , Biotina , Membrana Celular/metabolismo , Reactivos de Enlaces Cruzados , Potenciales Postsinápticos Excitadores , Miedo , Femenino , Hipocampo/citología , Inmunoglobulina G/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratas , Receptores AMPA/inmunología , Sinapsis/metabolismo , Transmisión SinápticaRESUMEN
BACKGROUND: Particulate matter (PM) is one of the six criteria pollutant classes for which National Ambient Air Quality Standards have been set by the United States Environmental Protection Agency. Exposures to PM have been correlated with increased cardio-pulmonary morbidity and mortality. Butadiene soot (BDS), generated from the incomplete combustion of 1,3-butadiene (BD), is both a model PM mixture and a real-life example of a petrochemical product of incomplete combustion. There are numerous events, including wildfires, accidents at refineries and tank car explosions that result in sub-acute exposure to high levels of airborne particles, with the people exposed facing serious health problems. These real-life events highlight the need to investigate the health effects induced by short-term exposure to elevated levels of PM, as well as to assess whether, and if so, how well these adverse effects are resolved over time. In the present study, we investigated the extent of recovery of mouse lungs 10 days after inhalation exposures to environmentally-relevant levels of BDS aerosols had ended. METHODS: Female BALB/c mice exposed to either HEPA-filtered air or to BDS (5 mg/m(3) in HEPA filtered air, 4 h/day, 21 consecutive days) were sacrificed immediately, or 10 days after the final BDS exposure. Bronchoalveolar lavage fluid (BALF) was collected for cytology and cytokine analysis. Lung proteins and RNA were extracted for protein and gene expression analysis. Lung histopathology evaluation also was performed. RESULTS: Sub-acute exposures of mice to hydrocarbon-rich ultrafine particles induced: (1) BALF neutrophil elevation; (2) lung mucosal inflammation, and (3) increased BALF IL-1ß concentration; with all three outcomes returning to baseline levels 10 days post-exposure. In contrast, (4) lung connective tissue inflammation persisted 10 days post-exposure; (5) we detected time-dependent up-regulation of biotransformation and oxidative stress genes, with incomplete return to baseline levels; and (6) we observed persistent particle alveolar load following 10 days of recovery. CONCLUSION: These data show that 10 days after a 21-day exposure to 5 mg/m(3) of BDS has ended, incomplete lung recovery promotes a pro-biotransformation, pro-oxidant, and pro-inflammatory milieu, which may be a starting point for potential long-term cardio-pulmonary effects.
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Butadienos/toxicidad , Contaminantes Ambientales/toxicidad , Pulmón/efectos de los fármacos , Neumonía/inducido químicamente , Hollín/toxicidad , Administración por Inhalación , Aerosoles , Animales , Líquido del Lavado Bronquioalveolar/química , Butadienos/administración & dosificación , Contaminantes Ambientales/administración & dosificación , Femenino , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Mediadores de Inflamación/metabolismo , Interleucina-1beta/metabolismo , Pulmón/metabolismo , Pulmón/patología , Ratones Endogámicos BALB C , Infiltración Neutrófila/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Tamaño de la Partícula , Neumonía/genética , Neumonía/metabolismo , Neumonía/patología , Recuperación de la Función , Medición de Riesgo , Hollín/administración & dosificación , Factores de TiempoAsunto(s)
Anomalías Múltiples , Cromosomas Humanos Par 16 , Cultura , Toma de Decisiones/ética , Cuidados para Prolongación de la Vida/ética , Trisomía , Anomalías Múltiples/terapia , Ética Médica , Resultado Fatal , Asesoramiento Genético , Humanos , Recién Nacido , Masculino , Padres , Rol del Médico , Relaciones Médico-Paciente , Pronóstico , ConfianzaRESUMEN
BACKGROUND: Brain tumours are the second most common form of childhood cancer, accounting for over 20% of all cases in European children. Understanding the impact of diagnosis and treatment of a brain tumour on the family is an essential pre-requisite to identifying ways to provide effective support. AIM: (1) To explore the impact of having a child with a brain tumour on the main caregiver in the family; (2) to describe mothers' experiences of coping with their child's illness, including personal barriers and strengths; and (3) to identify causes of stress and sources of support to inform improvements in care delivery. METHOD: Participants were drawn from a group of caregivers enrolled in a longitudinal study of outcome following diagnosis of a childhood brain tumour. Six caregivers took part, two from each of the high-, medium- and low-impact groups based on their Impact on Families Scale scores. Semi-structured interviews were used, with questions covering: (1) impact of the diagnosis on main caregiver and family; (2) personal barriers and strengths; and (3) causes of stress and sources of support. Interviews were transcribed verbatim and coded manually into five themes, which comprised 19 subthemes. FINDINGS: Coping methods and provision of help and support were major preoccupations for main caregivers from all impact groups. Caregivers in the high-impact group reported less conflict. High- and medium-impact group caregivers had experienced less 'hindrance and heartache', than those with low impact scores, suggesting that the stress associated with diagnosis and treatment of the tumour may have increased cohesion and acceptance within these families. CONCLUSION: Families of children diagnosed with a brain tumour experience considerable negative impact and may perceive themselves as struggling to cope. Provision of help and support, within and outside the extended family, including from health, education and other services, is perceived as helpful.
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Neoplasias Encefálicas/psicología , Cuidadores/psicología , Madres/psicología , Estrés Psicológico/etiología , Adaptación Psicológica , Adolescente , Niño , Empatía , Conflicto Familiar , Femenino , Humanos , Estudios Longitudinales , Masculino , Calidad de VidaRESUMEN
OBJECTIVE: To compare neonatal intensive care unit and special care unit (NICU) admission rates between term neonates exposed to antenatal magnesium sulfate (MS) and those unexposed. STUDY DESIGN: We performed a retrospective cohort study of all singleton neonates ≥37 weeks born to women with pre-eclampsia from August 2006 to July 2008. Cases were defined by antenatal exposure to MS and controls by absence of MS exposure. The primary outcome was NICU admission. Data were analyzed via univariable and multivariable regression analyses. RESULT: In all, 28 (14.7%) out of 190 MS-exposed neonates ≥37 weeks were admitted to the NICU, compared with 4 (5.4%) of 74 non-exposed neonates (P=0.04). This association persisted after controlling for potential confounding variables including severe pre-eclampsia and cesarean delivery (AOR 3.69, 1.13 to 11.99). NICU admission was associated in a dose-dependent relationship with total hours and mean dose of MS exposure. Number needed to harm with MS was 11 per NICU admission. Among neonates admitted to the NICU, MS-exposed were more likely to require fluid and nutritional support than unexposed neonates (60.7 vs 0%, P=0.04), and trended toward more frequent requirement for respiratory support and greater length of stay. CONCLUSION: In term neonates, MS exposure may be associated independently with NICU admission in a dose-dependent relationship. Requirements for fluid and nutritional support are common in this group, likely due to feeding difficulties in exposed neonates. Assessment of acute care needs among all neonates exposed to MS for maternal eclampsia prophylaxis should be considered.
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Sulfato de Magnesio/farmacología , Efectos Tardíos de la Exposición Prenatal , Nacimiento a Término/efectos de los fármacos , Tocolíticos/farmacología , Adulto , Relación Dosis-Respuesta a Droga , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Sulfato de Magnesio/administración & dosificación , Embarazo , Estudios Retrospectivos , Tocolíticos/administración & dosificación , Adulto JovenRESUMEN
OBJECTIVE: To elucidate and categorize the murine placental hormones expressed across gestation, including the expression of hormones with previously undescribed roles. STUDY DESIGN: Expression levels of all genes with known or predicted hormone activity expressed in two separate tissues, the placenta and maternal decidua, were assessed across a timecourse spanning the full lifetime of the placenta. Novel expression patterns were confirmed by in situ hybridization and protein level measurements. RESULTS: A combination of temporal and spatial information defines five groups that can accurately predict the patterns of uncharacterized hormones. Our analysis identified Secretin, a novel placental hormone that is expressed specifically by the trophoblast at levels many times greater than in any other tissue. CONCLUSIONS: The characteristics of Secretin fit the paradigm of known placental hormones and suggest that it may play an important role during pregnancy.
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Perfilación de la Expresión Génica , Placenta/metabolismo , Hormonas Placentarias/genética , Secretina/genética , Animales , Células Cultivadas , Análisis por Conglomerados , Femenino , Regulación del Desarrollo de la Expresión Génica , Genoma , Ratones , Análisis por Micromatrices , Hormonas Placentarias/metabolismo , Placentación/genética , Embarazo , Secretina/metabolismoRESUMEN
OBJECTIVES: To characterize the acute response of the vein wall to venous hypertension and associated altered fluid shear stress and to test the effect of micronized purified flavonoid fraction (MPFF, Daflon 500), on this response. MATERIAL AND METHODS: A femoral arteriovenous fistula was created in Wistar rats (n=48). A cohort of 24 rats received oral treatment with MPFF (100 mg/kg/day body weight), 24 rats underwent the arteriovenous fistula procedure and received no treatment. At days 1, 7 and 21 the animals (n=8 at each time point) were killed. Experimental parameters measured included limb circumference, blood flow at the sapheno-femoral junction, leukocyte infiltration and gelatinase activity (matrix metalloproteinase, MMP). RESULTS: The acute rise in venous hypertension was accompanied by limb edema and venous reflux together with an eventual loss of valve leaflets in the saphenous vein. There was an increase in granulocyte and macrophage infiltration into the venous wall and the surrounding tissue, and a lesser increase in T- and B-lymphocyte infiltration. These changes were accompanied by a local increase in the proteolytic enzymes, MMP-2 and MMP-9. Administration of MPFF reduced the edema and lessened the venous reflux produced by the acute arteriovenous fistula. Decreased levels of granulocyte and macrophage infiltration into the valves were also observed compared with untreated animals. CONCLUSIONS: Venous hypertension caused by an arteriovenous fistula resulted in the development of venous reflux and an inflammatory reaction in venous valves culminating in their destruction. MPFF was able to delay the development of reflux and suppress damage to the valve structures in this rat model of venous hypertension.
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Fármacos Cardiovasculares/farmacología , Diosmina/farmacología , Vena Femoral/efectos de los fármacos , Vena Safena/efectos de los fármacos , Insuficiencia Venosa/tratamiento farmacológico , Presión Venosa/efectos de los fármacos , Animales , Derivación Arteriovenosa Quirúrgica , Velocidad del Flujo Sanguíneo , Fármacos Cardiovasculares/uso terapéutico , Quimiotaxis de Leucocito/efectos de los fármacos , Diosmina/uso terapéutico , Modelos Animales de Enfermedad , Edema/etiología , Edema/fisiopatología , Edema/prevención & control , Arteria Femoral/cirugía , Vena Femoral/enzimología , Vena Femoral/patología , Vena Femoral/fisiopatología , Vena Femoral/cirugía , Granulocitos/efectos de los fármacos , Granulocitos/patología , Linfocitos/efectos de los fármacos , Linfocitos/patología , Macrófagos/efectos de los fármacos , Macrófagos/patología , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Ratas , Ratas Wistar , Flujo Sanguíneo Regional , Vena Safena/enzimología , Vena Safena/patología , Vena Safena/fisiopatología , Estrés Mecánico , Factores de Tiempo , Insuficiencia Venosa/complicaciones , Insuficiencia Venosa/enzimología , Insuficiencia Venosa/patología , Insuficiencia Venosa/fisiopatologíaRESUMEN
A major goal for neonatology training programs is to produce neonatologists who will pursue careers that combine clinical and research responsibilities. However, there appears to be a continuing decline in the number of trainees who choose academic, as opposed to private sector, jobs. The reason for this decline is perhaps best addressed by the people making career choices now, the recent trainees. Although many factors influence any individual's career choice, information from recent fellows indicates that several major factors play a strong role: finances; time demands; adequacy of research training; and academic institutions' attitudes toward recent trainees. Whereas the first two factors have been addressed by prior studies, the latter two factors have been less explored. The responses of a few recent trainees to an informal survey will be used to guide a discussion that focuses on the factors of research training and academic status. Ways to improve the success of training programs in producing academic neonatologists will be suggested, including the proposal of a research training curriculum, changes in the structure of post-fellowship academic status and increased encouragement of collaborative research efforts. A future survey of a broad group of recent trainees about their career choices and about proposals for training changes, such as those considered here, is needed to evaluate programs aimed at increasing the number of neonatologists engaged in research. Journal of Perinatology (2006) 26, S53-S56. doi:10.1038/sj.jp.7211527.
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Investigación Biomédica , Selección de Profesión , Neonatología , HumanosRESUMEN
AIM: To determine the differences in outcome in a group of children with idiopathic intracranial hypertension (IIH) who do not present with headaches. METHODS: Differences in epidemiological and aetiological factors, clinical presentation, and visual outcome were investigated in children with a diagnosis of IIH presenting with and without headaches to the Paediatric Neurology and Paediatric Ophthalmology Services at Guy's & St Thomas' Hospitals NHS Trust between 1997 and 2002. RESULTS: Compared to the 29 children with headaches, the 12 children in the non-headache group were younger (7.3 v 9.5 years), presented with more neurological signs (33% v 10%), and were more likely to present with severe visual failure (33% v 4%), with a tenfold increased risk of an enlarged blind spot or field defects (50% v 5%). Permanent visual failure affected a third of all children in the non-headache group, but was rare in children presenting with headaches (33% v 3%), with one patient registered blind and two severely visually impaired. CONCLUSION: The management of IIH is difficult in the absence of headache. Visual surveillance is vital. These children were treated with an aggressive management programme to reduce cerebrospinal fluid pressure by repeated lumbar puncture, medication, and early surgical intervention if required. Non-invasive monitoring techniques might contribute to a better understanding of the natural history of IIH, improved management, and visual outcome.
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Cefalea/complicaciones , Hipertensión Intracraneal/complicaciones , Trastornos de la Visión/etiología , Niño , Preescolar , Femenino , Humanos , Masculino , Pronóstico , Factores de Riesgo , Agudeza Visual/fisiologíaRESUMEN
Myasthenia gravis (MG) in childhood is rare comprising 10 to 20 % of all myasthenic patients. We studied 18 patients with MG whose first symptoms started from 1 to 12 years of age, followed at the Department of Neurology of the UNIFESP-EPM, from January 1983 to August 1997. There were 10 girls and 8 boys (1.2:1). Eleven patients (61%) presented moderate or severe generalized disease and 4 (22%) had at least one myasthenic crisis. EMG with supramaximal repetitive nerve stimulation was diagnostic in 8 (47%) out of 17 patients, and chest CT was normal in 14 patients. Seropositivity to acetylcholine receptor antibodies was found in 81.6% (9 out of 11 tested) and the levels had no relation to clinical severity. Nine out of 16 patients (56%) worsened with pyridostigmine alone and were treated with prednisone. Four out of those nine continued worsening despite steroids and were subjected to thymectomy (all showed thymic lymphoid follicular hyperplasia). Three patients (75%) improved markedly after thymectomy and one (25%) worsened, eventually getting better with intravenous immunoglobulin and oral azathioprine. MG treatment, using all resources available, has to be individualized for each child.
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Miastenia Gravis , Edad de Inicio , Niño , Preescolar , Inhibidores de la Colinesterasa/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Miastenia Gravis/diagnóstico , Miastenia Gravis/tratamiento farmacológico , Miastenia Gravis/cirugía , Prednisona/uso terapéutico , Bromuro de Piridostigmina/uso terapéutico , Receptores Colinérgicos/sangre , Receptores Colinérgicos/inmunología , Timectomía , Tomografía Computarizada por Rayos XRESUMEN
One of the leading theories of the neuropathology of schizophrenia is that it is a developmental disorder of "neural connectivity." To assess this theory, it is first necessary to understand how precise neural connections normally are established. Sensory-driven neural activity has been widely recognized as crucial for this process. Recent studies have revealed a similar requirement for endogenous neural activity generated by the nervous system itself, long before there is any sensory input. These patterns of sensory-driven and endogenously generated neural activity sculpt the precise circuits that are crucial to the many complex functions of the adult brain. This article summarizes the principles of activity-dependent neural development as determined from basic neuroscience experiments, particularly those done using the mammalian visual system, to illustrate the role of patterned activity, neuronal competition, and critical periods in shaping neural circuitry. The potential molecular mechanisms involved in these features of activity-dependent neurodevelopment are discussed and possible links to the etiology of schizophrenia are briefly explored.
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Encéfalo/fisiopatología , Red Nerviosa/fisiología , Esquizofrenia/fisiopatología , Axones/fisiología , Encéfalo/metabolismo , AMP Cíclico/metabolismo , Cuerpos Geniculados/metabolismo , Cuerpos Geniculados/fisiología , Humanos , N-Metilaspartato/metabolismo , Factores de Crecimiento Nervioso/metabolismo , Red Nerviosa/metabolismo , Células Ganglionares de la Retina/metabolismo , Células Ganglionares de la Retina/fisiología , Esquizofrenia/metabolismo , Sinapsis/fisiología , Corteza Visual/fisiología , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Adverse health effects of airborne toxicants, especially small respirable particles and their associated adsorbed chemicals, are of growing concern to health professionals, governmental agencies, and the general public. Areas rich in petrochemical processing facilities (e.g., eastern Texas and southern California) chronically have poor air quality. Atmospheric releases of products of incomplete combustion (e.g., soot) from these facilities are not subject to rigorous regulatory enforcement. Although soot can include respirable particles and carcinogens, the toxicologic and epidemiologic consequences of exposure to environmentally relevant complex soots have not been well investigated. Here we continue our physico-chemical analysis of butadiene soot and report effects of exposure to this soot on putative targets, normal human bronchial epithelial (NHBE) cells. We examined organic extracts of butadiene soot by gas chromatography-mass spectrometry (GC-MS), probe distillation MS, and liquid chromatography (LC)-MS-MS. Hundreds of aromatic hydrocarbons and polycyclic aromatic hydrocarbons with molecular mass as high as 1,000 atomic mass units were detected, including known and suspected human carcinogens (e.g., benzo(a)pyrene). Butadiene soot particles also had strong, solid-state free-radical character in electron spin resonance analysis. Spin-trapping studies indicated that fresh butadiene soot in a buffered aqueous solution containing dimethylsulfoxide (DMSO) oxidized the DMSO, leading to CH(3)* radical formation. Butadiene soot DMSO extract (BSDE)-exposed NHBE cells displayed extranuclear fluorescence within 4 hr of exposure. BSDE was cytotoxic to > 20% of the cells at 72 hr. Morphologic alterations, including cell swelling and membrane blebbing, were apparent within 24 hr of exposure. These alterations are characteristic of oncosis, an ischemia-induced form of cell death. BSDE treatment also produced significant genotoxicity, as indicated by binucleated cell formation. The combination of moderate cytotoxicity and genotoxicity, as occurred here, can be pro-carcinogenic.