RESUMEN
PURPOSE: Previous studies have associated developmental stuttering with difficulty learning new motor skills. We investigated non-speech motor sequence learning in children with persistent developmental stuttering (CWS), children who have recovered from developmental stuttering (CRS) and typically developing controls (CON). METHODS: Over the course of two days, participants completed the Multi-Finger Sequencing Task, consisting of repeated trials of a10-element sequence, interspersed with trials of random sequences of the same length. We evaluated motor sequence learning using accuracy and response synchrony, a timing measure for evaluation of sequencing timing. We examined error types as well as recognition and recall of the repeated sequences. RESULTS: CWS demonstrated lower performance accuracy than CON and CRS on the first day of the finger tapping experiment but improved to the performance level of CON and CRS on the second day. Response synchrony showed no overall difference among CWS, CRS and CON. Learning scores of repeated sequences did not differ from learning scores of random sequences in CWS, CRS and CON. CON and CRS demonstrated an adaptive strategy to response errors, whereas CWS maintained a high percentage of corrected errors for both days. CONCLUSIONS: Our study examined non-speech sequence learning across CWS, CRS and CON. Our preliminary findings support the idea that developmental stuttering is not associated with sequence learning per se but rather with general fine motor performance difficulties.
Asunto(s)
Aprendizaje , Destreza Motora , Tartamudeo/fisiopatología , Niño , Desarrollo Infantil , Preescolar , Femenino , Humanos , Masculino , Recuerdo Mental , Tartamudeo/diagnósticoRESUMEN
Radiation therapy is a mainstay in the therapeutic management of Head and Neck Squamous Cell Carcinoma (HNSCC). Despite significant progress in this field, radioresistance still accounts for most treatment failures. Gadolinium-based nanoparticles (GBNs) have shown great promises as radiosensitizers but the underlying sensitizing mechanism is still largely unknown with regards to the disparities obtained in in vitro studies. In this study, we show that a new formulation of GBNs, AGuIX®, can radiosensitize HNSCC after cell uptake and further accumulation in lysosomes. Although radiation alone triggered late apoptosis and mitochondrial impairment, the pre-treatment with GBNs led to complex DNA damage and a specific increase of autophagic cell death. In addition, a significant radio-enhancement effect was obtained after the pre-conditioning of cells with a glutathione inhibitor before GBNs treatment and radiation exposure. Overall, our results provide additional information on the radio-enhancing properties of GBNs in the management of radioresistant HNSCC.
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Autofagia , Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Apoptosis , Línea Celular Tumoral , Gadolinio , Humanos , Nanopartículas del MetalRESUMEN
Few studies have focused on the protective role of selenium (Se) against skin aging and photoaging even though selenoproteins are essential for keratinocyte function and skin development. To the best of our knowledge, the impact of Se supplementation on skin cells from elderly and young donors has not been reported. Therefore, the main objective of our study was to evaluate the effects of Se supplementation on skin keratinocytes at baseline and after exposure to ultraviolet A (UVA) irradiation. Low doses of Se (30 nM) were very potently protective against UVA-induced cytotoxicity in young keratinocytes, whereas the protection efficiency of Se in old keratinocytes required higher concentrations (240 nM). Additionally, the DNA repair ability of the old keratinocytes drastically decreased compared with that of the young keratinocytes at baseline and after the UVA exposure. The Se supplementation significantly enhanced the DNA repair of 8-oxoguanine (8oxoG) only in the keratinocytes isolated from young donors. Therefore, aged keratinocytes have an increased vulnerability to oxidative DNA damage, and the Se needs in the elderly should be considered. Strengthening DNA repair activities with Se supplementation may represent a new strategy to combat aging and skin photoaging.
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Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Selenio/uso terapéutico , Rayos Ultravioleta , Adulto , Factores de Edad , Anciano , Células Cultivadas , Reparación del ADN/efectos de los fármacos , Reparación del ADN/genética , Humanos , Queratinocitos/efectos de la radiación , Persona de Mediana Edad , Adulto JovenRESUMEN
For some decades production of titanium dioxide nanoparticle (TiO2-NP) has been increasing at a considerable rate; concerns as to the toxicity of these particles upon inhalation have been raised. Indeed, TiO2-NPs have been shown to induce significant genotoxicity and to adversely affect both major DNA repair mechanisms: base excision repair (BER) and nucleotide excision repair (NER). The aims of the present study were to (i) compare the genotoxicity of TiO2-NPs and their impact on DNA repair processes on A549 alveolar carcinoma and BEAS-2B normal bronchial lung cell lines and (ii) delve deeper into the mechanisms leading to these effects. To achieve these goals, TiO2-NPs effects on cytotoxicity, genotoxicity, DNA repair activity and DNA repair gene expression were investigated in both cell lines upon exposure to 1-100 µg/mL of anatase/rutile, 21 nm TiO2-NPs. Our results show that TiO2-NPs induce comparable cytotoxic and genotoxic responses in BEAS-2B and A549 cells. Functional response to DNA damage is observed in both cell lines and consists of an overall downregulation in DNA repair processes. When evaluating the relative importance of the two DNA repair pathways, we observed a lower impact on BER compared with NER activities, suggesting that repair of oxidatively generated DNA damage is still triggered in these cells. This response becomes measureable at 4 h of exposure in BEAS-2B but only after 48 h of exposure in A549 cells. The delayed response in A549 cells is due to an initial overall and intense downregulation of the genes encoding DNA repair proteins. This overall downregulation correlates with increased methylation of DNA repair gene promoters and downregulation of NRF2 and BRCA1, which may thus be considered as upstream regulators. These results strengthen the evidence that TiO2-NP induces indirect genotoxicity in lung cells, via modulation of DNA repair processes, and shed some light on the mechanisms behind this effect.
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Metilación de ADN , Enzimas Reparadoras del ADN/efectos de los fármacos , Reparación del ADN/efectos de los fármacos , Nanopartículas del Metal/toxicidad , Titanio/toxicidad , Células A549 , Línea Celular , ADN/efectos de los fármacos , ADN/metabolismo , Daño del ADN , Reparación del ADN/genética , Enzimas Reparadoras del ADN/genética , Regulación hacia Abajo , Humanos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Nanopartículas del Metal/química , Pruebas de Mutagenicidad , Estrés Oxidativo , Regiones Promotoras GenéticasRESUMEN
Asthma imposes considerable patient and economic burdens, with the most severe cases causing the greatest affliction. Identifying stimuli that worsen asthma severity is an essential step to controlling both disease morbidity and the lessening economic impact. This study provides the first mechanistic investigation into how acute ethanol exposure will increase asthma severity in a murine model of mild cockroach allergen (CRA)-induced asthma. Outbred mice were sensitized to induce mild allergic asthma, with intratracheal CRA exposures on days 0 and 14. On day 21 mice were gavaged with water or 32% ethanol, and the third allergen exposure was given 30 min post-gavage. Asthmatic responses were measured at several time-points up to 42 h after the third allergen challenge. Ethanol-gavaged mice showed increased asthma severity within 90 min post-allergen challenge, with exacerbations lasting for 24 h. Ethanol caused greater airways obstruction, including an eightfold increase in epithelial cell mucin and increased mucus plugs, resulting in a 50% reduction in bronchiole patency. Ethanol gavage also induced significant increases in airways hyperreactivity. While T helper type 1 (Th1) and Th2 cytokines were not altered by ethanol gavage, pulmonary neutrophil and eosinophil recruitment were augmented. This increase was associated with increased chemokine production. Administration 2 h prior to ethanol gavage of a neutralizing antibody cocktail to keratinocyte-derived chemokine, macrophage inflammatory protein-2, eotaxin-1 and eotaxin-2 prevented ethanol-induced eosinophil recruitment and airways hyperreactivity. These data provide evidence that acute alcohol exposure immediately prior to a mild allergen-triggered asthmatic episode will exacerbate asthma severity mediated by increased production of chemokines.
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Alérgenos/inmunología , Asma/fisiopatología , Cucarachas/inmunología , Etanol/farmacología , Proteínas de Insectos/inmunología , Animales , Asma/inmunología , Hiperreactividad Bronquial/inmunología , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Quimiocina CCL11/inmunología , Quimiocina CCL24/inmunología , Quimiocina CXCL2/inmunología , Quimiocinas/inmunología , Eosinófilos/efectos de los fármacos , Eosinófilos/inmunología , Femenino , Ratones , Ratones Endogámicos ICR , Mucinas/biosíntesis , Mucinas/efectos de los fármacos , Células TH1/efectos de los fármacos , Células TH1/inmunología , Células TH1/metabolismo , Células Th2/efectos de los fármacos , Células Th2/inmunología , Células Th2/metabolismoRESUMEN
Vorticity control is employed by marine animals to enhance performance in maneuvering and propulsion. Studies on fish-like robots and experimental apparatus modelling rigid and flexible fins provide some of the basic mechanisms employed for controlling vorticity.
RESUMEN
Formaldehyde, less volatile aldehydes, and terpene hydrocarbons are generally the predominant air contaminants in new manufactured and site-built houses. This study was conducted to identify the major sources of these compounds in a typically constructed, new manufactured house and to evaluate several source reduction practices. Specimens of materials used within the house were collected. These were individually pre-conditioned for 19 +/- 4 days, and tested for emissions of formaldehyde and other target compounds using small-scale chambers. Several cabinetry materials, passage doors, and the plywood subfloor were the predominant sources of formaldehyde and other aldehydes. The plywood subfloor was the predominant terpene source. Whole-house emission rates for combined materials were predicted based on the emission factors and the corresponding material quantities. These predicted rates were compared with whole-house emission rates derived from measurements made at the house 3 months after its installation. For 10 of 14 target compounds including formaldehyde, the predicted and derived rates were within a factor of two. Four emission barriers applied to plywood were shown to reduce emission factors for formaldehyde, hexanal, and other aldehydes.
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Contaminación del Aire Interior/análisis , Aldehídos/análisis , Desinfectantes/análisis , Formaldehído/análisis , Vivienda , Materiales Manufacturados , Terpenos/análisis , Monitoreo del Ambiente , PredicciónAsunto(s)
Antagonistas de Aminoácidos Excitadores/historia , Ibogaína/historia , Trastornos Relacionados con Sustancias/historia , Europa (Continente) , Antagonistas de Aminoácidos Excitadores/uso terapéutico , Alucinógenos/historia , Historia del Siglo XX , Humanos , Ibogaína/uso terapéutico , Defensa del Paciente/historia , Trastornos Relacionados con Sustancias/tratamiento farmacológico , Estados UnidosRESUMEN
Conversational conventions predict that receivers weigh later information more heavily than earlier information because they presume that communicators add later information only when it is particularly relevant and important. Drawing on Pettigrew's observation of the ultimate attribution error, the present research predicted that intergroup bias could override this conversational convention when individuals received multiple explanations (one beneficial, one condemning) for acts committed by out-group members vs. in-group members. Specifically, subsequently presented mitigating explanations for negative acts should not temper impressions of out-group members, and subsequently presented crediting explanations for positive acts should not enhance impressions of out-group members. Results supported this pattern, and the discussion considers these findings in light of communication rules, and in-group/out-group definition.
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Relaciones Interpersonales , Prejuicio , Predominio Social , Análisis de Varianza , Causalidad , Femenino , Humanos , Louisiana , Masculino , Teoría Psicológica , Identificación Social , Percepción Social , Estereotipo , EstudiantesRESUMEN
Concentrations of 54 volatile organic compounds (VOCs) and ventilation rates were measured in four new manufactured houses over 2-9.5 months following installation and in seven new site-built houses 1-2 months after completion. The houses were in four projects located in hot-humid and mixed-humid climates. They were finished and operational, but unoccupied. Ventilation rates ranged from 0.14-0.78 h-1. Several of the site-built houses had ventilation rates below the ASHRAE recommended value. In both manufactured and site-built houses, the predominant airborne compounds were alpha-pinene, formaldehyde, hexanal, and acetic acid. Formaldehyde concentrations were below or near 50 ppb with a geometric mean value for all houses of 40 ppb. Similarities in the types of VOCs and in VOC concentrations indicated that indoor air quality in the houses was impacted by the same or similar sources. Major identified sources included plywood flooring, latex paint and sheet vinyl flooring. One site-built house was operated at ventilation rates of 0.14 and 0.32 h-1. VOC emission rates calculated at the two conditions agreed within +/- 10% for the most volatile compounds. Generally, the ratios of emission rates at the low and high ventilation rates decreased with decreasing compound volatility. Changes in VOC emission rates in the manufactured houses over 2-9.5 months after installation varied by compound. Only several compounds showed a consistent decrease in emission rate over this period.
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Contaminación del Aire Interior/análisis , Compuestos Orgánicos/análisis , Ventilación , Desinfectantes/análisis , Formaldehído/análisis , Vivienda , Humanos , Materiales Manufacturados , Exposición ProfesionalRESUMEN
Quantitative magnetic resonance imaging (MRI) studies from our laboratory have reported that patients with schizophrenia show a widespread cortical gray matter volume deficit, which is especially pronounced in the prefrontal and anterior superior temporal cortices. The present study compared two separate samples of schizophrenic patients -- 71 men from a Veterans Administration (VA) hospital and a sample of 57 severely ill men from a state hospital (SH) -- in an effort to test whether the pattern of brain volume abnormalities previously observed in VA schizophrenic patients can be generalized to other groups of schizophrenic patients. MRI-derived brain volumes of gray matter, white matter and sulcal cerebrospinal fluid (CSF) in six cortical regions, and CSF in the lateral and third ventricles were computed. All MRI volumes were adjusted for normal variation in head size and age and were expressed as standardized Z-scores, which also permitted structures of different sizes to be compared directly. The two schizophrenic groups displayed similar patterns of volume abnormalities: cortical gray matter but not white matter volume deficits that were widespread but especially notable in the prefrontal and temporal regions. The regional gray matter deficits in the SH group were generally greater than those in the VA group, particularly in the prefrontal and posterior superior temporal regions. Both schizophrenic groups had abnormally large volumes of the cortical sulci and lateral and third ventricles; however, the SH group showed greater enlargements, the most prominent occurring in the ventricles and temporal sulci. The overlapping patterns of cortical gray matter deficits in the two groups provide evidence for generality of this pattern of regional brain volume abnormalities in schizophrenia.
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Corteza Cerebral/patología , Ventrículos Cerebrales/patología , Esquizofrenia/patología , Adulto , Anciano , Alcoholismo/patología , Análisis de Varianza , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esquizofrenia/diagnósticoRESUMEN
Fludarabine phosphate (FDR) has demonstrated a remarkable clinical activity in chronic lymphocytic leukemia (CLL). Myelosuppression is the main toxicity although autoimmune hemolytic anemia (AIHA) is frequently reported. The pathogenesis of AIHA is still unknown however the role of T-cell immunosuppression is suspected. One case of thrombopenia after FDR has been described in a patient with a previous history of an autoimmune thrombocytopenia. We here report a 73-year-old man with a B-CLL and no previous autoimmune disorder who received six courses of fludarabine phosphate and developed afterwards an autoimmune thrombocytopenia.
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Enfermedades Autoinmunes/inducido químicamente , Inmunosupresores/efectos adversos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Trombocitopenia/inducido químicamente , Fosfato de Vidarabina/análogos & derivados , Anciano , Esquema de Medicación , Humanos , Leucemia Linfocítica Crónica de Células B/complicaciones , Masculino , Fosfato de Vidarabina/efectos adversosRESUMEN
A mixed hamartoma of the liver in a 39 year old man is reported. Abdominal ultrasound revealed a 4 cm inhomogeneous echogenic mass with acoustic shadowing. MRI T1 weighted images showed a inhomogeneous low intensity mass with lower gadolinium enhancement than normal liver, a moderate low signal intensity on proton density weighted images, and heterogeneous isosignal intensity on T2 weighted images. Peripheric calcifications were found on pathologic examination.
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Hamartoma/diagnóstico , Neoplasias Hepáticas/diagnóstico , Imagen por Resonancia Magnética , Adulto , Hamartoma/diagnóstico por imagen , Hamartoma/patología , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Masculino , RadiografíaRESUMEN
PURPOSE: To observe and quantify white matter hyperintensities on MR images in adults with schizophrenialike symptoms who had had congenital rubella, in order to elucidate the neuropathologic sequelae of this perinatal viral infection and to explore the potential relationship of these lesions to schizophrenia. METHODS: Eleven deaf adult patients with documented prenatal rubella virus infection and schizophrenialike symptoms were compared with 19 age-matched patients with early-onset schizophrenia who did not have congenital rubella and with 18 age-matched control subjects. All MR images (obtained at 1.5 T) were evaluated by a neuroradiologist who was blinded to diagnosis and were rated for white matter lesions on a five-point scale: 0 = no lesions; 1 = 1 lesion less than 1 mm in diameter; 2 = 1 to 4 lesions 1 mm or greater; 3 = 5 to 10 lesions; 4 = more than 10 lesions or a single lesion more than 1 cm in diameter. In addition, the white matter hyperintensities were volumed objectively with a manual threshold technique. RESULTS: Ratings of white matter lesions were significantly higher in the rubella patients than in the control subjects: 6 of the 11 patients had ratings greater than 1 compared with 1 of the 18 control subjects and none of the 19 schizophrenic patients. Also, MR images in five rubella patients received ratings at the highest end of the scale of abnormality (3 or 4). The white matter hyperintensities were characterized as bilateral T2 signal hyperintensities in periventricular and subcortical regions, punctate or linear in shape; they were observed predominantly in parietal lobes. CONCLUSION: This quantitative MR study of adult rubella patients disclosed abnormal white matter lesions that may correspond to neurovascular lesions known neuropathologically. They do not appear to be directly related to schizophrenialike symptoms.
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Daño Encefálico Crónico/diagnóstico , Encéfalo/patología , Imagen por Resonancia Magnética , Trastornos Neurocognitivos/diagnóstico , Síndrome de Rubéola Congénita/diagnóstico , Esquizofrenia/diagnóstico , Adulto , Femenino , Humanos , Masculino , Examen Neurológico , Valores de ReferenciaRESUMEN
Brain morphology was quantified with magnetic resonance imaging (MRI) in adult patients with congenital rubella who also had schizophrenialike symptoms. MRIs were compared with those of adult early-onset schizophrenic patients without congenital rubella and age-matched healthy control subjects. The rubella patients had significantly smaller intracranial volumes and shorter stature than the schizophrenic patients or the controls; however, both patient groups had smaller cortical gray matter, but not white matter, volumes than the control group, even when the MRI volumes were corrected for head size and age. In addition, both patient groups showed significant enlargement of the lateral ventricles but not cortical sulci when compared with expected values of normal adults of the same age and head size. Overall, the pattern of dysmorphology was identical in the rubella and the schizophrenic groups. The observations in the rubella group are consistent with a developmental lesion that limits full brain growth, with the small intracranial volume due at least in part to a severe cortical gray matter volume deficit. Thus, the brain dysmorphology of congenital rubella may provide an instance of prenatal viral infection that models the schizophrenic pattern and provides indirect support for a developmental hypothesis of the neuropathogenesis of schizophrenia.
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Encéfalo/anomalías , Imagen por Resonancia Magnética , Trastornos Neurocognitivos/diagnóstico , Síndrome de Rubéola Congénita/diagnóstico , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Adulto , Atrofia , Encéfalo/patología , Daño Encefálico Crónico/congénito , Daño Encefálico Crónico/diagnóstico , Daño Encefálico Crónico/psicología , Cefalometría , Corteza Cerebral/anomalías , Corteza Cerebral/patología , Ventrículos Cerebrales/anomalías , Ventrículos Cerebrales/patología , Femenino , Humanos , Inteligencia/fisiología , Masculino , Trastornos Neurocognitivos/psicología , Escalas de Valoración Psiquiátrica , Valores de Referencia , Síndrome de Rubéola Congénita/psicologíaRESUMEN
Four patients with C5-C6 root avulsion after brachial plexus injury were treated with a transfer of part of a normal functioning nerve in the arm to the motor nerve of the biceps. Ten percent of the bulk of the ulnar nerve was harvested for a suture directly to the motor nerve of the biceps with no significant impairment of hand function.
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Plexo Braquial/lesiones , Articulación del Codo/fisiología , Mano/fisiología , Transferencia de Nervios/métodos , Raíces Nerviosas Espinales/lesiones , Nervio Cubital/cirugía , Adolescente , Adulto , Brazo , Femenino , Humanos , Masculino , Músculos/cirugíaRESUMEN
An anatomical study of 30 cases has been performed on the vascularisation of the distal third of the antero-lateral compartment of the leg, with particular reference to the relations of the infero-lateral collateral artery of the anterior tibial artery, the perforating branch of the peroneal artery, and the antero-lateral malleolar artery. A fascio-cutaneous pedicle flap based on the infero-lateral collateral artery is described noting that the superior, anterior, and posterior limits are similar to those of the lateral supramalleolar flap of Masquelet. The inferior limit of this new flap is 15 mm distal to the site of emergence of the perforating branch of the peroneal artery. The advantages of this flap are; a large surface area for cover, antegrade vascularisation, and no significant vascular sacrifice. The distal half of the calf can be covered both medially and posteriorly as well as the proximal half of the dorsum of the foot, the medial and lateral arch areas, the perimalleolar region, and the region behind the Achilles tendon. The flap requires the presence of the infero-lateral collateral artery of the tibialis anterior which can be confirmed either peroperatively or preoperatively by angiography.
Asunto(s)
Pierna/irrigación sanguínea , Colgajos Quirúrgicos , Arterias Tibiales/anatomía & histología , Circulación Colateral , Humanos , Colgajos Quirúrgicos/métodosRESUMEN
The authors review a series of 36 total GUEPAR trapezometacarpal arthroplasties, performed between 1981 and 1990 in 32 patients, with a Dell stage III or IV carpometacarpal arthritis of the thumb (primary arthritis = 34 cases; secondary arthritis: 2 cases, 1 case of chondrocalcinosis, 1 case of osteochondromatosis). Scaphotrapezial arthritis present in 7 cases is not a contraindication to total arthroplasty. The mean follow-up period was 3 and a half years, with a range of 1 to 9 years. Functional results were considered to be good in 89%, without limitation of activity. X-ray study shows: 1) A radioclinical concordence in 64% of cases with good clinical and X-ray results, stable in the long term. 2) A radioclinical discordance in 22% of cases with good functional result but mobilisation of metacarpal stem. 3) Failure in 5 cases (14%) with unsealing and trapezial fracture. This radioclinical study yields two failure factors: preoperative destruction of trapezium in all the failures and these cases are now a contraindication to the prosthesis and inadaptation between stem arthroplasty and metacarpal cavity. This study supports total arthroplasty in trapezometacarpal arthritis of the thumb: III or IV Dell's stage, with preserved trapezium configuration.