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AIMS AND BACKGROUND: Mutations in the TARDBP gene, which encodes the TAR DNA binding protein (TDP-43), have been described in individuals with familial and sporadic amyotrophic lateral sclerosis (ALS). We screened the TARDBP gene in 285 French sporadic ALS patients to assess the frequency of TARDBP mutations in ALS. RESULTS: Six individuals had potentially deleterious mutations of which three were novel including a Y374X truncating mutation and P363A and A382P missense mutations. This suggests that TARDBP mutations may predispose to ALS in approximately 2% of the individuals followed in this study. CONCLUSION: Our findings, combined with those from other collections, brings the total number of mutations in unrelated ALS patients to 17, further suggesting that mutations in the TARDBP gene have an important role in the pathogenesis of ALS.
Assuntos
Esclerose Lateral Amiotrófica/genética , Proteínas de Ligação a DNA/genética , Mutação , Esclerose Lateral Amiotrófica/metabolismo , Sequência de Bases , Estudos de Coortes , Análise Mutacional de DNA , Proteínas de Ligação a DNA/metabolismo , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência MolecularRESUMO
PURPOSE: The aim of this work is to evaluate the anatomical changes of the glandular structures during the NPC IMRT and to study their dosimetric impacts. PATIENTS AND METHODS: Twenty patients receiving IMRT for NPC were included. For each patient, a second dosimetric CT was performed at a dose of 38Gy, which was fused with the initial planning dosimetric CT. We calculated the volume percent change, the positional and dosimetric variation between the 2 scanners for the glandular structures (parotid, submaxillary, thyroid and pituitary). RESULTS: We observed a decrease in the volume of right and left parotids (-27.9% and -27.54%). It was correlated with the initial dose planned at its level. For the sub maxillary glands, the decrease was -36.1% on the right and -27.28% on the left. The value of reduction of the thyroid gland was -18.01%. A medial supra-millimeter migration of 2 and 1.15mm was found for right and left parotid glands respectively, correlated with GTV N reduction volume. We found a significant increase in mean doses for the parotid glands. It was 1.8±2.3Gy for the right and 1.5±2.7Gy for the left. For the right sub maxillary gland, the increase was about 0.35±2Gy and 3.79±5.2Gy for the thyroid. CONCLUSION: The modifications observed for glandular structures during NPC IMRT can explain the different toxicities caused by radiation. It seems also that a careful adaptation of the treatment plan should be considered during therapy.
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Neoplasias Nasofaríngeas/radioterapia , Órgãos em Risco , Radioterapia de Intensidade Modulada , Carcinoma/diagnóstico por imagem , Carcinoma/radioterapia , Humanos , Neoplasias Nasofaríngeas/diagnóstico por imagem , Glândula Parótida/efeitos da radiação , Hipófise/efeitos da radiação , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Glândula Submandibular/efeitos da radiação , Glândula Tireoide/efeitos da radiação , Tomografia Computadorizada por Raios XRESUMO
A single-centre interrupted time series quasi-experimental study was undertaken to assess whether a hospital policy of selective digestive decontamination (SDD, gentamicin/amikacin with neomycin) administered to carbapenem-resistant Enterobacterales (CRE) carriers would reduce the duration of carriage and contain the spread of CRE. No significant difference in time to CRE eradication was observed between the observation (12 months, 120 patients) and intervention (12 months, 101 patients) periods. No change in the trend of new in-hospital CRE acquisitions or bacteraemia during the intervention was detected. As such, administration of SDD to CRE carriers was not effective for the eradication of carriage or controlling in-hospital CRE transmissions.
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Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Descontaminação/métodos , Farmacorresistência Bacteriana Múltipla , Enterobacteriaceae/efeitos dos fármacos , Hospitais/normas , Estudos Controlados Antes e Depois , Descontaminação/normas , Infecções por Enterobacteriaceae/prevenção & controle , Infecções por Enterobacteriaceae/transmissão , Humanos , Análise de Séries Temporais Interrompida , Ensaios Clínicos Controlados não Aleatórios como Assunto , Estudos ProspectivosRESUMO
INTRODUCTION: Described and recognized for the first time as a pathological entity by Virchow in 1857, chordoma is a tumour of embryonic origin secondary to an attack of the notochord. In most cases it is asymptomatic, resulting in fairly late diagnosis. PATIENTS AND METHODS: We report the case of a 62-year-old patient presenting a bulky tumefaction, nodular in places, not very painful, and extending towards the anal area, scrotum and the posterior aspect of the upper left thigh. Histopathological examination of a macrobiopsy sample of this tumefaction pointed to chordoma. On magnetic resonance imaging (MRI), the tumour presented multiple ramifications extending towards the scrotal area, the sciatic area and the posterior aspect of the left thigh. Palliative tumorectomy was performed. Given the very slow progression of the tumour and the risk of adverse effects in such a large tumoral exposure field, radiotherapy was ruled out. DISCUSSION: This is a typical observation of a rare tumour that dermatologists may encounter.
Assuntos
Neoplasias Ósseas/patologia , Cordoma/patologia , Sacro/patologia , Nádegas , Cordoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Sacro/cirurgiaRESUMO
PURPOSE: We report in this study, the dosimetric and carcinologic results of intensity-modulated technique for the reirradiation of nasopharyngeal carcinomas. PATIENTS AND METHODS: Eight patients reirradiated with intensity-modulation technique between January 2015 and December 2017 were included. We noted for each patient: the minimum, maximum and average doses, the dose received by 95% (D95%), 98% (D98%) and 2% (D2%) of the volume to be irradiated, the homogeneity and conformity indices and doses to the organs at risk. RESULTS: Target volume coverage was satisfactory with a median of D95% greater than 57Gy (95% of the prescribed dose). The median maximum dose received by the spinal cord and brainstem were 8.2Gy and 18.25Gy, respectively. After a median follow-up of 14.5 months [1-29 months], five patients were in complete remission of their disease. Overall survival at 2 years was 66.7%. An increase in preexisting late toxicity after the first irradiation (now grade 2 or above) was found in four patients (50% of cases). CONCLUSION: Intensity-modulation is an attractive technique for reirradiation of the nasopharynx. It allows a better conformity of the dose to the target and a reduction of the doses on the already irradiated critical organs. This offers good control of the disease with fewer severe late toxicities.
Assuntos
Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Recidiva Local de Neoplasia/radioterapia , Radioterapia de Intensidade Modulada , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/mortalidade , Órgãos em Risco , Dosagem Radioterapêutica , Indução de Remissão , Retratamento , Estudos Retrospectivos , Tunísia/epidemiologiaAssuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Códon sem Sentido , Exoma , Deficiência Intelectual/genética , Fatores de Transcrição/genética , Criança , Estudos de Associação Genética , Testes Genéticos/métodos , Humanos , Deficiência Intelectual/patologia , Pais , Fator de Transcrição 4RESUMO
OBJECTIVE:: To compare prey and snake paradigms performed in complex environments to the elevated plus-maze (EPM) and T-maze (ETM) tests for the study of panic attack- and anticipatory anxiety-like behaviors in rodents. METHODS:: PubMed was reviewed in search of articles focusing on the plus maze test, EPM, and ETM, as well as on defensive behaviors displayed by threatened rodents. In addition, the authors' research with polygonal arenas and complex labyrinth (designed by the first author for confrontation between snakes and small rodents) was examined. RESULTS:: The EPM and ETM tests evoke anxiety/fear-related defensive responses that are pharmacologically validated, whereas the confrontation between rodents and snakes in polygonal arenas with or without shelters or in the complex labyrinth offers ethological conditions for studying more complex defensive behaviors and the effects of anxiolytic and panicolytic drugs. Prey vs. predator paradigms also allow discrimination between non-oriented and oriented escape behavior. CONCLUSIONS:: Both EPM and ETM simple labyrinths are excellent apparatuses for the study of anxiety- and instinctive fear-related responses, respectively. The confrontation between rodents and snakes in polygonal arenas, however, offers a more ethological environment for addressing both unconditioned and conditioned fear-induced behaviors and the effects of anxiolytic and panicolytic drugs.
Assuntos
Transtornos de Ansiedade/psicologia , Comportamento Animal/fisiologia , Instinto , Transtorno de Pânico/psicologia , Serpentes , Animais , Medo/fisiologia , Medo/psicologia , Aprendizagem em Labirinto , Comportamento Predatório , Ratos , Ratos WistarRESUMO
It is generally agreed that there is a genetic component in the etiology of schizophrenia which may be tested by the application of linkage analysis to multiply-affected families. One genetic region of interest is the long arm of chromosome 11 because of previously reported associations of genetic variation in this region with schizophrenia, and because of the fact that it contains the locus for the dopamine D2 receptor gene. In this study we have examined the segregation of schizophrenia with microsatellite dinucleotide repeat DNA markers along chromosome 11q in 5 Israeli families multiply-affected for schizophrenia. The hypothesis of linkage under genetic homogeneity of causation was tested under a number of genetic models. Linkage analysis provided no evidence for significant causal mutations within the region bounded by INT and D11S420 on chromosome 11q. It is still possible, however, that a gene of major effect exists in this region, either with low penetrance or with heterogeneity.
Assuntos
Cromossomos Humanos Par 11/genética , Ligação Genética , Marcadores Genéticos , Esquizofrenia/genética , Mapeamento Cromossômico , Repetições de Dinucleotídeos , Feminino , Humanos , Israel , Escore Lod , Masculino , Modelos Genéticos , Mutação , LinhagemRESUMO
The well-known reaction between thiols and mercuric salts can be used for determination of the former. The method has been extended to determination of several organomercurials. Cysteine is used for titration of hydroxyaryl mercury compounds. The presence of a chloride or sulphur atom bound to the metal makes the method inapplicable, however.
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Vértebras Lombares , Imageamento por Ressonância Magnética/métodos , Doenças da Coluna Vertebral/diagnóstico , Cisto Sinovial/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Feminino , Humanos , Articulações , Laminectomia , Vértebras Lombares/cirurgia , Pessoa de Meia-Idade , Doenças da Coluna Vertebral/cirurgia , Cisto Sinovial/diagnóstico por imagem , Cisto Sinovial/cirurgiaRESUMO
The microstructure of the as-cast AlCoCrFeNi high entropy alloy has been investigated by transmission electron microscopy and atom probe tomography. The alloy shows a very pronounced microstructure with clearly distinguishable dendrites and interdendrites. In both regions a separation into an Al-Ni rich matrix and Cr-Fe-rich precipitates can be observed. Moreover, fluctuations of single elements within the Cr-Fe rich phase have been singled out by three dimensional atom probe measurements. The results of investigations are discussed in terms of spinodal decomposition of the alloying elements inside the Cr-Fe-rich precipitates.
RESUMO
OBJECTIVE: To describe the phenotype and phenotype-genotype correlations in patients with amyotrophic lateral sclerosis (ALS) with TARDBP gene mutations. METHODS: French TARDBP+ patients with ALS (n = 28) were compared first to 3 cohorts: 737 sporadic ALS (SALS), 192 nonmutated familial ALS (FALS), and 58 SOD1 + FALS, and then to 117 TARDBP+ cases from the literature. Genotype-phenotype correlations were studied for the most frequent TARDBP mutations. RESULTS: In TARDBP+ patients, onset was earlier (p = 0.0003), upper limb (UL) onset was predominant (p = 0.002), and duration was longer (p = 0.0001) than in patients with SALS. TARDBP+ and SOD1+ groups had the longest duration but diverged for site of onset: 64.3% UL onset for TARDBP+ and 74.1% on lower limbs for SOD1+ (p < 0.0001). The clinical characteristics of our 28 patients were similar to the 117 cases from the literature. In Caucasians, 51.3% of had UL onset, while 58.8% of Asians had bulbar onset (p = 0.02). The type of mutation influenced survival (p < 0.0001), and the G298S1, lying in the TARDBP super rich glycine-residue domain, was associated with the worst survival (27 months). CONCLUSION: Differences in phenotype between the groups as well as the differential influence of TARBDP mutations on survival may help physicians in ALS management and allow refining the strategy of genetic diagnosis.
Assuntos
Esclerose Lateral Amiotrófica/genética , Proteínas de Ligação a DNA/genética , Adulto , Idade de Início , Idoso , Esclerose Lateral Amiotrófica/mortalidade , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Análise de SobrevidaRESUMO
Objective: To compare prey and snake paradigms performed in complex environments to the elevated plus-maze (EPM) and T-maze (ETM) tests for the study of panic attack- and anticipatory anxiety-like behaviors in rodents. Methods: PubMed was reviewed in search of articles focusing on the plus maze test, EPM, and ETM, as well as on defensive behaviors displayed by threatened rodents. In addition, the authors’ research with polygonal arenas and complex labyrinth (designed by the first author for confrontation between snakes and small rodents) was examined. Results: The EPM and ETM tests evoke anxiety/fear-related defensive responses that are pharmacologically validated, whereas the confrontation between rodents and snakes in polygonal arenas with or without shelters or in the complex labyrinth offers ethological conditions for studying more complex defensive behaviors and the effects of anxiolytic and panicolytic drugs. Prey vs. predator paradigms also allow discrimination between non-oriented and oriented escape behavior. Conclusions: Both EPM and ETM simple labyrinths are excellent apparatuses for the study of anxiety- and instinctive fear-related responses, respectively. The confrontation between rodents and snakes in polygonal arenas, however, offers a more ethological environment for addressing both unconditioned and conditioned fear-induced behaviors and the effects of anxiolytic and panicolytic drugs.
Assuntos
Animais , Ratos , Transtornos de Ansiedade/psicologia , Serpentes , Comportamento Animal/fisiologia , Transtorno de Pânico/psicologia , Instinto , Comportamento Predatório , Ratos Wistar , Aprendizagem em Labirinto , Medo/fisiologia , Medo/psicologiaAssuntos
Macula Lutea/irrigação sanguínea , Neovascularização Patológica , Transtornos da Visão/etiologia , Adulto , Idoso , Feminino , Humanos , Degeneração Macular/complicações , Masculino , Pessoa de Meia-Idade , Miopia/complicações , Neovascularização Patológica/patologia , Doenças Retinianas/complicações , Vasos Retinianos/patologia , Acuidade VisualAssuntos
Emigração e Imigração , Família , Aculturação , Adulto , Argélia/etnologia , Delusões/psicologia , Transtorno Depressivo/psicologia , Disfunção Erétil/psicologia , Feminino , Humanos , Masculino , Casamento , Pessoa de Meia-Idade , Transtornos Psicofisiológicos/psicologia , Transtornos Somatoformes/psicologiaRESUMO
BACKGROUND: The identification of mutations in the TARDBP and more recently the identification of mutations in the FUS gene as the cause of amyotrophic lateral sclerosis (ALS) is providing the field with new insight about the mechanisms involved in this severe neurodegenerative disease. METHODS: To extend these recent genetic reports, we screened the entire gene in a cohort of 200 patients with ALS. An additional 285 patients with sporadic ALS were screened for variants in exon 15 for which mutations were previously reported. RESULTS: In total, 3 different mutations were identified in 4 different patients, including 1 3-bp deletion in exon 3 of a patient with sporadic ALS and 2 missense mutations in exon 15 of 1 patient with familial ALS and 2 patients with sporadic ALS. CONCLUSIONS: Our study identified sporadic patients with mutations in the FUS gene. The accumulation and description of different genes and mutations helps to develop a more comprehensive picture of the genetic events underlying amyotrophic lateral sclerosis.
Assuntos
Esclerose Lateral Amiotrófica/genética , Mutação , Proteína FUS de Ligação a RNA/genética , Canadá , Cromossomos Humanos Par 16/genética , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Testes Genéticos , Humanos , MasculinoRESUMO
The blockade of GABA-mediated Cl(-) influx with pentylenetetrazol (PTZ) was used in the present work to induce seizures in Rattus norvegicus. The aim of this work was to study the involvement of monoamines in the antinociception induced by convulsions elicited by peripheral administration of PTZ (64 mg/kg). The analgesia was measured by the tail-flick test in seven or eight Wistar rats per group. Convulsions were followed by statistically significant increase in the tail-flick latencies (TFL), at least for 120 min of the postictal period. Peripheral administration of methysergide (0.5, 1, 2, and 3 mg/kg) caused a significant decrease in the TFL in seizing animals, as compared to controls, in all postictal periods studied. These findings were corroborated by the pretreatment with ketanserin, a 5-HT(2A/2C)-serotonergic/alpha(1)-noradrenergic receptors antagonist, at the same doses. Peripheral administration of yohimbine (0.5, 1, 2, and 3 mg/kg), alpha(2)-noradrenergic antagonist, also decreased the postictal analgesia either at initial or more terminal periods of the postictal analgesia. These data were corroborated with peripheral administrations of propranolol, a beta-noradrenergic receptor blocker that caused a decrease in the postictal analgesia consistently in later stages (after the first 20-min post-tonic-clonic convulsive reactions) of the post-seizure analgesia, except for the highest dose. These results indicate that monoamines may be involved in the postictal analgesia. The blockade of 5-HT(2A/2C)-serotoninergic, alpha(1)-noradrenergic, or alpha(2)-noradrenergic receptors before tonic clonic seizure-induced analgesia antagonized the increase in the nociceptive threshold caused by seizures in initial steps of the temporal antinociceptive curve, as compared to the blockade of beta-noradrenergic ones. These findings suggest that the recruitment of alpha-noradrenergic receptor and serotonergic receptors was made immediately after convulsions and in other initial periods of the postictal analgesia, as compared to the involvement of beta-noradrenergic receptor. Neurochemical lesions of the locus coeruleus (LC) and neuronal damage of the dorsal raphe nucleus induced a significant decrease of the postictal analgesia, suggesting the involvement of these nuclei in this antinociceptive process. The functional neuroanatomical study of the neural link between the mesencephalic tectum and nuclei of the central pain inhibitory system showed evidence for the interconnection between superior colliculus, both dorsal and ventral periaqueductal gray matter (PAG), and inferior colliculus. Defensive substrates of the inferior colliculus, also involved with wild running and epilepsy, send inputs toward dorsal raphe nucleus and locus coeruleus. Since these nuclei are rich in monoamines and send neural connections toward other monoaminergic nuclei of the brainstem involved with the control of the nociceptive inputs in the dorsal horn of the spinal cord, the present results offer a neuroanatomical and psychopharmacological basis for the antinociceptive processes following tonic-clonic seizures.