Crises focais benignas do adolescente: disfunção neuropsicológica leve em pacientes da comunidade

RATIONALE: Benign focal seizures of adolescence (BFSA) described by Loiseau et al in 1972, is considered a rare entity, but maybe underdiagnosed. Although mild neuropsychological deficits have been reported in patients with benign epilepsies of childhood, these evaluations have not so far been described in BFSA. The aim of this study is to evaluate neuropsychological functions in BFSA with new onset seizures (<12 months). METHODS: Eight patients with BFSA (according to Loiseau et al, 1972, focal or secondarily tonic clonic generalized seizures between the ages of 10-18 yrs., normal neurologic examination, normal EEG or with mild focal abnormalities) initiated in the last 12 months were studied between July 2008 to May 2009. They were referred from the Pediatric Emergency Section of the Hospital Universitário of the University of Sao Paulo, a secondary care regionalized facility located in a district of middle-low income in Sao Paulo city, Brazil. The study was approved by the Ethics Committee of the Institution. All patients performed neurological, EEG, brain CT and neuropsychological evaluation which consisted of Raven's Special Progressive Matrices - General and Special Scale (according to different ages), Wechsler Children Intelligence Scale-WISC III with ACID Profile, Trail Making Test A/B, Stroop Test, Bender Visuo-Motor Test, Rey Complex Figure, Rey Auditory Verbal Learning Test-RAVLT, Boston Naming Test, Fluency Verbal for phonological and also conceptual patterns - FAS/Animals and Hooper Visual Organization Test. For academic achievement, we used a Brazilian test for named "Teste do Desempenho Escolar", which evaluates abilities to read, write and calculate according to school grade. RESULTS: There were 2 boys and 6 girls, with ages ranging from 10 yrs. 9 m to 14 yrs. 3 m. Most (7/8) of the patients presented one to two seizures and only three of them received antiepileptic drugs (AEDs). Six had mild EEG focal abnormalities and all had normal brain CT. All were literate, attended regular public schools and scored in a median range for IQ, and seven showed discrete higher scores for the verbal subtests. There were low scores for attention in different modalities in six patients, mainly in alternated attention as well as inhibitory subtests (Stroop test and Trail Making Test part B). Four of the latter cases who showed impairment both in alternated and inhibitory attention were not taking AEDs. Visual memory was impaired in five patients (Rey Complex Figure). Executive functions analysis showed deficits in working memory in five, mostly observed in Digits Indirect Order and Arithmetic tests (WISC III). Reading and writing skills were below the expected average for school grade in six patients according to the achievement scholar performance test utilized. One patient of this series who had the best scores in all tests was taking phenobarbital. CONCLUSIONS: Neuropsychological imbalance between normal IQ and mild dysfunctions such as in attention domain and in some executive abilities like working memory and planning, as well as difficulties in visual memory and in reading and writing, were described in this group of patients with BFSA from community. This may reflect mild higher level neurological dysfunctions in adolescence idiopathic focal seizures probably caused by an underlying dysmaturative epileptogenic process. Although academic problems often have multiple causes, a specific educational approach may be necessary in these adolescents, in order to improve their scholastic achievements, helping in this way, to decrease the stigma associated to epileptic seizures in the community.INTRODUÇÃO: Crises focais benignas do adolescente (CFBA) descritas por Loiseau et al. em 1972, são consideradas raras, mas podem ser subdiagnosticadas. Déficits neuropsicológicos leves foram relatados em pacientes com epilepsias benignas da infância, mas até o momento tais avaliações não foram descritas na CFBA. O objetivo deste estudo é avaliar as funções neuropsicológicas na CFBA de início recente (<12 meses). MÉTODOS: Oito pacientes com CFBA (segundo Loiseau et al. 1972, caracterizada por crises focais ou secundariamente tonico-clonico-generalizadas entre as idades de 10 a 18 anos), iniciadas nos últimos 12 meses, com exame neurológico normal, EEG normal ou com anormalidades focais, tomografia de crânio normal no período de Julho de 2008 a Maio de 2009. Os pacientes foram encaminhados do Setor de Emergência Pediátrica do Hospital Universitário da Universidade de São Paulo, que é hospital de atendimento secundário regionalizado localizado em um distrito de classe média da cidade de São Paulo, SP. O projeto foi aprovado pelo Comitê de Ética da Instituição. Todos pacientes realizaram exame neurológico, EEG e tomografia de crânio. A avaliação neuropsicológica consistiu dos seguintes testes: Matrizes Progressivas Especiais do Raven - Escala Geral e Especial (de acordo com as diferentes idades), Escala de Inteligência Wechsler para crianças - WISC III - com perfil ACID, Teste Trail Making A/B, Teste de Stroop, Teste Visuo-Motor de Bender, Figura Complexa de Rey, Teste de Aprendizado Auditivo Verbal de Rey - RAVLT, Teste de Nomeação de Boston, Teste de Fluência Verbal para padrões fonológicos e conceptuais-FAS/Animais e Teste de Organizacão Visual de Hooper. Para o desempenho escolar, foi usado o teste brasileiro chamado "Teste do Desempenho Escolar", que avalia as habilidades de leitura, escrita de acordo com o grau de escolaridade. RESULTADOS: Foram estudados seis pacientes do sexo feminino e dois, do masculino, com idades variando de 10 anos e 9 meses a 14 anos e 3 meses. A maioria (7/8) dos pacientes apresentou uma a duas crises e somente três receberam drogas antiepilépticas (DAEs). Seis pacientes apresentaram anormalidades focais leves no EEG. Todos estavam alfabetizados, frequentavam escolas regulares do sistema público e apresentaram avaliação de Quociente Intelectual na faixa média para idade e sete mostravam discretos valores maiores nos subtestes verbais. Havia valores menores para atenção em diferentes modalidades em seis pacientes, especialmente na atenção alternada e no controle inibitório (Testes Stroop-like e Trail Making parte B). Quatro dos últimos casos que mostraram prejuízo tanto na atenção alternada como inibitória não estavam tomando DAEs. A memória visual estava prejudicada em cinco pacientes (Figura Complexa de Rey). As funções executivas mostraram déficits na memória operacional em cinco, especialmente observados nos subtestes de Aritmética e na Ordem Indireta de Dígitos (WISC III). A leitura e escrita estavam abaixo da média esperada para a série escolar segundo o teste de desempenho escolar utilizado, em seis pacientes. Um dos pacientes que apresentava os maiores valores do grupo em todos os testes estava recebendo fenobarbital. CONCLUSÕES: Uma desproporção entre QI normal e disfunções neuropsicológicas leves tais como na esfera atencional e em algumas funções executivas como memória operacional e planejamento de ação, assim como na memória visual e problemas acadêmicos na leitura e escrita, foram descritos neste grupo de pacientes com CBFA da comunidade. Isto pode refletir disfunções neuropsicológicas leves em pacientes com crises idiopáticas do adolescente provavelmente causadas por um processo epileptogênico dismaturativo sobrejacente. Embora problemas acadêmicos escolares frequentemente apresentem múltiplas causas, uma abordagem educacional específica pode ser necessária nestes adolescentes, a fim de melhorar seu desempenho, ajudando desta forma a minimizar o estigma associado às crises epilépticas na comunidade

Breath analysis for early detection of malignant pleural mesothelioma: Volatile organic compounds (VOCs) determination and possible biochemical pathways

Malignant pleural mesothelioma (MPM) is a rare neoplasm, mainly caused by asbestos exposure, with a high mortality rate. The management of patients with MPM is controversial due to a long latency period between exposure and diagnosis and because of non-specific symptoms generally appearing at advanced stage of the disease. Breath analysis, aimed at the identification of diagnostic Volatile Organic Compounds (VOCs) pattern in exhaled breath, is believed to improve early detection of MPM. Therefore, in this study, breath samples from 14 MPM patients and 20 healthy controls (HC) were collected and analyzed by Thermal Desorption-Gas Chromatography-Mass Spectrometry (TD-GC/MS). Nonparametric test allowed to identify the most weighting variables to discriminate between MPM and HC breath samples and multivariate statistics were applied. Considering that MPM is an aggressive neoplasm leading to a late diagnosis and thus the recruitment of patients is very difficult, a promising data mining approach was developed and validated in order to discriminate between MPM patients and healthy controls, even if no large population data are available. Three different machine learning algorithms were applied to perform the classification task with a leave-one-out cross-validation approach, leading to remarkable results (Area Under Curve AUC = 93%). Ten VOCs, such as ketones, alkanes and methylate derivates, as well as hydrocarbons, were able to discriminate between MPM patients and healthy controls and for each compound which resulted diagnostic for MPM, the metabolic pathway was studied in order to identify the link between VOC and the neoplasm. Moreover, five breath samples from asymptomatic asbestos-exposed persons (AEx) were exploratively analyzed, processed and tested by the validated statistical method as blinded samples in order to evaluate the performance for the early recognition of patients affected by MPM among asbestos-exposed persons. Good agreement was found between the information obtained by gold-standard diagnostic methods such as computed tomography CT and model output

Boletim Especial COVID-19 - Mercados, segurança alimentar e sanidade.

bitstream/item/220354/1/P-BOLETIM-ESPECIAL-COVID-19-n.-1-2-3-e-4-Mercado-seguranca-alimentar.pd

Cerebrospinal fluid levels of L-glutamate signal central inflammatory neurodegeneration in multiple sclerosis

Excessive extracellular concentrations of L-glutamate (L-Glu) can be neurotoxic and contribute to neurodegenerative processes in multiple sclerosis (MS). The association between cerebrospinal fluid (CSF) L-Glu levels, clinical features, and inflammatory biomarkers in patients with MS remains unclear. In 179 MS patients (relapsing remitting, RR, N = 157; secondary progressive/primary progressive, SP/PP, N = 22), CSF levels of L-Glu at diagnosis were determined and compared with those obtained in a group of 40 patients with non-inflammatory/non-degenerative disorders. Disability at the time of diagnosis, and after 1 year follow-up, was assessed using the Expanded Disability Status Scale (EDSS). CSF concentrations of lactate and of a large set of pro-inflammatory and anti-inflammatory molecules were explored. CSF levels of L-Glu were slightly reduced in MS patients compared to controls. In RR-MS patients, L-Glu levels correlated with EDSS after 1 year follow-up. Moreover, in MS patients, significant correlations were found between L-Glu and both CSF levels of lactate and the inflammatory molecules interleukin (IL)-2, IL-6, and IL-1 receptor antagonist. Altered expression of L-Glu is associated with disability progression, oxidative stress, and inflammation. These findings identify CSF L-Glu as a candidate neurochemical marker of inflammatory neurodegeneration in MS. (Figure presented.)

Cerebrospinal fluid levels of L-glutamate signal central inflammatory neurodegeneration in multiple sclerosis

Excessive extracellular concentrations of L-glutamate (L-Glu) can be neurotoxic and contribute to neurodegenerative processes in multiple sclerosis (MS). The association between cerebrospinal fluid (CSF) L-Glu levels, clinical features, and inflammatory biomarkers in patients with MS remains unclear. In 179&nbsp;MS patients (relapsing remitting, RR, N&nbsp;=&nbsp;157; secondary progressive/primary progressive, SP/PP, N&nbsp;=&nbsp;22), CSF levels of L-Glu at diagnosis were determined and compared with those obtained in a group of 40 patients with non-inflammatory/non-degenerative disorders. Disability at the time of diagnosis, and after 1&nbsp;year follow-up, was assessed using the Expanded Disability Status Scale (EDSS). CSF concentrations of lactate and of a large set of pro-inflammatory and anti-inflammatory molecules were explored. CSF levels of L-Glu were slightly reduced in MS patients compared to controls. In RR-MS patients, L-Glu levels correlated with EDSS after 1&nbsp;year follow-up. Moreover, in MS patients, significant correlations were found between L-Glu and both CSF levels of lactate and the inflammatory molecules interleukin (IL)-2, IL-6, and IL-1 receptor antagonist. Altered expression of L-Glu is associated with disability progression, oxidative stress, and inflammation. These findings identify CSF L-Glu as a candidate neurochemical marker of inflammatory neurodegeneration in MS. (Figure presented.)

Patient-reported impact of spondyloarthritis on work disability and working life: the ATLANTIS survey

Background: The aim was to establish how patients experience the impact of spondyloarthritis (SpA) on work disability and working life. Methods: The survey was performed in 17/20 regions in Italy (1 January to 31 March 2013). A multiple-choice questionnaire was published on the official website of the sponsor - the National Association of Rheumatic Patients (ANMAR) - and hard-copies were distributed at outpatient clinics for rheumatic patients. Results: Respondents (n = 770) were of both sexes (56 % men), educated (62 % at high school or more), of working age (75 % aged 6460 years), and affected by SpA. The most common types diagnosed were ankylosing spondylitis (AS) (39 %) and psoriatic arthritis (PsA) (36 %). Respondents were working full-time (45 %), part-time (8 %) or had retired (22 %); 15 % were unemployed (for reasons linked to the disease or for other reasons, students or housewives). Patients reported disability (39 %), were receiving disability benefits (34 %), were experiencing important limitations that were hindering their professional development/career (36 %) and some had to change/leave their job or lost it because of SpA (21 %). Employed respondents (n = 383) had worked on average 32.2 h in the last 7 days. More hours of work were lost over the last 7 days due to SpA (2.39 h vs 1.67 h). The indirect costs of the disease amounted to \u20ac106/week for patients reporting well-being/good physical conditions/improvement and \u20ac216/week for those reporting permanent impairment. Conclusions: Most patients were in the midst of their productive years and were experiencing considerable difficulties in carrying out their job because of the disease: half of them reported disability and one third were experiencing important limitations in their career perspective

Patient-reported impact of spondyloarthritis on work disability and working life: the ATLANTIS survey

Background: The aim was to establish how patients experience the impact of spondyloarthritis (SpA) on work disability and working life. Methods: The survey was performed in 17/20 regions in Italy (1 January to 31 March 2013). A multiple-choice questionnaire was published on the official website of the sponsor - the National Association of Rheumatic Patients (ANMAR) - and hard-copies were distributed at outpatient clinics for rheumatic patients. Results: Respondents (n = 770) were of both sexes (56 % men), educated (62 % at high school or more), of working age (75 % aged ≤60 years), and affected by SpA. The most common types diagnosed were ankylosing spondylitis (AS) (39 %) and psoriatic arthritis (PsA) (36 %). Respondents were working full-time (45 %), part-time (8 %) or had retired (22 %); 15 % were unemployed (for reasons linked to the disease or for other reasons, students or housewives). Patients reported disability (39 %), were receiving disability benefits (34 %), were experiencing important limitations that were hindering their professional development/career (36 %) and some had to change/leave their job or lost it because of SpA (21 %). Employed respondents (n = 383) had worked on average 32.2 h in the last 7 days. More hours of work were lost over the last 7 days due to SpA (2.39 h vs 1.67 h). The indirect costs of the disease amounted to €106/week for patients reporting well-being/good physical conditions/improvement and €216/week for those reporting permanent impairment. Conclusions: Most patients were in the midst of their productive years and were experiencing considerable difficulties in carrying out their job because of the disease: half of them reported disability and one third were experiencing important limitations in their career perspective

Evaluation of receptor and chemical transport models for PM10 source apportionment

In this study, the performance of two types of source apportionment models was evaluated by assessing the results provided by 40 different groups in the framework of an intercomparison organised by FAIRMODE WG3 (Forum for air quality modelling in Europe, Working Group 3). The evaluation was based on two performance indicators: z-scores and the root mean square error weighted by the reference uncertainty (RMSEu), with pre-established acceptability criteria. By involving models based on completely different and independent input data, such as receptor models (RMs) and chemical transport models (CTMs), the intercomparison provided a unique opportunity for their cross-validation. In addition, comparing the CTM chemical profiles with those measured directly at the source contributed to corroborate the consistency of the tested model results. The most commonly used RM was the US EPA- PMF version 5. RMs showed very good performance for the overall dataset (91% of z-scores accepted) while more difficulties were observed with the source contribution time series (72% of RMSEu accepted). Industrial activities proved to be the most difficult sources to be quantified by RMs, with high variability in the estimated contributions. In the CTMs, the sum of computed source contributions was lower than the measured gravimetric PM10 mass concentrations. The performance tests pointed out the differences between the two CTM approaches used for source apportionment in this study: brute force (or emission reduction impact) and tagged species methods. The sources meeting the z-score and RMSEu acceptability criteria tests were 50% and 86%, respectively. The CTM source contributions to PM10 were in the majority of cases lower than the RM averages for the corresponding source. The CTMs and RMs source contributions for the overall dataset were more comparable (83% of the z-scores accepted) than their time series (successful RMSEu in the range 25% - 34%). The comparability between CTMs and RMs varied depending on the source: traffic/exhaust and industry were the source categories with the best results in the RMSEu tests while the most critical ones were soil dust and road dust. The differences between RMs and CTMs source reconstructions confirmed the importance of cross validating the results of these two families of models

Positive Selection Results in Frequent Reversible Amino Acid Replacements in the G Protein Gene of Human Respiratory Syncytial Virus

Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a “flip-flop” phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites

Results of the first European Source Apportionment intercomparison for Receptor and Chemical Transport Models

In this study, the performance of the source apportionment model applications were evaluated by comparing the model results provided by 44 participants adopting a methodology based on performance indicators: z-scores and RMSEu, with pre-established acceptability criteria. Involving models based on completely different and independent input data, such as receptor models (RMs) and chemical transport models (CTMs), provided a unique opportunity to cross-validate them. In addition, comparing the modelled source chemical profiles, with those measured directly at the source contributed to corroborate the chemical profile of the tested model results. The most used RM was EPA- PMF5. RMs showed very good performance for the overall dataset (91% of z-scores accepted) and more difficulties are observed with SCE time series (72% of RMSEu accepted). Industry resulted the most problematic source for RMs due to the high variability among participants. Also the results obtained with CTMs were quite comparable to their ensemble reference using all models for the overall average (>92% of successful z-scores) while the comparability of the time series is more problematic (between 58% and 77% of the candidates’ RMSEu are accepted). In the CTM models a gap was observed between the sum of source contributions and the gravimetric PM10 mass likely due to PM underestimation in the base case. Interestingly, when only the tagged species CTM results were used in the reference, the differences between the two CTM approaches (brute force and tagged species) were evident. In this case the percentage of candidates passing the z-score and RMSEu tests were only 50% and 86%, respectively. CTMs showed good comparability with RMs for the overall dataset (83% of the z-scores accepted), more differences were observed when dealing with the time series of the single source categories. In this case the share of successful RMSEu was in the range 25% - 34%.JRC.C.5-Air and Climat