RESUMO
BACKGROUND: Inborn errors of immunity (IEI) are a group of monogenic diseases that confer susceptibility to infection, autoimmunity, and cancer. Despite the life-threatening consequences of some IEI, their genetic cause remains unknown in many patients. OBJECTIVE: We investigated a patient with an IEI of unknown genetic etiology. METHODS: Whole-exome sequencing identified a homozygous missense mutation of the gene encoding ezrin (EZR), substituting a threonine for an alanine at position 129. RESULTS: Ezrin is one of the subunits of the ezrin, radixin, and moesin (ERM) complex. The ERM complex links the plasma membrane to the cytoskeleton and is crucial for the assembly of an efficient immune response. The A129T mutation abolishes basal phosphorylation and decreases calcium signaling, leading to complete loss of function. Consistent with the pleiotropic function of ezrin in myriad immune cells, multidimensional immunophenotyping by mass and flow cytometry revealed that in addition to hypogammaglobulinemia, the patient had low frequencies of switched memory B cells, CD4+ and CD8+ T cells, MAIT, γδ T cells, and centralnaive CD4+ cells. CONCLUSIONS: Autosomal-recessive human ezrin deficiency is a newly recognized genetic cause of B-cell deficiency affecting cellular and humoral immunity.
Assuntos
Linfócitos T CD8-Positivos , Citoesqueleto , Humanos , Citoesqueleto/metabolismo , Membrana Celular/metabolismo , Imunidade HumoralRESUMO
BACKGROUND: Guillain-Barré syndrome (GBS) is an acute inflammatory neuropathy with a heterogeneous presentation. Although some evidences support the role of autoantibodies in its pathogenesis, the target antigens remain unknown in a substantial proportion of GBS patients. The objective of this study is to screen for autoantibodies targeting peripheral nerve components in Guillain-Barré syndrome. METHODS: Autoantibody screening was performed in serum samples from all GBS patients included in the International GBS Outcome study by 11 different Spanish centres. The screening included testing for anti-ganglioside antibodies, anti-nodo/paranodal antibodies, immunocytochemistry on neuroblastoma-derived human motor neurons and murine dorsal root ganglia (DRG) neurons, and immunohistochemistry on monkey peripheral nerve sections. We analysed the staining patterns of patients and controls. The prognostic value of anti-ganglioside antibodies was also analysed. RESULTS: None of the GBS patients (n = 100) reacted against the nodo/paranodal proteins tested, and 61 (61%) were positive for, at least, one anti-ganglioside antibody. GBS sera reacted strongly against DRG neurons more frequently than controls both with IgG (6% vs 0%; p = 0.03) and IgM (11% vs 2.2%; p = 0.02) immunodetection. No differences were observed in the proportion of patients reacting against neuroblastoma-derived human motor neurons. Reactivity against monkey nerve tissue was frequently detected both in patients and controls, but specific patterns were only detected in GBS patients: IgG from 13 (13%) patients reacted strongly against Schwann cells. Finally, we confirmed that IgG anti-GM1 antibodies are associated with poorer outcomes independently of other known prognostic factors. CONCLUSION: Our study confirms that (1) GBS patients display a heterogeneous repertoire of autoantibodies targeting nerve cells and structures; (2) gangliosides are the most frequent antigens in GBS patients and have a prognostic value; (3) further antigen-discovery experiments may elucidate other potential antigens in GBS.
Assuntos
Autoanticorpos/sangue , Síndrome de Guillain-Barré/sangue , Síndrome de Guillain-Barré/diagnóstico , Idoso , Animais , Linhagem Celular Tumoral , Estudos de Coortes , Feminino , Gânglios Espinais/metabolismo , Gânglios Espinais/patologia , Síndrome de Guillain-Barré/epidemiologia , Humanos , Macaca , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Ratos , Espanha/epidemiologiaRESUMO
BACKGROUND: The aim of this study was to evaluate the effectiveness of selective neck dissection (SND) in patients with laryngeal cancer and clinically positive cervical nodes. SUBJECTS AND METHODS: A retrospective review of the clinical records of 58 consecutive untreated patients affected by laryngeal carcinoma and submitted to surgical treatment was performed. RESULTS: Twenty-six (44.8%) patients received monolateral neck dissection and 32 (55.2%) bilateral neck dissection. A total of 90 hemineck dissections were performed. Histopathological examination revealed that 25 of the 58 patients had negative nodes (pN0) and 33 had positive nodes (pN+). Extracapsular spread was found in 12 of the 33 pN+ patients. Twenty-eight of the 58 (48.2%) patients were submitted to adjuvant radiotherapy. Six of the 58 patients submitted to neck dissection had neck recurrence (rate of 10.3%). The only independent prognostic factor for neck recurrence was extracapsular spread. For the 58 patients, the 5-year overall survival was 50% and the disease-specific survival 68.9%. The 5-year disease-specific survival was 76% for pN0 patients and 63.6% for pN+ patients. CONCLUSIONS: SND can represent a therapeutic procedure because it has shown oncological results comparable to those of comprehensive neck dissection, especially when SND is combined with adjuvant radiotherapy.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias Laríngeas/cirurgia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical/métodos , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Resultado do TratamentoRESUMO
Diuron and Irgarol are common antifouling biocides used in paints to prevent the attachment and growth of fouling organisms on ship hulls and other submerged structures. Concerns about their toxicity to non-target aquatic organisms have led to various restrictions on their use in antifouling paints worldwide. Previous studies have shown the widespread presence of these substances in port areas along the Brazilian coast, with a concentration primarily in the southern part of the country. In this study, we conducted six sampling campaigns over the course of 1 year to assess the presence and associated risks of Diuron and Irgarol in water collected from areas under the influence of the Maranhão Port Complex in the Brazilian Northeast. Our results revealed the absence of Irgarol in the study area, irrespective of the sampling season and site. In contrast, the mean concentrations of Diuron varied between 2.0 ng L-1 and 34.1 ng L-1 and were detected at least once at each sampling site. We conducted a risk assessment of Diuron levels in this area using the risk quotient (RQ) method. Our findings indicated that Diuron levels at all sampling sites during at least one campaign yielded an RQ greater than 1, with a maximum of 22.7, classifying the risk as "high" based on the proposed risk classification. This study underscores the continued concern regarding the presence of antifouling biocides in significant ports and marinas in Brazilian ports, despite international bans.
Assuntos
Incrustação Biológica , Desinfetantes , Poluentes Químicos da Água , Diurona/análise , Desinfetantes/análise , Brasil , Estuários , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Triazinas/análiseRESUMO
We investigated the occurrence and the environmental risk of eight contaminants of emerging concern (CECs; acetaminophen, naproxen, diclofenac, methylparaben, 17ß-estradiol, sulfathiazole, sulfadimethoxine, and sulfamethazine) in three Brazilian water bodies, namely, the Monjolinho River Basin (São Paulo State), the Mogi Guaçu River (São Paulo State), and the Itapecuru River (Maranhão State) in three sampling campaigns. The CECs were only quantified in surface water samples collected at the Monjolinho River Basin. Acetaminophen, naproxen, and methylparaben were detected in the range of <200 to 575.9 ng L-1, <200 to 224.7 ng L-1, and <200 to 303.6 ng L-1, respectively. The detection frequencies of the three measured compounds were between 33% and 67%. The highest concentrations of CECs were associated with intense urbanization and untreated sewage discharge. Furthermore, CEC concentrations were significantly correlated with total organic carbon, electrical conductivity, and dissolved oxygen levels, suggesting that domestic pollution from urban areas is an important source in the distribution of CECs in the Monjolinho River Basin. The environmental risk assessment indicated a high risk for acetaminophen (risk quotient [RQ] values between 2.1 and 5.8), a medium risk for naproxen (RQs between 0.6 and 0.7), and a low risk for methylparaben (RQs < 0.1) to the freshwater biota of the Monjolinho River Basin. Our findings show potential threats of CECs in Brazilian water bodies, especially in vulnerable areas, and reinforce the need for improvements in environmental regulations to include monitoring and control of these compounds in aquatic systems. Environ Toxicol Chem 2024;00:1-12. © 2024 SETAC.
RESUMO
Antifouling biocides, such as irgarol and diuron, are commonly used in antifouling paints. Recently, studies carried out in a Brazilian region of ecological concern have warned for extremely high levels of these biocides. So, this work focused on a 4-year (2015-2018) evaluation considering the occurrence, environmental fate, seasonal variations and ecological risk assessment of irgarol and diuron in water and sediment from São Marcos Bay, Brazil, which is an area of international relevance located in the Amazon region. The results showed the ubiquitous presence of antifouling biocides, as well as their wide distribution along the bay. The concentration range of irgarol was between <0.8 and 89.4 ng L-1 in water and between <0.5 and 9.2 ng g-1dw in sediments, whereas diuron showed a range between <1.4 and 22.0 ng L-1 in water and between <2.0 and 15.0 ng g-1dw in sediments. The distribution of the biocides was mainly related to the intense Bay hydrodynamics. The environmental risk assessment showed that irgarol and diuron posed "high risk" to the aquatic biota of São Marcos Bay, exceeding international Environmental Quality Guidelines. The results represent a robust study on the environmental fate of such biocides and intend to be a useful data source for eventual legislation since regulation concerning antifouling substances is necessary for Brazil.
Assuntos
Desinfetantes/análise , Brasil , Diurona , Monitoramento Ambiental , Medição de Risco , Triazinas , Poluentes Químicos da ÁguaRESUMO
Despite the fact that the occurrence of emerging contaminants in the environment has become frequent in recent decades, the seasonal dynamics of contaminants in different environmental compartments are little studied in protected areas influenced by effluent discharges. In this study, the seasonal and spatial occurrence of 33 pharmaceuticals and personal care products (PPCPs) was investigated in surface waters and sediments from Anil and Bacanga rivers (northeast of Brazil). The studied area is located within a Wetland of International Importance by Ramsar Convention (Amazon Estuary and its Mangroves). Sample preparation was carried out using solid-phase extraction and QuEChERS, for water and sediment samples, respectively and all determinations were performed by liquid chromatography tandem mass spectrometry. Eleven PPCPs were detected in water samples and 14 in sediments. In aqueous samples, caffeine was the most occurring compound reaching 13,798 ng L-1. In addition, high levels of acetaminophen, ibuprofen, sulfamethoxazole, carbamazepine and diclofenac were also observed. In the sediment samples, triclocarban, benzophenone-3, ketoconazole and methylparaben were also detected. The spatial and temporal distribution of the assessed molecules indicates urbanization and anthropic activities as relevant sources of PPCPs in the region. Moreover, the levels of acetaminophen, caffeine, diclofenac, ibuprofen, benzophenone-3, triclosan and triclocarban measured within the Ramsar site pose a high risk to aquatic and terrestrial organisms. These findings indicate potential threats to the allegedly protected biodiversity and, therefore, urgent actions are needed to effectively protect this unique and vulnerable area.
Assuntos
Cosméticos , Áreas Alagadas , Brasil , Monitoramento Ambiental , Preparações Farmacêuticas , Medição de Risco , Poluentes Químicos da ÁguaRESUMO
Fouling organisms attach and grow on submerged surfaces causing several economic losses. Thus, biocides have been introduced in antifouling paints in order to avoid this phenomenon, but their widespread use became a global problem, mainly in ports, leisure and fishing boat harbors, since these substances can be highly toxic to non-target organisms. The occurrence and environmental behavior of antifouling biocides are especially unknown in some peculiar regions, such as Amazon areas. Thus, the aim of this work was to evaluate, for the first time, levels and the partitioning behavior of the antifouling organic biocides irgarol, diuron and also stable degradation products of dichlofluanid and diuron (DMSA and DCPMU, respectively) in sediments and porewaters from a high boat traffic area located in the Northeast of Brazil, a pre-Amazon region. Our results showed high concentrations of irgarol (<1.0-89.7⯵gâ¯kg-1) and diuron (<5.0-55.2⯵gâ¯kg-1) in sediments. In porewater, DCPMU (<0.03-0.67⯵gâ¯L-1) and DMSA (<0.008-0.263⯵gâ¯L-1) were the mainly substances detected. High Kd and Koc obtained for both irgarol and diuron showed a partitioning preference in the solid phase. This work represents one of the few registers of contamination by antifouling substances in Amazonian areas, despite their environmental relevance.
Assuntos
Desinfetantes/análise , Monitoramento Ambiental/métodos , Sedimentos Geológicos/química , Água do Mar/química , Poluentes Químicos da Água/análise , Compostos de Anilina/análise , Brasil , Diurona/análise , Pintura/análise , Navios , Triazinas/análiseRESUMO
BACKGROUND: Cigarette smoke has been identified as the main cause of oral cavity carcinoma. Recently, the electronic cigarette, a battery-operated device, was developed to help smokers stop their tobacco addiction. This study aimed to evaluate the safety of electronic cigarettes and to establish the possible role of such device in the primary prevention of oral cavity cancer. SUBJECTS AND METHODS: This study included 65 subjects who were divided into three groups (smokers, e-cigarette smokers, and nonsmokers). All subjects were submitted to cytologic examination by scraping of oral mucosa. The slides were microscopically evaluated through a micronucleus assay test. RESULTS: The prevalence of micronuclei was significantly decreased in the e-cigarette smoker group. There were no statistically significant differences in micronuclei distribution according to the type of cigarette, gender, and age. CONCLUSIONS: The use of electronic cigarettes seems to be safe for oral cells and should be suggested as an aid to smoking cessation.
RESUMO
Glyphosate, the active ingredient in Monsanto's broad-spectrum herbicide Roundup, consists of one of the most used pesticides worldwide, but its effects on the marine flora are still not well understood. Were examined Roundup toxic effects on Ruppia maritima specimens collected from Jansen Lagoon (São Luís, MA, Brazil) and acclimatized under laboratory conditions. The numbers of new and dead leaves, the root and leaf length, the chlorophyll a content, and the weight of R. maritima branches were determined before and after exposure to different Roundup concentrations for seven days. High concentrations caused a significant lethal effect. In addition, significant changes were observed in the wet and dry weights, the number and length of the leaves, and the chlorophyll a content. Leaf elongation was observed in the branches exposed to low concentrations, and this change was likely activated as a compensatory mechanism. The results indicate that high concentrations of this herbicide may compromise estuarine flora.
Assuntos
Alismatales/efeitos dos fármacos , Glicina/análogos & derivados , Herbicidas/toxicidade , Alismatales/fisiologia , Organismos Aquáticos/efeitos dos fármacos , Brasil , Clorofila/metabolismo , Clorofila A , Glicina/toxicidade , Folhas de Planta/efeitos dos fármacos , Testes de Toxicidade/métodos , GlifosatoAssuntos
Procedimentos Cirúrgicos Ambulatórios , Hiperidrose/cirurgia , Dor Pós-Operatória/prevenção & controle , Simpatectomia/métodos , Cirurgia Torácica Vídeoassistida , Adulto , Analgesia/métodos , Feminino , Humanos , Masculino , Pneumotórax/etiologia , Simpatectomia/efeitos adversos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Lingual thyroid represents 90% of ectopic thyroid tissue localizations. The first case was described by Hickman in 1869. An ectopic thyroid is often asymptomatic, but pathological or physiological conditions inducing hyperproduction of thyroid-stimulating hormone can lead an ectopic thyroid to become symptomatic. Treatment of the symptomatic ectopic thyroid can be medical, with hormone-suppressing therapy, or surgical. CASE PRESENTATION: A 17-year-old female presented to our outpatient clinic complaining of a sensation of a lump in her throat. Ear, nose, and throat (ENT) examination identified a swelling of the base of the tongue in the glossoepiglottic area. Thyroid scintigraphy showed a single contrast enhancement in the sublingual region, instead of in the normal anatomical position of the thyroid. She was treated surgically after failed hormone-suppressing therapy. An arteriography performed before the surgery showed vascular anomalies and was useful in surgical planning. CONCLUSION: Recognition of vascular anomalies in an ectopic thyroid is fundamental before surgical planning, therefore, accurate radiological study of the vasculature should always be planned before surgical treatment of this disease.
RESUMO
BACKGROUND: Supracricoid laryngectomy is an organ preservation surgical technique for early-stage glottic tumors. Modified supracricoid laryngectomy using sternohyoid muscles for neoglottis reconstruction is a new surgical technique. This report evaluates oncological and functional outcomes of this new technique and its feasibility in elderly patients. METHODS: Clinical records from 21 consecutive patients affected by glottic cancer and treated by modified SCL between 2004 and 2009 were retrospectively reviewed. Postoperative parameters and quality of voice after modified SCL were retrospectively reviewed. Actuarial overall survival, disease-specific survival rates, and recurrence-free survival rates were assessed. The functional and oncological outcomes of patients over 65 years were compared with those of patients younger than 65 years of age. RESULTS: There were no postoperative complications and all of the patients had complete swallowing rehabilitation. Twenty of the 21 patients had decannulation. Two patients received total laryngectomy for locoregional relapse. Overall survival and disease-specific survival rates were 100%. Recurrence-free survival rates were 90.1% and 90% in patients younger and older than 65 years of age, respectively. The larynx preservation index was lower in patients who were older than 65 years of age. The postoperative courses with regard to functional outcome and voice quality in elderly patients were similar to those of patients younger than 65 years of age. CONCLUSION: Modified SCL is a new open organ preservation surgical technique that is oncologically safe. The positive functional and oncological outcomes of this surgical procedure allow it to be performed in elderly patients.
Assuntos
Neoplasias Laríngeas/cirurgia , Laringectomia/métodos , Adulto , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Laringectomia/efeitos adversos , Laringectomia/estatística & dados numéricos , Masculino , Recidiva Local de Neoplasia , Estudos RetrospectivosRESUMO
The purposes of this study were to detect S. mutans and S. sobrinus by polymerase chain reaction (PCR) amplification, and to relate their presence to the incidence of dental caries in 42 Brazilian preschool children. Dental plaque samples were collected from the cervical margin of all erupted teeth of 5-6 years old children with primary dentition, using a sterile explorer. Examination of the dmft (decayed, missing, filled teeth) index, performed following the World Health Organization (WHO) caries diagnostic criteria, showed a 2.71 score. Prevalence of S. mutans and S. sobrinus was respectively, of 85.7% and 14.3%; no dental plaque sample was either positive or negative for both bacterial species. Children harboring either S. mutans or S. sobrinus presented the same caries prevalence. PCR showed good discriminative ability for differentiation between these species, and suggested that it is a technique suitable for epidemiological studies on mutans streptococci.
Assuntos
Placa Dentária/microbiologia , Reação em Cadeia da Polimerase , Streptococcus mutans/isolamento & purificação , Streptococcus sobrinus/isolamento & purificação , Brasil , Criança , Pré-Escolar , Contagem de Colônia Microbiana , Índice CPO , DNA Bacteriano/análise , Feminino , Humanos , Masculino , Fatores Sexuais , Streptococcus mutans/genética , Streptococcus sobrinus/genética , Colo do Dente/microbiologia , Dente Decíduo/microbiologiaRESUMO
Se modificó la técnica de Perls para disponer de un medio que pudiera revelar la presencia del pigmento férrico y poder utilizarlo en el diagnóstico histopatológico; para ello se elevó a 58 grados centígrados la temperatura en los reactivos, lo cual no se hace en el procedimiento habitual, y el citado pigmento se tiñó de verde o azul, de manera que fue posible identificarlo en los núcleos grises de la base en un paciente con síndrome de Hallervordem - Spatz, que falleció en esta institución.
The technique of Perls was modified to have a mean that could reveal the presence of the ferric pigment and to be able to use it in the histopathological diagnosis; for this purpose the temperature was rised to 58º centigrades in the reagents, which is not done in the habitual procedure, and the mentioned pigment was stained of green or blue, so that it was possible to identify it in the gray nuclei of the base in a patient with syndrome of Hallervordem - Spatz, who died in this institution.
Assuntos
Humanos , Masculino , Adolescente , Técnicas e Procedimentos Diagnósticos , Serviço Hospitalar de Patologia , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/sangue , Distúrbios do Metabolismo do Ferro/diagnóstico , Distúrbios do Metabolismo do Ferro/sangueRESUMO
The purposes of this study were to detect S. mutans and S. sobrinus by polymerase chain reaction (PCR) amplification, and to relate their presence to the incidence of dental caries in 42 Brazilian preschool children. Dental plaque samples were collected from the cervical margin of all erupted teeth of 5-6 years old children with primary dentition, using a sterile explorer. Examination of the dmft (decayed, missing, filled teeth) index, performed following the World Health Organization (WHO) caries diagnostic criteria, showed a 2.71 score. Prevalence of S. mutans and S. sobrinus was respectively, of 85.7 percent and 14.3 percent; no dental plaque sample was either positive or negative for both bacterial species. Children harboring either S. mutans or S. sobrinus presented the same caries prevalence. PCR showed good discriminative ability for differentiation between these species, and suggested that it is a technique suitable for epidemiological studies on mutans streptococci.
A presença de Streptococcus mutans e S. sobrinus, detectadas através da técnica da reação em cadeia da polimerase (PCR) foi comparada com a incidência de cárie dental em 42 crianças pré-escolares brasileiras. As amostras da placa dental foram obtidas utilizando-se um explorador estéril, o qual foi passado na margem cervical de todos os dentes erupcionados nas crianças de 5-6 anos de idade, as quais possuíam a dentição primária. Foi realizado um exame dental para a avaliação do índice ceod (índice de dentes decíduos cariados, extraídos por cárie ou obturados) de acordo com os critérios de diagnóstico de cárie preconizados pela Organização Mundial de Saúde (OMS). O índice ceod foi de 2,71. A presença de S. mutans e S. sobrinus foi detectada em 85,7 por cento e 14,3 por cento das crianças analisadas respectivamente, nenhuma amostra da placa dental foi positiva ou negativa para a presença das duas bactérias ao mesmo tempo. As crianças que apresentavam S. mutans ou S. sobrinus isoladamente apresentaram o mesmo índice de cárie. A técnica de PCR apresentou um grande poder discriminatório entre as duas espécies o que sugere que ela é adequada para estudos epidemiológicos no grupo mutans.