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INTRODUCTION: Hereditary transthyretin amyloidosis (ATTRv) is a severe autosomal dominant systemic disease. It affects the peripheral and autonomic nervous systems, heart, kidneys, and eyes. Amyloid deposition has been demonstrated in the glomerular and tubulointerstitial compartments of the kidney. Therefore, urinary acidification disorders such as renal tubular acidosis (RTA) may be early manifestations of renal involvement in this population. OBJECTIVE: To evaluate the prevalence of RTA in individuals with ATTRv. METHODS: We included symptomatic and asymptomatic individuals with TTR mutation, older than 18 years, GFR >45 mL/min/1.73m2, without systemic metabolic acidosis. Urinary acidification protocol was performed with furosemide and fludrocortisone after 12 h of water deprivation (water deprivation test - WDT) and measurements of urine ammonium ( UNH 4 + ) and titratable acidity (UTA). Proximal RTA (pRTA) was diagnosed when FEHCO3>10%. Incomplete form distal RTA (dRTA) was diagnosed if UpH>5.3. RESULTS: We selected 49 individuals with a mean age of 40 (35.5-56.5) years, 63% of which were female, 84% were Caucasian, and mean GFR was 85.5 ± 20.5 mL/min/1.73m2. 94% had the genetic variant Val50Met and 57% were symptomatic. The prevalence of pRTA was 2% and of dRTA was 16.3%. In the subgroup with dRTA, there was no significant increase in excretion of UNH 4 + and UTA. We observed a good correlation between UpH by potentiometry and UpH dipstick. A UpH<5.5 on the dipstick had 100% sensitivity and negative predictive value to exclude dRTA. CONCLUSION: A high prevalence of RTA was found in individuals with TTR mutations. The UpH dipstick after WDT had good accuracy for screening for dRTA. Further studies are needed to evaluate the impact of early diagnosis and treatment of RTA in this population.
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Acidose Tubular Renal , Neuropatias Amiloides Familiares , Humanos , Feminino , Masculino , Neuropatias Amiloides Familiares/complicações , Neuropatias Amiloides Familiares/genética , Neuropatias Amiloides Familiares/diagnóstico , Neuropatias Amiloides Familiares/epidemiologia , Pessoa de Meia-Idade , Adulto , Acidose Tubular Renal/genética , Acidose Tubular Renal/diagnóstico , Acidose Tubular Renal/epidemiologia , Acidose Tubular Renal/complicações , Prevalência , Estudos Transversais , MutaçãoRESUMO
The mechanisms underlying regeneration of the central nervous system (CNS) following lesions have been studied extensively in both vertebrate and invertebrate models. To shed light on regeneration, ascidians, a sister group of vertebrates and with remarkable ability to regenerate their brains, constitute an appropriate model system. Glial cells have been implicated in regeneration in vertebrates; however, their role in the adult ascidian CNS regeneration is unknown. A model of degeneration and regeneration using the neurotoxin 3-acetylpyridine (3AP) in the brain of the ascidian Styela plicata was used to identify astrocyte-like cells and investigate their role. We studied the CNS of control ascidians (injected with artificial sea water) and of ascidians whose CNS was regenerating (1 and 10 days after the injection with 3AP). Our results show that the mRNA of the ortholog of glutamine synthetase (GS), a glial-cell marker in vertebrates, is increased during the early stages of regeneration. Confirming the identity of GS, the protein was identified via immunostaining in a cell population during the same regeneration stage. Last, a single ortholog of GS (GSII) is present in ascidian and amphioxus genomes, while two types exist in fungi, some invertebrates, and vertebrates, suggesting that ascidians have lost the GSI type. Taken together, our findings revealed that a cell population expressing glial-cell markers may play a role in regeneration in adult ascidians. This is the first report of astrocyte-like cells in the adult ascidian CNS, and contributes to understanding of the evolution of glial cells among metazoans.
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The study evoluated an in-house Spike Receptor Binding Domain Enzyme-Linked Immunosorbent Assay (RBD-IgG-ELISA) for detecting SARS-CoV-2 IgG antibodies in infected and vaccinated individuals. The assay demonstrated a sensitivity of 91%, specificity of 99.25%, and accuracy of 95.13%. Precision and reproducibility were highly consistent. The RBD-IgG-ELISA was able to detect 96.25% of Polymerase chain reaction (PCR) confirmed cases for SARS-CoV-2 infection, demonstrating positive and negative predictive values of 99,18% and 91,69%, respectively. In an epidemiological survey, ELISA, lateral flow immunochromatographic assay (LFIA), and electrochemiluminescence immunoassay (ECLIA) exhibited diagnostic sensitivities of 68.29%, 63.41%, and 70.73%, respectively, along with specificities of 82.93%, 80.49%, and 80.49%, respectively. Agreement between RBD-IgG-ELISA/PCR was moderate (k index 0.512). However, good agreement between different assays (RBD-IgG-ELISA/LFIA k index 0.875, RBD-IgG-ELISA/ECLIA k index 0.901). Test performance on individuals' samples were inferior due to seroconversion time and chronicity. The IgG-RBD-ELISA assay demonstrated its effectiveness in monitoring antibody levels among healthcare professionals, revealing significant differences both before and after the administration of the third vaccine dose, with heightened protection levels observed following the third dose in five Coronavirus disease (COVID-19) vaccine regimens. In conclusion, the RBD-IgG-ELISA exhibits high reproducibility, specificity, and sensitivity, making it a suitable assay validated for serosurveillance and for obtaining information about COVID-19 infections or vaccinations.
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Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , Ensaio de Imunoadsorção Enzimática/métodos , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vacinas contra COVID-19/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Reprodutibilidade dos Testes , Pessoa de Meia-Idade , Masculino , Feminino , Adulto , Teste Sorológico para COVID-19/métodos , Sensibilidade e Especificidade , Idoso , Vacinação , Adulto JovemRESUMO
In an era of unprecedented industrial and agricultural growth, metal contamination in marine environments is a pressing concern. Sentinel organisms such as the mangrove oyster Crassostrea gasar provide valuable insights into these environments' health. However, a comprehensive understanding of the molecular mechanisms underlying their response to metal exposure remains elusive. To address this gap, we reanalyzed the 454-sequencing data of C. gasar, utilizing an array of bioinformatics workflow of CDTA (Combined De Novo Transcriptome Assembly) to generate a more representative assembly. In parallel, C. gasar individuals were exposed to two concentrations of zinc (850 and 4500 µg L-1 Zn) for 48 h to understand their molecular responses. We utilized Trinotate workflow for the 11,684-CDTA unigenes annotation, with most transcripts aligning with the genus Crassostrea. Our analysis indicated that 67.3% of transcript sequences showed homology with Pfam, while 51.4% and 54.5%, respectively had GO and KO terms annotated. We identified potential metal pollution biomarkers, focusing on metal-related genes, such as those related to the GSH biosynthesis (CHAC1 and GCLC-like), to zinc transporters (ZNT2-like), and metallothionein (MT-like). The evolutionary conservation of these genes within the Crassostrea genus was assessed through phylogenetic analysis. Further, these genes were evaluated by qPCR in the laboratory exposed oysters. All target genes exhibited significant upregulation upon exposure to Zn at both 850 and 4500 µg L-1, except for GCLC-like, which showed upregulation only at the higher concentration of 4500 µg L-1. This result suggests distinct activation thresholds and complex interactions among these genes in response to varying Zn concentrations. Our study provides insights into the molecular responses of C. gasar to Zn, adding valuable tools for monitoring metal pollution in marine ecosystems using the mangrove oyster as a sentinel organism.
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Crassostrea , Transcriptoma , Poluentes Químicos da Água , Zinco , Animais , Crassostrea/genética , Crassostrea/metabolismo , Zinco/metabolismo , Poluentes Químicos da Água/toxicidade , Biomarcadores/metabolismoRESUMO
BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv) is an inherited, progressive, and fatal disease still largely underdiagnosed. Mutations in the transthyretin (TTR) gene cause the TTR protein to destabilize, misfold, aggregate, and deposit in body tissues, which makes ATTRv a disease with heterogeneous clinical phenotype. OBJECTIVE: To describe the long-term efficacy and safety of inotersen therapy in patients with ATTRv peripheral neuropathy (ATTRv-PN). METHODS: Patients who completed the NEURO-TTR pivotal study and the NEURO-TTR OLE open-label extension study migrated to the present study and were followed-up for at least 18 more months to an average of 67 months and up to 76 months since day 1 of the inotersen therapy (D1-first dose of inotersen). Disease progression was evaluated by standard measures. RESULTS: Ten ATTRv-PN patients with Val30Met mutation were included. The mean disease duration on D1 was of 3 years, and the mean age of the patients was of 46.8 years. During an additional 18-month follow up, neurological function, based on the Neuropathy Impairment Score and the Polyneuropathy Disability Score, functionality aspects (Karnofsky Performance Status), and nutritional and cardiac aspects were maintained. No new safety signs have been noted. CONCLUSION: The treatment with inotersen was effective and well tolerated for the average of 67 months and up to 76 months. Our results are consistent with those of larger phase-III trials.
ANTECEDENTES: Amiloidose hereditária por transtirretina (ATTRv) é uma doença hereditária, progressiva e fatal ainda largamente subdiagnosticada. Mutações no gene transtirretina (TTR) promovem desestabilização, desdobramento, agregação e depósito da proteína TTR em tecidos do corpo, o que faz da ATTRv uma doença de fenótipo clínico heterogêneo. OBJETIVO: Descrever a eficácia e segurança da terapia com inotersena no longo prazo em pacientes com neuropatia periférica ATTRv (ATTRv-PN). MéTODOS: Pacientes que completaram o estudo pivotal NEURO-TTR e o estudo de extensão aberta NEURO-TTR OLE migraram para este estudo e foram acompanhados por no mínimo 18 meses adicionais, em média por 67 meses, e por até 76 meses, desde o dia 1 da terapia com inotersena (D1primeira dose de inotersena). A progressão da doença foi avaliada por medidas padronizadas. RESULTADOS: Dez pacientes com ATTRv-PN com mutação Val30Met foram incluídos. A duração média da doença no D1 era de 3 anos, e a média de idade dos pacientes era de 46,8 anos. Durante o período de acompanhamento adicional de 18 meses, a função neurológica, baseada no Neuropathy Impairment Score e no Polyneuropathy Disability Score, os aspectos de funcionalidade (Karnofsky Performance Status), nutricional e cardíacos estavam mantidos. Não se observou nenhum novo sinal de segurança. CONCLUSãO: O tratamento com inotersena foi eficaz e bem tolerado por 67 meses em média, e por até 76 meses. Nossos resultados são consistentes com os de estudos maiores de fase III.
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Neuropatias Amiloides Familiares , Polineuropatias , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Brasil , Oligonucleotídeos/uso terapêutico , Neuropatias Amiloides Familiares/tratamento farmacológico , Neuropatias Amiloides Familiares/genética , Polineuropatias/etiologiaRESUMO
Spontaneous rupture of the patellar (PTR) and quadriceps (QTR) tendon is infrequent. Systemic diseases such as diabetes mellitus, CKD, and secondary hyperparathyroidism (SHPT) are risk factors. The present cohort study aimed to evaluate risk factors associated with tendon rupture in hemodialysis (HD) patients with SHPT, as well as outcomes including surgical complications, re-ruptures, and fracture. Baseline clinical, laboratorial data, and radiographs were analyzed. Patients were followed up from March 2012 to March 2020. One-hundred thirty-one patients (≥18 yr of age, on HD ≥ 6 mo, with SHPT) were included. Incidence rates of PTR and QTR were 2.3 and 1.7/10000 HD patients/yr, respectively. The mean age of patients with tendon rupture was 44.0 ± 11.2 yr. These patients exhibited higher serum levels of phosphorus (6.3 ± 1.5 mg/dL vs 5.6 ± 1.1 mg/dL; P = .005), PTH (2025.7 ± 667.6 pg/mL vs 1728.4 ± 684.8 pg/mL; P = .035), and C-reactive-protein (35.4 ± 32.9 mg/dL vs 17 ± 24.5 mg/dL; P = .002) compared to the group without tendon rupture. The mean follow-up was 56.7 ± 27.1 mo. No patient required a new surgical approach or experienced re-rupture. Of all patients, 31% experienced hip fracture: 50% in the group with rupture (29.5 ± 17.4 mo after the tendon rupture) vs 26% without tendon rupture (P = .015). After adjustment, the hazard ratio for hip fracture was 2.87 (95% CI, 1.27-6.49; P = .012). Patients with SHPT and high levels of phosphorus, PTH, and inflammatory markers were at greater risk for tendon rupture. Surgical complication rates were low. However, results suggest that tendon rupture of knee extensor mechanism in HD patient with SHPT should be regarded as a "red flag" for future hip fracture.
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Coastal environments, such as those in the Santa Catarina State (SC, Brazil), are considered the primary receptors of anthropogenic pollutants. In this study, our objective was to evaluate the levels of emerging contaminants (ECs) and persistent organic pollutants (POPs) in indigenous Crassostrea gasar oysters from different regions of SC coast in the summer season (March 2022). Field collections were conducted in the São Francisco do Sul, Itajaí, Florianópolis and Laguna coastal zones. We analyzed the bioaccumulation levels of 75 compounds, including antibiotics (AB), endocrine disruptors (ED), non-steroidal anti-inflammatory drugs (NSAIDs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and pesticides. Furthermore, we assessed biomarker responses related to biotransformation, antioxidant defense, heat shock protection and oxidative damage in oysters' gills. Prevalence of ECs was observed in the central and southern regions, while the highest concentrations of POPs were detected in the central-northern regions of SC. Oysters exhibited an induction in biotransformation systems (cyp2au1 and cyp356a1, sult and GST activity) and antioxidant enzymes activities (SOD, CAT and GPx). Higher susceptibility to lipid peroxidation was observed in the animals from Florianópolis compared to other regions. Correlation analyses indicated possible associations between contaminants and environmental variables in the biomarker responses, serving as a warning related to climate change. Our results highlight the influence of anthropogenic activities on SC, serving as baseline of ECs and POPs levels in the coastal areas of Santa Catarina, indicating more critical zones for extensive monitoring, aiming to conserve coastal regions.
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Crassostrea , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Animais , Crassostrea/fisiologia , Brasil , Antioxidantes/análise , Biomarcadores/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodosRESUMO
The discharge of sanitary sewage into the bays of the Florianópolis Metropolitan Area (Southern Brazil), has led to the contamination of oyster farms. Consequently, linear alkylbenzenes (LABs) were quantified in the sediment, and the biochemical responses in gills and digestive gland of oysters from six farms were assessed. Our findings revealed elevated levels of LABs in the sediment of the Imaruim and Serraria farms. Additionally, alterations were observed in the antioxidant enzymes: catalase, glutathione peroxidase and superoxide dismutase in both oyster tissue from the Serraria, Santo Antonio de Lisboa and Sambaqui farms. Furthermore, correlation analyses indicated strong and moderate associations between biochemical responses, organic contaminants, and certain physicochemical parameters. Consequently, our results demonstrated the activation of the antioxidant system in oysters, representing a protective response to the presence of sanitary sewage and other contaminants. Therefore, we propose the utilization of biochemical biomarkers for monitoring the environmental quality of farms.
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Crassostrea , Poluentes Químicos da Água , Animais , Antioxidantes/análise , Esgotos/análise , Poluentes Químicos da Água/análise , Aquicultura , Monitoramento Ambiental/métodosRESUMO
The study aimed to obtain environmentally relevant microfibers (MFs) from polyester fabric and assess their impact on the oyster Crassostrea gasar. MFs were obtained by grinding the fabric, and their accumulation in oysters gills and digestive glands was analyzed after exposure to 0.5 mg/L for 2 and 24 h. Additionally, a 48 h depuration was conducted on the oysters exposed for 24 h. Sublethal effects were assessed in oysters exposed for 24 h and depurated for 48 h, using biomarkers like Catalase (CAT), Glutathione S-transferase (GST), and Glutathione Peroxidase (GPx), along with histological analyses. Polyester fabric grinding produced significant MFs (average length: 570 µm) with degraded surface and increased malleability. Oysters showed increased MF accumulation in digestive glands post-exposure, with no impact on antioxidant enzymes. Depuration decreased MFs accumulation. Histological analysis revealed accumulation in the stomach and brown cells, possibly indicating inflammation. This raises concerns about MFs bioaccumulation in marine organisms, impacting the food chain and safety.
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Crassostrea , Poluentes Químicos da Água , Animais , Crassostrea/metabolismo , Poliésteres/metabolismo , Antioxidantes , Ingestão de Alimentos , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/metabolismoRESUMO
The production efficiency factor is widely used to measure the zootechnical performance of a batch of broilers. The unit cost of production brings new elements to improve efficiency evaluation and financial sustainability for this activity in agriculture. This research aims to evaluate the production efficiency level of the crop to maximize the return on investment. This study uses Data Envelopment Analysis (DEA) with the computational processing of the SIAD software (Integrated Decision Support System). The variables selected were poultry housing, age at slaughter, feed consumed, mortality, and unit cost. The chosen output variable was the total available weight. The analysis spans 31 decision-making units (DMUs) composed of integrated producers, unveiling a frontier of efficiency delineated by the most exemplary DMUs. Notably, only two DMUs, specifically DMU 4 and DMU 23, approached the threshold of maximum relative efficiency. This research illuminates the critical role of unit cost in enhancing the assessment of production efficiency and financial sustainability within the agriculture environment. By setting benchmarks for efficient management and operational protocols, our findings serve as a cornerstone for improving practices among less efficient DMUs, contributing significantly to the literature on agricultural efficiency and offering actionable insights for the poultry farming sector.
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This study aimed to carry out a general diagnosis of the contamination of the coastal marine environment of the Santa Catarina state (SC, Brazil) by different classes of environmental pollutants, as well as to evaluate possible adverse effects of the contaminants on biochemical biomarkers of oysters, Crassostrea gasar and Crassostrea rhizophorae. 107 chemicals were evaluated in water, sediment and oyster samples from nine sites along the coastline of SC. We also examined various biochemical biomarkers in the oysters' gills and digestive glands to assess potential effects of contaminants. In general, the northern and central regions of the littoral of SC presented higher occurrences and magnitudes of contaminants than the southern region, which is probably related to higher urbanization of center and northern areas of the littoral. The biomarker analysis in the oysters reflected these contamination patterns, with more significant alterations observed in regions with higher levels of pollutants. Our results may serve as a first baseline for future and more extensive monitoring actions and follow-up of the degree of contamination in the state, allowing for inspection actions and management of areas most affected by marine pollutants.
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Crassostrea , Poluentes Ambientais , Poluentes Químicos da Água , Animais , Brasil , Biomarcadores , Brânquias , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodosRESUMO
Abstract Background Hereditary transthyretin amyloidosis (ATTRv) is an inherited, progressive, and fatal disease still largely underdiagnosed. Mutations in the transthyretin (TTR) gene cause the TTR protein to destabilize, misfold, aggregate, and deposit in body tissues, which makes ATTRv a disease with heterogeneous clinical phenotype. Objective To describe the long-term efficacy and safety of inotersen therapy in patients with ATTRv peripheral neuropathy (ATTRv-PN). Methods Patients who completed the NEURO-TTR pivotal study and the NEURO-TTR OLE open-label extension study migrated to the present study and were followed-up for at least 18 more months to an average of 67 months and up to 76 months since day 1 of the inotersen therapy (D1-first dose of inotersen). Disease progression was evaluated by standard measures. Results Ten ATTRv-PN patients with Val30Met mutation were included. The mean disease duration on D1 was of 3 years, and the mean age of the patients was of 46.8 years. During an additional 18-month follow up, neurological function, based on the Neuropathy Impairment Score and the Polyneuropathy Disability Score, functionality aspects (Karnofsky Performance Status), and nutritional and cardiac aspects were maintained. No new safety signs have been noted. Conclusion The treatment with inotersen was effective and well tolerated for the average of 67 months and up to 76 months. Our results are consistent with those of larger phase-III trials.
Resumo Antecedentes Amiloidose hereditária por transtirretina (ATTRv) é uma doença hereditária, progressiva e fatal ainda largamente subdiagnosticada. Mutações no gene transtirretina (TTR) promovem desestabilização, desdobramento, agregação e depósito da proteína TTR em tecidos do corpo, o que faz da ATTRv uma doença de fenótipo clínico heterogêneo. Objetivo Descrever a eficácia e segurança da terapia com inotersena no longo prazo em pacientes com neuropatia periférica ATTRv (ATTRv-PN). Métodos Pacientes que completaram o estudo pivotal NEURO-TTR e o estudo de extensão aberta NEURO-TTR OLE migraram para este estudo e foram acompanhados por no mínimo 18 meses adicionais, em média por 67 meses, e por até 76 meses, desde o dia 1 da terapia com inotersena (D1-primeira dose de inotersena). A progressão da doença foi avaliada por medidas padronizadas. Resultados Dez pacientes com ATTRv-PN com mutação Val30Met foram incluídos. A duração média da doença no D1 era de 3 anos, e a média de idade dos pacientes era de 46,8 anos. Durante o período de acompanhamento adicional de 18 meses, a função neurológica, baseada no Neuropathy Impairment Score e no Polyneuropathy Disability Score, os aspectos de funcionalidade (Karnofsky Performance Status), nutricional e cardíacos estavam mantidos. Não se observou nenhum novo sinal de segurança. Conclusão O tratamento com inotersena foi eficaz e bem tolerado por 67 meses em média, e por até 76 meses. Nossos resultados são consistentes com os de estudos maiores de fase III.
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Abstract Introduction: Hereditary transthyretin amyloidosis (ATTRv) is a severe autosomal dominant systemic disease. It affects the peripheral and autonomic nervous systems, heart, kidneys, and eyes. Amyloid deposition has been demonstrated in the glomerular and tubulointerstitial compartments of the kidney. Therefore, urinary acidification disorders such as renal tubular acidosis (RTA) may be early manifestations of renal involvement in this population. Objective: To evaluate the prevalence of RTA in individuals with ATTRv. Methods: We included symptomatic and asymptomatic individuals with TTR mutation, older than 18 years, GFR >45 mL/min/1.73m2, without systemic metabolic acidosis. Urinary acidification protocol was performed with furosemide and fludrocortisone after 12 h of water deprivation (water deprivation test - WDT) and measurements of urine ammonium ( UNH 4 +) and titratable acidity (UTA). Proximal RTA (pRTA) was diagnosed when FEHCO3>10%. Incomplete form distal RTA (dRTA) was diagnosed if UpH>5.3. Results: We selected 49 individuals with a mean age of 40 (35.5-56.5) years, 63% of which were female, 84% were Caucasian, and mean GFR was 85.5 ± 20.5 mL/min/1.73m2. 94% had the genetic variant Val50Met and 57% were symptomatic. The prevalence of pRTA was 2% and of dRTA was 16.3%. In the subgroup with dRTA, there was no significant increase in excretion of UNH 4 + and UTA. We observed a good correlation between UpH by potentiometry and UpH dipstick. A UpH<5.5 on the dipstick had 100% sensitivity and negative predictive value to exclude dRTA. Conclusion: A high prevalence of RTA was found in individuals with TTR mutations. The UpH dipstick after WDT had good accuracy for screening for dRTA. Further studies are needed to evaluate the impact of early diagnosis and treatment of RTA in this population.
Resumo Introdução: A amiloidose hereditária por transtirretina (ATTRv) é uma doença sistêmica autossômica dominante grave. Afeta os sistemas nervoso periférico e autônomo, coração, rins e olhos. A deposição de amiloide foi demonstrada nos compartimentos glomerular e tubulointersticial do rim. Portanto, distúrbios de acidificação urinária, como acidose tubular renal (ATR), podem ser manifestações precoces de envolvimento renal nessa população. Objetivo: Avaliar a prevalência de ATR em indivíduos com ATTRv. Métodos: Incluímos indivíduos sintomáticos e assintomáticos com mutação na TTR, maiores de 18 anos, TFG >45 mL/min/1,73m2, sem acidose metabólica sistêmica. Realizou-se protocolo de acidificação urinária com furosemida e fludrocortisona após 12 horas de privação hídrica (teste de restrição hídrica - TRH) e medições de amônia urinária ( uNH 4 +) e acidez titulável (uTA) na urina. ATR proximal (ATRp) foi diagnosticada quando FEHCO3>10%. ATR distal (ATRd) de forma incompleta foi diagnosticada se pHu>5,3. Resultados: Selecionamos 49 indivíduos com idade média de 40 (35,5-56,5) anos, 63% mulheres, 84% caucasianos e TFG média de 85,5 ± 20,5 mL/min/1,73m2. 94% apresentaram a variante genética Val50Met; 57% eram sintomáticos. A prevalência de ATRp foi 2% e a de ATRd foi 16,3%. No subgrupo com ATRd, não houve aumento significativo na excreção de uNH 4 + e uTA. Observamos uma boa correlação entre pHU por potenciometria e pHU por fita reagente. Um pHU<5,5 na fita reagente apresentou 100% de sensibilidade e valor preditivo negativo para excluir a ATRd. ConclusÃO: Uma alta prevalência de ATR foi encontrada em indivíduos com mutações na TTR. O pHU por fita reagente após TRH teve boa precisão para triagem de ATRd. São necessários mais estudos para avaliar o impacto do diagnóstico e tratamento precoces da ATR nessa população.
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Objective: This study aimed to assess whether a music therapy (MT) intervention could improve memory decline in older adults with and without cognitive impairment. A dual-retrieval model of episodic memory was employed to estimate memory processes. Methods: Forty-three older adults with a mean age of 76.49 years (n = 25 with Alzheimer's disease (AD) and mixed dementia, and n = 18 healthy older adults) were randomly selected for the experimental and control groups. The study design was a double-blind randomized controlled clinical trial and a certified music therapist delivered the MT. The primary outcomes were measures of working memory, episodic memory, and autobiographical memory. Results: In the primary outcome measures, MT effects were restricted to episodic memory measures like the Figure Memory Test of the BCSB and the Speech and Sing Memory Test. In both tests, the experimental group improved from pre-test to post-test in delayed recall, but in the Speech and Sing Memory Test, the improvement was restricted to the AD and mixed dementia group. MT had no effects on the secondary outcome measures. Conclusions: These findings suggest that a structured MT intervention can be promising for rehabilitating episodic memory in older adults with dementia.
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PURPOSE: This cross-sectional study aimed to assess bone mineral density (BMD), bone microarchitecture and fracture prevalence in women with chronic postsurgical hypoparathyroidism (hypoPT). METHODS: Twenty-seven women with postsurgical hypoPT and 44 age-matched healthy women were included. Dual-energy X-ray absorptiometry was used to evaluate areal BMD and vertebral fracture assessment. High-resolution peripheral quantitative computed tomography assessed microarchitecture and volumetric BMD at the distal radius and tibia. Biochemical parameters, including fibroblast growth factor 23, C-terminal cross-linking telopeptide of type I collagen (ICTP), and procollagen type I N-terminal propeptide (P1NP), were also measured. Previous low-impact fractures were assessed and the 10-year fracture risk was estimated using the FRAX tool for the Brazilian population. RESULTS: No participant had prevalent clinical fractures, and both groups showed low risk for major and hip based on FRAX tool, but two hypoPT patients had moderate to severe morphometric vertebral fractures. Women with hypoPT had increased aBMD in the lumbar spine, femoral neck and total hip (p < 0.05) and higher cortical vBMD in the radius (p = 0.020) and tibia (p < 0.001). Trabecular bone was not affected. Both P1NP and ICTP suggested low bone turnover rates, but no significant correlation was observed between bone density or microstructure and any of the biochemical parameters. CONCLUSIONS: The prevalence of fragility fractures was low in HypoPT women and compatible with low fracture risk estimated by the FRAX tool. Patients had a higher aBMD and cortical vBMD than those of healthy control women, but the association with decreased bone turnover remains unclear.
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Fraturas Ósseas , Hipoparatireoidismo , Fraturas da Coluna Vertebral , Humanos , Feminino , Estudos Transversais , Densidade Óssea , Fraturas Ósseas/epidemiologia , Absorciometria de Fóton , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Tomografia Computadorizada por Raios X/métodos , Rádio (Anatomia)/diagnóstico por imagem , Hipoparatireoidismo/diagnóstico por imagem , Hipoparatireoidismo/epidemiologia , Osso CorticalRESUMO
Introduction: Rapamycin is an immunosuppressor that acts by inhibiting the serine/threonine kinase mechanistic target of rapamycin complex 1. Therapeutic use of rapamycin is limited by its adverse effects. Proteinuria is an important marker of kidney damage and a risk factor for kidney diseases progression and has been reported in patients and animal models treated with rapamycin. However, the mechanism underlying proteinuria induced by rapamycin is still an open matter. In this work, we investigated the effects of rapamycin on parameters of renal function and structure and on protein handling by proximal tubule epithelial cells (PTECs). Methods: Healthy BALB/c mice were treated with 1.5 mg/kg rapamycin by oral gavage for 1, 3, or 7 days. At the end of each treatment, the animals were kept in metabolic cages and renal function and structural parameters were analyzed. LLC-PK1 cell line was used as a model of PTECs to test specific effect of rapamycin. Results: Rapamycin treatment did not change parameters of glomerular structure and function. Conversely, there was a transient increase in 24-h proteinuria, urinary protein to creatinine ratio (UPCr), and albuminuria in the groups treated with rapamycin. In accordance with these findings, rapamycin treatment decreased albumin-fluorescein isothiocyanate uptake in the renal cortex. This effect was associated with reduced brush border expression and impaired subcellular distribution of megalin in PTECs. The effect of rapamycin seems to be specific for albumin endocytosis machinery because it did not modify renal sodium handling or (Na++K+)ATPase activity in BALB/c mice and in the LLC-PK1 cell line. A positive Pearson correlation was found between megalin expression and albumin uptake while an inverse correlation was shown between albumin uptake and UPCr or 24-h proteinuria. Despite its effect on albumin handling in PTECs, rapamycin treatment did not induce tubular injury measured by interstitial space and collagen deposition. Conclusion: These findings suggest that proteinuria induced by rapamycin could have a tubular rather than a glomerular origin. This effect involves a specific change in protein endocytosis machinery. Our results open new perspectives on understanding the undesired effect of proteinuria generated by rapamycin.
RESUMO
Personal care products, such as UV filters, are frequently present in aquatic ecosystems, but studies on their impact on marine organisms are still scarce. Here we addressed the effects of benzophenone-3 (BP-3) on the antioxidant status of Perna perna mussels exposed to concentrations of 0.1 and 3 µg.L-1 for 72 h and 7 days. Glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), glucose-6-phosphate dehydrogenase (G6PDH) activity and lipoperoxidation (MDA) were evaluated in the gills. A significant reduction (p < 0.05) in the activity of G6PDH and GPx was observed after exposure for 7 days to 0.1 µg.L-1. However, no significant differences were observed in GST activity and MDA levels, independently of the exposure time. Principal component analysis (PCA) showed an association of BP-3 highest concentration with GR and MDA at 72 h and only with GR at 7 days of exposure. Similarly, the integrated biomarker response (IBR) demonstrated GR and MDA alterations. In conclusion, environmentally relevant concentrations of BP-3 altered antioxidant and auxiliary enzymes, which could cause long-term damage to P.perna mussels. The need to implement more efficient techniques in wastewater treatment systems is pointed out, especially in summer, when UV filters are used more frequently and abundantly.
Assuntos
Perna (Organismo) , Poluentes Químicos da Água , Animais , Antioxidantes , Perna (Organismo)/fisiologia , Ecossistema , Catalase , Glutationa Transferase , Glutationa Redutase/farmacologia , Glutationa Peroxidase/farmacologia , Poluentes Químicos da Água/toxicidade , BiomarcadoresRESUMO
Tomato plants are sensitive to drought stress throughout their growth cycle. To be considered drought-tolerant, a cultivar should display tolerance at all developmental stages. This study aimed to evaluate whether Solanum pennellii introgression lines (ILs) previously selected as drought-tolerant during germination/seedling growth maintained this tolerance in the vegetative/reproductive stage. We then investigated these ILs to uncover candidate genes. The plants were subjected to two different environmental conditions: well-watered and drought-stressed (water withheld for ≤ 20 d after flowering). Phenotyping for morphological, physiological, fruit quality, and yield-related traits was performed, and the data was analyzed using a mixed-model approach. Using a multi-trait index that relies on factor analysis and genotype-ideotype distance (FAI-BLUP index), the genotypes were ordered based on how far they were from the drought-tolerant ideotype. Afterward, the tomato IL population map furnished by the SOL Genomics Network was utilized to identify introgressed segments of significance for the identification of candidate genes. Significant genotypic differences were found in the yield, water content, mean weight, length, and width of the fruit, the percentage of fruits displaying blossom-end rot, and titratable acidity. The drought-tolerance ideotype was built considering the maximum values for the fruit water content, number of fruits, mean fruit weight, and yield, minimum values for blossom-end rot, and mean values for titratable acidity. IL 1-4-18, IL 7-4-1, IL 7-1, IL 7-5-5, and IL 1-2 were ranked above M-82 and therefore considered drought-tolerant during the vegetative/reproductive stage. IL 1-4-18 and IL1-2 sustained drought tolerance displayed during germination/seedling growth into the vegetative/reproductive stage. The following candidate genes associated with drought tolerance were identified: AHG2, At1g55840, PRXIIF, SAP5, REF4-RELATED 1, PRXQ, CFS1, LCD, CCD1, and SCS. Because they are already associated with genetic markers, they can be transferred to elite tomato cultivars through marker-assisted technology after validation.
Assuntos
Solanum lycopersicum , Solanum , Solanum lycopersicum/genética , Solanum/genética , Resistência à Seca , Interleucina-7 , Secas , Água , Interleucina-1RESUMO
The mangrove oyster (Crassostrea gasar) is Brazil's second most cultured species and presents a high potential for aquaculture. However, artificial selection in a highly fecund species and significant variance in reproductive success can result in the loss of genetic diversity and increases the inbreeding rate, especially in cultivated populations. In this study, we investigated the genetic structure and diversity of C. gasar in wild and cultivated populations using 14 microsatellites. Spatial genetic comparisons revealed the existence of two main genetic groups of C. gasar, one comprising the population in cultivation and the other formed by wild populations along the southern and southeastern Brazilian coasts. Although no common genetic structure exists among wild populations, it is possible to observe a distribution gradient based on discriminant analysis of principal components consistent with their geographic distribution. However, it is insufficient to differentiate them genetically. Despite artificial reproduction, the genetic diversity values of the cultivated population remained relatively high and did not show a reduction. Therefore, monitoring the cultivated population and establishing reference values for genetic diversity will allow the adoption of strategies both for the viability of the cultivated population and the management of wild populations.
Assuntos
Crassostrea , Animais , Crassostrea/genética , Brasil/epidemiologia , Alimentos Marinhos , Aquicultura , Estruturas GenéticasRESUMO
BACKGROUND: The gubernacular canal (GC) is an important dental structure that enables the alveolar bone ridge cohesion of permanent teeth, although GC absence may indicate a dental eruption that might be associated with certain syndromes such as Down's syndrome. This study aims to correlate the eruptive delay of permanent teeth in individuals with Down's syndrome (Ds) and the gubernacular canal (GC) through cone-beam computed tomography (CBCT). METHODS AND RESULTS: This cross-sectional study was conducted between January and July 2022 with a total of 31 individuals (G1 = 16 nonsyndromic and G2 = 15 Down's syndrome) who went through imaging evaluation using CBCT with the following acquisition parameters: tube voltage of 95 kVp, tube current of 7 mA, exposure time of 5.9 s and voxel sizes and field of view 0.15 mm and 0.30 mm, respectively. The imaging evaluation was to assess whether all teeth analyzed had the presence of GC and/or teeth eruption disturbance, with a descriptive statistical analysis of relative frequencies and quantitative variables as well as the p-value (p < 0.005) by G Test. RESULTS: A total of 618 teeth among 31 individuals were analyzed, 475 (76.8%) GC were detected by CBCT in 23/31 patients and of these, 6 belonged to G2. G2 had a decreased GC detection rate (n = 180-37.9%) and the most common tooth with GC detected was the mandibular 1st molar (21 GC/25 teeth-84%) and the absence of GC was most frequently observed in impacted and delayed/unerupted teeth of Ds individuals. CONCLUSION: We concluded that GC absence was higher among Ds individuals, explaining the increased rates of unerupted or impacted teeth in Ds individuals.