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Given the increased extraction of trace elements for use by new and emerging technologies, monitoring the environmental fate and potential effects of these compounds within the aquatic environment has never been more critical. Here, hepatic trace element concentrations were assessed in a key sentinel predator, the common dolphin (Delphinus delphis), using a long-term dataset. Variation in concentrations were assessed in relation to other elements, time period, decomposition state, sex, age, total body length, sexual maturity and nutritional status, and cause of death. Additionally, mercury toxicity thresholds for evaluating risk were reviewed and employed. Concentrations of elements which bioaccumulate, THg, MeHg, Cd, and Pb, in addition to Se and V, were strongly correlated with age, and/or body length. An association was observed between Zn concentrations and disease status, with significantly higher concentrations measured in individuals that died from infectious disease, compared to other causes. Strong inter-elemental relationships were detected, namely between Hg and Se, MeHg and Se, Cd and Se, and Cu and Zn. While THg:Se molar ratio values were observed to increase with age and body length, approaching equimolarity. THg was largely comprised of inorganic Hg in older individuals, potentially bound to Se, therefore the effects from THg toxicity may possibly be less important than originally assumed. In contrast, higher MeHg:Hg ratio values were reported in juveniles, suggesting a poorer efficiency in demethylation and a higher sensitivity. The generation of data on proportions of hepatic MeHg and inorganic Hg is highly informative to both future toxicity threshold assessments within pollutant indicator assessments, and to understanding the ultimate fate of mercury in the marine web.
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Fenótipo , RNA Polimerase III , Humanos , RNA Polimerase III/genética , RNA Polimerase III/imunologia , Masculino , Feminino , MutaçãoRESUMO
RFC1 disease, caused by biallelic repeat expansion in RFC1, is clinically heterogeneous in terms of age of onset, disease progression and phenotype. We investigated the role of the repeat size in influencing clinical variables in RFC1 disease. We also assessed the presence and role of meiotic and somatic instability of the repeat. In this study, we identified 553 patients carrying biallelic RFC1 expansions and measured the repeat expansion size in 392 cases. Pearson's coefficient was calculated to assess the correlation between the repeat size and age at disease onset. A Cox model with robust cluster standard errors was adopted to describe the effect of repeat size on age at disease onset, on age at onset of each individual symptoms, and on disease progression. A quasi-Poisson regression model was used to analyse the relationship between phenotype and repeat size. We performed multivariate linear regression to assess the association of the repeat size with the degree of cerebellar atrophy. Meiotic stability was assessed by Southern blotting on first-degree relatives of 27 probands. Finally, somatic instability was investigated by optical genome mapping on cerebellar and frontal cortex and unaffected peripheral tissue from four post-mortem cases. A larger repeat size of both smaller and larger allele was associated with an earlier age at neurological onset [smaller allele hazard ratio (HR) = 2.06, P < 0.001; larger allele HR = 1.53, P < 0.001] and with a higher hazard of developing disabling symptoms, such as dysarthria or dysphagia (smaller allele HR = 3.40, P < 0.001; larger allele HR = 1.71, P = 0.002) or loss of independent walking (smaller allele HR = 2.78, P < 0.001; larger allele HR = 1.60; P < 0.001) earlier in disease course. Patients with more complex phenotypes carried larger expansions [smaller allele: complex neuropathy rate ratio (RR) = 1.30, P = 0.003; cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) RR = 1.34, P < 0.001; larger allele: complex neuropathy RR = 1.33, P = 0.008; CANVAS RR = 1.31, P = 0.009]. Furthermore, larger repeat expansions in the smaller allele were associated with more pronounced cerebellar vermis atrophy (lobules I-V ß = -1.06, P < 0.001; lobules VI-VII ß = -0.34, P = 0.005). The repeat did not show significant instability during vertical transmission and across different tissues and brain regions. RFC1 repeat size, particularly of the smaller allele, is one of the determinants of variability in RFC1 disease and represents a key prognostic factor to predict disease onset, phenotype and severity. Assessing the repeat size is warranted as part of the diagnostic test for RFC1 expansion.
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Idade de Início , Proteína de Replicação C , Humanos , Masculino , Feminino , Proteína de Replicação C/genética , Adulto , Expansão das Repetições de DNA/genética , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Criança , Fenótipo , Índice de Gravidade de Doença , Pré-Escolar , Progressão da DoençaRESUMO
Introduction The introduction of the CyberKnife® system has marked a significant advancement in the field of radiosurgery, offering unparalleled precision in targeting and treating cranial and extracranial lesions. This paper details the first experience from the United Arab Emirates in implementing 6D skull tracking and intrafractional motion monitoring in CyberKnife® radiosurgery. The study aims to evaluate the system's efficacy in tracking and adjusting patient movement during treatment, enhancing treatment accuracy and patient safety. Methods and materials This retrospective study analyzed 732 images from six patients treated at the UAE's first CyberKnife® center. Patients were divided into two groups based on their treatment regimens: Patients 1 to 4 (P1 to P4) received multifractionated stereotactic radiotherapy, while Patients 5 and 6 (P5 and P6) underwent single-fraction stereotactic radiosurgery (SRS). The movements recorded included supero-inferior, lateral, antero-posterior, roll, pitch, and yaw. Statistical tools were employed to interpret the data, including heat maps, box-and-whisker plots, and correlation analysis. Results The study's results indicate varied patterns of intrafractional movement across the different axes and between the two treatment groups. Multifractionated therapy patients exhibited a specific range and frequency of movements compared to those undergoing single-fraction treatment. The most significant movements were observed in the supero-inferior and lateral axes. Discussion The findings suggest that the CyberKnife® system's real-time tracking and adaptive capabilities are crucial in managing patient movements, especially in prolonged treatment sessions. The differences in movement patterns between multifractionated and single-fraction treatments underscore the need for tailored approaches in intrafractional motion monitoring. Conclusion The initial experience of the UAE's first CyberKnife® center demonstrates the system's effectiveness in addressing intrafractional movements, enhancing the precision and safety of radiosurgery treatments. This study contributes valuable insights into optimizing treatment protocols and underscores the importance of continuous monitoring and adaptive strategies in advanced radiosurgery.
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BACKGROUND AND PURPOSE: Tay-Sachs disease is a rare and often fatal, autosomal recessive, lysosomal storage disease. Deficiency in ß-hexosaminidase leads to accumulation of GM2 ganglioside resulting in neuronal swelling and degeneration. Typical onset is in infancy with developmental regression and early death. Late-onset Tay-Sachs disease (LOTS) is extremely rare, especially in the non-Ashkenazi Jewish population, and is characterized by a more indolent presentation typically encompassing features of cerebellar and anterior horn cell dysfunction in addition to extrapyramidal and neuropsychiatric symptoms. CASES: A case series of four unrelated patients of non-Ashkenazi Jewish origin with a predominantly, and in some cases pure, neuromuscular phenotype with evidence of a motor neuronopathy on electromyography is presented. Cerebellar atrophy, reported to be a ubiquitous feature in LOTS, was absent in all patients. CONCLUSION: This case series provides evidence to support a pure neuromuscular phenotype in LOTS, which should be considered in the differential diagnosis of anterior horn cell disorders.