Eficácia de intervenções imunomoduladoras para o tratamento da Esclerose Lateral Amiotrófica (ELA)

A esclerose lateral amiotrófica (ELA) é uma doença neurodegenerativa que afeta as células nervosas responsáveis pelo controle dos músculos voluntários, resultando em fraqueza muscular e atrofia. Nesse contexto, as intervenções imunomoduladoras têm como objetivo modular a resposta imune do organismo, ao reduzir a inflamação e possibilitar a neuroproteção, a partir do uso de anticorpos monoclonais, inibidores de citocinas e moduladores do sistema imunológico. No entanto, a eficácia de tais intervenções no tratamento da ELA ainda é incerta. Nesse sentido, o presente estudo tem como objetivo analisar a eficácia de intervenções imunomoduladoras para o tratamento da esclerose lateral amiotrófica. Para isso, foram selecionados cinco artigos que abordavam sobre a sua eficácia, por meio de uma estratégia de busca com recorte temporal entre 2017 e 2023, nas bases de dados PubMed (Medline), Cochrane Library e Embase. As intervenções imunomoduladoras, como o uso de inibidores de citocinas, têm demonstrado eficácia no tratamento da esclerose lateral amiotrófica (ELA). Além disso, há evidências de que a inflamação crônica pode estar envolvida em sua patogênese, o que sugere que a modulação do sistema imunológico pode ser uma abordagem terapêutica promissora. Em estudos clínicos recentes, a terapia com inibidores de citocinas mostrou-se capaz de reduzir a progressão da doença e melhorar a qualidade de vida dos pacientes com ELA. Ademais, há evidências que o uso de células-tronco pode melhorar o status funcional em pacientes com a doença. Entretanto, são necessários mais estudos, como ensaios clínicos randomizados e revisões sistemáticas com meta-análises, a fim de ratificar a eficácia das estratégias imunomoduladoras para a patologia

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Terapias voltadas para o tratamento do transtorno dissociativo de identidade

O transtorno dissociativo de identidade compreende uma condição psicológica complexa provavelmente causada por inúmeros fatores, envolvendo trauma grave na primeira infância, como abuso sexual, físico ou emocional repetitivo e extremo e repetitivo. Este estudo teve como objetivo identificar as terapias voltadas para o tratamento do transtorno dissociativo de identidade. Para isso, foi realizada uma revisão integrativa de literatura, selecionando fontes a partir das bases de dados Medline e Lilacs. A partir da análise qualitativa de dados, concluiu-se que há vários tipos de terapias para o tratamento de pessoas transtorno dissociativo de identidade, devendo essas serem aplicadas conforme cada realidade. Nos estudos, foram identificados os modelos de tratamento psicanalítico relacional, fásico, psicoativo e psicotraumatológico. Em todos esses, foram registrados resultados satisfatórios, tais como a diminuição na dissociação e o aumento do funcionamento adaptativo do paciente, revelando a possibilidade de desconstruir crenças solidamente cultivadas e trazendo esperança aos pacientes no sentido de amenizar ou superar esse transtorno e garantir uma boa interação social

Long-Lived Conformational Isomerism of Protein Dimers: The Role of the Free Energy of Subunit Association

The association of protein subunits to form N-mers (N ≥ 3) does not follow the dependence on the law of mass action predicted by the classical thermodynamic description used for the equilibrium of association of small molecules. For those anomalous cases, a so-called deterministic model has been previously proposed. The latter model was based on the empirical observation that the dynamics of subunit exchange between protein oligomers can be very slow, leading to the existence of long-lived conformational isomers and to a persistently heterogeneous ensemble of oligomers in solution. Contrary to the expectation for a protein dimer, we have recently shown that the subunit association of triosephosphate isomerase (TIM) could also be described as a deterministic process and that long-lived conformational isomers of TIM could be isolated in solution. Here we show that a), observation of hysteresis in pressure dissociation curves is an additional indicator of deterministic behavior; b), the extent of deviation from the classical thermodynamic behavior correlates with the free-energy change of subunit association; and c), experimental manipulation of the free energy of subunit association through the addition of a subdenaturing concentration of a chaotropic agent restores the concentration dependence of subunit association of TIM. A model that explains these features and its biological relevance is discussed

Apical Sealing and Bioactivity of an Experimental Gutta-Percha Containing Niobium Phosphate Bioglass

This study evaluated the apical sealing ability and bioactivity of an experimental gutta-percha containing niobium phosphate bioglass. Thirty-six human premolars were endodontically prepared and divided into three groups: GPC—filling with conventional gutta-percha; GBC—filling with bioceramic gutta-percha (EndoSequence BC); GNB—filling with experimental gutta-percha containing niobophosphate. Teeth were stored in tubes containing 2 mL of simulated body fluid (SBF) solution in an oven for 30 days. Then, the samples were immersed in lanthanum nitrate solution and analyzed for apical nanoleakage (NI) with a scanning electron microscope (SEM/EDS) and transmission electron microscope (TEM). Gutta-percha specimens were immersed for 28 days (SBF) and analyzed in SEM/EDS and X-ray diffraction (XRD) to assess bioactivity. NI data originated from the SEM/EDS were analyzed using the Kruskal–Wallis test (α = 5%). NI data originated from TEM and bioactivity were descriptively reported. Statistical analysis did not detect a significant difference between groups (p = 0.13) for NI. In the bioactivity analysis, an abundant layer of hydroxyapatite was identified only in the surface of the GNB group samples. The gutta-percha containing niobophosphate bioglass promoted an apical sealing similar to EndoSequence BC, in addition to demonstrating bioactivity through the deposition of hydroxyapatite on the surface of the material after immersion in SBF