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Atomoxetine is a drug widely used for the treatment of the attention deficit hyperactivity disorder (ADHD) with reduced risk of adverse motor reactions and chemical dependence. However, the pharmacokinetics characteristics as well as the toxicological risk of atomoxetine deserves further investigation to comprehensively analyze the therapeutic and safety aspects of this drug. This study aimed to predict the physicochemical profile and medicinal chemistry characteristics of atomoxetine, alongside its pharmacokinetic properties-namely absorption, distribution, metabolism, and excretion-as well as its toxicology (ADMET) potential through the utilization of web-based in silico tools. This research emphasizes predicted physicochemical, medicinal chemistry, and absorption parameters of atomoxetine that could influence the efficacy and safety of this drug for ADHD treatment. Additionally, atomoxetine also presents noteworthy predicted risks of hepatotoxicity, cardiotoxicity, neurotoxicity, nephrotoxicity, respiratory system toxicity, skin toxicity, and carcinogenicity. These findings underscore the necessity for further assessments of atomoxetine's safety profile, particularly considering different patient populations and durations of drug treatment. The data reported here from in silico predictions suggest that closer monitoring is warranted when atomoxetine is administered to patients with ADHD. Moreover, controlled studies detailing reliable protocols for personalized dosing, considering the multifactorial variability in metabolism efficiency and toxicological potential, would enable a more comprehensive assessment of atomoxetine's safety profile.

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Yellow fever outbreaks are prevalent, particularly in endemic regions. Given the lack of an established treatment for this disease, significant attention has been directed toward managing this arbovirus. In response, we developed a multiepitope vaccine designed to elicit an immune response, utilizing advanced immunoinformatic and molecular modeling techniques. To achieve this, we predicted B- and T-cell epitopes using the sequences from all structural (E, prM, and C) and nonstructural proteins of 196 YFV strains. Through comprehensive analysis, we identified 10 cytotoxic T-lymphocyte (CTL) and 5T-helper (Th) epitopes that exhibited overlap with B-lymphocyte epitopes. These epitopes were further evaluated for their affinity to a wide range of human leukocyte antigen system alleles and were rigorously tested for antigenicity, immunogenicity, allergenicity, toxicity, and conservation. These epitopes were linked to an adjuvant ( ß -defensin) and to each other using ligands, resulting in a vaccine sequence with appropriate physicochemical properties. The 3D structure of this sequence was created, improved, and quality checked; then it was anchored to the Toll-like receptor. Molecular Dynamics and Quantum Mechanics/Molecular Mechanics simulations were employed to enhance the accuracy of docking calculations, with the QM portion of the simulations carried out utilizing the density functional theory formalism. Moreover, the inoculation model was able to provide an optimal codon sequence that was inserted into the pET-28a( +) vector for in silico cloning and could even stimulate highly relevant humoral and cellular immunological responses. Overall, these results suggest that the designed multi-epitope vaccine can serve as prophylaxis against the yellow fever virus.

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SARS-CoV-2 genome underwent mutations since it started circulating within the human population. The aim of this study was to understand the fluctuation of the spike clusters concomitant to the population immunity either due to natural infection and/or vaccination in a state of Brazil that had both high rate of natural infection and vaccination coverage. A total of 1725 SARS-CoV-2 sequences from the state of Rio Grande do Norte, Brazil, were retrieved from GISAID and subjected to cluster analysis. Immunoinformatics were used to predict T- and B-cell epitopes, followed by simulation to estimate either pro- or anti-inflammatory responses and to correlate with circulating variants. From March 2020 to June 2022, the state of Rio Grande do Norte reported 579,931 COVID-19 cases with a 1.4% fatality rate across the three major waves: May-Sept 2020, Feb-Aug 2021, and Jan-Mar 2022. Cluster 0 variants (wild type strain, Zeta) were prevalent in the first wave and Delta (AY.*), which circulated in Brazil in the latter half of 2021, featuring fewer unique epitopes. Cluster 1 (Gamma (P.1 + P.1.*)) dominated the first half of 2021. Late 2021 had two new clusters, Cluster 2 (Omicron, (B.1.1.529 + BA.*)), and Cluster 3 (BA.*) with the most unique epitopes, in addition to Cluster 4 (Delta sub lineages) which emerged in the second half of 2021 with fewer unique epitopes. Cluster 1 epitopes showed a high pro-inflammatory propensity, while others exhibited a balanced cytokine induction. The clustering method effectively identified Spike groups that may contribute to immune evasion and clinical presentation, and explain in part the clinical outcome.

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The COVID-19-19 pandemic's global impact has accelerated the need for effective vaccines, challenging traditional, time-consuming, and costly vaccinology methods. Immunoinformatics emerges as a promising alternative to expedite vaccine development, thus this study aims to provide a comprehensive bibliometric analysis of its application in formulating SARS-CoV-2 vaccine prototypes. Employing VOSviewer software and data from the Web of Science database, this study conducted a bibliometric analysis. Key metrics included the global distribution of scientific publications, the most productive countries and institutions, influential authors, co-citation and co-authorship networks, and prevalent keywords in immunoinformatics research related to SARS-CoV-2 vaccines. The analysis encompassed 138 scholarly articles, with India emerging as a pivotal contributor, particularly through notable contributions from Adamas and Fakir Mohan universities. The most cited article, authored by Bhattacharya, received 226 citations, while Doytchinova was a prominent cited source, referenced in 96 of the 138 analyzed documents. The study observed substantial collaborative efforts among authors from 45 nations, with 85% of the research concentrated in just six countries. Pakistan demonstrated the highest level of international collaboration, contributing to 15/20 collaborative publications. Keywords such as 'SARS-CoV-2', 'immunoinformatics', and 'prediction' were frequently encountered across most of these documents. This bibliometric analysis elucidates the primary research trends in the field and delineates the global scope and distribution of immunoinformatics studies in the realm of SARS-CoV-2 vaccine development. These findings offer a vital overview of the current landscape, guiding future research directions and potential collaborative efforts in the pursuit of effective COVID-19 vaccines.

El impacto global de la pandemia de COVID-19 ha acelerado la necesidad de vacunas efectivas, lo que ha desafiado los métodos tradicionales de vacunología que son costosos y consumen mucho tiempo. La inmunoinformática surge como una alternativa prometedora para acelerar el desarrollo de vacunas. Este estudio tuvo como objetivo proporcionar un análisis bibliométrico exhaustivo de su aplicación en la formulación de prototipos de vacunas contra el SARS-CoV-2. Utilizando el software VOSviewer y datos de la base de datos Web of Science, se realizó un análisis bibliométrico. Las métricas clave incluyeron: la distribución global de publicaciones científicas, los países e instituciones más productivos, autores influyentes, redes de cocitación y coautoría y palabras clave prevalentes en la investigación de inmunoinformática relacionada con las vacunas contra el SARS-CoV-2. El análisis abarcó 138 artículos académicos; la India emergió como un contribuyente principal, particularmente a través de contribuciones notables de las universidades Adamas y Fakir Mohan. El artículo más citado fue el de Bhattacharya, que recibió 226 citas; mientras que Doytchinova fue una fuente citada prominente, referenciada en 96 de los 138 documentos analizados. El estudio observó esfuerzos colaborativos sustanciales entre autores de 45 naciones con el 85 % de la investigación concentrada en seis países. Pakistán demostró el nivel más alto de colaboración internacional, al contribuir con 15 de los 20 artículos colaborativos. Palabras clave como 'SARS-CoV-2', 'immunoinformatics' y 'prediction' se encontraron frecuentemente en la mayoría de estos documentos. Este análisis bibliométrico aclara las principales tendencias de investigación en el campo y delinea el alcance global y la distribución de los estudios de inmunoinformática en el ámbito del desarrollo de vacunas contra el SARS-CoV-2. Los hallazgos ofrecen una visión vital del panorama actual, guían investigaciones futuras y posibles esfuerzos colaborativos en la búsqueda de vacunas efectivas contra la COVID-19.

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O cigarro eletrônico surgiu como uma tentativa para minimizar a dependência ao uso de tabaco, entretanto, engloba controvérsias e dúvidas acerca das reais implicações para o organismo humano. Diante disso, o presente estudo tem como objetivo realizar uma revisão da literatura a fim de relacionar o uso de cigarro eletrônico com suas consequências para os humanos. Os estudos analisados relatam experimentos in vitro e in vivo em camundongos, demonstrando menor concentração de poluentes e nocividades no cigarro eletrônico comparado ao convencional, porém, seu potencial efeito maléfico está relacionado à composição do e-líquido, à maneira do uso e à variedade de aromas presentes nos produtos. Além disso, foram verificadas lesões celulares, hiperreatividade das vias aéreas, liberação de citocinas ­ IL-8, IL-10 e TNF, redução da ação antimicrobiana de queratinócitos e potencial apoptose nas células alveolares. Foi observado também um aumento em até cinco vezes da concentração de carboxihemoglobina em comparação ao cigarro comum e um aumento na auto renovação de células de adenocarcinoma pulmonar de células não pequenas, devido à expressão de SOX2. Observa-se também que em casos de DPOC, o cigarro eletrônico não apresenta agravamentos na fisiologia respiratória, contrapondo outras ocorrências como asma, pneumonia, câncer de pulmão e doenças infecciosas que podem ser ocasionadas ou exacerbadas pelo seu uso. Contudo, pelo curto prazo de observação de seus efeitos, não é possível determinar com precisão a segurança dos cigarros eletrônicos, dessa forma, faz-se necessário que mais pesquisas longitudinais sejam desenvolvidas, auxiliando, assim, na construção de evidências sobre a segurança dos cigarros eletrônicos e na regulamentação futura do produto.

Electronic cigarettes emerged as an attempt to minimize tobacco dependence. However, its use is surrounded by controversies and doubts about the real implications for the human organism. Therefore, this study aims at performing a review of the most recent literature to corelate the use of e-cigarettes with their consequences for the human body. The analyzed studies relate in vitro and in vivo experiments on mice, demonstrating lower concentration of pollutants and harmfulness in the electronic cigarette than in conventional cigarettes. However, its potential harmful effect is related to the composition of the e-liquid, in its use and in the variety of aromas in the products. In addition, cellular lesions, airway hyperreactivity, release of IL-8, IL-10 and TNF cytokines could be observed, as well as reduced keratinocyte antimicrobial action and potential apoptosis in alveolar cells. An increase of up to five-fold the concentration of carboxyhemoglobin in comparison to ordinary cigarettes and an increase in self-renewal of non-small pulmonary adenocarcinoma cells due to the expression of SOX2 have also been related. It could also be observed that in COPD cases, e-cigarettes do not present worsening in respiratory physiology, which contrasts with other occurrences such as asthma, pneumonia, lung cancer, and infectious diseases that can be caused or exacerbated by its use. However, due to the short term of observation of the effects, the safety of e-cigarettes could not be accurately determined, thus, the need for further longitudinal research is necessary, which could be used to help build evidence about the safety of e-cigarettes and also to create future regulation of the product.

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COVID-19 is a viral disease caused by SARS-CoV-2 that compromises the host immune response in severe cases, promoting a hyperinflammation that results in acute lung injury and multiple organs failure. In this context, patients presenting with immune-related diseases, such as Crohn's disease, affected by COVID-19, may have an uncertain prognosis. We report on a case of a young female patient with a severe Crohn's disease that presented with COVID-19 pneumonia and a favorable outcome even maintaining the use of adalimumab, TNF - alpha inhibitor and prednisone. This case raises the hypothesis that aside from prednisone, TNF-α inhibitors such as adalimumab could be used to stop the progression to COVID-19 complications by blocking the TNF-alpha-driven inflammatory process that occurs in severe COVID-19.

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