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1.
Vaccines (Basel) ; 12(7)2024 Jul 18.
Article de Anglais | MEDLINE | ID: mdl-39066430

RÉSUMÉ

Several technological approaches have been used to develop vaccines against COVID-19, including those based on inactivated viruses, viral vectors, and mRNA. This study aimed to monitor the maintenance of anti-SARS-CoV-2 antibodies in individuals from Brazil according to the primary vaccination regimen, as follows: BNT162b2 (group 1; 22) and ChAdOx1 (group 2; 18). Everyone received BNT162b2 in the first booster while in the second booster CoronaVac, Ad26.COV2.S, or BNT162b2. Blood samples were collected from 2021 to 2023 to analyze specific RBD (ELISA) and neutralizing antibodies (PRNT50). We observed a progressive increase in anti-RBD and neutralizing antibodies in each subsequent dose, remaining at high titers until the end of follow-up. Group 1 had higher anti-RBD antibody titers than group 2 after beginning the primary regimen, with significant differences after the 2nd and 3rd doses. Group 2 showed a more expressive increase after the first booster with BNT162B2 (heterologous booster). Group 2 also presented high levels of neutralizing antibodies against the Gamma and Delta variants until five months after the second booster. In conclusion, the circulating levels of anti-RBD and neutralizing antibodies against the two variants of SARS-CoV-2 were durable even five months after the 4th dose, suggesting that periodic booster vaccinations (homologous or heterologous) induced long-lasting immunity.

2.
J Med Virol ; 96(8): e29828, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-39081145

RÉSUMÉ

The condition commonly referred to as long coronavirus disease (COVID) is characterized by the continuation of symptoms, sometimes accompanied by new symptoms that persist after the resolution of acute coronavirus disease 2019 (COVID-19). This observational cross-sectional study investigated 332 patients with long COVID in the Brazilian Amazon region. The study aimed to elucidate the systemic interactions associated with long COVID by compiling the findings related to hematological, coagulation, immunological, metabolic, hepatic, renal, and muscular profiles. Participants with long COVID were identified using rigorous criteria and underwent thorough laboratory examinations. The obtained data were subsequently analyzed, allowing for comparisons, associations, and correlations between findings within distinct groups in the study. Significant associations were observed between hospitalization during the acute phase and persistent laboratory abnormalities, suggesting a potential link between acute severity and long-term effects. Notably, individuals with long COVID for over a year exhibited elevated levels of monocytes, prolonged prothrombin times, reduced prothrombin activity, high levels of lactate dehydrogenase, and an increased frequency of qualitative C-reactive protein detection. This study provides valuable insights into the laboratory risk profile of patients with long COVID, particularly in the unique context of the Amazon region, where patients exhibit persistent symptoms lasting up to 1261 days.


Sujet(s)
COVID-19 , Humains , COVID-19/sang , COVID-19/épidémiologie , COVID-19/diagnostic , Brésil/épidémiologie , Études transversales , Mâle , Femelle , Adulte d'âge moyen , Sujet âgé , Adulte , SARS-CoV-2 , Hospitalisation/statistiques et données numériques , Protéine C-réactive/analyse , Sujet âgé de 80 ans ou plus
3.
Dermatol Online J ; 30(2)2024 Apr 15.
Article de Anglais | MEDLINE | ID: mdl-38959934

RÉSUMÉ

Nodular hidradenoma is an infrequent benign tumor originating from the proximal portion of the sweat glands, most commonly associated with the apocrine glands. Owing to its variable clinical presentation, correctly diagnosing nodular hidradenoma can be challenging, with several potential conditions in the differential diagnosis to consider. This article presents a healthy 52-year-old woman with an atypical location of nodular hidradenoma, highlighting the critical role of integrating clinical, dermoscopic, and histopathological characteristics for an accurate diagnosis. We discuss the clinical features, dermoscopic findings, histological examination, differential diagnosis, and treatment options for nodular hidradenoma, emphasizing the importance of surgical intervention in preventing potential malignant transformation.


Sujet(s)
Acrospirome , Dermoscopie , Tumeurs des glandes sudoripares , Humains , Femelle , Adulte d'âge moyen , Tumeurs des glandes sudoripares/anatomopathologie , Tumeurs des glandes sudoripares/diagnostic , Acrospirome/anatomopathologie , Acrospirome/diagnostic , Diagnostic différentiel
4.
Front Psychol ; 15: 1394068, 2024.
Article de Anglais | MEDLINE | ID: mdl-38873510

RÉSUMÉ

Purpose: This study aimed to assess the association of anxiety, headache, and insomnia on the QoL of patients with long COVID-19. Methods: We conducted a cross-sectional survey between August 2020 and March 2023. A total of 200 participants were eligible, 53 were excluded and 147 patients with long COVID were included. QoL was evaluated across eight domains using the 36-Item Short Form Health Survey (SF-36). Standardized protocols including the Beck Anxiety Inventory (BAI) (n = 103), Pittsburgh Sleep Quality Index (PSQI) (n = 73), and Migraine Disability Assessment (MIDAS) (n = 67) were also used. Results: Participants with sleep disorders had significantly lower Vitality (p < 0.001). Participants with anxiety disorders had significantly lower Vitality (p = 0.001), poorer Mental Health (p = 0.008), and more severe Bodily Pain (p = 0.008). Participants with headache had significantly lower Vitality (p = 0.032), poorer Mental Health (p = 0.036), and poorer Physical Functioning (p = 0.016). Participants with both headache and anxiety had significantly lower Vitality (p = 0.005) and Mental Health (p = 0.043) domain scores. Correlation analysis revealed that higher scores for anxiety, sleep disorder, and headache were independently correlated with poorer QoL across various domains. The presence of sleep disorder was associated with a fourfold increase in risk of experiencing diminished Vitality (odds ratio [OR]4.47; 95% CI 1.01-19.69; p = 0.048). Conclusion: Participants with anxiety, sleep, and headache disorders tended to have a worse QoL. The Vitality and Mental Health domains were the most adversely affected in patients with long COVID. Sleep disorders were associated with a fourfold increase in the risk of poor Vitality.

5.
Front Artif Intell ; 7: 1382356, 2024.
Article de Anglais | MEDLINE | ID: mdl-38800763

RÉSUMÉ

The threat landscape of biological hazards with the evolution of AI presents challenges. While AI promises innovative solutions, concerns arise about its misuse in the creation of biological weapons. The convergence of AI and genetic editing raises questions about biosecurity, potentially accelerating the development of dangerous pathogens. The mapping conducted highlights the critical intersection between AI and biological threats, underscoring emerging risks in the criminal manipulation of pathogens. Technological advancement in biology requires preventative and regulatory measures. Expert recommendations emphasize the need for solid regulations and responsibility of creators, demanding a proactive, ethical approach and governance to ensure global safety.

6.
Virology ; 596: 110095, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38761641

RÉSUMÉ

Dengue virus (DENV) is a major global health concern, causing millions of infections annually. Understanding the cellular response to DENV infection is crucial for developing effective therapies. This study provides an in-depth analysis of the cellular response to Dengue virus (DENV) infection, with a specific focus on the interplay between microRNAs (miRNAs), apoptosis, and viral load across different DENV serotypes. Utilizing a variety of cell lines infected with four DENV serotypes, the research methodically quantifies viral load, and the expression levels of miRNA-15, miRNA-16, and BCL2 protein, alongside measuring apoptosis markers. Methodologically, the study employs quantitative PCR for viral load and miRNA expression analysis, and Western blot for apoptosis and BCL2 detection, with a statistical framework that includes ANOVA and correlation analysis to discern significant differences and relationships. The findings reveal that despite similar viral loads across DENV serotypes, DENV-2 exhibits a marginally higher load. A notable upregulation of miRNA-15 and miRNA-16 correlates positively with increased viral load, suggesting their potential role in modulating viral replication. Concurrently, a marked activation of caspases 3 and 7, along with changes in BCL2 protein levels, underscores the role of apoptosis in the cellular response to DENV infection. Conclusively, the study enhances the understanding of miRNA involvement in DENV pathogenesis, highlighting miRNA-15 and miRNA-16 as potential regulatory agents in viral replication and apoptosis. These findings pave the way for further exploration into miRNA-based therapeutic strategies against DENV infection.


Sujet(s)
Apoptose , Virus de la dengue , Dengue , microARN , Protéines proto-oncogènes c-bcl-2 , Charge virale , Réplication virale , microARN/génétique , microARN/métabolisme , Virus de la dengue/physiologie , Virus de la dengue/génétique , Humains , Protéines proto-oncogènes c-bcl-2/génétique , Protéines proto-oncogènes c-bcl-2/métabolisme , Dengue/virologie , Lignée cellulaire , Caspase-3/métabolisme , Caspase-3/génétique , Caspase-7/métabolisme , Caspase-7/génétique , Sérogroupe
8.
Oncol Lett ; 27(5): 219, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38586206

RÉSUMÉ

Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. The initial treatment of lung cancer depends on the definition of the tumor type and its staging. The most common treatment is chemotherapy, and the first-line treatment is a combination of carboplatin and paclitaxel. Although this treatment has good efficacy, there is a high prevalence of adverse events, particularly hematological reactions. Studies on new biomarkers related to these adverse events, such as circulating microRNAs (miRNAs/miRs), are important for optimizing the quality of life of patients. miRNAs have high stability in several biological fluids and they have specific expressions in different tissues or pathologies. Thus, the present study aimed to assess the relationship between circulating miRNAs and adverse hematologic reactions caused by treatment with carboplatin + paclitaxel in patients with lung cancer. Blood was collected from patients before and 15 days after chemotherapy for hematological adverse reaction analysis, microarray and quantitative (q)PCR validation. Adverse reactions were classified according to the Common Terminology Criteria for Adverse Events v4.0. Microarray analysis was performed using plasma from six patients without anemia and six patients with anemia, and nine miRNAs were differentially expressed. miR-1273g-3p, miR-3613-5p and miR-455-3p, identified using microarray, were assessed using qPCR in 20 patients without anemia and 26 patients with anemia. Bioinformatic analyses of miR-455-3p were performed using miRWalk, the Database for Annotation, Visualization and Integrated Discovery and GeneMania software. Microarray analysis of patients with and without anemia revealed nine significant differentially-expressed plasma miRNAs among these patients. Of these, miR-1273g-3p, miR-3613-5p and miR-455-3p were chosen for further assessment. Only miR-455-3p demonstrated a significant reduction in expression (P=0.04) between the groups before chemotherapy with carboplatin + paclitaxel. Bioinformatics analysis of miR-455-3p revealed a relationship between this miRNA and the hematopoietic pathway, particularly with respect to the RUNX family transcription factor 1 (RUNX1) and TAL bHLH transcription factor 1, erythroid differentiation factor (TAL1) genes. The most prevalent adverse reactions in patients with lung cancer treated with carboplatin + paclitaxel were hematological, particularly anemia. This adverse reaction, caused by dysfunction of the hematopoietic system, may be explained by a possible association between the important genes in this system, RUNX1 and TAL1, and hsa-miR-455-3p.

9.
Acta Med Port ; 37(4): 315, 2024 Apr 01.
Article de Portugais | MEDLINE | ID: mdl-38631063

RÉSUMÉ

On page 215, list of authors, where it reads (in red): Mário FERREIRA1, Carlos GRIJÓ2, Joana PAULO1, Marta FONSECA1, Zélia NEVES1 It should read (in bold): Mário FERREIRA1, Carlos GRIJÓ2, Joana PAULO1, Marta FONSECA1, Zélia NEVES1, Rita BOUCEIRO MENDES3, Pedro VASCONCELOS3 On the same page 215, footer (authors affiliation), where it reads (in red): 1. Medicina III. Hospital Fernando Fonseca. Amadora. Portugal. 2. Serviço de Medicina Interna. Centro Hospitalar Universitário de São João. Porto. Portugal. It should read (in bold): 1. Medicina III. Hospital Fernando Fonseca. Amadora. Portugal. 2. Serviço de Medicina Interna. Centro Hospitalar Universitário de São João. Porto. Portugal. 3. Serviço de Dermatologia. Hospital de Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisboa. Portugal. Article published with errors: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/20599.


Na página 215, na linha de autoria onde se lê, (a vermelho): Mário FERREIRA1, Carlos GRIJÓ2, Joana PAULO1, Marta FONSECA1, Zélia NEVES1 Deverá ler-se (a negrito): Mário FERREIRA1, Carlos GRIJÓ2, Joana PAULO1, Marta FONSECA1, Zélia NEVES1, Rita BOUCEIRO MENDES3, Pedro VASCONCELOS3 Na mesma página 215, em rodapé (afiliação dos autores), onde se lê (a vermelho): 1. Medicina III. Hospital Fernando Fonseca. Amadora. Portugal. 2. Serviço de Medicina Interna. Centro Hospitalar Universitário de São João. Porto. Portugal. Deverá ler-se (a negrito): 1. Medicina III. Hospital Fernando Fonseca. Amadora. Portugal. 2. Serviço de Medicina Interna. Centro Hospitalar Universitário de São João. Porto. Portugal. 3. Serviço de Dermatologia. Hospital de Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisboa. Portugal. Artigo publicado com erros: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/20599.

14.
Viruses ; 15(12)2023 11 23.
Article de Anglais | MEDLINE | ID: mdl-38140542

RÉSUMÉ

Monkeypox virus (MPXV), belonging to the Poxviridae family and Orthopoxvirus genus, is closely related to the smallpox virus. Initial prodromal symptoms typically include headache, fever, and lymphadenopathy. This review aims to detail various ocular manifestations and immune evasion associated with the monkeypox viral infection and its complications, making it appropriate as a narrative review. Common external ocular manifestations of MPXV typically involve a generalized pustular rash, keratitis, discharges, and dried secretions related to conjunctival pustules, photophobia, and lacrimation. Orthopoxviruses can evade host immune responses by secreting proteins that antagonize the functions of host IFNγ, CC and CXC chemokines, IL-1ß, and the complement system. One of the most important transcription factors downstream of pattern recognition receptors binding is IRF3, which controls the expression of the crucial antiviral molecules IFNα and IFNß. We strongly recommend that ophthalmologists include MPXV as part of their differential diagnosis when they encounter similar cases presenting with ophthalmic manifestations such as conjunctivitis, blepharitis, or corneal lesions. Furthermore, because non-vaccinated individuals are more likely to exhibit these symptoms, it is recommended that healthcare administrators prioritize smallpox vaccination for at-risk groups, including very young children, pregnant women, older adults, and immunocompromised individuals, especially those in close contact with MPXV cases.


Sujet(s)
Maladies de la cornée , Virus de la variole simienne , Enfant , Humains , Femelle , Grossesse , Enfant d'âge préscolaire , Sujet âgé , Échappement immunitaire , Vaccination , Paupières
15.
Int Immunopharmacol ; 124(Pt B): 110994, 2023 Nov.
Article de Anglais | MEDLINE | ID: mdl-37804653

RÉSUMÉ

INTRODUTION AND OBJECTIVE: The present study sought to characterize the pattern of monocyte subpopulations in patients during the course of the infections caused by SARS-CoV-2 virus or who presented long COVID-19 syndrome compared to monocytes from patients with zika virus (Zika) or chikungunya virus (CHIKV). CASUISTRY: Study with 89 peripheral blood samples from patients, who underwent hemogram and serology (IgG and IgM) for detection of Zika (Control Group 1, n = 18) or CHIKV (Control Group 2, n = 9), and from patients who underwent hemogram and reverse transcription polymerase chain reaction for detection of SARS-CoV-2 at the acute phase of the disease (Group 3, n = 19); and of patients who presented long COVID-19 syndrome (Group 4, n = 43). The monocyte and subpopulations counts were performed by flow cytometry. RESULTS: No significant difference was observed in the total number of monocytes between the groups. The classical (CD14++CD16-) and intermediate (CD14+CD16+) monocytes counts were increased in patients with acute infection or with long COVID-19 syndrome. The monocytes subpopulations counts were lower in patients with infection Zika or CHIKV. CONCLUSION: Increase in the monocyte subpopulations in patients with acute infection or with long COVID-19 syndrome may be an important finding of differentiated from the infection Zika or CHIKV.


Sujet(s)
COVID-19 , Virus du chikungunya , Infection par le virus Zika , Virus Zika , Humains , Monocytes , Syndrome de post-COVID-19 , SARS-CoV-2 , Infection par le virus Zika/diagnostic , Récepteurs du fragment Fc des IgG , Antigènes CD14
16.
J Med Virol ; 95(10): e29042, 2023 10.
Article de Anglais | MEDLINE | ID: mdl-37885152

RÉSUMÉ

Rabies is an ancient neuroinvasive viral (genus Lyssavirus, family Rhabdoviridae) disease affecting approximately 59,000 people worldwide. The central nervous system (CNS) is targeted, and rabies has a case fatality rate of almost 100% in humans and animals. Rabies is entirely preventable through proper vaccination, and thus, the highest incidence is typically observed in developing countries, mainly in Africa and Asia. However, there are still cases in European countries and the United States. Recently, demographic, increasing income levels, and the coronavirus disease 2019 (COVID-19) pandemic have caused a massive raising in the animal population, enhancing the need for preventive measures (e.g., vaccination, surveillance, and animal control programs), postexposure prophylaxis, and a better understanding of rabies pathophysiology to identify therapeutic targets, since there is no effective treatment after the onset of clinical manifestations. Here, we review the neuroimmune biology and mechanisms of rabies. Its pathogenesis involves a complex and poorly understood modulation of immune and brain functions associated with metabolic, synaptic, and neuronal impairments, resulting in fatal outcomes without significant histopathological lesions in the CNS. In this context, the neuroimmunological and neurochemical aspects of excitatory/inhibitory signaling (e.g., GABA/glutamate crosstalk) are likely related to the clinical manifestations of rabies infection. Uncovering new links between immunopathological mechanisms and neurochemical imbalance will be essential to identify novel potential therapeutic targets to reduce rabies morbidity and mortality.


Sujet(s)
Virus de la rage , Rage (maladie) , Humains , Animaux , États-Unis , Rage (maladie)/épidémiologie , Vaccination , Europe , Résultat thérapeutique , Prophylaxie après exposition/méthodes
17.
Front Immunol ; 14: 1239572, 2023.
Article de Anglais | MEDLINE | ID: mdl-37711609

RÉSUMÉ

Normally, the host immunological response to viral infection is coordinated to restore homeostasis and protect the individual from possible tissue damage. The two major approaches are adopted by the host to deal with the pathogen: resistance or tolerance. The nature of the responses often differs between species and between individuals of the same species. Resistance includes innate and adaptive immune responses to control virus replication. Disease tolerance relies on the immune response allowing the coexistence of infections in the host with minimal or no clinical signs, while maintaining sufficient viral replication for transmission. Here, we compared the virome of bats, rodents and migratory birds and the molecular mechanisms underlying symptomatic and asymptomatic disease progression. We also explore the influence of the host physiology and environmental influences on RNA virus expression and how it impacts on the whole brain transcriptome of seemingly healthy semipalmated sandpiper (Calidris pusilla) and spotted sandpiper (Actitis macularius). Three time points throughout the year were selected to understand the importance of longitudinal surveys in the characterization of the virome. We finally revisited evidence that upstream and downstream regulation of the inflammatory response is, respectively, associated with resistance and tolerance to viral infections.


Sujet(s)
Chiroptera , Maladies virales , Animaux , Rodentia , Oiseaux , Tolérance immunitaire
18.
SciELO Preprints; set. 2023.
Preprint de Portugais | SciELO Preprints | ID: pps-6635

RÉSUMÉ

Formative assessment consists of a qualitative verification of the skills and competencies of an individual in a formal instructional process. This evaluation is fundamental for the progress of the tutorial groups, present in the methodology of Problem-Based Learning, widely used in medical courses in Brazil. However, factors such as lack of knowledge and fear of the evaluation process prevent it from being carried out. Therefore, this study aims to analyze how formative assessment occurs in tutorial groups, based on Emotional Didactic Suitability. That is, it aims to understand how formative assessment affects the interest, attitude and emotions of students participating in the tutorial group. La investigación se caracteriza por ser cualitativa, teniendo como informantes a estudiantes y a un tutor del curso de Medicina de una universidad del interior de Bahía.Para la recolección de datos, se utilizó la Observación Participante utilizando cuestionarios estructurados y observación de dinámicas tutoriales en 2021. Data analysis was performed through the Criterion of Emotional Didactic Suitability adapted to the medical course, which aims to measure how students are interested and affected in the teaching-learning process. As a result, it was noticed that students and teachers still value summative evaluation more than formative evaluation, creating aversive behaviors to the evaluation process, such as anxiety and fear. The notion of the importance of evaluation at the end of tutoring was perceived as a way to stimulate the development of skills and attitudes, although it does not follow a standardization of self-evaluation, peer evaluation, tutor evaluation and tutor evaluation.


La evaluación formativa consiste en una verificación cualitativa de las habilidades y competencias de un individuo en un proceso formal de instrucción. Esta evaluación es fundamental para el progreso de los grupos tutoriales, presentes en la metodología del Aprendizaje Basado en Problemas, ampliamente utilizada en los cursos de medicina en Brasil. Sin embargo, factores como el desconocimiento y el miedo al proceso de evaluación impiden que se lleve a cabo. Por lo tanto, este estudio tiene como objetivo analizar cómo se produce la evaluación formativa en grupos tutoriales, basada en la Idoneidad Didáctica Emocional. Es decir, pretende comprender cómo afecta la evaluación formativa al interés, la actitud y las emociones de los estudiantes que participan en el grupo tutorial. La investigación se caracteriza por ser cualitativa, teniendo como informantes a estudiantes y a un tutor del curso de Medicina de una universidad del interior de Bahía.Para la recolección de datos, se utilizó la Observación Participante utilizando cuestionarios estructurados y observación de dinámicas tutoriales en 2021. El análisis de los datos se realizó a través del Criterio de Idoneidad Didáctica Emocional adaptado al curso de medicina, que tiene como objetivo medir cómo los estudiantes están interesados y afectados en el proceso de enseñanza-aprendizaje. Como resultado, se notó que los estudiantes y los maestros todavía valoran la evaluación sumativa más que la evaluación formativa, creando comportamientos aversivos al proceso de evaluación, como la ansiedad y el miedo. La noción de la importancia de la evaluación al final de la tutoría fue percibida como una forma de estimular el desarrollo de habilidades y actitudes, aunque no sigue una estandarización de autoevaluación, evaluación por pares, evaluación del tutor y evaluación del tutor.


A avaliação formativa consiste em uma verificação qualitativa das habilidades e competências de um indivíduo em processo instrucional formal. Essa avaliação constitui-se como fundamental para o andamento dos grupos tutoriais, presentes na metodologia da Aprendizagem Baseada em Problemas, utilizada amplamente nos cursos de Medicina do Brasil. Porém, fatores como a falta de conhecimento e medo do processo avaliativo impedem que ela seja efetivada. Portanto, esse estudo visa analisar como ocorre a avaliação formativa em grupos tutoriais, com base na Idoneidade Didática Emocional. Ou seja, pretende compreender como a avaliação formativa afeta o interesse, a atitude e as emoções dos alunos que participam do grupo tutorial. A pesquisa caracteriza-se como qualitativa, tendo como informantes alunos e uma tutora do curso de Medicina de uma faculdade do interior da Bahia. Para coleta de dados foi utilizada a Observação Participante com utilização de questionários estruturados e observação da dinâmica tutorial no ano de 2021. A análise dos dados se deu através do Critério de Idoneidade Didática Emocional adaptados para o curso de Medicina, que tem a finalidade de medir como discentes se interessam e são afetados no processo ensino-aprendizagem. Como resultado percebeu-se que os discentes e docente ainda valorizam mais a avaliação somativa em detrimento à formativa, criando comportamentos aversivos ao processo avaliativo, tais como ansiedade e medo. Percebeu-se a noção da importância da avaliação ao final da tutoria como forma de estimular o desenvolvimento de habilidades e atitudes, embora ela não siga uma padronização de autoavaliação, avaliação dos pares, avaliação do tutor e avaliação pelo tutor.

19.
Cytokine ; 169: 156306, 2023 09.
Article de Anglais | MEDLINE | ID: mdl-37542834

RÉSUMÉ

The present study was designed as an exploratory investigation to characterize the overall profile of chemokines, growth factors, and pro-inflammatory/regulatory cytokines during acute DENV infection according to DENV-1, DENV-2, DENV-4 serotypes and age: children: <1-10-year-old (yo); adolescents:11-20 yo; adults 21-40 yo; and older adults: 41-75 yo. The levels of soluble immunemediators were measured in serum by high-throughput microbeads array in 636 subjects including 317 DENV-infected and 319 age-matching non-infected control (NI). Overall, most soluble mediators were increased in DENV-infected patients as compared to NI group regardless of age and DENV serotype, with high magnitude order of increase for CCL2, CXCL10, IL-1ß, IFN-γ, IL1-Ra (fold change >3x), except PDGF in which no fold change was observed. Moreover, despite the age ranges, DENV-1 and DENV-4 presented increased levels of VEGF, IL-6, and TNF-α in serum but decreased levels of PDGF, while DENV-2 exhibited increased levels of CXCL8, CCL4, and IL-12. Noteworthy was that DENV-2 showed increased levels of IL-12, IL-15, IL-17, IL-4, IL-9, and IL-13, and maintained an unaltered levels of PDGF at younger ages (<1-10 yo and 11-20 yo), whereas in older ages (21-40 yo and 41-75 yo), the results showed increased levels of CCL2, IL-6, and TNF-α, but lower levels of PDGF. In general, DENV infection at younger age groups exhibited more complex network immunoclusters as compared to older age groups. Multivariate analysis revealed a clustering of DENV cases according to age for a set of soluble mediators especially in subjects infected with DENV-2 serotype. Altogether, our findings demonstrate that the profile of circulating soluble mediators differs substantially in acute DENV according to age and DENV serotypes suggesting the participation of serotype-associated immune response, which may represent a potential target for development of therapeutics and could be used to assist medical directive for precise clinical management of severe cases.


Sujet(s)
Virus de la dengue , Dengue , Maladies virales , Adolescent , Sujet âgé , Enfant , Enfant d'âge préscolaire , Humains , Nourrisson , Cytokines , Virus de la dengue/physiologie , Immunité , Interleukine-12 , Interleukine-6 , Sérogroupe , Facteur de nécrose tumorale alpha , Jeune adulte , Adulte , Adulte d'âge moyen
20.
Cancers (Basel) ; 15(14)2023 Jul 22.
Article de Anglais | MEDLINE | ID: mdl-37509381

RÉSUMÉ

Hematopoietic stem cell transplant (HSCT) is an important treatment option for hematologic malignancies. Acute kidney injury (AKI) is a common complication in HSCTs and is related to worse outcomes. We aimed to create a predictive risk score for AKI in HSCT considering variables available at the time of the transplant. We performed a retrospective cohort study. AKI was defined by the KDIGO classification using creatinine and urinary output criteria. We used survival analysis with competing events. Continuous variables were dichotomized according to the Liu index. A multivariable analysis was performed with a backward stepwise regression. Harrel's C-Statistic was used to evaluate the performance of the model. Points were attributed considering the nearest integer of two times each covariate's hazard ratio. The Liu index was used to establish the optimal cut-off. We included 422 patients undergoing autologous (61.1%) or allogeneic (38.9%) HSCTs for multiple myeloma (33.9%), lymphoma (27.3%), and leukemia (38.8%). AKI cumulative incidence was 59.1%. Variables eligible for the final score were: hematopoietic cell transplant comorbidity index ≥2 (HR: 1.47, 95% CI: 1.08-2.006; p = 0.013), chronic kidney disease (HR: 2.10, 95% CI: 1.31-3.36; p = 0.002), lymphoma or leukemia (HR: 1.69, 95% CI: 1.26-2.25; p < 0.001) and platelet-to-lymphocyte ratio > 171.9 (HR: 1.43, 95% CI: 1.10-1.86; p = 0.008). This is the first predictive risk score for AKI in patients undergoing HSCTs and the first study where the platelet-to-lymphocyte ratio is independently associated with AKI.

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