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1.
Article in English | MEDLINE | ID: mdl-38994465

ABSTRACT

Objective: To analyze marital outcomes, divorce or separation, and its association with demographic, socioeconomic, and clinicopathological factors among breast cancer (BC) survivors after 2-years of diagnosis. Methods: We performed a retrospective analysis of marital status at baseline and at years 1 and 2 of follow-up of women aged ≥ 18 years diagnosed with invasive BC participating in the AMAZONA III (GBECAM0115) study. The BC diagnosis occurred between January 2016 and March 2018 at 23 institutions in Brazil. Results: Of the 2974 women enrolled in AMAZONA III, 599 were married or living under common law at baseline. Divorce or separation occurred in 35 (5.8%) patients at 2 years of follow-up. In the multivariate analysis, public health insurance coverage was associated with a higher risk of marital status change (8.25% vs. 2.79%, RR 3.09, 95% CI 1.39 - 7.03, p = 0.007). Women who underwent mastectomy, adenomastectomy or skin-sparing mastectomy were associated with a higher risk of divorce or separation (8.1% vs. 4.49%, RR 1.97, 95 CI 1.04 - 3.72, p = 0.0366) than those who underwent breast-conserving surgery. Conclusion: Women covered by the public health system and those who underwent mastectomy, adenomastectomy or skin-sparing mastectomy were associated with a higher risk of divorce or separation. This evidence further supports the idea that long-term marital stability is associated with a complex interplay between socioeconomic conditions and stressors, such as BC diagnosis and treatment. ClinicalTrials Registration: NCT02663973.


Subject(s)
Breast Neoplasms , Divorce , Humans , Female , Divorce/statistics & numerical data , Breast Neoplasms/diagnosis , Breast Neoplasms/surgery , Retrospective Studies , Middle Aged , Adult , Brazil/epidemiology , Marital Status , Socioeconomic Factors , Aged , Risk Factors , Cancer Survivors/statistics & numerical data
2.
Front Oncol ; 14: 1395970, 2024.
Article in English | MEDLINE | ID: mdl-38978731

ABSTRACT

Introduction: Approximately 10% of breast cancer (BC) cases result from hereditary causes. Genetic testing has been widely implemented in BC care to determine hereditary cancer syndromes and personalized medicine. Thus, identification of individuals carrying germline pathogenic variants could be useful to provide appropriate prophylactic or screening measures for each BC subtype, however, there are few formal recommendations for genetic testing in this sense so far. In this study, we assessed rare germline variants in a specific group of genes in order to determine the association with human epidermal growth factor 2 enriched (HER2+) BC phenotype through a systematic review and meta-analysis comparing subtypes overexpressing HER2 with other clinically recognized subtypes of BC. This review was registered with PROSPERO (ID: CRD42023447571). Methods: We conducted an online literature search in PubMed (MEDLINE), Scopus, and EMBASE databases. We included original studies that investigated germline variants in HER2+ BC patients and selected the studies that reported only rare and/or pathogenic germline variants. We assessed the risk of bias and quality of the studies using the Joanna Briggs Institute Critical Appraisal checklists and the Modified Newcastle-Ottawa Scale for Genetic Studies, respectively. Considering hormone receptor and HER2 expression status, we compared gene-based risks initially in HR-HER2-, HR+HER2-, HR+HER2+, and HR-HER2+ groups, conducting separate meta-analyses using the random effects model for each comparison, and within them for each gene. Results: Of the total 36 studies describing germline variants, 11 studies provided information on the prevalence of variants in the different clinically relevant BC subtypes and allowed comparisons. Germline variants within eight genes showed significant differences when meta-analyzed between the BC groups: BRCA1, BRCA2, TP53, ATM, CHEK2, PALB2, RAD51C, and BARD1. Notably, TP53, ATM, and CHEK2 germline variants were identified as predisposing factors for HER2+ subtypes, whereas BRCA1, BRCA2, PALB2, RAD51C, and BARD1 germline variants were associated with a predisposition to low HER2 expression. Main concerns about bias and quality assessment were the lack of confounding factors control; and comparability or outcome assessment, respectively. Discussion: Our findings underscore the connection between germline variants and differential expression of the HER2 protein and BC subtypes. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023447571.

3.
Front Immunol ; 15: 1396603, 2024.
Article in English | MEDLINE | ID: mdl-38846944

ABSTRACT

Background: The Coronaviridae family comprises seven viruses known to infect humans, classified into alphacoronaviruses (HCoV-229E and HCoV-NL63) and betacoronaviruses (HCoV-OC43 and HCoV-HKU1), which are considered endemic. Additionally, it includes SARS-CoV (severe acute respiratory syndrome), MERS-CoV (Middle East respiratory syndrome), and the novel coronavirus SARS-CoV-2, responsible for COVID-19. SARS-CoV-2 induces severe respiratory complications, particularly in the elderly, immunocompromised individuals and those with underlying diseases. An essential question since the onset of the COVID-19 pandemic has been to determine whether prior exposure to seasonal coronaviruses influences immunity or protection against SARS-CoV-2. Methods: In this study, we investigated a cohort of 47 couples (N=94), where one partner tested positive for SARS-CoV-2 infection via real-time PCR while the other remained negative. Plasma samples, collected at least 30 days post-PCR reaction, were assessed using indirect ELISA and competition assays to measure specific antibodies against the receptor-binding domain (RBD) portion of the Spike (S) protein from SARS-CoV-2, HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1. Results: IgG antibody levels against the four endemic coronavirus RBD proteins were similar between the PCR-positive and PCR-negative individuals, suggesting that IgG against endemic coronavirus RBD regions was not associated with protection from infection. Moreover, we found no significant IgG antibody cross-reactivity between endemic coronaviruses and SARS-CoV-2 RBDs. Conclusions: Taken together, results suggest that anti-RBD antibodies induced by a previous infection with endemic HCoVs do not protect against acquisition of COVID-19 among exposed uninfected individuals.


Subject(s)
Antibodies, Viral , COVID-19 , Immunoglobulin G , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Humans , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Immunoglobulin G/immunology , Immunoglobulin G/blood , Male , Female , Antibodies, Viral/immunology , Antibodies, Viral/blood , Adult , Middle Aged , Spike Glycoprotein, Coronavirus/immunology , Coronavirus/immunology , Endemic Diseases , Cross Reactions/immunology
6.
J Neuroimmunol ; 389: 578327, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38489978

ABSTRACT

Individuals who experience mild COVID-19 can suffer from long-lasting cognitive symptoms. Notably, 26% of these individuals experience difficulties with visuospatial abilities six months after infection. However, among those who initially exhibited visuoconstructive impairments, 66% showed improvement or complete reversal over time. Additionally, changes in cytokine levels, particularly CCL11, HGF, and CXCL10, were observed. These results suggest a potential link between ongoing cognitive issues and elevated levels of pro-inflammatory cytokines, which merits further investigation.


Subject(s)
COVID-19 , Cognitive Dysfunction , Humans , Follow-Up Studies , COVID-19/complications , Cognitive Dysfunction/etiology , Cytokines
7.
Front Oncol ; 14: 1350162, 2024.
Article in English | MEDLINE | ID: mdl-38544834

ABSTRACT

Background: Breast and prostate cancers are the most common malignancies diagnosed in women and men respectively, and present with great clinical heterogeneity, even in tumors with the same histology and same site of origin. Somatic and germline molecular alterations in DNA may have prognostic and predictive impact, influencing response to therapies and overall survival. Our aim is to characterize the somatic and germline genomic landscape of women with locally advanced HER2-positive breast cancer and men with metastatic prostate cancer in Brazil. Secondarily, we aim to identify genetic variants associated with tumor prognosis and treatment response, identify patients carrying pathogenic alterations in cancer-predisposing genes, and characterize the genetic ancestry of the population included in the study. Methods: This observational multicenter cohort study will include 550 adult patients from the five macro-regions of Brazil, divided into two arms: 1) breast cancer and 2) prostate cancer. Clinical and pathological data will be collected, as well as DNA samples from peripheral blood and tumor samples. In arm 1, the inclusion criteria are a histological diagnosis of breast carcinoma with overexpression of HER-2, clinical stage II or III, and current neoadjuvant treatment with chemotherapy plus trastuzumab. In arm 2, the criterion is a histological diagnosis of prostate adenocarcinoma, clinical stage IV. Whole-exome sequencing (WES) will be performed to identify variants that may be drivers and/or actionable in a specific patient or tumor. These variants will be interpreted and classified according to their population frequencies, in silico predictors, functional studies, and literature data, following international guidelines proposed by expert societies. Discussion: This trial will contribute to the construction of a robust database that should provide a better understanding of the genomic profile of patients with breast and prostate cancer in Brazil. Considering the miscegenation of the Brazilian population, knowledge generated from these data will have implications for future studies of this specific population. Clinical trial registration: [clinicaltrial.gov], identifier [NCT05306600].

8.
PLoS One ; 18(12): e0295597, 2023.
Article in English | MEDLINE | ID: mdl-38127882

ABSTRACT

PURPOSE: This study aimed to describe the demographic and clinical characteristics of cancer patients with COVID-19, exploring factors associated with adverse outcomes. PATIENTS AND METHODS: This retrospective cohort study methodically extracted and curated data from electronic medical records (EMRs) of numerous healthcare institutions on cancer patients diagnosed with a confirmed SARS-CoV-2 infection between May 2020 and August 2021, to identify risk factors linked to extended hospitalization and mortality. The retrieved information encompassed the patients' demographic and clinical characteristics, including the incidence of prolonged hospitalization, acute complications, and COVID-19-related mortality. RESULTS: A total of 1446 cancer patients with COVID-19 were identified (mean [Standard deviation] age, 59.2 [14.3] years). Most patients were female (913 [63.1%]), non-white (646 [44.7%]), with non-metastatic (818 [56.6%]) solid tumors (1318 [91.1%]), and undergoing chemotherapy (647 [44.7%]). The rate of extended hospitalization due to COVID-19 was 46% (n = 665), which was significantly impacted by age (p = 0.012), sex (p = 0.003), race and ethnicity (p = 0.049), the presence of two or more comorbidities (p = 0.006), hematologic malignancies (p = 0.013), metastatic disease (p = 0.002), and a performance status ≥ 2 (p = 0.001). The COVID-19-related mortality rate was 18.9% (n = 273), and metastatic disease (<0.001), performance status ≥2 (<0.001), extended hospitalization (p = 0.028), renal failure (p = 0.029), respiratory failure (p < 0.001), sepsis (p = 0.004), and shock (p = 0.040) significantly and negatively influenced survival. CONCLUSION: The rate of extended hospitalization and COVID-19-specific death in cancer patients was notably high and could be influenced by comorbidities, cancer treatment status, and clinical fragility. These observations may aid in developing risk counseling strategies regarding COVID-19 in individuals diagnosed with cancer.


Subject(s)
COVID-19 , Neoplasms , Humans , Female , Middle Aged , Male , COVID-19/epidemiology , SARS-CoV-2 , Retrospective Studies , Brazil/epidemiology , Comorbidity , Neoplasms/complications , Neoplasms/epidemiology , Risk Factors , Hospitalization
9.
Sleep Breath ; 2023 Oct 14.
Article in English | MEDLINE | ID: mdl-37833518

ABSTRACT

PURPOSE: To evaluate the effects of nocturnal asthma on sleep parameters and inflammatory markers according to the severity of the condition in participants in the São Paulo Epidemiologic Sleep Study (EPISONO). METHODS: Data from the 2007 and 2018 editions of the EPISONO study were utilized. Subjects completed validated sleep and respiratory questionnaires, underwent nocturnal polysomnography and spirometry tests, and provided blood samples for the assessment of inflammatory parameters. RESULTS: Of 72 participants (67% women), 53% (n = 38) had intermittent nocturnal asthma symptoms and 47% (n = 34) had persistent asthma (mild, moderate, and severe). Individuals with persistent nocturnal symptoms had a higher body mass index (BMI), were more likely to have respiratory symptoms, and had worse lung function, a higher apnea-hypopnea index (AHI), and higher desaturation index than individuals with intermittent nocturnal symptoms. Positive associations were identified between nocturnal asthma and obstructive sleep apnea (OSA). A higher frequency of OSA was observed in participants with persistent asthma and participants with OSA were more likely to have persistent than intermittent asthma. However, there were no significant differences between the immunological parameters of those with intermittent or persistent asthma. CONCLUSIONS: This study highlights the relevance of nocturnal symptoms as a valuable indicator of asthma severity. The findings also add to the existing body of evidence linking nocturnal asthma and OSA.

10.
Front Vet Sci ; 10: 1235299, 2023.
Article in English | MEDLINE | ID: mdl-37701528

ABSTRACT

This study included 47 free-ranging bats from the State of Minas Gerais, Brazil. Six bats (12.8%) had genital inflammatory lesions, and two of them (one Artibeus lituratus and one Glossophaga soricina, a frugivorous and a nectarivorous, respectively) were diagnosed with Brucella sp. infection through PCR, and antigens in intralesional macrophages were detected using immunohistochemistry.

11.
Sci Rep ; 13(1): 16097, 2023 09 26.
Article in English | MEDLINE | ID: mdl-37752283

ABSTRACT

Acute ischemic stroke is a sudden neurological event caused by brain ischemia. Patients with large vessel occlusion are at high risk of developing significant cerebral edema, which can lead to rapid neurological decline. The optimal timing for decompressive hemicraniectomy to prevent further brain damage is still uncertain. This study aimed to identify potential predictors of severe brain edema. The data indicate that specific cytokines may help identify patients with a higher risk of developing life-threatening brain swelling in the early phase post-stroke. The association between a positive biomarker and the outcome was calculated, and three biomarkers-S100B protein, MMP-9, and IL-10-were found to be significantly associated with malignant edema. A model was derived for early predicting malignant cerebral edema, including S100B protein and IL-1 beta. These findings suggest that molecular biomarkers related to the ischemic cascade may be a helpful way of predicting the development of malignant cerebral edema in ischemic stroke patients, potentially widening the time window for intervention and assisting in decision-making. In conclusion, this study provides insights into the molecular mechanisms of severe brain edema and highlights the potential use of biomarkers in predicting the course of ischemic stroke.


Subject(s)
Brain Edema , Brain Ischemia , Ischemic Stroke , Stroke , Humans , Brain Edema/etiology , Ischemic Stroke/diagnosis , Ischemic Stroke/complications , Stroke/complications , Brain Ischemia/complications , Biomarkers , Case-Control Studies , S100 Calcium Binding Protein beta Subunit
12.
rev.cuid. (Bucaramanga. 2010) ; 14(3): 1-13, 20230901.
Article in Spanish | COLNAL, BDENF - Nursing, LILACS | ID: biblio-1525812

ABSTRACT

Introducción: La cobertura de vacunación contra el virus del papiloma humano no se ha realizado en la totalidad de la población, existen factores que interfieren en que los padres de las adolescentes acepten su aplicación. Objetivo: Relacionar el conocimiento sobre el virus del papiloma humano, el conocimiento sobre la vacuna contra el virus, las creencias sobre la vacuna con la aceptabilidad de la vacuna por los padres de las adolescentes de 9-12 años escolarizadas en Chihuahua, México.Materiales y Métodos: Estudio de tipo descriptivo, correlacional y transversal, la muestra fue de tipo censal, se conformó por 145 padres de niñas entre 9 a 12 años inscritas en tres primarias públicas ubicadas en una zona urbana de Chihuahua, México. Resultados: El conocimiento sobre el virus del papiloma humano se relacionó con la aceptabilidad de la vacuna (p < 0,009), de igual manera con el conocimiento acerca de la vacuna del virus del papiloma humano (p < 0,030) mientras que las creencias sobre el VPH y la vacuna no se relacionaron (p < 0, 747). Discusión: Los resultados coinciden con literatura previa en que el conocimiento sobre el virus y su vacuna es bajo, sin embargo, en este estudio las puntuaciones fueron más bajas. Mientras que la aceptabilidad de la vacuna contra el VPH tiende a ser alta al igual que estudios previos. Conclusiones: El conocimiento sobre el virus del papiloma humano y la vacuna se relacionaron con la aceptabilidad de los padres para aplicar la vacuna a sus hijas.


Introduction: Human papillomavirus vaccination coverage has not been achieved in the general population. There are factors that interfere with the acceptance of the vaccine by the parents of adolescent girls. Objective: To correlate knowledge of human papillomavirus, knowledge of the vaccine against the virus, and beliefs about the vaccine with vaccine acceptance among parents of adolescent girls aged 9-12 years in Chihuahua, Mexico. Materials and Methods: A descriptive, correlational, and cross-sectional study was conducted with a census sample of 145 parents of girls between the ages of 9 and 12 enrolled in three public elementary schools in an urban area of Chihuahua, Mexico. Results: Knowledge of human papillomavirus was related to vaccine acceptance (p < 0.009), as was knowledge of the human papillomavirus vaccine (p < 0.030). In contrast, beliefs about HPV and the vaccine were not related (p < 0.747). Discussion: The results are consistent with previous literature in that knowledge of the virus and its vaccine is low, but the scores were lower in this study. In contrast, HPV vaccine acceptance tends to be high, as in previous studies. Conclusions: Knowledge about human papillomavirus and the vaccine was associated with parental acceptance of giving it to their daughters.


Introdução: A cobertura vacinal contra o papilomavírus humano não tem sido realizada em toda a população, existem fatores que interferem na aceitação da sua aplicação pelos pais de meninas adolescentes. Objetivo: Relacionar o conhecimento sobre o papilomavírus humano, o conhecimento sobre a vacina contra o vírus, as crenças sobre a vacina com a aceitabilidade da vacina pelos pais de meninas adolescentes de 9 a 12 anos que frequentam a escola em Chihuahua, México. Materiais e Métodos: Estudo descritivo, correlacional e transversal, a amostra foi do tipo censitária, composta por 145 pais de meninas entre 9 e 12 anos matriculadas em três escolas primárias públicas localizadas em uma área urbana de Chihuahua, México. Resultados: O conhecimento sobre o papilomavírus humano esteve relacionado com a aceitabilidade da vacina (p < 0,009), da mesma forma com o conhecimento sobre a vacina contra o papilomavírus humano (p < 0,030), enquanto as crenças sobre o HPV e a vacina não foram relacionadas (p < 0,747). Discussão: Os resultados coincidem com a literatura anterior na medida em que o conhecimento sobre o vírus e sua vacina é baixo, porém, neste estudo as pontuações foram inferiores. Embora a aceitabilidade da vacina contra o HPV tenda a ser elevada como em estudos anteriores. Conclusões: O conhecimento sobre o papilomavírus humano e a vacina esteve relacionado à aceitabilidade dos pais em aplicar a vacina em suas filhas.


Subject(s)
Parents , Patient Acceptance of Health Care , Knowledge , Papillomavirus Vaccines
13.
Clin Immunol ; 255: 109740, 2023 10.
Article in English | MEDLINE | ID: mdl-37586673

ABSTRACT

Anti-fibroblast antibodies (AFA) have been reported in systemic sclerosis (SSc) and are known to promote fibroblast activation. Aim of this study was to characterize the fine specificity of AFA and to analyze any correlations with clinical parameters associated to fibrosis. To this end, AFA were affinity-purified from a patient with diffuse cutaneous SSc (dcSSc) and interstitial lung disease (ILD). Panning of a phage display peptide library with purified AFA identified the motif . The peptide p121, bearing the AFA-specific motif, was used in ELISA to screen sera from 186 SSc patients and 81 healthy donors. Anti-p121 Ab serum levels were statistically higher in SSc than in healthy groups, and directly associated with dcSSc, reduced FVC (FVC < 70), and ILD. Given these clinical correlates, this study lays the groundwork for the identification of the antigen recognized by anti-p121 Ab, which might represent a novel therapeutic target for ILD.


Subject(s)
Lung Diseases, Interstitial , Scleroderma, Diffuse , Scleroderma, Systemic , Humans , Lung Diseases, Interstitial/complications , Fibroblasts , Enzyme-Linked Immunosorbent Assay , Lung
14.
Rev Assoc Med Bras (1992) ; 69(suppl 1): e2023S120, 2023.
Article in English | MEDLINE | ID: mdl-37556639

ABSTRACT

OBJECTIVE: Cancer imposes a profound burden on low- and middle-income countries where 65% of the global cancer deaths occurred in 2020. The objective of the present review was to describe female cancer epidemiology in Brazil, barriers to prevention, screening, and treatment, and to propose strategies to a better control. METHODS: For the process of literature search and scientific acquisition, we have utilized the terms "female cancer" AND "breast cancer," AND "cervical cancer" AND "endometrial cancer" AND "ovarian cancer" AND "Brazil" in PubMed. References of the articles included in this review were manually searched in order to identify relevant studies on the topic. The official Brazilian epidemiology data were extensively analyzed at the governmental site www.inca.gov.br. RESULTS: Considering cases of breast and gynecologic cancers together, 105,770 new cases are expected to be diagnosed yearly, positioning female cancer as the highest cancer incidence in Brazil. Female breast cancer is the most common and the leading cause of death from cancer in the female population in all regions of Brazil, except in the North, where cervical cancer ranks first. Cervical cancer, a preventable disease, corresponds to the third-most common neoplasia in women, with higher incidences in the North and Northeast regions of Brazil. An upward trend has been observed in endometrial cancer incidence, a tendency that follows the increase of its two most common risk factors: population aging and obesity. Ovarian cancer currently occupies the eighth position among female cancers in Brazil, but it is the most lethal gynecologic cancer. The main strategies to reduce female cancer mortality rates are the reduction of inequalities in healthcare services and the early diagnosis of cases. The lack of a specific national cancer program results in a reactive and unplanned approach to healthcare provision, ultimately leading to suboptimal resource utilization and higher expenditure. CONCLUSION: Analyzed together, breast and gynecologic cancers correspond to the leading cause of cancer in Brazil. A heterogeneous group, female cancer includes diseases with a high primary and secondary prevention potential. The organization of a female cancer program in Brazil prioritizing primary and secondary prevention strategies, such as adequate mammography screening and human papillomavirus vaccination coverage, could significantly improve female cancer control in the country.


Subject(s)
Breast Neoplasms , Endometrial Neoplasms , Ovarian Neoplasms , Papillomavirus Infections , Papillomavirus Vaccines , Uterine Cervical Neoplasms , Female , Humans , Health Priorities , Brazil/epidemiology , Papillomavirus Infections/diagnosis , Papillomavirus Infections/prevention & control , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/prevention & control , Uterine Cervical Neoplasms/diagnosis , Breast Neoplasms/epidemiology , Breast Neoplasms/diagnosis , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/prevention & control
15.
J Cardiovasc Echogr ; 33(1): 10-16, 2023.
Article in English | MEDLINE | ID: mdl-37426709

ABSTRACT

Coronavirus disease 2019 (COVID-19) is characterized by multi-organ involvement, including respiratory and cardiac events. Echocardiography is widely considered the first-choice tool for the evaluation of cardiac structures and function because of its reproducibility, feasibility, easy to use at bedside, and for good cost-effectiveness. The aim of our literature review is to define the utility of echocardiography in the prediction of prognosis and mortality in COVID-19 patients with mild to critical respiratory illness, with or without known cardiovascular disease. Moreover, we focused our attention on classical echocardiographic parameters and the use of speckle tracking to predict the evolution of respiratory involvement. Finally, we tried to explore the possible relationship between pulmonary disease and cardiac manifestations.

16.
Medicina (Kaunas) ; 59(7)2023 Jul 23.
Article in English | MEDLINE | ID: mdl-37512160

ABSTRACT

Background: Adult-onset Still's disease (AOSD) is a rare rheumatic inflammatory condition with an extremely heterogeneous clinical presentation and systemic impairment. Uncommon manifestations may be challenging to manage, especially in patients with previous severe acute SARS-CoV-2 infection. For the first time, we report the case of a patient affected by refractory AOSD presenting with severe pancytopenia as a long-COVID manifestation. The purpose of this case report is to illustrate the clinical presentation, diagnostic and therapeutic management of this unusual manifestation. Moreover, we examine the mechanisms that are potentially responsible for the onset of the pancytopenia observed in our patient. Case presentation: We describe the case of a 40-year-old male who presented with a history of fever for 2 years, arthralgia, maculopapular salmon-pink rash and a previous SARS-CoV-2 infection which required admission to intensive care. The patient's laboratory results revealed elevated inflammatory markers levels (erythrocyte sedimentation rate and C-reactive protein), hyperferritinemia and severe pancytopenia that needed multiple transfusions. A diagnosis of AOSD was made based on clinical and laboratory presentation after excluding neoplastic, infectious and other rheumatic diseases. The previous empirical treatment was not adequate to control the condition; therefore, treatment with high-dose steroids, canakinumab and epoetin alfa was started and led to the resolution of the man's symptoms and a reduction in inflammatory marker levels, whereas blood cell count remained stable without a need for further blood transfusions. The patient is currently under rheumatologic and hematologic follow-up every month. Conclusions: Neither AOSD nor SARS-CoV-2 infection usually manifests with pancytopenia, except in hemophagocytic syndrome or immunodeficient patients, respectively. Identifying the underlying etiology of pancytopenia is mandatory to establish a prompt treatment that generally resolves the disorder. However, in our case, all common causes of pancytopenia were excluded, suggesting a potential manifestation of the long-COVID syndrome. Despite the resolution of the acute infection and the remarkable treatment of AOSD, pancytopenia persists. Herein, we propose for refractory AOSD patients with previous SARS-CoV-2 infection a novel approach to the diagnosis and treatment of pancytopenia.


Subject(s)
COVID-19 , Pancytopenia , Still's Disease, Adult-Onset , Adult , Male , Humans , Still's Disease, Adult-Onset/complications , Still's Disease, Adult-Onset/diagnosis , Still's Disease, Adult-Onset/drug therapy , Pancytopenia/etiology , Post-Acute COVID-19 Syndrome , COVID-19/complications , SARS-CoV-2
17.
Int J Mol Sci ; 24(13)2023 Jun 23.
Article in English | MEDLINE | ID: mdl-37445695

ABSTRACT

Chikungunya virus (CHIKV) has become a significant public health concern due to the increasing number of outbreaks worldwide and the associated comorbidities. Despite substantial efforts, there is no specific treatment or licensed vaccine against CHIKV to date. The E2 glycoprotein of CHIKV is a promising vaccine candidate as it is a major target of neutralizing antibodies during infection. In this study, we evaluated the immunogenicity of two DNA vaccines (a non-targeted and a dendritic cell-targeted vaccine) encoding a consensus sequence of E2CHIKV and a recombinant protein (E2*CHIKV). Mice were immunized with different homologous and heterologous DNAprime-E2* protein boost strategies, and the specific humoral and cellular immune responses were accessed. We found that mice immunized with heterologous non-targeted DNA prime- E2*CHIKV protein boost developed high levels of neutralizing antibodies, as well as specific IFN-γ producing cells and polyfunctional CD4+ and CD8+ T cells. We also identified 14 potential epitopes along the E2CHIKV protein. Furthermore, immunization with recombinant E2*CHIKV combined with the adjuvant AS03 presented the highest humoral response with neutralizing capacity. Finally, we show that the heterologous prime-boost strategy with the non-targeted pVAX-E2 DNA vaccine as the prime followed by E2* protein + AS03 boost is a promising combination to elicit a broad humoral and cellular immune response. Together, our data highlights the importance of E2CHIKV for the development of a CHIKV vaccine.


Subject(s)
Chikungunya virus , Vaccines, DNA , Viral Vaccines , Animals , Mice , Chikungunya virus/genetics , Antibodies, Neutralizing , CD8-Positive T-Lymphocytes , Antibodies, Viral , Immunity, Cellular , DNA
18.
J Clin Med ; 12(9)2023 May 01.
Article in English | MEDLINE | ID: mdl-37176688

ABSTRACT

Patients with chronic Inflammatory Arthritis (IA), such as Rheumatoid Arthritis (RA) and Spondyloarthritis (SpA) are more likely to experience psychosocial impairment. Gastrointestinal (GI) symptoms are also present, especially in Spondyloarthritis. No data are available on the relationship between gut and brain manifestations and their impact on daily activities in this setting; thus, this study aimed to assess these symptoms in an IA population and identify potential associations. IA patients and a control group were enrolled. The Patient-Reported Outcome Measurement Instrument System (PROMIS®) questionnaire was used to evaluate GI and psychosocial domains. The study included 389 subjects (238 controls and 151 with IA); demographic and clinical data were collected for each participant. IA patients reported both higher psychosocial and GI impairment compared with controls. The logistic regression model revealed a strong association between depression and belly pain (p = 0.035), diarrhea (p = 0.017), bloating (p = 0.018), and reflux (p = 0.01); anxiety was associated with belly pain (p = 0.004), diarrhea (p = 0.019), swallowing alterations (p = 0.004), flatulence (p < 0.001) and reflux (p = 0.008). Moreover, fatigue, sleep disorders, and pain interference were associated with almost all GI symptoms, whereas high physical function scores and satisfaction in social roles decreased the odds of most GI symptoms. IA patients had more significant impairment in both dimensions compared with controls. To address reported symptoms and improve the overall quality of life in rheumatologic patients, a new holistic approach is required.

19.
Front Immunol ; 14: 1071041, 2023.
Article in English | MEDLINE | ID: mdl-37006270

ABSTRACT

Introduction: In the present study we evaluated the features of different recombinant forms of Zika virus (ZIKV) proteins produced in either bacterial (Eschericha coli) or insect cells (Drosophila melanogaster). The ZIKV-envelope glycoprotein (EZIKV) is responsible for virus entry into host cells, is the main target of neutralizing antibodies and has been used as a target antigen either for serological tests or for the development of subunit vaccines. The EZIKV is composed of three structural and functional domains (EDI, EDII, and EDIII), which share extensive sequence conservation with the corresponding counterparts expressed by other flaviviruses, particularly the different dengue virus (DENV) subtypes. Methods: In this study, we carried out a systematic comparison of the antigenicity and immunogenicity of recombinant EZIKV, EDI/IIZIKV and EDIIIZIKV produced in E. coli BL21 and Drosophila S2 cells. For the antigenicity analysis we collected 88 serum samples from ZIKV-infected participants and 57 serum samples from DENV-infected. For immunogenicity, C57BL/6 mice were immunized with two doses of EZIKV, EDI/IIZIKV and EDIIIZIKV produced in E. coli BL21 and Drosophila S2 cells to evaluate humoral and cellular immune response. In addition, AG129 mice were immunized with EZIKV and then challenge with ZIKV. Results: Testing of samples collected from ZIKV-infected and DENV-infected participants demonstrated that the EZIKV and EDIIIZIKV produced in BL21 cells presented better sensitivity and specificity compared to proteins produced in S2 cells. In vivo analyses were carried out with C57BL/6 mice and the results indicated that, despite similar immunogenicity, antigens produced in S2 cells, particularly EZIKV and EDIIIZIKV, induced higher ZIKV-neutralizing antibody levels in vaccinated mice. In addition, immunization with EZIKV expressed in S2 cells delayed the onset of symptoms and increased survival rates in immunocompromised mice. All recombinant antigens, either produced in bacteria or insect cells, induced antigen-specific CD4+ and CD8+ T cell responses. Conclusion: In conclusion, the present study highlights the differences in antigenicity and immunogenicity of recombinant ZIKV antigens produced in two heterologous protein expression systems.


Subject(s)
Zika Virus Infection , Zika Virus , Animals , Mice , Zika Virus/genetics , Viral Envelope Proteins/chemistry , Antibodies, Viral , Drosophila melanogaster , Escherichia coli/genetics , Mice, Inbred C57BL , Vaccines, Subunit
20.
Genome Biol Evol ; 15(4)2023 04 06.
Article in English | MEDLINE | ID: mdl-36911979

ABSTRACT

Permeable phylogeographic barriers characterize the vast open ocean, boosting gene flow and counteracting population differentiation and speciation of widely distributed and migratory species. However, many widely distributed species consists of distinct populations throughout their distribution, evidencing that our understanding of how the marine environment triggers population and species divergence are insufficient. The sailfish is a circumtropical and highly migratory billfish that inhabits warm and productive areas. Despite its ecological and socioeconomic importance as a predator and fishery resource, the species is threatened by overfishing, requiring innovative approaches to improve their management and conservation status. Thus, we presented a novel high-quality reference genome for the species and applied a seascape genomics approach to understand how marine environmental features may promote local adaptation and how it affects gene flow between populations. We delimit two populations between the Atlantic and Indo-Western Pacific oceans and detect outlier loci correlated with sea surface temperature, salinity, oxygen, and chlorophyll concentrations. However, the most significant explanatory factor that explains the differences between populations was isolation by distance. Despite recent population drops, the sailfish populations are not inbred. For billfishes in general, genome-wide heterozygosity was found to be relatively low compared to other marine fishes, evidencing the need to counteract overfishing effects. In addition, in a climate change scenario, management agencies must implement state-of-the-art sequencing methods, consider our findings in their management plans, and monitor genome-wide heterozygosity over time to improve sustainable fisheries and the long-term viability of its populations.


Subject(s)
Conservation of Natural Resources , Perciformes , Animals , Phylogeography , Fisheries , Genomics
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