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We aimed to describe the landscape, including molecular, epidemiological, and clinical aspects of CHIKV infections in the Ribeirao Preto region, an area endemic to dengue. We randomly screened 3744 plasma samples that had undergone DENV diagnosis to evaluate CHIKV-RNA using an in-house RT-PCR assay. Positive samples were followed clinically, and RNA samples were submitted to whole genome sequencing. Seventeen cases (0.5 %) were positive for CHIKV-RNA despite being negative for DENV-RNA. Notably, half of the patients experienced prolonged arthralgia lasting more than 90 days. Compared with the healthy control group, leukopenia and thrombocytopenia were observed in all CHIKV-positive individuals with statistically significant P values (P < 0.0001 and P = 0.0003, respectively). The genomic analysis revealed that the CHIKV strains being studied are classified within the East-Central-South-African (ECSA) genotype. This analysis identified new mutations, E1: K211E and E2: V264A, while the previously known mutation E1: A226V was not detected among these strains. This study highlights the need for epidemiological surveillance and preparedness for potential CHIKV epidemics in Brazil, particularly where other arboviruses co-circulate.
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Febre de Chikungunya , Vírus Chikungunya , Dengue , Genótipo , RNA Viral , Humanos , Brasil/epidemiologia , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/sangue , Febre de Chikungunya/virologia , Vírus Chikungunya/genética , Vírus Chikungunya/isolamento & purificação , Dengue/epidemiologia , Dengue/virologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , RNA Viral/genética , Adulto Jovem , Doenças Endêmicas , Adolescente , Sequenciamento Completo do Genoma , Idoso , Criança , Filogenia , Mutação , Pré-Escolar , Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Vírus da Dengue/classificação , Trombocitopenia/epidemiologia , Trombocitopenia/virologiaRESUMO
Background: Dengue virus (DENV) and Chikungunya virus (CHIKV) pose significant public health threats in Brazil, where favorable conditions facilitated the proliferation of Aedes mosquitoes. Since the mid-1980s, Brazil has experienced annual outbreaks of DENV, with recent increases in confirmed cases. In addition, CHIKV, which was first reported in 2014, has spread across the country. The concurrent presence of these viruses has triggered public health alerts in endemic regions, underscoring the complexity of managing vector-borne diseases. Case Presentation: This report details a case of simultaneous DENV and CHIKV infections. A 77-year-old female patient who has diabetes and arrhythmia exhibited symptoms including fever, myalgia, and severe arthralgia. Laboratory tests confirmed the coinfection through RNA detection. The patient received supportive care, showed gradual improvement, and was eventually discharged. Conclusions: Coinfection with DENV and CHIKV cases reported here developed with mild outcomes. However, one of the patients did not recover from the arthralgia after presenting diagnostic challenges, which underscores the need for accurate differentiation to manage symptoms effectively. The reported cases, amidst increasing DENV outbreaks, highlight the urgency for preparedness in the healthcare system. The Ribeirão Preto region's endemicity for DENV, coupled with the rising incidence of CHIKV, emphasizes the evolving landscape of arbovirus transmission. Studies on Aedes mosquitoes suggest potential implications for human infection dynamics, warranting further investigation into arbovirus transmission efficacy and coinfection dynamics.
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The aim of this study was to describe epidemiological characteristics and perform SARS-CoV-2 genomic surveillance in the southeastern region of São Paulo State. During the first months of 2022, we compared weekly SARS-CoV-2 infection prevalence considering age, Ct value, and variants' lineages. An increase in the number of SARS-CoV-2-positive cases until the fourth epidemiological week of 2022 was observed. From the fourth epidemiological week onwards, the number of tests for SARS-CoV-2 diagnosis began to decrease, but the number of positive samples for SARS-CoV-2 remained high, reaching its most expressive level with a rate of 60% of infected individual cases. In this period, we observed a progressive increase in SARS-CoV-2 infection within the 0-10 age group throughout the epidemiological weeks, from 2.8% in the first epidemiological week to 9.2% in the eighth epidemiological week of 2022. We further observed significantly higher Ct values within younger patient samples compared to other older age groups. According to lineage assignment, SARS-CoV-2 (BA.1) was the most prevalent (74.5%) in the younger group, followed by BA.1.1 (23%), BA.2 (1.7%), and Delta (1%). Phylogenetic analysis showed that BA.2 sequences clustered together, indicating sustained transmission of this Omicron VOC sub-lineage by that time. Our results suggest the initial dissemination steps of the Omicron's sub-linage BA.2 into the younger group, due to specific genomic features of the detected sequences. These data provide interesting results related to the spread, emergence, and evolution of the Omicron variant in the southeast Brazilian population.
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Vírus da Dengue , Dengue , Humanos , Brasil/epidemiologia , Vírus da Dengue/genética , Dengue/epidemiologia , GenótipoRESUMO
BACKGROUND: Steroid-refractory acute graft-vs.-host disease (SR-aGVHD) is a complication of allogeneic hematopoietic stem cell transplantation with a dismal prognosis and for which there is no consensus-based second-line therapy. Ruxolitinib is not easily accessible in many countries. A possible therapy is the administration of mesenchymal stromal cells (MSCs). METHODS: In this retrospective study, 52 patients with severe SR-aGVHD were treated with MSCs from umbilical cord (UC-MSCs) in nine institutions. RESULTS: The median (range) age was 12.5 (0.3-65) years and the mean ± SD dose (×106/kg) was 4.73 ± 1.3 per infusion (median of four infusions). Overall (OR) and complete response (CR) rates on day 28 were 63.5% and 36.6%, respectively. Children (n = 35) had better OR (71.5% vs. 47.1%, p = 0.12), CR (48.6% vs. 11.8%, p = 0.03), overall survival (p = 0.0006), and relapse-free survival (p = 0.0014) than adults (n = 17). Acute adverse events (all of them mild or moderate) were detected in 32.7% of patients, with no significant difference in children and adult groups (p = 1.0). CONCLUSIONS: UC-MSCs are a feasible alternative therapy for SR-aGVHD, especially in children. The safety profile is favorable.
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Background: The long-term humoral immune response after vaccination varies between vaccines and is dependent on the accuracy of the antibody test. A better understanding of the vaccine immune response may help to define vaccination strategies against coronavirus disease 2019 (COVID-19). Objective: To investigate the long-term immunological response to CoronaVac vaccine and determinants of breakthrough COVID-19 infection. Methods: A long-term, prospective cohort study involving vaccinated adult and elderly subjects was conducted to investigate the presence of anti-RBD-specific immunoglobulin (Ig)G, anti-nucleocapsid IgG and anti-spike trimeric protein IgG. Antibody level dynamics and risk factors associated with breakthrough COVID-19 infection were investigated. Results: In total, 3902 participants were included in this study. Vaccination with two doses of CoronaVac and a booster dose increased the levels of anti-RBD-specific IgG, anti-nucleocapsid IgG and anti-spike trimeric IgG significantly. In adults, anti-nucleocapsid IgG and anti-spike trimeric IgG levels decreased significantly 7 months after the second dose. In adults and the elderly, the levels of anti-spike trimeric IgG and anti-RBD IgG decreased significantly 4 and 6 months after the booster dose, respectively. Previous exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and anti-spike trimeric IgG titres was independently associated with a lower probability of post-vaccination infection. Conclusions: A significant increase in antibody levels was found after two doses of CoronaVac and a booster dose. Antibody titres declined significantly 7 months post-vaccination in participants who did not receive a booster dose. Higher levels of antibodies and previous SARS-CoV-2 infection were associated with protection against breakthrough COVID-19.
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From a country with one of the highest SARS-CoV-2 morbidity and mortality rates, Brazil has implemented one of the most successful vaccination programs. Brazil's first model city vaccination program was performed by the CoronaVac vaccine (Sinovac Biotech) in the town of Serrana, São Paulo State. To evaluate the vaccination effect on the SARS-CoV-2 molecular dynamics and clinical outcomes, we performed SARS-CoV-2 molecular surveillance on 4375 complete genomes obtained between June 2020 and April 2022 in this location. This study included the period between the initial SARS-CoV-2 introduction and during the vaccination process. We observed that the SARS-CoV-2 substitution dynamics in Serrana followed the viral molecular epidemiology in Brazil, including the initial identification of the ancestral lineages (B.1.1.28 and B.1.1.33) and epidemic waves of variants of concern (VOC) including the Gamma, Delta, and, more recently, Omicron. Most probably, as a result of the immunization campaign, the mortality during the Gamma and Delta VOC was significantly reduced compared to the rest of Brazil, which was also related to lower morbidity. Our phylogenetic analysis revealed the evolutionary history of the SARS-CoV-2 in this location and showed that multiple introduction events have occurred over time. The evaluation of the COVID-19 clinical outcome revealed that most cases were mild (88.9%, 98.1%, 99.1% to Gamma, Delta, and Omicron, respectively) regardless of the infecting VOC. In conclusion, we observed that vaccination was responsible for reducing the death toll rate and related COVID-19 morbidity, especially during the gamma and Delta VOC; however, it does not prevent the rapid substitution rate and morbidity of the Omicron VOC.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Brasil/epidemiologia , Filogenia , COVID-19/epidemiologia , COVID-19/prevenção & controle , VacinaçãoRESUMO
The authors hereby request the inclusion of two authors (Olivia Teixeira and Maria Cristina Nonato) in the recently published article in Viruses entitled "Nucleocapsid (N) gene mutations of SARS-CoV-2 can affect real-time RT-PCR diagnostic and impact false-negative results" [...].
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BACKGROUND AND AIMS: Over 4 million deaths from coronavirus disease (COVID)-19 have been reported in the world. Several biomarkers have been identified that predict disease severity, but there is still a need to identify biomarkers for death risk in severe COVID-19. We aim to define amongst the biomarkers already identified those which are mostly associated with increased death rate in patients with severe COVID-19. METHODS: In this retrospective study conducted in three public hospitals linked to the Medical School of Ribeirão Preto, Brazil, patients with severe COVID-19 were evaluated regarding biomarkers (neutrophil-to-lymphocyte ratio-NLR, D-dimer, fibrinogen) of death risk, obtained before administration of corticosteroids. RESULTS: Thirty-nine (32.8%) of the 119 patients included (104 [87.4%] on mechanical ventilation) died during hospitalization. Non-survivor group had higher median (range) NLR (12.63 [2.6-115] vs 7.43 [0.43-31.8]; P = .001), D-dimer (2.17 [0.27-20.00] vs 1.57 [0.28-20.00]; P = .03), but lower fibrinogen (631 [353-1078] vs 705 [407-1200]; P = .02). The group with NLR ≥ 10 and D-dimer ≥ 2 µg/mL had a higher death risk than the group with NLR < 10 and D-dimer < 2 µg/mL (OR: 5.39; CI 95%: 1.5-19.42; P = .01). CONCLUSION: High NLR and D-dimer, especially when combined, are predictors of death risk for patients with severe COVID-19 and should be incorporated into their evaluation.
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The SARS-CoV-2 alpha VOC (also known as lineage B.1.1.7) initially described in the autumn, 2020 in UK, rapidly became the dominant lineage across much of Europe. Despite multiple studies reporting molecular evidence suggestive of its circulation in Brazil, much is still unknown about its genomic diversity in the state of São Paulo, the main Brazilian economic and transportation hub. To get more insight regarding its transmission dynamics into the State we performed phylogenetic analysis on all alpha VOC strains obtained between February and August 2021 from the Sao Paulo state Network for Pandemic Alert of Emerging SARS-CoV-2 variants. The performed phylogenetic analysis showed that most of the alpha VOC genomes were interspersed with viral strains sampled from different Brazilian states and other countries suggesting that multiple independent Alpha VOC introductions from Brazil and overseas have occurred in the São Paulo State over time. Nevertheless, large monophyletic clusters were also observed especially from the Central-West part of the São Paulo State (the city of Bauru) and the metropolitan region of the São Paulo city. Our results highlight the Alpha VOC molecular epidemiology in the São Paulo state and reinforce the need for continued genomic surveillance strategies for the real-time monitoring of potential emerging SARS-CoV-2 variants during the ever-growing vaccination process.
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COVID-19 , Filogenia , SARS-CoV-2/genética , Brasil/epidemiologia , COVID-19/epidemiologia , COVID-19/virologia , Genômica , Humanos , Organização Mundial da SaúdeRESUMO
The current COVID-19 pandemic demands massive testing by Real-time RT-PCR (Reverse Transcription Polymerase Chain Reaction), which is considered the gold standard diagnostic test for the detection of the SARS-CoV-2 virus. However, the virus continues to evolve with mutations that lead to phenotypic alterations as higher transmissibility, pathogenicity or vaccine evasion. Another big issue are mutations in the annealing sites of primers and probes of RT-PCR diagnostic kits leading to false-negative results. Therefore, here we identify mutations in the N (Nucleocapsid) gene that affects the use of the GeneFinder COVID-19 Plus RealAmp Kit. We sequenced SARS-CoV-2 genomes from 17 positive samples with no N gene detection but with RDRP (RNA-dependent RNA polymerase) and E (Envelope) genes detection, and observed a set of three different mutations affecting the N detection: a deletion of 18 nucleotides (Del28877-28894), a substitution of GGG to AAC (28881-28883) and a frameshift mutation caused by deletion (Del28877-28878). The last one cause a deletion of six AAs (amino acids) located in the central intrinsic disorder region at protein level. We also found this mutation in 99 of the 14,346 sequenced samples by the Sao Paulo state Network for Pandemic Alert of Emerging SARS-CoV-2 variants, demonstrating the circulation of the mutation in Sao Paulo, Brazil. Continuous monitoring and characterization of mutations affecting the annealing sites of primers and probes by genomic surveillance programs are necessary to maintain the effectiveness of the diagnosis of COVID-19.
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Teste de Ácido Nucleico para COVID-19 , COVID-19/diagnóstico , Proteínas do Nucleocapsídeo de Coronavírus/genética , SARS-CoV-2/isolamento & purificação , Brasil/epidemiologia , COVID-19/epidemiologia , RNA-Polimerase RNA-Dependente de Coronavírus/genética , Primers do DNA , Reações Falso-Negativas , Genoma Viral/genética , Humanos , Mutação , Fosfoproteínas/genética , RNA Viral/genética , SARS-CoV-2/genéticaRESUMO
Metabolic and hormonal outcomes of polycystic ovary syndrome (PCOS) have implications on telomere biology and physical activity may prevent telomere erosion. We sought to observe the effects of continuous (CAT) and intermittent (IAT) aerobic training on telomere length, inflammatory biomarkers, and its correlation with metabolic, hormonal, and anthropometric parameters of PCOS. This randomized controlled clinical trial study included 87 PCOS randomly stratified according to body mass index (BMI) in CAT (n = 28), IAT (n = 29) and non-training control group (CG, n = 30). The exercises were carried out on a treadmill, three times per week for 16 weeks. The participants' anthropometric characteristics and biochemical and hormonal concentrations were measured before and after aerobic training or observation period, as the telomere length that was evaluated using quantitative real-time PCR. Four months of aerobic exercises (CAT or IAT) did not alter telomere length and inflammatory biomarkers in PCOS women. Obesity index as BMI and waist circumference (WC), and inflammatory biomarkers negatively affect telomeres. The hyper-andro-genism measured by testosterone levels was reduced after both exercises (CAT, p ≤ 0.001; IAT, p = 0.019). In particular, the CAT reduced WC (p = 0.045), hip circumference (p = 0.032), serum cholesterol (p ≤ 0.001), and low-density lipoprotein (p = 0.030). Whereas, the IAT decreased WC (p = 0.014), waist-to-hip ratio (p = 0.012), free androgen index (FAI) (p = 0.037). WC (p = 0.049) and body fat (p = 0.015) increased in the non-training group while total cholesterol was reduced (p = 0.010). Booth exercises reduced obesity indices and hyperandrogenism on PCOS women without changes in telomere length or inflammatory biomarkers.
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Resistência à Insulina , Síndrome do Ovário Policístico , Índice de Massa Corporal , Exercício Físico , Feminino , Humanos , Obesidade , Telômero , TestosteronaRESUMO
The Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of an unprecedented worldwide pandemic. Brazil demonstrates one of the highest numbers of confirmed SARS-CoV-2 cases, and São Paulo State is the epicenter of the pandemics in the country. Nevertheless, little is known about the SARS-CoV-2 circulation in other cities in the State than São Paulo city. The objective of this study was to analyze phylogenetically SARS-CoV-2 strains circulating in city of Ribeirão Preto at the beginning of the pandemic and during the actual second wave. Twenty-nine nasopharyngeal SARS-CoV-2 RNA positive samples were sequenced by nanopore technology (18 obtained at the initial period of the pandemic and 11 during the second wave) and analyzed them phylogenetically. The performed analysis demonstrated that the majority of the strains obtained in the initial period of the pandemic in Ribeirão Preto belonged mainly to the B1.1.33 lineage (61.1%), but B.1.1 (27.8%) and B.1.1.28 (11.1%) lineages were also identified. In contrast, the second wave strains were composed exclusively by the Brazilian variant of concern (VOC) P.1 (91%) and P.2 (9%) lineages. The obtained phylogenetic results were suggestive of successive SARS-CoV-2 lineage substitution in this Brazilian region by the P.1 VOC. The performed study examines the SARS-CoV-2 genotypes in Ribeirão Preto city via genomic surveillance data. The obtained findings can contribute for continuous long-term genomic surveillance of SARS-CoV-2 due to the accelerated dynamics of viral lineage substitution, predict further waves and examine lineage behavior during SARS-CoV-2 vaccination.
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COVID-19/epidemiologia , SARS-CoV-2/genética , Adulto , Brasil/epidemiologia , COVID-19/virologia , Evolução Molecular , Feminino , Genoma Viral , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , SARS-CoV-2/isolamento & purificaçãoRESUMO
BACKGROUND: Idiopathic central precocious puberty (iCPP) presents a disproportionate advancement of bone age and maturation, as well as metabolic and endocrinological changes that may be related to effects on telomere biology. OBJECTIVE: To investigate the telomere length in iCPP girls treated with GnRHa. STUDY DESIGN: Observational case-control study with 85 girls, including 45 iCPP treated with GnRHa and 40 controls. It was analyzed age, height, weight and body mass index (BMI), insulin, triglycerides, testosterone, insulin resistance by HOMA, and telomere length by real-time PCR. Statistical analyses were determined by Wilcoxon test and Spearman correlation was carried out. RESULTS: Weight, BMI, insulin level and HOMA index were higher in the iCPP than in the control group (p < .01); without difference between mean ages. The telomere length did not differ between iCPP and control group. However, a negative correlation was observed between the telomere length and age in iCPP (p = .0009) and control group (p = .014), and weight in the iCPP (p = .017). CONCLUSIONS: We did not observe any difference in the telomere length in the iCPP and control group. Even though, some characteristics of the disease, such as increased weight and body fat, negatively influence the telomere biology.
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Hormônio Liberador de Gonadotropina/análogos & derivados , Leuprolida/uso terapêutico , Puberdade Precoce/metabolismo , Telômero/metabolismo , Adolescente , Fatores Etários , Composição Corporal , Índice de Massa Corporal , Peso Corporal , Estudos de Casos e Controles , Criança , Impedância Elétrica , Feminino , Humanos , Insulina/sangue , Resistência à Insulina , Puberdade Precoce/tratamento farmacológico , Homeostase do Telômero , Adulto JovemRESUMO
OBJECTIVE: To describe the clinical, functional, and radiological features of index cases of familial pulmonary fibrosis (FPF) in Brazil. METHODS: We evaluated 35 patients with FPF - of whom 18 (51.4%) were women - with a median age of 66.0 years (range, 35.5-89.3 years). All of the patients completed a standardized questionnaire, as well as undergoing pulmonary function tests and HRCT of the chest. In 6 cases, lung tissue samples were obtained: from surgical biopsies in 5 cases; and from an autopsy in 1 case. RESULTS: A history of smoking and a history of exposure to birds or mold were reported in 45.7% and 80.0% of the cases, respectively. Cough and marked dyspnea were reported by 62.8% and 48.6% of the patients, respectively. Fine crackles were detected in 91.4% of the patients. In 4 patients, the findings were suspicious for telomere disease. The median FVC and DLCO, as percentages of the predicted values, were 64.9% (range, 48.8-105.7%) and 38.9% (range, 16.0-60.0%), respectively. Nine patients had reduced DLCO despite having normal spirometry results. Regarding HRCT, patterns typical of usual interstitial pneumonia were found in 6 patients (17.1%). In 25 cases (71.5%), the HRCT features were consistent with a diagnosis other than idiopathic pulmonary fibrosis. In 11 cases (31.4%), the radiological patterns were uncharacteristic of interstitial lung disease. Of the six lung tissue samples analyzed, four showed interstitial pneumonia with bronchiolocentric accentuation, and, on the basis of the clinical and radiological data, the corresponding patients were diagnosed with hypersensitivity pneumonitis. CONCLUSIONS: Patients with FPF can present with a wide variety of clinical features. Most HRCT scans of these patients exhibit patterns not typical of usual interstitial pneumonia. The family history of fibrotic lung diseases should be investigated in all patients under suspicion, regardless of their age.
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Doenças Pulmonares Intersticiais/patologia , Fibrose Pulmonar/patologia , Adulto , Distribuição por Idade , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Biópsia , Brasil/epidemiologia , Feminino , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/epidemiologia , Masculino , Pessoa de Meia-Idade , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/epidemiologia , Testes de Função Respiratória , Distribuição por Sexo , Tomografia Computadorizada por Raios XRESUMO
Varicocele pathophysiology is related to increased oxidative stress, which might result in loss sperm DNA integrity as well as in genomic instability. Sperm telomere shortening and loss of global DNA methylation are the main features of genomic instability, leading to cell senescence and death, whereas sperm DNA fragmentation (SDF) characterizes the loss of chromatin integrity. We hypothesize that sperm genomic stability and DNA integrity is reduced in infertile men with moderate and large-sized varicoceles, thus being candidate markers of sperm quality in varicocele-related infertility. Here, we assessed the sperm global DNA methylation, telomere length, and SDF in men with and without clinically palpable varicoceles. While the rates of SDF and telomere length were not statistically different between varicocele patients and controls, global sperm DNA methylation seems to be lower in men with varicocele (49.7% ± 20.7%) than controls (64.7% ± 17.1%). A negative correlation between SDF and sperm motility and a positive correlation between sperm morphology and telomere length were observed. Our results suggest that varicocele may result in genomic instability, in particular, global DNA hypomethylation. However, a large sample size may confirm these findings. The understanding of the molecular mechanisms involved in the pathophysiology of varicocele-related infertility may help to better select candidates for varicocele repair.
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Metilação de DNA , Telômero , Varicocele/genética , Adulto , Estudos Transversais , Fragmentação do DNA , Humanos , Infertilidade Masculina/genética , Masculino , Espermatozoides/metabolismoRESUMO
ABSTRACT Objective: To describe the clinical, functional, and radiological features of index cases of familial pulmonary fibrosis (FPF) in Brazil. Methods: We evaluated 35 patients with FPF - of whom 18 (51.4%) were women - with a median age of 66.0 years (range, 35.5-89.3 years). All of the patients completed a standardized questionnaire, as well as undergoing pulmonary function tests and HRCT of the chest. In 6 cases, lung tissue samples were obtained: from surgical biopsies in 5 cases; and from an autopsy in 1 case. Results: A history of smoking and a history of exposure to birds or mold were reported in 45.7% and 80.0% of the cases, respectively. Cough and marked dyspnea were reported by 62.8% and 48.6% of the patients, respectively. Fine crackles were detected in 91.4% of the patients. In 4 patients, the findings were suspicious for telomere disease. The median FVC and DLCO, as percentages of the predicted values, were 64.9% (range, 48.8-105.7%) and 38.9% (range, 16.0-60.0%), respectively. Nine patients had reduced DLCO despite having normal spirometry results. Regarding HRCT, patterns typical of usual interstitial pneumonia were found in 6 patients (17.1%). In 25 cases (71.5%), the HRCT features were consistent with a diagnosis other than idiopathic pulmonary fibrosis. In 11 cases (31.4%), the radiological patterns were uncharacteristic of interstitial lung disease. Of the six lung tissue samples analyzed, four showed interstitial pneumonia with bronchiolocentric accentuation, and, on the basis of the clinical and radiological data, the corresponding patients were diagnosed with hypersensitivity pneumonitis. Conclusions: Patients with FPF can present with a wide variety of clinical features. Most HRCT scans of these patients exhibit patterns not typical of usual interstitial pneumonia. The family history of fibrotic lung diseases should be investigated in all patients under suspicion, regardless of their age.
RESUMO Objetivo: Descrever as características clínicas, funcionais e radiológicas de um grupo de casos índice diagnosticados com fibrose pulmonar familiar (FPF) no Brasil. Métodos: Trinta e cinco pacientes com FPF (18 mulheres; 51,4%), com mediana de idade de 66,0 anos (variação: 35,5-89,3 anos), responderam a um questionário padronizado e foram submetidos a testes de função pulmonar e TCAR de tórax. Tecido pulmonar foi obtido para revisão em 6 casos: a partir de biópsias cirúrgicas em 5 e de autópsia em 1. Resultados: Antecedentes de tabagismo e de exposição a aves ou mofo foram referidos por 45,7% e 80,0% dos casos, respectivamente. Tosse e dispneia significante foram referidas por 62,8% e 48,6% dos pacientes, respectivamente. Estertores finos foram detectados em 91,4% dos indivíduos. Em 4 pacientes, os achados levantaram suspeitas de doença dos telômeros. As medianas da CVF e da DLCO foram, respectivamente, de 64,9% (variação: 48,8-105,7%) e 38,9% (variação: 16,0-60,0%) em porcentagem dos valores previstos. Apesar de espirometria normal, 9 pacientes exibiram DLCO reduzida. Em relação às TCAR, padrões típicos de pneumonia intersticial usual foram encontrados em 6 pacientes (17,1%). Em 25 casos (71,5%) os achados tomográficos foram mais consistentes com um diagnóstico de não relacionado a fibrose pulmonar idiopática. Em 11 pacientes (31,4%) o padrão radiológico foi incaracterístico para doença pulmonar intersticial. Das seis amostras de tecido pulmonar analisadas, quatro mostraram pneumonias intersticiais com acentuação bronquiolocêntrica e, em função de outros dados clínicos e radiológicos, pneumonite de hipersensibilidade foi diagnosticada. Conclusões: Pacientes com FPF podem apresentar características clínicas diversas. A maioria das TCAR desses pacientes exibe padrões não típicos de pneumonia intersticial usual. A pesquisa da história clínica de outros casos de pneumopatias fibrosantes na família deve ser feita em todos os pacientes em investigação, independentemente da idade.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Fibrose Pulmonar/patologia , Doenças Pulmonares Intersticiais/patologia , Fibrose Pulmonar/epidemiologia , Fibrose Pulmonar/diagnóstico por imagem , Testes de Função Respiratória , Biópsia , Brasil/epidemiologia , Tomografia Computadorizada por Raios X , Distribuição por Sexo , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Idade de Início , Distribuição por IdadeRESUMO
ABSTRACT Background: Human aplastic anemia is a hematologic disease characterized by low peripheral blood cell counts associated with reduced numbers of hematopoietic stem and progenitor cells and a hypocellular bone marrow. Thrombopoietin (THPO) regulates megakaryocytes, but it also stimulates hematopoietic stem and progenitor cells. Biallelic mutations in the THPO gene have been reported in a family with recessive inherited aplastic anemia. Methods: This study screened 83 patients diagnosed with acquired aplastic anemia and 92 paired healthy controls for germline variants in the THPO gene using Sanger sequencing. Results: Three common single nucleotide polymorphisms were identified in patients and controls at comparable allele frequencies. There was no correlation between the single nucleotide polymorphism carrier status and platelet counts at diagnosis. Conclusion: The presence of THPO polymorphisms is comparable between patients with acquired aplastic anemia and healthy individuals.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Trombopoetina , Anemia AplásticaRESUMO
OBJECTIVE: We evaluated the association between cognitive deficits and leukocyte telomere length (LTL) in HIV-1-infected individuals. DESIGN: 73 HIV-1-infected patients undergoing neuropsychological evaluation and 91 healthy controls were included in this study. Fifteen HIV-1 positive patients did not have cognitive disorders whereas 26 had asymptomatic neurocognitive disorder (ANI), 13 presented mild to moderate neurocognitive disorder (MND), and 10 had HIV-associated dementia (HAD). METHODS: DNA from the peripheral blood of HIV-1-infected patients was used for measurement of telomere length by real-time PCR. HIV-1 viral load was determined in blood. RESULTS: LTL decreased with age in healthy controls (p=0.0001). Regardless of the HIV status, age-matched LTL from HIV patients, including those with ANI and MND, were shortened in comparison to the healthy control group (p=0.0073); however, no association was found among the HIV-1-infected individuals with cognitive deficits (p=0.01). In addition, no gender-related association with LTL was observed (p=0.80), smoking, physical exercise, and plasma viral load were not correlated to telomere length (p=0.66). CONCLUSIONS: We concluded that leukocyte telomere length may not be a marker of cellular senescence in individuals with HIV infection and neurocognitive disorders.
Assuntos
Infecções por HIV/genética , Infecções por HIV/psicologia , HIV-1 , Transtornos Neurocognitivos/genética , Transtornos Neurocognitivos/virologia , Homeostase do Telômero/genética , Telômero/genética , Fatores Etários , Análise de Variância , Estudos de Casos e Controles , Feminino , Humanos , Leucócitos/virologia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Estatísticas não Paramétricas , Inquéritos e Questionários , Carga ViralRESUMO
Leishmaniasis is a spectrum of diseases caused by parasites of the genus Leishmania that affects millions of people around the world. During infection, the parasites use different strategies to survive the host's defenses, including overcoming exposure to reactive oxidant species (ROS), responsible for causing damage to lipids, proteins and DNA. This damage especially affects telomeres, which frequently results in genome instability, senescence and cell death. Telomeres are the physical ends of the chromosomes composed of repetitive DNA coupled with proteins, whose function is to protect the chromosomes termini and avoid end-fusion and nucleolytic degradation. In this work, we induced acute oxidative stress in promastigote forms of Leishmania amazonensis by treating parasites with 2mM hydrogen peroxide (H2O2) for 1h, which was able to increase intracellular ROS levels. In addition, oxidative stress induced DNA damage, as confirmed by 8-oxodGuo quantification and TUNEL assays and the dissociation of LaRPA-1 from the 3' G-overhang, leading to telomere shortening. Moreover, LaRPA-1 was observed to interact with newly formed C-rich single-stranded telomeric DNA, probably as a consequence of the DNA damage response. Nonetheless, acute oxidative stress caused the death of some of the L. amazonensis population and induced cell cycle arrest at the G2/M phase in survivor parasites, which were able to continue proliferating and replicating DNA and became more resistant to oxidative stress. Taken together, these results suggest that adaptation occurs through the selection of the fittest parasites in terms of repairing oxidative DNA damage at telomeres and maintaining genome stability in a stressful environment.